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Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
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Low CE, Ge G, Yeong TJJM, Rana S, Loke S, Kow WC, Lee ARYB, Ho CSH. Burden of psychological symptoms and disorders among individuals with hepatitis B: a systematic review, meta-analysis and meta-regression. Front Psychiatry 2025; 16:1546545. [PMID: 40195970 PMCID: PMC11973283 DOI: 10.3389/fpsyt.2025.1546545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 03/06/2025] [Indexed: 04/09/2025] Open
Abstract
Introduction Hepatitis B is a highly contagious viral infection that has long been a significant global health concern. Given its adverse effects on the course of the disease, evaluating psychiatric outcomes is important. Despite indications of an increased risk of psychological outcomes among those with hepatitis B, the extent of this association remains unclear. Methods This PRISMA-adherent systematic review (PROSPERO: CRD42024564246) searched PubMed, Embase, Cochrane, and PsycINFO for all studies evaluating the prevalence and risk of anxiety and depressive symptoms in individuals with hepatitis B. Random effects meta-analyses and meta-regression were used for primary analysis. Results A total of 31 studies were included. We identified a high prevalence of depressive symptoms (Proportion=19%, 95% CI: 11-31) and anxiety (Proportion=30%, 95% CI: 18-45) among individuals with hepatitis B. There was also a significantly increased risk of depressive symptoms (RR=1.45, 95% CI: 1.00-2.09, P=0.049) and anxiety (RR=1.40, 95% CI: 1.11-1.78) in individuals with hepatitis B compared to controls. Subgroup analyses indicated that older age and chronic hepatitis B infection were associated with a higher prevalence of anxiety and depressive symptoms. The systematic review found that being single, unemployed, having a lower income, a lower education level, high comorbidities, and a family history of mental illness were significant risk factors for poorer psychological outcomes. Conclusion Our study highlights an increased vulnerability to anxiety and depressive symptoms among individuals with hepatitis B. We emphasize the urgent need for early detection and additional support for this at-risk group. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024564246.
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Affiliation(s)
- Chen Ee Low
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Genevieve Ge
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | - Sounak Rana
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Sean Loke
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wei Chieh Kow
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore, Singapore
| | | | - Cyrus Su Hui Ho
- Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Psychological Medicine, National University Hospital, Singapore, Singapore
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Chen YC, Tsai PC, Huang CF, Chen CY, Hung CH, Chen CH, Tai CM, Cheng PN, Kuo HT, Mo LR, Lo CC, Huang YH, Lin HC, Lee PL, Bair MJ, Chang TS, Lin CY, Wang SJ, Hsieh TY, Yang TH, Peng CY, Yang CC, Chong LW, Huang CW, Lin CW, Chu CH, Tsai MC, Kao JH, Liu CJ, Chuang WL, Tseng KC, Yu ML. High-normal and abnormal alanine transaminase levels linked to increased risk of hepatoma following treatment for chronic hepatitis C. J Formos Med Assoc 2025:S0929-6646(25)00042-7. [PMID: 39919992 DOI: 10.1016/j.jfma.2025.01.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 01/04/2025] [Accepted: 01/24/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND/PURPOSE The risk of hepatocellular carcinoma (HCC) is increased in patients with chronic hepatitis C (CHC) and elevated alanine transaminase (ALT) levels. The association between HCC and ALT levels after interferon (IFN) or direct-acting antivirals (DAA) therapy is unclear. METHODS Patients with CHC receiving antiviral therapy were included in two large-scale cohorts in Taiwan (T-COACH and TACR). Posttreatment ALT levels were assessed at 24-weeks/12-weeks after the end-of-treatment with IFN/DAA. HCC risk after antiviral therapy were identified for evaluation. RESULTS Of 29,926 CHC patients enrolled in the study, 64%, 22.5%, and 13.5% had posttreatment healthy-normal (female, ≤19 U/L; male ≤30 U/L), high-normal (female, 19-40 U/L; male, 30-40 U/L), and abnormal (>40 U/L) ALT levels, respectively. During a median follow-up of 2.4 years, 1245 patients developed HCC. The 5-year cumulative HCC incidence was 11.2% and 5.2% in the abnormal and high-normal ALT groups, respectively, compared to 2.7% in the healthy ALT group. In Cox regression analysis, factors associated with a higher HCC risk were advanced fibrosis, abnormal and high-normal posttreatment ALT levels, cirrhosis, and old age; whereas a sustained virological response (SVR) was associated with a lower HCC risk. The aforementioned impacts of abnormal and high-normal posttreatment ALT levels were observed across the SVR, non-SVR, and non-cirrhotic subgroups. CONCLUSION Patients with CHC with high-normal and abnormal posttreatment ALT levels have an increased risk of HCC; thus, HCC surveillance is still necessary in this population.
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Affiliation(s)
- Yen-Chun Chen
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsing Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, 710, Taiwan
| | | | - Ching Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Yi-Hsiang Huang
- Healthcare and Service Center, Taipei Veterans General Hospital, Division of Gastroenterology and Hepatology, Department of Medicine, Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Pei-Lun Lee
- Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taiwan; Mackay Medical College, New Taipei City, Taiwan
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzeng-Hue Yang
- Lotung Pohai Hospital, Lo-Hsu Medical Foundation, Yilan, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, and School of Medicine, College of Medicine, I-Shou University, Taiwan
| | | | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzuchi University, Hualien, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine, Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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Solomon MB, Ghebremeskel GG, Achila OO, Mebrahtu AR, Hamida ME, Mesfin AB. Real-world experience with nucleos(t)ide analogue therapy and patient survival rates in chronic viral hepatitis B treatment centers in Eritrea. Sci Rep 2025; 15:824. [PMID: 39755688 PMCID: PMC11700113 DOI: 10.1038/s41598-024-79600-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 11/11/2024] [Indexed: 01/06/2025] Open
Abstract
Real-world data on treatment outcomes or the quality of large-scale chronic hepatitis B (CHB) treatment programs in sub-Saharan Africa (SSA) is extremely difficult to obtain. In this study, we aimed to provide data on the prevalence and incidence of mortality, loss to follow-up (LFTU), and their associated factors in patients with CHB in three treatment centres in Eritrea. Additional information includes baseline clinical profiles of CHB patients initiated on nucleos(t)ide analogue (NUCs) along with a comparison of treatment with Tenofovir disoproxil fumarate (TDF) vs. TDF + Lamuvudine (LAM) using specific biochemical, haematological and virologic parameters. A multicenter retrospective cohort study was conducted on CHB patients in Asmara, Eritrea (2018-2021). Demographic, clinical, and laboratory information was collected from medical records using a structured checklist. Relevant parametric and nonparametric statistics were employed to explore treatment outcomes and to evaluate differences between groups. Where appropriate, Kaplan-Meier (KM) curves and univariate and multivariate Cox regression models were implemented. A two-sided p-value < 0.05 was considered significant. A total of 413 patients with HBV (median age (IQR) at diagnosis: 39 (IQR: 28-50 years; females: 118(28.6%); followed for a total of 22,921 person days) were studied. HBV/HIV co-infection was observed in 15(3.6%) and baseline ALT and AST were elevated in 99(31.2%) and 101(32.8%), respectively. The Fibrosis-4 (FIB-4) index estimates suggested that cirrhosis was highly likely in 33 (14%) patients with 49 (20.8%) patients in the indeterminate FIB-4 score category. During the follow-up period, 4.6% (95% CI: 2.5-6.6%) died, while 23.9% (95% CI: 19.8-28%) were LTFU. In the adjusted Cox proportional hazards model, LTFU were independently associated with baseline serum HBV DNA (IU/mL) (aHR = 1.3, 95% CI 1.04-1.7; p-value = 0.02); Not initiated on NUC (aHR = 3.9, 95% CI: 1.1-13.7, p-value = 0.02); and FIB-4 Score (aHR = 1.05, 95% CI: 1-1.1; p-value = 0.01). Of the 413 patients enrolled in the study, 98 cases (23.73%) were initiated on treatment. In the head-to-head comparison of the results in TDF and TDF + LAM after 12 weeks of treatment, VR was observed in 14(45.2%) vs. 17(54.8%), respectively, translating into an overall VR of 60.7% (95% CI 46.9-74.6). Furthermore, VR in TDF vs. TDF + LAM were similar, 14(45.2%) vs. 17(54.4%) respectively, p-value = 0.3). This study uncovered multiple systems- and patient-centered gaps in the three HBV treatment programs in Asmara, Eritrea. These include late presentation, high incidence of LTFU, inconsistencies in routine data, and poor data management. Interventions should target improvements in laboratory infrastructure, adherence to patient monitoring guidelines, HBV literacy, better tracking of patients, and documentation of patient's information.
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Affiliation(s)
| | | | - Oliver Okoth Achila
- Unit of Clinical Laboratory Science, Orotta College of Medicine and Health Sciences, Asmara, Eritrea
| | | | - Mohammed Elfatih Hamida
- Department of Medical Microbiology, Orotta College of Medicine and Health Sciences, Asmara, Eritrea
| | - Araia Berhane Mesfin
- Division of National Control of Communicable Diseases, Ministry of Health, Asmara, Eritrea
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Tu T, McQuaid TJ, Jacobson IM. HBV-Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment. Liver Int 2025; 45:e16202. [PMID: 39720865 DOI: 10.1111/liv.16202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 10/29/2024] [Accepted: 11/26/2024] [Indexed: 12/26/2024]
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection is a common but underdiagnosed and undertreated health condition and is the leading cause of hepatocellular carcinoma (HCC) worldwide. HBV (rated a Grade 1 carcinogen by the International Agency for Research on Cancer) drives the transformation of hepatocytes in multiple ways by inducing viral DNA integrations, genetic dysregulation, chromosomal translocations, chronic inflammation, and oncogenic pathways facilitated by some HBV proteins. Importantly, these mechanisms are active throughout all phases of HBV infection. Nevertheless, most clinical guidelines for antiviral therapy recommend treatment based on a complex combination of HBV DNA levels, transaminasemia, liver histology, and demographic factors, rather than prompt treatment for all people with infection. AIMS To determine if current frameworks for antiviral treatment address the impacts of chronic HBV infection particularly preventing cancer development. MATERIALS AND METHODS We reviewed the recent data demonstrating pro-oncogenic factors acting throughout a chronic HBV infection can be inhibited by antiviral therapy. RESULTS We extensively reviewed Hepatitis B virology data and correlating clinical outcome data. From thi, we suggest that new findings support simplifying and expanding treatment initiation to reduce the incidence ofnew infections, progressive liver disease, and risk of hepatocellular carcinoma. We also consider lessons learned from other blood-borne pathogens, including the benefits of antiviral treatment in preventing transmission, reducing stigma, and reframing treatment as cancer prevention. CONCLUSION Incorporating these practice changes into treatment is likely to reduce the overall burden of chronic HBV infections and HCC. Through this, we may better achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat and minimise its impact on people's lives.
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Affiliation(s)
- Thomas Tu
- Storr Liver Centre, Westmead Clinical School, Centre for Infectious Diseases and Microbiology and Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
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Zhang J, Yu S, Zhu K, Li S, Huang Y. Probability analysis of hepatocellular carcinoma in hepatitis patients in the gray zone. Front Med (Lausanne) 2024; 11:1464981. [PMID: 39776842 PMCID: PMC11703914 DOI: 10.3389/fmed.2024.1464981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Objective To investigate the probability of hepatocellular carcinoma (HCC) in a large number of gray-zone (GZ) patients with chronic hepatitis B (CHB) in clinical practice. Methods The patients with CHB who were diagnosed and treated in our hospital from January 2013 to January 2023 were analyzed retrospectively. Results According to the different levels of HBeAg, ALT and HBV DNA, GZ patients were divided into four categories: (1) Gray zone A (GZ-A): HBeAg positive, normal ALT level, HBV DNA ≤ 106 IU/ml; (2) Gray zone B (GZ-B): HBeAg positive, ALT>ULN, HBV DNA ≤ 2 × 104 IU/ml; (3) Gray zone C (GZ-C): HBeAg negative, normal ALT level, HBV DNA ≥ 2 × 103 IU/ml; and (4) Gray zone D (GZ-D): HBeAg negative, ALT > ULN, serum HBV DNA ≤ 2 × 103 IU/ml. This observational study showed that after adjustment using inverse probability of treatment weighting (IPTW), the probability of developing HCC in the GZ group was similar to that in the immune-tolerant, HBeAg-positive immune active, and inactive groups. The IPTW-adjusted analysis revealed that the probability of developing HCC in the GZ-B subgroup was similar to that in the immune-active and HBeAg-negative immune-active groups. Conclusion The GZ group and GZ-B subgroup have a higher risk of HCC. Anti-hepatitis B virus therapy should be considered as early as possible for patients in the GZ group, especially in the GZ-B subgroup.
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Affiliation(s)
- Jianna Zhang
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Sijie Yu
- Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China
| | - Kailu Zhu
- Department of Infectious Diseases, Taizhou First People's Hospital, Taizhou, China
| | - Shibo Li
- Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, China
| | - Yu Huang
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Suzuki T, Matsuura K, Inoue T, Kawamura H, Fujiwara K, Kataoka H, Tanaka Y. Factors associated with low hepatitis B surface antigen levels in chronic hepatitis B patients treated with nucleot(s)ide analogs. Hepatol Res 2024. [PMID: 39460959 DOI: 10.1111/hepr.14129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 10/09/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024]
Abstract
OBJECTIVES Several studies have reported that chronic hepatitis B (CHB) patients with low hepatitis B surface antigen (HBsAg) levels (100 or 10 IU/mL) at the cessation of nucleot(s)ide analogs (NA) have a favorable prognosis. In this retrospective study, we evaluated the duration of NA treatment and the factors associated with achieving these low HBsAg levels. We also examined the relationship between HBsAg and hepatitis B core-related antigen (HBcrAg) levels at the time of NA discontinuation and subsequent clinical outcomes. METHODS This study included 153 CHB patients who initiated NA therapy at our hospital, received treatment, and were followed up for over 1 year. RESULTS The cumulative incidence rates of achieving low HBsAg levels at 5 and 10 years post-NA administration were as follows: 19.0% and 29.2% for HBsAg <100 IU/mL, 13.8% and 17.6% for HBsAg <10 IU/mL, and 9.5% and 13.5% for HBsAg <0.05 IU/mL, respectively. Hepatitis B virus genotypes other than genotype C (hazard ratio [HR] 3.47; p < 0.001) and an HBsAg level <1000 IU/mL at the start of NA therapy (HR 2.49; p = 0.008) were significantly associated with achieving HBsAg levels <100 IU/mL. Among 27 patients who discontinued NA therapy, 5 patients with HBsAg levels <100 IU/mL and HBcrAg levels <3 log U/mL at the time of discontinuation did not experience virological relapse. CONCLUSIONS The cumulative rates of achieving HBsAg levels <100 IU/mL were relatively high. Discontinuation of NA may be considered based on HBsAg and HBcrAg levels during the course of NA therapy.
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takako Inoue
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan
| | - Hayato Kawamura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan
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Xu C, Zhao Y, Chen H, Ren W, Yang X, Zheng W, Yin Q, Pan H. Risk factors for significant histological changes in both HBeAg positive and negative treatment-naive chronic hepatitis B with persistently normal alanine aminotransferase level. BMC Infect Dis 2024; 24:1120. [PMID: 39379873 PMCID: PMC11460226 DOI: 10.1186/s12879-024-10015-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 09/30/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters. METHODS We retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis. RESULTS Among the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients. CONCLUSIONS A substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group.
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Affiliation(s)
- Chengan Xu
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Yue Zhao
- School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Hanzhu Chen
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Wenya Ren
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Xingdi Yang
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Wei Zheng
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Qiaoqiao Yin
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Hongying Pan
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
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Choi WM, Yip TCF, Kim WR, Yee LJ, Brooks-Rooney C, Curteis T, Clark LJ, Jafry Z, Chen CH, Chen CY, Huang YH, Jin YJ, Jun DW, Kim JW, Park NH, Peng CY, Shin HP, Shin JW, Yang YH, Wong GLH, Lim YS. Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients. Hepatology 2024; 80:428-439. [PMID: 38436992 PMCID: PMC11251501 DOI: 10.1097/hep.0000000000000752] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 12/12/2023] [Indexed: 03/05/2024]
Abstract
BACKGROUND AND AIMS A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.
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Affiliation(s)
- Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - W. Ray Kim
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | | | | | | | | | - Zarena Jafry
- Costello Medical Inc, Boston, Massachusetts, USA
| | - Chien-Hung Chen
- Department of Internal Medicine, Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Division of Hepatogastroenterology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Yi-Hsiang Huang
- Department of Medicine, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Young-Joo Jin
- Department of Internal Medicine, Digestive Disease Center, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Jin-Wook Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Neung Hwa Park
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
- Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Cheng-Yuan Peng
- Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Hyun Phil Shin
- Department of Gastroenterology and Hepatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jung Woo Shin
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Yao-Hsu Yang
- Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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10
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Su R, Yan L, Jiang B, Li J, Li P, Liu Y, Miao J, Chen C, Xu L, Ren L, Mi Y. A novel model based on serum N-glycan markers for evaluating stage of liver necroinflammation in treatment-naïve chronic hepatitis B patients. J Med Virol 2024; 96:e29863. [PMID: 39164985 DOI: 10.1002/jmv.29863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 07/23/2024] [Accepted: 08/06/2024] [Indexed: 08/22/2024]
Abstract
This study aimed to establish a novel noninvasive model based on the serum N-glycan spectrum for providing an objective value for determining the stage of liver necroinflammation related to chronic hepatitis B (CHB) patients. N-glycan profiles of the sera of 295 treatment-naïve CHB patients were analyzed. N-glycan profiles were tested for different liver necroinflammation stages using DNA sequence-assisted fluorophore-assisted carbohydrate electrophoresis. A serum N-glycan model named N-glycan-LI (NGLI) using support vector machine was selected to evaluate the classification of liver necroinflammation (G < 2 and G ≥ 2). The area under the receiver operating characteristic curves (AUROCs) was 0.898 (training set, n = 236) and 0.911 (validation set, n = 59) regardless of the stage of liver fibrosis (AUROC = 0.886 and 0.926, respectively, in S < 2 and S ≥ 2 group). The NGLI correspondingly had the highest specificity (SP) of 90.79% and negative predictive value of 92.00% in an inactive stage (including immune-tolerant [IT] and inactive-carrier [IC] stage), had the highest positive predictive value of 95.18% in stage immune-active, and had the highest SP of 93.94% in grey zone IT + IC. N-glycan profiles appear to correlate well with hepatic necroinflammation in CHB when compared with liver biopsy. The newly developed model appears to reliably predict liver damage in naïve-treatment patients with CHB.
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Affiliation(s)
- Rui Su
- School of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin, China
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
| | - Lihua Yan
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
| | - Bei Jiang
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Jia Li
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
| | - Ping Li
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
| | - Yonggang Liu
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
| | - Jing Miao
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
| | - Cuiying Chen
- Department of Research and Development, Sysdiagno (Nanjing) Biotech Co. Ltd, Nanjing, Jiangsu Province, China
| | - Liang Xu
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
| | - Li Ren
- National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Yuqiang Mi
- Tianjin Institute of Heptology, Tianjin Second People's Hospital, Tianjin, China
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11
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Duan M, Xiao H, Shi M, Xie Y, Zhao P, Li S, Chi X, Liu X, Zhuang H. Significant liver histological change is common in HBeAg-positive chronic hepatitis B with normal ALT. BMC Infect Dis 2024; 24:723. [PMID: 39044129 PMCID: PMC11264461 DOI: 10.1186/s12879-024-09617-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 07/15/2024] [Indexed: 07/25/2024] Open
Abstract
BACKGROUND AND AIMS Numerous HBeAg-positive chronic hepatitis B (CHB) patients with persistently normal ALT have significant liver histopathology. It is imperative to identify true "immune tolerant" patients. We aimed to evaluate the liver histopathology features of HBeAg-positive CHB patients with normal ALT and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. METHODS 179 HBeAg-positive CHB patients with normal ALT who performed liver biopsy from 2009 to 2018 were retrospectively analyzed. Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2 was defined as significant liver histopathological change. RESULTS 57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident liver necroinflammation was higher in the high-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs. 30.0%, p < 0.05), and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs. 39.9%, p < 0.05). The percentages of patients with ≥ S2 and ≥ G2/S2 in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs. 40.1%, p < 0.01; 81.8% vs. 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. CONCLUSIONS HBeAg-positive CHB patients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate. Liver biopsy or noninvasive approaches are recommended to evaluate liver histopathology, and antiviral therapy is recommended for patients with significant liver histopathology.
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Affiliation(s)
- Menghui Duan
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China
- The Clinical Laboratory of Tianjin Chest Hospital, Tianjin, China
| | - Huanming Xiao
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Meijie Shi
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Yubao Xie
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Pengtao Zhao
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Sheng Li
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Xiaoling Chi
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China.
| | - Xueen Liu
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Hui Zhuang
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
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12
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Huang D, Lai H, Zhu Z, Yu H, Peng J, Chen Y, Liao X, Chen J. Inverse relationship between HBV DNA levels and liver histopathological changes in immune-tolerant CHB patients. J Viral Hepat 2024; 31:363-371. [PMID: 38581159 DOI: 10.1111/jvh.13940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/21/2024] [Accepted: 03/23/2024] [Indexed: 04/08/2024]
Abstract
Limited data exist regarding the association between hepatitis B virus (HBV) DNA levels and liver histopathological changes in patients with chronic hepatitis B (CHB) during the immune tolerant (IT) phase. In this study, we retrospectively analysed liver biopsy results from 150 adult IT-CHB patients. The liver tissue necroinflammation and fibrosis were evaluated by the Scheuer scoring system. Multivariate logistic regression, smooth curve fitting, and segmented regression models were used to examine the association between HBV DNA levels and liver histopathological changes. A total of 26%, 30.67% and 42% of IT patients had significant necroinflammation (≥G2), significant fibrosis (≥S2) and significant histopathological changes (≥G2 and/or ≥S2), respectively. HBV DNA levels were independently and non-linear inversely associated with significant necroinflammation and histopathological changes in IT-CHB patients. Patients with HBV DNA levels <107 IU/mL had a higher risk of significant histopathological changes compared to those with levels >107 IU/mL. The findings were further confirmed by smooth curve fitting analyses, subgroup and sensitivity analyses. In segmented regression model analyses, the optimal DNA value for the lowest odds ratio of significant histopathological changes was 7.26 log10 IU/mL. A non-linear inverse association between HBV DNA levels and significant histopathological changes in IT-CHB patients. DNA 7.26 log10 IU/mL may serve as a potential cut-off point to define a 'true immune tolerant phase' with minimal liver histopathological changes.
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Affiliation(s)
- Deliang Huang
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Huiyi Lai
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Zhibin Zhu
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Hong Yu
- Department of Pathology, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Jinghan Peng
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Yuanyuan Chen
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Xuejiao Liao
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Jun Chen
- Department of Liver Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
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13
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Zhang M, Kong Y, Xu X, Sun Y, Jia J, You H. "Treat-all" Strategy for Patients with Chronic Hepatitis B Virus Infection in China: Are We There Yet? J Clin Transl Hepatol 2024; 12:589-593. [PMID: 38974957 PMCID: PMC11224901 DOI: 10.14218/jcth.2024.00091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 04/07/2024] [Accepted: 04/26/2024] [Indexed: 07/09/2024] Open
Abstract
Chronic hepatitis B remains the primary cause of liver-related events in China. The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030. However, achieving this goal appears challenging due to the current low rates of diagnosis and treatment. The "Treat-all" strategy, which proposes treating all patients with detectable hepatitis B virus (HBV) DNA or even all patients with positive HBsAg, has been suggested to simplify anti-HBV treatment. In 2022, the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China, expanding antiviral indications and simplifying the treatment algorithm. According to this latest guideline, nearly 95% of patients with detectable HBV DNA are eligible for antiviral treatment. This review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022) and to identify gaps in achieving the "Treat-all" strategy in China.
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Affiliation(s)
- Mengyang Zhang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, State Key Lab of Digestive Health, Beijing, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China
| | - Xiaoqian Xu
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China
| | - Yameng Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, State Key Lab of Digestive Health, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, State Key Lab of Digestive Health, Beijing, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, State Key Lab of Digestive Health, Beijing, China
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14
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Thakur S, Kumar V, Das R, Sharma V, Mehta DK. Biomarkers of Hepatic Toxicity: An Overview. CURRENT THERAPEUTIC RESEARCH 2024; 100:100737. [PMID: 38860148 PMCID: PMC11163176 DOI: 10.1016/j.curtheres.2024.100737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 01/31/2024] [Indexed: 06/12/2024]
Abstract
Background Hepatotoxicity is the foremost issue for clinicians and the primary reason for pharmaceutical product recalls. A biomarker is a measurable and quantifiable attribute used to evaluate the efficacy of a treatment or to diagnose a disease. There are various biomarkers which are used for the detection of liver disease and the intent of liver damage. Objective This review aims to investigate the current state of hepatotoxicity biomarkers and their utility in clinical settings. Using hepatic biomarkers, the presence of liver injury, its severity, prognosis, causative agent, and type of hepatotoxicity can all be determined. Methods Relevant published articles up to 2022 were systematically retrieved from MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as drug toxicity, hepatotoxicity biomarkers, biochemical parameters, and nonalcoholic fatty liver disease. Results In clinical trials and everyday practice, biomarkers of drug-induced liver injury are essential for spotting the most severe cases of hepatotoxicity. Hence, developing novel biomarker approaches to enhance hepatotoxicity diagnosis will increase specificity and/or identify the person at risk. Importantly, early clinical studies on patients with liver illness have proved that some biomarkers such as aminotransferase, bilirubin, albumin, and bile acids are even therapeutically beneficial. Conclusions By assessing the unique signs of liver injury, health care professionals can rapidly and accurately detect liver damage and evaluate its severity. These measures contribute to ensuring prompt and effective medical intervention, hence reducing the risk of long-term liver damage and other major health concerns.
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Affiliation(s)
- Simran Thakur
- Department of Pharmacy Practice, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India
| | - Vishal Kumar
- Department of Pharmacy Practice, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India
| | - Rina Das
- Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India
| | - Vishal Sharma
- Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India
| | - Dinesh Kumar Mehta
- Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India
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15
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Tang J, Zhang J, Zhang G, Peng W, Ling N, Zhou Y, Xu H, Ren H, Chen M. Stat3 activation-triggered transcriptional networks govern the early stage of HBV-induced hepatic inflammation. mBio 2024; 15:e0306823. [PMID: 38440978 PMCID: PMC11005361 DOI: 10.1128/mbio.03068-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 02/01/2024] [Indexed: 03/06/2024] Open
Abstract
The chronic carrier state of the hepatitis B virus (HBV) often leads to the development of liver inflammation as carriers age. However, the exact mechanisms that trigger this hepatic inflammation remain poorly defined. We analyzed the sequential processes during the onset of liver inflammation based on time-course transcriptome and transcriptional regulatory networks in an HBV transgenic (HBV-Tg) mice model and chronic HBV-infected (CHB) patients (data from GSE83148). The key transcriptional factor (TF) responsible for hepatic inflammation occurrence was identified and then validated both in HBV-Tg mice and liver specimens from young CHB patients. By time-course analysis, an early stage of hepatic inflammation was demonstrated in 3-month-old HBV-Tg mice: a marked upregulation of genes related to inflammation (Saa1/2, S100a8/9/11, or Il1β), innate immunity (Tlr2, Tlr7, or Tlr8), and cells chemotaxis (Ccr2, Cxcl1, Cxcl13, or Cxcl14). Within CHB samples, a unique early stage of inflammation activation was discriminated from immune tolerance and immune activation groups based on distinct gene expression patterns. Enhanced activation of TF Stat3 was strongly associated with increased inflammatory gene expression in this early stage of inflammation. Expression of phosphorylated Stat3 was higher in liver specimens from young CHB patients with relatively higher alanine aminotransferase levels. Specific inhibition of Stat3 activation significantly attenuated the degree of liver inflammation, the expression of inflammation-related genes, and the inflammatory monocytes and macrophages in 3-month-old HBV-Tg mice. Stat3 activation is essential for hepatic inflammation occurrence and is a novel indicator of early-stage immune activation in chronic HBV carriers. IMPORTANCE Until now, it remains a mystery that chronic hepatitis B virus (HBV)-infected patients in the "immune tolerance phase" will transition to the "immune activation phase" as they age. In this study, we reveal that Stat3 activation-triggered hepatic transcriptional alterations are distinctive characteristics of the early stage of immune/inflammation activation in chronic HBV infection. For the first time, we discover a mechanism that might trigger the transition from immune tolerance to immune activation in chronic HBV carriers.
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Affiliation(s)
- Jinglin Tang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Transfusion Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Jiaxuan Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Laboratory Medicine, Bishan Hospital of Chongqing Medical University, Bishan Hospital of Chongqing, Chongqing, China
| | - Gaoli Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wenhui Peng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ning Ling
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yingzhi Zhou
- Department of Infection, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Hongmei Xu
- Department of Infection, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Hong Ren
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Chen
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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16
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Kang NL, Wu LY, Zheng Q, Yu XP, Hu AR, Guo Y, Li H, Ye XY, Ruan QF, Lu ZH, Wu L, Jin W, Liu YR, Pan C, Liu SS, Zhang JM, Jiang JJ, Zeng DW. Determining optimal ALT cut-off values for predicting significant hepatic histological changes in patients with normal ALT in the grey zone of chronic hepatitis B virus infection. Aliment Pharmacol Ther 2024; 59:692-704. [PMID: 38178641 DOI: 10.1111/apt.17862] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/04/2023] [Accepted: 12/20/2023] [Indexed: 01/06/2024]
Abstract
BACKGROUND AND AIMS We aimed to define gender-specific, optimal alanine aminotransferase (ALT) cut-off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. METHODS In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut-off values. Area under the curve (AUC) values were calculated to assess their predictive performance. RESULTS A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut-off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut-off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut-off values were greater than those of the current recommendations. CONCLUSION This study established novel optimal ALT cut-off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy.
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Affiliation(s)
- Na-Ling Kang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Clinical Research Center for Hepatopathy and Intestinal Diseases of Fujian Province, Fujian Medical University, Fuzhou, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Lu-Ying Wu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Clinical Research Center for Hepatopathy and Intestinal Diseases of Fujian Province, Fujian Medical University, Fuzhou, China
| | - Qi Zheng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Clinical Research Center for Hepatopathy and Intestinal Diseases of Fujian Province, Fujian Medical University, Fuzhou, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xue-Ping Yu
- Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Ai-Rong Hu
- Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo, China
| | - Yue Guo
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Huan Li
- Department of Infectious Diseases, Fujian Geriatric Hospital, Fujian Provincial Hospital North Branch, Fuzhou, Fujian, China
| | - Xiang-Yang Ye
- Department of Infectious Disease, The Affiliated Hospital of Putian College, Putian, Fujian, China
| | - Qing-Fa Ruan
- Hepatology Center, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Zhong-Hua Lu
- Department of Liver Disease, Wuxi No.5 People's Hospital Affiliated to Jiangnan University, Wuxi, China
| | - Ling Wu
- Department of Infectious Diseases, Anqing Municipal Hospital, Anqing, Anhui, China
| | - Wen Jin
- Department of Hepatology, Fujian Medical University Xiamen Humanity Hospital; Xiamen Quality Control Center of Infectious Diseases, Fujian, China
| | - Yu-Rui Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Clinical Research Center for Hepatopathy and Intestinal Diseases of Fujian Province, Fujian Medical University, Fuzhou, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Chen Pan
- Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Shan-Shan Liu
- Department of Liver Disease, Wuxi No.5 People's Hospital Affiliated to Jiangnan University, Wuxi, China
| | - Ji-Ming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jia-Ji Jiang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Clinical Research Center for Hepatopathy and Intestinal Diseases of Fujian Province, Fujian Medical University, Fuzhou, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Da-Wu Zeng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Clinical Research Center for Hepatopathy and Intestinal Diseases of Fujian Province, Fujian Medical University, Fuzhou, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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17
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Huang R, Liu J, Wang J, Qiu Y, Zhu L, Li Y, Liu Y, Zhan J, Xue R, Jiang S, Geng Y, Wan Y, Li M, Mao M, Gao D, Gu Y, Zhang Y, Yin S, Tong X, Xia J, Yan X, Ding W, Chen Y, Li J, Zhu C, Wu C. Histological features of chronic hepatitis B patients with normal alanine aminotransferase according to different criteria. Hepatol Commun 2024; 8:e0357. [PMID: 38206209 PMCID: PMC10786593 DOI: 10.1097/hc9.0000000000000357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 10/28/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND The upper limits of normal (ULNs) for alanine aminotransferase (ALT) are different among international guidelines for chronic hepatitis B (CHB). We aimed to investigate the proportion of significant histological disease in Asian patients with CHB with detectable hepatitis B virus (HBV) DNA under diverse ALT ULNs. METHODS Consecutive patients with CHB and detectable HBV DNA who underwent liver biopsy were retrospectively included from four tertiary hospitals. Above grade 2 inflammation and stage 2 fibrosis were defined as significant inflammation and significant fibrosis, respectively. Significant histological disease was defined as above grade 2 inflammation or stage 2 fibrosis. RESULTS Among the 414 patients with detectable HBV DNA and normal ALT, the proportion of those with significant histological disease was lower (59.7%) according to the ULN for ALT at 30/19 U/L (male/female), while the corresponding proportions were 66.7% and 62.3% according to the ULNs of 40 U/L and 35/25 U/L (male/female), respectively. In patients with detectable HBV DNA and normal ALT levels without significant fibrosis, the proportions of significant inflammation were comparable among different ULNs of ALT at 40 U/L (30.7%), 35/25 U/L (27.3%) and 30/19 U/L (25.0%). The proportion of significant histological disease was significantly lower in patients with normal ALT for 2 determinations at least 6 months apart compared to patients with normal ALT once. CONCLUSIONS Although a more stringent ALT ULN may reduce the risk of the presence of significant histological disease in patients with detectable HBV DNA, the rates of significant histological disease remain high. Persistently normal ALT levels are more important for excluding patients with CHB with a high probability of significant histological disease.
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Affiliation(s)
- Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yiguang Li
- Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Yilin Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jie Zhan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Suling Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yu Geng
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yawen Wan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, China
| | - Ming Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Minxin Mao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Dongmei Gao
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Yan Gu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yao Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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18
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Zhang L, Yang L, Gao Y, Bi X, Lin Y, Deng W, Jiang T, Lu Y, Hao H, Wan G, Yi W, Xie Y, Li M. Nomogram for evaluating obvious liver inflammation in treatment-naïve HBeAg positive chronic hepatitis B virus infection patients with normal ALT. Virulence 2023; 14:2158710. [PMID: 36600180 PMCID: PMC9828634 DOI: 10.1080/21505594.2022.2158710] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 12/11/2022] [Indexed: 01/06/2023] Open
Abstract
The purpose of this study was to develop an effective and non-invasive nomogram for evaluating liver obvious inflammation in untreated HBeAg positive patients with chronic hepatitis B virus (HBV) infection. A nomogram was established on a model cohort of 292 treatment-naïve HBeAg positive patients with normal alanine aminotransferase (ALT ≤40 U/L) at Beijing Ditan Hospital from January 2008 to March 2018. Then the nomogram was prospectively validated in a cohort of 88 patients from July 2019 to May 2021. Calibration curves and Concordance index were used to evaluate the accuracy of prediction and identification performance of the model. In untreated HBeAg positive chronic hepatitis B virus infection patients with normal ALT, the formula for predicting liver inflammation was Logit (P) =-0.91-0.41×log10 (qHBeAg)+0.11×AST-0.01×PLT. The nomogram had C-index of 0.751 (95% CI, 0.688-0.815), indicating a good consistency between prediction and real observation on the model cohort. The validation cohort confirmed its good performance. In this study, liver inflammation nomograms based on HBeAg, AST, and PLT were established and verified in treatment-naïve HBeAg positive chronic HBV patients with normal ALT.
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Affiliation(s)
- Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Yi
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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19
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Su F, Jacobson IM. Chronic Hepatitis B: Treat all Who Are Viremic? Clin Liver Dis 2023; 27:791-808. [PMID: 37778770 DOI: 10.1016/j.cld.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
The main aim of antiviral therapy in patients with chronic hepatitis B (CHB) is to prevent disease progression and reduce the risk of hepatocellular carcinoma (HCC). In general, treatment is recommended for select patient groups viewed as being at higher risk of developing adverse outcomes from CHB. However, patients who do not meet treatment criteria under current international guidelines may still benefit from antiviral therapy to reduce CHB-related complications. Moreover, well-tolerated antiviral drugs that are highly effective at suppressing viral replication are now widely available, and withholding therapy from patients with viremia is increasingly controversial. In this article, we review traditional treatment paradigms and argue the merits of expanding treatment eligibility to patients with CHB who do not meet current treatment criteria.
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Affiliation(s)
- Feng Su
- Department of Medicine, New York University Grossman School of Medicine, 150 East 32nd Street, Suite 101, New York, NY 10016, USA; New York University Langone Transplant Institute, 317 East 34th Street, 8th Floor, New York, NY 10016, USA.
| | - Ira M Jacobson
- Department of Medicine, New York University Grossman School of Medicine, 150 East 32nd Street, Suite 101, New York, NY 10016, USA
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20
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Kim SR, Kim SK. Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management with a Focus on the Prevention of Hepatitis B-Related Hepatocellular Carcinoma. Diagnostics (Basel) 2023; 13:3212. [PMID: 37892033 PMCID: PMC10605503 DOI: 10.3390/diagnostics13203212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/06/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Though the world-wide hepatitis B virus (HBV) vaccination program has been well completed for almost thirty years in many nations, almost HBV-related hepatocellular carcinoma (HCC) occurs in unvaccinated middle-aged and elderly adults. Apparently, treating 80% of qualified subjects could decrease HBV-related mortality by 65% in a short period. Nevertheless, globally, only 2.2% of CHB patients undergo antiviral therapy. The HBV markers related to HCC occurrence and prevention are as follows: the HCC risk is the highest at a baseline of HBV DNA of 6-7 log copies/mL, and it is the lowest at a baseline of an HBV DNA level of >8 log copies/mL and ≤4 log copies/mL (parabolic, and not linear pattern). The titer of an HBV core-related antigen (HBcrAg) reflecting the amount of HBV covalently closed circular DNA (ccc DNA) in the liver is related to HCC occurrence. The seroclearance of HBs antigen (HBsAg) is more crucial than HBV DNA negativity for the prevention of HCC. In terms of the secondary prevention of hepatitis B-related HCC involving antiviral therapies with nucleos(t)ide analogues (NAs), unsolved issues include the definition of the immune-tolerant phase; the optimal time for starting antiviral therapies with NAs; the limits of increased aminotransferase (ALT) levels as criteria for therapy in CHB patients; the normalization of ALT levels with NAs and the relation to the risk of HCC; and the relation between serum HBV levels and the risk of HCC. Moreover, the first-line therapy with NAs including entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) remains to be clarified. Discussed here, therefore, are the recent findings of HBV markers related to HCC occurrence and prevention, unsolved issues, and the current secondary antiviral therapy for the prevention of HBV-related HCC.
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Affiliation(s)
| | - Soo Ki Kim
- Department of Gastroenterology, Kobe Asahi Hospital, Kobe 653-0801, Japan;
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21
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Li S, Shi L, Xu X, Wang H, You H, Jia J, Kong Y. Systematic review with meta-analysis: Significant histological changes among treatment-naïve chronic hepatitis B patients with normal alanine aminotransferase levels by different criteria. Aliment Pharmacol Ther 2023; 58:648-658. [PMID: 37551720 DOI: 10.1111/apt.17658] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/21/2023] [Accepted: 07/21/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND The upper limits of normal (ULNs) of ALT are not consistent across the major international guidelines which may affect the eligibility for antiviral therapy for chronic hepatitis B (CHB). AIM To estimate the proportions of histological changes among treatment-naïve patients with CHB within differently defined ALT ULNs. METHODS We searched PubMed and Embase up to May 15th, 2023, to identify studies of treatment-naïve CHB patients with liver biopsies. We pooled proportions of moderate to severe necroinflammation, significant fibrosis, and cirrhosis in those patients within different ALT ULNs by using random-effect models. RESULTS We included 23 studies with 4010 participants. Within ALT ULN at 40 IU/L, the pooled proportions of moderate to severe necroinflammation, significant fibrosis, and cirrhosis were 33% (95% CI: 26%-42%), 32% (95% CI: 27%-38%), and 3% (95% CI: 1%-5%), respectively. Within ALT ULN at 30 IU/L for men and 19 IU/L for women, the pooled proportion of significant fibrosis remained at 30% (95% CI: 25%-34%; 432 participants). However, it was 21% (95% CI: 11%-37%; 361 participants) even in those within ALT ULN at 20 IU/L. Subgroup analyses suggested a significantly higher proportion of significant fibrosis among studies with prospective design or enrolled patients' mean age >35 or >40 years. CONCLUSIONS Significant histological changes occurred in approximately 1/3 of treatment-naïve CHB patients within ALT ULN at 40 IU/L, whereas the proportion of significant fibrosis was approximately 1/5 even in those within ALT ULN at 20 IU/L.
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Affiliation(s)
- Shun Li
- National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China
| | - Lichen Shi
- National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China
| | - Xiaoqian Xu
- National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China
| | - Hao Wang
- National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuanyuan Kong
- National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing, China
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22
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Zhan Y, Tao Q, Lang Z, Lin L, Li X, Yu S, Yu Z, Zhou G, Wu K, Zhou Z, Yu Z, Zheng J. Serum ribonucleotide reductase M2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B patients. J Med Virol 2023; 95:e29157. [PMID: 37814947 DOI: 10.1002/jmv.29157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 09/14/2023] [Accepted: 09/25/2023] [Indexed: 10/11/2023]
Abstract
It is known that ribonucleotide reductase M2 (RRM2) could be induced by hepatitis B virus (HBV) via DNA damage response. However, whether RRM2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B (CHB) patients is still unclear. In this study, CHB patients from GSE84044 (a transcriptome data from GEO data set) were downloaded and RRM2 was selected as a hub gene. Interestingly, a positive correlation was found between serum RRM2 and liver fibrosis stage. The similar results were found in CHB patients with normal alanine aminotransferase (ALT). Notably, RRM2 could effectively differentiate preliminary fibrosis from advanced fibrosis in CHB patients with/without normal ALT. In addition, RRM2 had a better performance in diagnosing liver fibrosis than two commonly used noninvasive methods (aspartate aminotransferase-to-platelet ratio index and fibrosis index based on the four factors), two classic fibrotic biomarkers (hyaluronic acid and type IV collagen) as well as Mac-2 binding protein glycosylation isomer, a known serum fibrosis marker. Moreover, CHB patients with high RRM2, who were associated with advanced fibrosis, had higher expressions of immune checkpoints. Overall, serum RRM2 may be a promising biomarker for diagnosing and monitoring liver fibrosis in CHB patients.
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Affiliation(s)
- Yating Zhan
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Qiqi Tao
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhichao Lang
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lifan Lin
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xinmiao Li
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Suhui Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhengping Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Guangyao Zhou
- Department of Infectious Diseases, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Kaifeng Wu
- Department of Laboratory Medicine, The First People's Hospital of Zunyi, Zunyi, China
| | - Zhenxu Zhou
- Department of Hernia and Abdominal Wall Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhixian Yu
- Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jianjian Zheng
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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23
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Razavi-Shearer D, Estes C, Gamkrelidze I, Razavi H. Cost-effectiveness of treating all hepatitis B-positive individuals in the United States. J Viral Hepat 2023; 30:718-726. [PMID: 37260095 DOI: 10.1111/jvh.13843] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 04/21/2023] [Accepted: 05/13/2023] [Indexed: 06/02/2023]
Abstract
Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and related mortality globally. However, most of the infected individuals in the United States remain undiagnosed and untreated. There is a need to understand more completely the economic and disease burden impact of removing treatment restrictions and increasing diagnosis and treatment. The PRoGReSs model, a dynamic HBV model that tracks the infected population by year, disease stage, and gender, was used to quantify the disease and economic burden of chronic HBV infection in the United States from 2020 to 2050 based on four scenarios: a status quo (base) scenario and three treat-all scenarios, in which screening, diagnosis, and treatment were maximized at different annual treatment price levels of $5382, $2000 and $750. Compared to the base scenario, the treat-all scenarios would avert 71,100 acute and 11,100 chronic incident cases of HBV, and 169,000 liver-related deaths from 2020 to 2050. At an annual treatment cost of $2000, treating all HBV infections would be highly cost-effective, and at $750 would be cost saving and would achieve a positive return on investment before 2050. Maximizing the diagnosed and treated HBV population in the United States would avert a significant number of cases of advanced liver disease and related mortality. Such interventions can also be cost-effective compared to the status quo strategy, and cost saving at a treatment price threshold of $750 annually, above the current lowest annual treatment cost of $362.
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Affiliation(s)
| | - Chris Estes
- Center for Disease Analysis Foundation, Lafayette, Colorado, USA
| | | | - Homie Razavi
- Center for Disease Analysis Foundation, Lafayette, Colorado, USA
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24
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Suzuki T, Matsuura K, Watanabe T, Matsui T, Ogawa S, Kawamura H, Kuno K, Fujiwara K, Nojiri S, Kataoka H, Tanaka Y. Kinetics of HBcrAg and HBsAg using highly sensitive iTACT assays in chronic hepatitis B patients with HBsAg seroclearance. J Med Virol 2023; 95:e29109. [PMID: 37721406 DOI: 10.1002/jmv.29109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 08/13/2023] [Accepted: 09/07/2023] [Indexed: 09/19/2023]
Abstract
Two novel assays have been developed, iTACT-hepatitis B core-related antigen (iTACT-HBcrAg) and iTACT-hepatitis B surface antigen (iTACT-HBsAg) assays. We investigated the longitudinal profiles of iTACT-HBcrAg- and -HBsAg in patients with HBsAg seroclearance (SC) (<0.05 IU/mL). This study comprises 60 HBV-infected patients with HBsAg SC, 27 in chronic hepatitis/liver cirrhosis (CH/LC) group and 33 in inactive carrier (IC) group. Longitudinal profiles of iTACT-HBcrAg and -HBsAg were examined using stored serum samples. The median period from HBsAg SC to iTACT-HBcrAg loss or to the last observation was longer in the CH/LC group than the IC group (39 vs. -3 months, p = 0.004), but this tendency was not observed in that by iTACT-HBsAg. Comparing the times of iTACT-HBcrAg and -HBsAg loss, the rate of patients who lost HBcrAg first was significantly higher in the IC group (p = 0.008). The cumulative incidence rate of iTACT-HBcrAg loss after HBsAg SC was higher in the IC group that the CH/LC group (p = 0.002). Patients in the CH/LC group had higher rates of detectable iTACT-HBcrAg than those in the IC group after HBsAg SC, suggesting that the presence of HBcrAg possibly contribute to the progression of chronic hepatitis B.
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takehisa Watanabe
- Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan
| | - Takeshi Matsui
- Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Hokkaido, Japan
| | - Shintaro Ogawa
- Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan
| | - Hayato Kawamura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kayoko Kuno
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shunsuke Nojiri
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan
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Huang LL, Yu XP, Ruan QF, Lin YX, Li H, Jin W, Liu RF, Liang YL, Liu YR, Zhu YY, Jiang JJ, Mao RC, Zeng DW. Liver Stiffness Measurement can Predict Liver Inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase. J Clin Transl Hepatol 2023; 11:817-826. [PMID: 37408816 PMCID: PMC10318296 DOI: 10.14218/jcth.2022.00329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/19/2022] [Accepted: 11/07/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND AND AIMS To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT). METHODS We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression. RESULTS Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM. CONCLUSIONS LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.
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Affiliation(s)
- Ling-Ling Huang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Xue-Ping Yu
- Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Qing-Fa Ruan
- Hepatology Center, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Yan-Xue Lin
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Huan Li
- Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Wen Jin
- Hepatology, Fujian Medical University Xiamen Humanity Hospital, Xiamen, Fujian, China
| | - Rui-Feng Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Yan-Lan Liang
- Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Yu-Rui Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Yue-Yong Zhu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Jia-Ji Jiang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Ri-Cheng Mao
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Da-Wu Zeng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated hospital, Fujian Medical University, Fuzhou, Fujian, China
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Zhang S, Wang C, Liu B, Lu QB, Shang J, Zhou Y, Jia J, Xu X, Rao H, Han B, Zhao T, Chen L, Xie M, Cui J, Du J, zeng J, huang N, Liu Y, Zhang L, Zhuang H, Cui F. Cost-effectiveness of expanded antiviral treatment for chronic hepatitis B virus infection in China: an economic evaluation. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2023; 35:100738. [PMID: 37424693 PMCID: PMC10326688 DOI: 10.1016/j.lanwpc.2023.100738] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 02/17/2023] [Accepted: 02/23/2023] [Indexed: 03/21/2023]
Abstract
Background China, which has the largest chronic hepatitis B virus (HBV) burden, may expand antiviral therapy to attain the World Health Organization (WHO)-2030 goal of 65% reduction in mortality. We evaluated health outcomes and cost-effectiveness of chronic HBV infection treatments based on alanine transaminase (ALT) antiviral treatment initiation thresholds and coverage in China to identify an optimal strategy. Methods A decision-tree Markov state-transition model evaluated the cost-effectiveness of expanded antiviral treatment for chronic HBV infection by simulating 136 scenarios by ALT treatment initiation thresholds (40 U/L, 35 U/L for males and 25 U/L for females, 30 U/L for males and 19 U/L for females, and treating HBsAg+ individuals regardless of ALT values), population age groups (18-80, 30-80, and 40-80 years), implementation durations (2023, 2028, and 2033) under and treatment coverages (20%, 40%, 60%, and 80%). Deterministic and probabilistic sensitivity analyses explored model uncertainty. Findings Besides the status quo, we finally simulated 135 treatment-expanding scenarios based on the cross combination of different thresholds of ALT, treatment coverages, population's age groups and implementation time. For the status quo, a cumulative incidence of 16,038-42,691 HBV-related complications and 3116-18,428 related deaths will happened between 2030 and 2050. When the treatment threshold is expanded to 'ALT > 35 in males & ALT > 25 in females' immediately without expanding treatment coverage, it will save 2554 HBV-related complications and 348 related deaths compared to the status quo among the whole cohort by 2030, and US$ 156 million more will be costed for gaining 2962 more QALYs. If we just expand the ALT threshold to ALT > 30 in males & ALT > 19 in females, 3247 HBV-related complications and 470 related deaths will be prevented by 2030 under the current treatment coverage of 20%, which will cost US$ 242 million, US$ 583 million or US$ 606 million more by the year of 2030, 2040 or 2050, respectively. Treatment expanded to HBsAg+ will save the largest number of HBV-related complications and death. This expanding strategy also results in large complications or death reduction when it is limited to patients older than 30 years or 40 years. Under this strategy, four scenarios (Treating HBsAg+ with coverage of 60% or 80% for patients older than 18 years or 30 years) showed the effectiveness in reaching the target before the year 2030. Among all the strategies, treatment expanded to HBsAg+ would cost the most while providing the highest total QALYs compared to other strategies with similar implementation scenarios. ALT thresholds of 30 U/L and 19 U/L for males and females, respectively, with 80% coverage for 18-80 years, can attain the goal by 2043. Interpretation Treating HBsAg+ individuals with 80% coverage for 18-80 years is optimal; earlier implementation of expanded antiviral treatment with a modified ALT threshold could decrease HBV-related complications and deaths to support the global target of 65% reduction in viral hepatitis B deaths. Funding This study was funded by Global Center for Infectious Disease and Policy Research (BMU2022XY030); Global Health and Infectious Diseases Group (BMU2022XY030); The Chinese Foundations for Hepatitis Control and Prevention (2021ZC032); National Science and Technology Project on Development Assistance for Technology, Developing China-ASEAN Public Health Research and Development Collaborating Center (KY202101004); in part by National Key R&D Program of China (2022YFC2505100).
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Affiliation(s)
- Sihui Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Chao Wang
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Bei Liu
- Vaccine Research Center, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Qing-Bin Lu
- Global Center for Infectious Disease and Policy Research & Global Health and Infectious Diseases Group, Peking University, Beijing, 100191, PR China
| | - Jia Shang
- Henan Provincial People's Hospital, Zhengzhou, 450000, PR China
| | - Yihua Zhou
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, PR China
| | - Jidong Jia
- Liver Research Centre, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, PR China
| | - Huiying Rao
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing, 100044, PR China
| | - Bingfeng Han
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Tianshuo Zhao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Linyi Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Mingzhu Xie
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Jiahao Cui
- Faculty of Medicine, Imperial College London, London, SW72AZ, UK
| | - Juan Du
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, PR China
- Vaccine Research Center, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Jing zeng
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, PR China
- Vaccine Research Center, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Ninghua huang
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, PR China
- Vaccine Research Center, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Yaqiong Liu
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, PR China
- Vaccine Research Center, School of Public Health, Peking University, Beijing, 100191, PR China
| | - Lei Zhang
- China-Australia Joint Research Centre for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Centre, Xi'an, 710049, PR China
- Central Clinical School, Faculty of Medicine, Monash University, Melbourne, 3800, Australia
- Artificial Intelligence and Modelling in Epidemiology Program, Melbourne Sexual Health Centre, Alfred Health, Melbourne 3800, Australia
| | - Hui Zhuang
- Department of Microbiology and Centre for Infectious Diseases, Peking University Health Science Centre, Beijing, 100191, PR China
| | - Fuqiang Cui
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, PR China
- Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing, 100191, PR China
- Vaccine Research Center, School of Public Health, Peking University, Beijing, 100191, PR China
- Global Center for Infectious Disease and Policy Research & Global Health and Infectious Diseases Group, Peking University, Beijing, 100191, PR China
- Department of Global Health, School of Public Health, Peking University, Beijing, 100191, PR China
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Kasuya K, Fukai K, Watanabe Y, Furuya Y, Nakazawa S, Honda T, Hayashi T, Nakagawa T, Tatemichi M, Korenaga M. Basic assessment on adding platelet measurement to legal health checkup in Japan: A cross-sectional and 20-year longitudinal study. Front Public Health 2023; 11:1106831. [PMID: 37077194 PMCID: PMC10106601 DOI: 10.3389/fpubh.2023.1106831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 03/08/2023] [Indexed: 04/05/2023] Open
Abstract
BackgroundIn Japan, health checkups for workers are legally compulsory. Considering legal health checkup items are important for Japanese workers' health problems. To date, the legal health checkup items for blood cell counts include only red blood cell counts and hemoglobin but not platelet counts. This study aimed to investigate the significance of measuring platelets in workers by showing the association between the FIB-4 index (FIB-4), which can be easily calculated from factors including platelet counts and viral hepatitis infection.MethodBoth cross-sectional and longitudinal analyses were conducted on the comprehensive medical examinations of male workers. In fiscal year (FY) 2019, a logistic regression model was applied to 12,918 examinees. For 13,459 examinees (mean age = 47.5 ± 9.3 SD), FY2000 was set to be followed until FY2019. A total of 149,956 records between FY2000 and FY2019 were analyzed cross-sectionally, and 8,038 men who were consecutively examined to FY2019 at the longest were analyzed longitudinally. Receiver operating characteristic (ROC) curve–area under the ROC curve (ROC–AUC) and Cox proportional methods were used to examine the association between platelet-related indices and viral hepatitis infection.ResultsLogistic regression showed that the risk of FIB-4 ≥ 2.67 was mostly associated with hepatitis C virus antibody (HCVAb) positivity [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.08–5.86], while negatively associated with body mass index (BMI) (OR = 0.54, 95% CI = 0.30–0.97), and not associated with the presence of fatty liver. To detect HVC Ab positivity, ROC–AUC showed more effectiveness in FIB-4 than in the AST/ALT ratio (0.776, 95% CI = 0.747–0.773 vs. 0.552; 95% CI = 0.543–0.561). The Cox analysis showed that the risk of FIB-4 ≥ 2.67 was closely associated with hepatitis B virus surface antigen (HBsAg) [hazard ratio (HR) = 3.1, 95% CI = 2.0–4.6] and HCV Ab positivity (HR = 3.2, 95% CI = 2.0–5.0).ConclusionOur results suggest that it might be worth considering that usage of information on platelets in legal health checkups could be some help not to overlook workers with hepatitis virus carriers as a complementary countermeasure, although further investigations are needed into its practical application.
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Affiliation(s)
| | - Kota Fukai
- Department of Preventive Medicine, School of Medicine, Tokai University, Isehara, Japan
- *Correspondence: Kota Fukai
| | | | - Yuko Furuya
- Department of Preventive Medicine, School of Medicine, Tokai University, Isehara, Japan
| | - Shoko Nakazawa
- Department of Preventive Medicine, School of Medicine, Tokai University, Isehara, Japan
| | - Toru Honda
- Hitachi Health Care Center, Hitachi, Japan
| | - Takeshi Hayashi
- Occupational Hygiene and Promotion Center, Hitachi Ltd., Tokyo, Japan
| | | | - Masayuki Tatemichi
- Department of Preventive Medicine, School of Medicine, Tokai University, Isehara, Japan
| | - Masaaki Korenaga
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
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28
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Zhao J, Bian D, Liao H, Wang Y, Ren Y, Jiang Y, Liu S, Chen X, Hu Z, Duan Z, Lu F, Zheng S. Serum HBsAg and HBcrAg is associated with inflammation in HBeAg-positive chronic hepatitis B patients. Front Cell Infect Microbiol 2023; 13:1083912. [PMID: 37065191 PMCID: PMC10102387 DOI: 10.3389/fcimb.2023.1083912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 03/08/2023] [Indexed: 04/03/2023] Open
Abstract
BACKGROUNDS & AIMS Liver inflammation is the main risk factor for developing liver fibrosis, cirrhosis, and even hepatocellular carcinoma in chronic hepatitis B (CHB) patients. To replace biopsy, additional non-invasive biomarkers to diagnose and grade liver necroinflammation are urgently required in clinical practice. METHOD Ninety-four CHB patients, including 74 HBeAg-positive and 20 HBeAg-negative patients, were enrolled and started entecavir or adefovir therapy. Serum HBV RNA, HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), ALT and AST levels, as well as intrahepatic HBV DNA and cccDNA were measured at baseline and during treatment. Liver inflammation was assessed at baseline and month 60 by liver biopsy. Inflammation regression was defined as a ≥1-grade decrease according to the Scheuer scoring system. RESULTS In HBeAg-positive CHB patients, at baseline, serum HBsAg and HBcrAg levels negatively correlated with inflammation grade, while ALT and AST levels positively correlated with inflammation grade. AST plus HBsAg exhibited excellent diagnostic ability for significant inflammation with an AUROC of 0.896. After 60 months of antiviral treatment, almost all the patients' liver inflammation ameliorated to G1, and no patients had inflammation progression. CONCLUSION Besides ALT and AST, serum HBsAg and HBcrAg correlated with inflammation grade in HBeAg-positive CHB patients before NAs treatment. Moreover, the combination of HBsAg and AST exhibited excellent diagnostic ability for significant inflammation.
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Affiliation(s)
- Jing Zhao
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Dandan Bian
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
- Department of Infectious Diseases, Electric Power Teaching Hospital, Capital Medical University, Beijing, China
| | - Hao Liao
- Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China
| | - Yang Wang
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Yan Ren
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Yingying Jiang
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Shuang Liu
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Xinyue Chen
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Zhongjie Hu
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Zhongping Duan
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Fengmin Lu
- Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China
| | - Sujun Zheng
- Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China
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29
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Wang J, Yan X, Zhu L, Liu J, Qiu Y, Li Y, Liu Y, Xue R, Zhan J, Jiang S, Geng Y, Wan Y, Li M, Mao M, Gao D, Yin S, Tong X, Xia J, Ding W, Chen Y, Li J, Zhu C, Huang R, Wu C. Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone. Aliment Pharmacol Ther 2023; 57:464-474. [PMID: 36324235 DOI: 10.1111/apt.17272] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/08/2022] [Accepted: 10/15/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ). AIMS To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. METHODS This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg-positive, normal ALT and HBV DNA ≤106 IU/ml (GZ-A); HBeAg-positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ-B); HBeAg-negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ-C) and HBeAg-negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ-D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2. RESULTS Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg-positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg-negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ-D (42.6%) was the dominant category, followed by GZ-C (38.8%), GZ-A (10.3%) and GZ-B (8.3%). The highest proportion of significant histological disease was observed patients in GZ-B (100.0%), followed by GZ-A (84.0%), GZ-D (69.9%) and GZ-C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg-negative GZ. CONCLUSIONS Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg-positive and HBeAg-negative GZ CHB patients with high PT.
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Affiliation(s)
- Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Yiguang Li
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Yilin Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jie Zhan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Suling Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yu Geng
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yawen Wan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, China
| | - Ming Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Minxin Mao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Dongmei Gao
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.,Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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30
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Clinical Utility of Quantitative HBV Core Antibodies for Solving Diagnostic Dilemmas. Viruses 2023; 15:v15020373. [PMID: 36851587 PMCID: PMC9965363 DOI: 10.3390/v15020373] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/20/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023] Open
Abstract
The present-day management of hepatitis B virus (HBV) infection relies on constant and appropriate monitoring of viral activity, disease progression and treatment response. Traditional HBV infection biomarkers have many limitations in predicting clinical outcomes or therapy success. Quantitation of HBV core antibodies (qAnti-HBc) is a new non-invasive biomarker that can be used in solving multiple diagnostic problems. It was shown to correlate well with infection phases, level of hepatic inflammation and fibrosis, exacerbations during chronic infection and presence of occult infection. Further, the level of qAnti-HBc was recognised as predictive of spontaneous or therapy-induced HBeAg and HBsAg seroclearance, relapse after therapy discontinuation, re-infection after liver transplantation and viral reactivation upon immunosuppression. However, qAnti-HBc cannot be relied upon as a single diagnostic test to solve all dilemmas, and its diagnostic and prognostic power can be much improved when combined with other diagnostic biomarkers (HBV DNA, HBeAg, qHBsAg and anti-HBs antibodies). The availability of commercial qAnti-HBc diagnostic kits still needs to be improved. The comparison of results from different studies and definitions of universal cut-off values continue to be hindered because many methods are only semi-quantitative. The clinical utility of qAnti-HBc and the methods used for its measurement are the focus of this review.
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Metabolic Syndrome, Nonalcoholic Fatty Liver Disease, and Chronic Hepatitis B: A Narrative Review. Infect Dis Ther 2023; 12:53-66. [PMID: 36441483 PMCID: PMC9868033 DOI: 10.1007/s40121-022-00725-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 11/03/2022] [Indexed: 11/29/2022] Open
Abstract
Chronic hepatitis B (CHB) remains a relatively major public health problem. Simultaneously, an unhealthy lifestyle causes a series of metabolic abnormalities, the most critical of which are metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). Therefore, it is increasingly common for MS and NAFLD to coexist with CHB. MS is a cluster of metabolic disorders, while NAFLD is always considered as the manifestation of MS in the liver. The aim of this article is to review recent advances to explain the complex relationship among MS, NAFLD, and hepatitis B virus (HBV) infection. MS and NAFLD both have obesity and insulin resistance as central factors and both can lead to adverse hepatic and extrahepatic outcomes. However, there is insufficient evidence to associate NAFLD with all components of MS, and genetically related NAFLD has little association with MS. Incidences of MS and NAFLD are inversely associated with HBV infection. However, the effect of HBV infection on the risk of insulin resistance and dyslipidemia is not well understood. Evidence from both clinical studies and animal experiments suggested that hepatic steatosis inhibits HBV replication. MS and NAFLD may have adverse effects on CHB disease progression and prognosis. Furthermore, in related studies of CHB with normal alanine aminotransferase (ALT), the roles of MS and NAFLD should also be emphasized. In conclusion, there are complicated interactions that are not yet fully defined among MS, NAFLD, and CHB. To control chronic liver disease effectively, the relationship among the three must be clarified.
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Choi WM, Choi J, Lim YS. Hepatitis B: epidemiology, natural history, and diagnosis. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:183-203. [DOI: 10.1016/b978-0-323-98368-6.00007-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Virological Changes of Chronic Hepatitis B Patients with Minimally Elevated Levels of Alanine Aminotransferase: A Meta-Analysis and Systematic Review. Can J Gastroenterol Hepatol 2022; 2022:7499492. [PMID: 36439633 PMCID: PMC9683979 DOI: 10.1155/2022/7499492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 10/17/2022] [Accepted: 11/02/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) patients with normal or minimally increased levels of alanine aminotransferase (ALT) are still at the risk of hepatocellular carcinoma, cirrhotic events, and mortality. However, there is a debate over the initiation of antiviral treatment for these patients. This systematic review and mate-analysis aimed to explore this problem. METHODS MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were systematically searched for retrieving relevant studies with risk ratios (RRs) or risk differences (RDs) for virological changes between antivirus-treated and no antivirus-treated CHB patients with ALT levels less than two-fold of the upper limit of normal. Retrieved data ranged from January 1990 to October 2020. RESULTS Of 6783 abstracts screened, 9 studies met the criteria for inclusion in the systematic review and had a low risk of bias. Among studies that were involved in the meta-analyses, it was found that the rates of HBsAg loss (RR = 12.22, 95% confidence interval (CI): 4.28-34.95, P < 0.001), HBsAg seroconversion (RR = 19.90, 95% CI: 2.75-144.09, P=0.003), and undetectable HBV DNA (RR = 11.89, 95% CI: 2.44-57.89, P=0.002) were both higher in the antiviral treatment group compared with placebo or no treatment group. Subgroup analysis suggested that patients who received interferon (IFN)-based therapy were more inclined to achieve HBsAg loss (P=0.010), HBsAg seroconversion (P=0.020), and HBeAg loss (P=0.002). CONCLUSION From a sizable population, it was revealed that CHB patients with normal or minimally increased levels of ALT could benefit from the antiviral therapy, especially those who received IFN-based treatment.
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Qian Z, Hu M, Wu H, Chen H, Liao G, Kang Z, Lin X, Peng J. The Efficacy of Antiviral Treatment for Chronic Hepatitis B Patients with Normal ALT Levels: A Systematic Review and Meta-analysis. HEPATITIS MONTHLY 2022; 22. [DOI: 10.5812/hepatmon-129836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 10/03/2022] [Accepted: 10/06/2022] [Indexed: 01/04/2025]
Abstract
Context: When nucleos(t)ide analogues (NAs) were applied clinically to manage chronic hepatitis B virus infection, the prognosis of chronic hepatitis B (CHB) patients greatly improved. However, certain CHB patients with normal alanine aminotransferase (ALT) levels were not used to be considered as the population with the need for antiviral treatment. Objectives: This systematic review and meta-analysis collected and analyzed data from clinical trials to assess and compare the efficacy of antiviral treatment among patients with elevated and normal ALT levels. Methods: A systematic search was performed to gather studies published from 1990.01 to 2022.08 in PubMed and Web of Science databases. The quality of the literature was assessed, and 16 studies were included for further analysis. Basic information on included studies and study populations was collected. A meta-analysis was carried out to evaluate three major outcomes of viral response, hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion after NAs treatment based on data extracted from these studies. Odds ratios (ORs) with 95% confidence intervals (CIs) for all outcomes were calculated using fixed-effects models. Results: In the 16 relevant studies, 5,345 patients met the inclusion criteria, including 3,687 patients receiving NAs treatment. All patients were grouped into one with elevated ALT and another with normal ALT based on whether their pretreatment ALT levels > 1*upper limit of normal (ULN). For patients receiving lamivudine, the viral response showed no significant difference between the groups with elevated and normal ALT levels (pooled log OR: 0.51 [-0.23 - 1.26], P = 0.79); the pooled log OR for HBeAg loss was 1.19 (0.63 - 1.76, P = 0.03) and pooled log OR for HBeAg seroconversion was 2.19 (0.91 - 3.47, P = 0.40). For patients receiving first-line therapy with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), the viral response showed no significant difference between the two groups: Pooled log OR (0.38 [-0.22 - 0.97], P = 0.10). The pooled log OR for HBeAg loss and HBeAg seroconversion was (-0.07 [-0.81 - 0.67], P = 0.68) and (0.40 [-0.84 - 1.63], P = 0.88), respectively. Conclusions: The efficacies of first-line therapy with TDF and ETV treatments were similar in groups with elevated and normal ALT levels for the outcomes of viral response and HBeAg loss. These findings may support further treatment of CHB patients with normal ALT levels.
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Dong H, Hong X, He Y, Bao Z, Zhang Y, Shen S, Wang G, Zhang J, Mo R. A carrier-free metal-organic hybrid nanoassembly with combination anti-viral and hepato-protective activity for hepatitis B treatment. Biomater Sci 2022; 10:4356-4366. [PMID: 35786722 DOI: 10.1039/d2bm00407k] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hepatitis B represents a major global public health burden, which is caused by the hepatitis B virus (HBV) with a high infection rate. Although several anti-HBV drugs have been developed for clinical treatment of hepatitis B, the current therapeutic strategies still suffer from undeniable adverse effects, insufficient efficacy after systemic administration and chronic inflammation. Here, we develop a carrier-free metal-organic hybrid nanoassembly that is co-loaded with tenofovir (TFV), an anti-viral agent and phosphorylated glycyrrhetinic acid (GAP), an anti-inflammatory compound (TFV/GAP/NA) to enhance the anti-HBV effect and alleviate the inflammatory response for hepatitis B treatment. The nanoassembly is easily prepared through the ionic interactions between the anionic phosphonate/phosphate groups from TFV/GAP and the zirconium cation, which has a stable nanostructure and a high drug-loading capacity. The nanoassembly prolongs the circulation time with reduced drug leakage in the blood and elevates drug accumulation in the liver after intravascular administration. After internalization mediated by the GAP ligand-GA receptor interaction, TFV/GAP/NA disassembles by the phosphatase-triggered degradation of the phosphate ester bonds in GAP and releases TFV, GAP and GA within the HBV-positive hepatocytes. The released TFV interferes with the HBV polymerase to inhibit the viral DNA replication, while the released GAP and GA suppress the pro-inflammatory protein expression. In mouse models, treatment with TFV/GAP/NA inhibits HBV production and alleviates inflammation-mediated liver injury.
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Affiliation(s)
- He Dong
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Xiaodan Hong
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Yingjiao He
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Zhengxiang Bao
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Ying Zhang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Shiyang Shen
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Guangji Wang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Jingwei Zhang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Ran Mo
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Metabolism and Pharmacokinetics and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
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Hu Q, Wang Q, Xu W, Huang C, Tao S, Qi X, Zhang Y, Li X, Jiang X, Song J, Li Q, Chen L, Huang Y. Development and Validation of a Non-invasive Model to Predict Liver Histological Lesions in Chronic Hepatitis B Patients With Persistently Normal Alanine Aminotransferase and Detectable Viremia. Front Med (Lausanne) 2022; 9:944547. [PMID: 35911415 PMCID: PMC9326251 DOI: 10.3389/fmed.2022.944547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 06/24/2022] [Indexed: 11/13/2022] Open
Abstract
Background A critical and controversial issue is whether antiviral therapy should be recommended in chronic hepatitis B virus (HBV) infection patients with persistently normal alanine aminotransferase (PNALT) and detectable HBV DNA. The study aimed to develop a non-invasive model for predicting significant liver histological changes (SLHC), which is the histological indication for antiviral therapy in chronic hepatitis B (CHB) patients with PNALT and detectable HBV DNA. Methods 398 chronic HBV infection patients with PNALT and detectable HBV DNA who underwent liver biopsy were divided into the estimation set (n = 256) and validation set (n = 142). A multivariate logistic regression model was developed to predict SLHC in the estimation set, and the diagnostic performance was further validated in the validation set. Results 132 patients (33.2%) with PNALT and detectable HBV DNA had SLHC. Aspartate aminotransferase (AST), cholinesterase (ChE), and liver stiffness measurement (LSM) were identified as the independent predictors of SLHC. The AUROC of the SLHC index, which combined AST, ChE, and LSM, was 0.824 and 0.816 in the estimation and validation set, respectively, for the prediction of SLHC. Applying the SLHC index ≤ 0.15, the presence of SLHC could be excluded with high negative predictive value in the estimation set (93.2%) and in the validation set (90.2%). Applying the SLHC index ≥ 0.55, the presence of SLHC could be considered with high positive predictive value in the estimation set (79.2%) and in the validation set (76.5%). Conclusion The SLHC index provides a high accuracy in predicting liver histological indication for antiviral therapy in CHB patients with PNALT and detectable HBV DNA.
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Affiliation(s)
- Qiankun Hu
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qianqian Wang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Wei Xu
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Chenlu Huang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Shuai Tao
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yi Zhang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xinyan Li
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xuhua Jiang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Jie Song
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qiang Li
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Qiang Li,
| | - Liang Chen
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Liang Chen,
| | - Yuxian Huang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
- *Correspondence: Yuxian Huang,
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Zhang X, You Y, Liu Q, Sun X, Chen W, Duan L. Reduced Circulating Soluble Receptor for Advanced Glycation End-products in Chronic Hepatitis B Are Associated with Hepatic Necroinflammation. Inflammation 2022; 45:2559-2569. [PMID: 35790658 DOI: 10.1007/s10753-022-01712-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/06/2022] [Accepted: 06/29/2022] [Indexed: 11/05/2022]
Abstract
The diagnosis and disease management of chronic hepatitis B (CHB) remain challenging due to the elusive assessment of disease severity. Recently, soluble receptor for advanced glycation end-products (sRAGE) has been implicated in the inflammatory-immune response initiated by liver injury. Nonetheless, its natural behavior and clinical importance in CHB remain elusive. One hundred and twenty CHB patients and forty healthy controls (HCs) were enrolled, and the serum sRAGE as well as RAGE expression in biopsy specimens from these subjects was analyzed, and correlation of sRAGE with clinical features as well as its potential predictive value for monitoring the CHB was also evaluated. Reduced serum sRAGE levels and decreased tissular RAGE expression were observed in CHB patients. sRAGE and RAGE were inversely correlated with gradually increased grades of hepatic necroinflammation as well as the routine indicator ALT. Furthermore, receiver operating characteristic (ROC) analysis showed that combination of ALT and sRAGE exerted better predictive power (area under the ROC curve (AUC) of 0.86) for hepatic necroinflammation than that of ALT (AUC of 0.82), sRAGE (AUC of 0.81), or sRAGE-to-ALT ratio (sRAGE/ALT) (AUC of 0.85) alone. More importantly, circulating sRAGE alone exerted valuable predictive power for hepatic moderate-to-severe necroinflammation in CHB patients but with normal ALT (AUC of 0.81) or minimally elevated ALT (AUC of 0.85). In conclusion, reduced serum sRAGE levels may imply an increased severity for necroinflammation, and it may serve as a potential alternative biomarker for monitoring hepatic necroinflammation in CHB.
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Affiliation(s)
- Xiuyu Zhang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China
| | - Yan You
- Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Qiao Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Xiaoyu Sun
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China
| | - Weixian Chen
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China
| | - Liang Duan
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yu Zhong District, Chongqing, 400010, China.
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Chen Y, Gao WK, Shu YY, Ye J. Clinical treatment of chronic hepatitis B virus infection in indeterminate phase: Current status and future prospects. Shijie Huaren Xiaohua Zazhi 2022; 30:436-443. [DOI: 10.11569/wcjd.v30.i10.436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The natural history of chronic hepatitis B virus (HBV) infection is usually divided into four stages: Immune tolerant phase (IT), hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) (i.e., immune clearance phase), immune control (IC) phase, and HBeAg negative CHB (i.e., reactivation phase). Patients whose HBeAg, alanine aminotransferase (ALT), HBV DNA, and hepatic histopathology fall into an indeterminate phase are divided into the following four groups: (1) Indeterminate phase related to IT: HBV DNA < 106 IU/mL or significant inflammation and fibrosis, while other indicators are in line with IT; (2) Indeterminate phase related to HBeAg positive CHB: HBV DNA < 2 × 104 IU/mL or ALT 1-2 times the upper limit of normal (ULN), while the rest indicators are consistent with HBeAg positive CHB; (3) Indeterminate phase related to IC: HBV DNA > 2 × 103 IU/mL or significant inflammation and fibrosis, while other indicators meet IC; and (4) Indeterminate phase related to HBeAg negative CHB: HBV DNA < 2 × 103 IU/mL or ALT 1-2 ULN, while the remaining indicators are in accordance with HBeAg negative CHB. In China, it is estimated that about 70 million people have chronic HBV infection, of which about 20-30 million are CHB patients. The percentage of liver cirrhosis and hepatocellular carcinoma caused by HBV infection is 77% and 84%, respectively. Chronic HBV infection brings severe burden to people's life and health as well as the national health care system. Although existing guidelines recommend dynamic monitoring of serum ALT and HBV DNA levels and assessment of liver histology of indeterminate zone, whether to initiate antiviral therapy in these patients remains controversial. This review mainly introduces the clinical treatment status of CHB patients in IC and indeterminate phase related to IC, and the future prospects of antiviral treatment for these patients.
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Affiliation(s)
- Yue Chen
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Wen-Kang Gao
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Yan-Yun Shu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Jin Ye
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Zhao XA, Wang J, Wei J, Liu J, Chen G, Wang L, Wang G, Xia J, Wu W, Yin S, Tong X, Yan X, Ding W, Xiang X, Huang R, Wu C. Gamma-glutamyl Transpeptidase to Platelet Ratio Predicts Liver Injury in Hepatitis B e Antigen-negative Chronic Hepatitis B Patients With Normal Alanine Aminotransferase. J Clin Transl Hepatol 2022; 10:247-253. [PMID: 35528978 PMCID: PMC9039718 DOI: 10.14218/jcth.2021.00151] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/24/2021] [Accepted: 06/16/2021] [Indexed: 12/07/2022] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis B virus (HBV) infection is a serious health problem worldwide. Evaluating liver injury in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with detectable HBV DNA and normal alanine aminotransferase (ALT) is crucial to guide their clinical management. We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in these patients. METHODS A total of 184 treatment-naïve HBeAg-negative CHB patients with detectable HBV DNA and normal ALT were enrolled. The Scheuer scoring system was used to classify liver inflammation and fibrosis. RESULTS The distribution of patients with different liver inflammation grades were as follows: G0, 0 (0%); G1, 97 (52.7%); G2, 68 (37.0%); G3, 12 (6.5%); and G4, 7 (3.8%). The distribution of patients with different liver fibrosis stages were as follows: S0, 22 (12.0%); S1, 72 (39.1%); S2, 42 (22.8%); S3, 19 (10.3%); and S4, 29 (15.8%). The areas under the receiver operating characteristic (AUROC) curves of GPR in predicting significant inflammation, severe inflammation, and advanced inflammation were 0.723, 0.895, and 0.952, respectively. The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation. The AUROCs of GPR in predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.691, 0.780, and 0.803, respectively. The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) in identifying advanced fibrosis and cirrhosis, and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis. CONCLUSIONS Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis. GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.
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Affiliation(s)
- Xiang-An Zhao
- Department of Gastroenterology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jie Wei
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Guangmei Chen
- Department of Infectious Diseases, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Li Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Guiyang Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weihua Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Xiaoxing Xiang
- Department of Gastroenterology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Correspondence to: Chao Wu and Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. ORCID: https://orcid.org/0000-0002-1657-010X (CW), https://orcid.org/0000-0002-3189-7960 (RH). Tel: +86-25-8310-5890 (CW), +86-25-8310-6666-20201 (RH), Fax: +86-25-8330-7115 (CW), +86-25-8330-7115 (RH), E-mail: (CW), (RH)
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Correspondence to: Chao Wu and Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China. ORCID: https://orcid.org/0000-0002-1657-010X (CW), https://orcid.org/0000-0002-3189-7960 (RH). Tel: +86-25-8310-5890 (CW), +86-25-8310-6666-20201 (RH), Fax: +86-25-8330-7115 (CW), +86-25-8330-7115 (RH), E-mail: (CW), (RH)
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Yıldız İE, Bahçeci İ, Ilgar T, Beyazal M, Kostakoğlu U, Ertürk A. Is Liver Biopsy Necessary in Patients with Chronic Hepatitis B with Normal Alanine Aminotransferase Level? Egypt J Immunol 2022. [DOI: 10.4274/vhd.galenos.2021.2021-7-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
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Abstract
The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its associated complications. Hence, assessment of liver in cirrhosis should include assessment of its structural, function of both hepatic and non-hepatic tissue and haemodynamic assessment of portal hypertension. There is no single test that can evaluate all functions of liver and assess prevalence and severity of portal hypertension. Commonly available tests like serum bilirubin, liver enzymes (alanine [ALT] and aspartate aminotransferase [AST], serum alkaline phosphatase [ALP], gamma glutamyl transpeptidase [GGT]), serum albumin and prothrombin time for assessment of liver functions partly assess liver functions. quantitative liver functions like indocyanine clearance tests [ICG-K], methacetin breath test [MBT] were developed to assess dynamic status of liver but has its own limitation and availability. Imaging based assessment of liver by transient elastography, MRI based 99 mTc-coupled asialoglycoprotein mebrofenin scan help the clinician to assess liver function, functional volume of liver left after surgery and portal hypertension [PH]. Hepatic venous pressure gradient still remains the gold standard for the assessment of portal hypertension but is invasive and not available in all centres. Combinations of blood parameters in form of various indices like fibrosis score of 4 [FIB-4], Lok index, scores like model for end stage liver disease (MELD) and Child-Turcotte Pugh score are commonly used for assessing liver function in clinical practice.
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Key Words
- 99mTc-GSA, technetium-99m galactosyl human serum albumin
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- ARFI, Acoustic Radiation Force Impulse
- AST, aspartate aminotransferase
- BUN, blood urea nitrogen
- CLD, chronic liver disease
- ESLD, end-stage liver disease
- FIB-4, fibrosis score of 4
- GGT, gamma glutamyl transpeptidase
- HVPG, Hepatic venous pressure gradient
- ICG-K, indocyanine clearance tests
- INR, International normalised ratio
- LFTs, liver function tests
- MBT, methacetin breath test
- NAFLD, non-alcoholic fatty liver disease
- PBS, primary biliary cholangitis
- PHT, portal hypertension
- PSC, primary Sclerosing cholangitis
- cirrhosis
- liver function tests
- portal hypertension
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Affiliation(s)
- Praveen Sharma
- Address for correspondence: Praveen Sharma, Associate Professor, Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India.
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Suzuki T, Matsuura K, Nagura Y, Iio E, Ogawa S, Fujiwara K, Nojiri S, Kataoka H, Tanaka Y. Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection. PLoS One 2021; 16:e0261878. [PMID: 34962955 PMCID: PMC8714106 DOI: 10.1371/journal.pone.0261878] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 12/11/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND & AIMS There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period. DESIGN We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups. RESULTS Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients. CONCLUSIONS HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words).
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshihito Nagura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shunsuke Nojiri
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Wang M, Chen L, Dong M, Li J, Zhu B, Yang Z, Gong Q, Han Y, Yu D, Zhang D, Zoulim F, Zhang J, Zhang X. Viral quasispecies quantitative analysis: a novel approach for appraising the immune tolerant phase of chronic hepatitis B virus infection. Emerg Microbes Infect 2021; 10:842-851. [PMID: 33870846 PMCID: PMC8812768 DOI: 10.1080/22221751.2021.1919033] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 04/06/2021] [Accepted: 04/14/2021] [Indexed: 10/24/2022]
Abstract
Few non-invasive models were established for precisely identifying the immune tolerant (IT) phase from chronic hepatitis B (CHB). This study aimed to develop a novel approach that combined next-generation sequencing (NGS) and machine learning algorithms using our recently published viral quasispecies (QS) analysis package. 290 HBeAg positive patients from whom liver biopsies were taken were enrolled and divided into a training group (n = 148) and a validation group (n = 142). HBV DNA was extracted and QS sequences were obtained by NGS. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) based on viral operational taxonomic units (OTUs) were performed to explore the correlations among QS and clinical phenotypes. Three machine learning algorithms, including K-nearest neighbour, support vector machine, and random forest algorithm, were used to construct diagnostic models for IT phase classification. Based on histopathology, 90 IT patients and 200 CHB patients were diagnosed. HBsAg titres for IT patients were higher than those of CHB patients (p < 0.001). HCA and PCA analysis grouped IT and CHB patients into two distinct clusters. The relative abundance of viral OTUs differed mainly within the BCP/precore/core region and was significantly correlated with liver inflammation and fibrosis. For the IT phase classification, all machine-learning models showed higher AUC values compared to models based on HBsAg, APRI, and FIB-4. The relative abundance of viral OTUs reflects the severity of liver inflammation and fibrosis. The novel QS quantitative analysis approach could be used to diagnose IT patients more precisely and reduce the need for liver biopsy.
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Affiliation(s)
- Mingjie Wang
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - Li Chen
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - MinHui Dong
- Department of Infectious Diseases, Huashan Hospital and Key Laboratory of Medical Molecular Virology (MOH & MOE), Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China
| | - Jing Li
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - Beidi Zhu
- Department of Infectious Diseases, Huashan Hospital and Key Laboratory of Medical Molecular Virology (MOH & MOE), Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China
| | - Zhitao Yang
- Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - Qiming Gong
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - Yue Han
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - Demin Yu
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - Donghua Zhang
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
| | - Fabien Zoulim
- INSERM U1052, Cancer Research Centre of Lyon (CRCL), Lyon, France
| | - Jiming Zhang
- Department of Infectious Diseases, Huashan Hospital and Key Laboratory of Medical Molecular Virology (MOH & MOE), Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China
| | - Xinxin Zhang
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China
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Yang L, Zhang Y, Zhang K, Liu Z, He T, Zheng X, Li L, Arnér ESJ, Zhang Z, Zhang J. Evaluation of dithiothreitol-oxidizing capacity (DOC) as a serum biomarker for chronic hepatitis B in patients exhibiting normal alanine aminotransferase levels: a pilot study towards better monitoring of disease. EClinicalMedicine 2021; 42:101180. [PMID: 34765954 PMCID: PMC8569636 DOI: 10.1016/j.eclinm.2021.101180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 10/14/2021] [Accepted: 10/14/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Alanine aminotransferase (ALT) is the most commonly used serum biomarker for chronic liver diseases (CLDs) but may not accurately reflect hepatic disorders and easily underestimates hepatic fibrosis. The previously revised upper limit of normal (ULN) of ALT (19 U/L for women and 30 U/L for men) increases its sensitivity but yields higher numbers of false-positives. Moreover, CLDs patients with ALT lower than the revised ULN may nonetheless have progression of disease. Therefore there is a need of novel biomarkers to complement the use of ALT. Here we have evaluated measurements of serum dithiothreitol-oxidizing capacity (DOC) in cohorts of chronic hepatitis B patients with different stages of disease as an exploratory pilot study for this purpose. METHODS Serum samples obtained from healthy persons and from chronic hepatitis B patients with normal ALT values were used for sensitivity evaluation. The hepatitis B patients encompassed end-stage liver diseases (ELD), chronic hepatitis B (CHB), CHB with persistently normal ALT (CHB-P) and inactive carriers (ICs). Sensitivity was also evaluated with samples from patients with other diseases. The study period was March 2018 to December 2020. FINDINGS DOC was found to be a robust biomarker that may become complementary to ALT measurements, especially in patients displaying low ALT levels. ROC analyses indicated that the AUC values of DOC reached 0.983 and 0.956 in ELD and CHB patients exhibiting normal ALT levels, respectively. Importantly, the AUC values of DOC reached 0.852 and 0.844 in CHB-P patients and ICs, respectively. Such AUC values permit screening and continued monitoring, corresponding to over 30% and 50% sensitivity with 99% and 95% specificity for CHB-P and ICs, respectively. DOC was also significantly correlated with indicators for fibrosis, assessing both APRI (Pearson r = 0.4905, P < 0.0001) and FIB-4 (Pearson r = 0.4421, P < 0.0001). Surprisingly, the AUC values of DOC in the hepatitis B patients with ALT levels lower than the revised ULN were not compromised. In examined non-liver diseases, DOC was low and normal, including in patients with acute myocardial infection displaying increased ALT levels. INTERPRETATIONS The results suggest that DOC can be promising as a complementary biomarker used in addition to ALT for monitoring of disease in chronic hepatitis B patients, especially when ALT levels are normal. DOC should be further evaluated for possible clinical use as biomarker also in other CLDs. FUNDING This study was funded by the National Natural Science Foundation of China (Grant numbers: 31771971 and 32001013).
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Affiliation(s)
- Lumin Yang
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China
| | - Yafei Zhang
- Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Ke Zhang
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China
| | - Zhongping Liu
- Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Tengfei He
- Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xiaowei Zheng
- Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
- Department of Infectious Disease, Anhui Provincial Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Lei Li
- Department of Infectious Disease, Anhui Provincial Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Elias S J Arnér
- Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden and Department of Selenoprotein Research, National Institute of Oncology, Budapest, Hungary
| | - Zhenhua Zhang
- Department of Infectious Diseases and Institute of Clinical Virology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jinsong Zhang
- State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, China
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45
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Teng W, Chang TT, Yang HI, Peng CY, Su CW, Su TH, Hu TH, Yu ML, Yang HC, Wu JC. Risk scores to predict HCC and the benefits of antiviral therapy for CHB patients in gray zone of treatment guidelines. Hepatol Int 2021; 15:1421-1430. [PMID: 34741723 DOI: 10.1007/s12072-021-10263-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/18/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUNDS ALT ≥ 80 U/L and HBV DNA ≥ 2000 IU/ml are treatment criteria of APASL guidelines for chronic hepatitis B (CHB) patients. The need of antiviral therapy for patients in gray zone (ALT < 80 U/L or HBV DNA < 2000 IU/ml) is controversial. This study aimed to develop a scoring system to predict hepatocellular carcinoma (HCC) and evaluate the benefit of antiviral therapy in these patients. METHODS Seven hundred and forty-nine patients were analyzed. Significant variables were weighted to develop a scoring system for HCC prediction. The area under receiver operating curves (AUROC) were estimated and validated by REVEAL-HBV cohort (n = 3527). RESULTS Older age (p < 0.001), male sex (p = 0.036), family history of HCC (p = 0.002) and HBV DNA ≥ 2000 IU/ml (p = 0.045) were independently associated with HCC. A 14-point risk score system predicts 3 and 5-years HCC risk to be 0.866 and 0.868 of AUROC, respectively in the derivation cohort; 0.821 and 0.820, in the REVEAL-HBV cohort. The cumulative HCC incidence was higher in the high risk (score ≥ 8) group both in derivation and validation cohorts (p < 0.001). Patients with antiviral therapy had lower HCC incidence compared to those without (p = 0.016). Of note, antiviral therapy significantly decreased HCC in the high risk group (p = 0.005), but not in the low risk group (p = 0.705). CONCLUSIONS A risk scoring system is established and validated. Of CHB patients in gray zone of APASL guidelines, those with risk scores ≥ 8 had higher risk of HCC, but the risk could be significantly reduced by antiviral therapy.
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Affiliation(s)
- Wei Teng
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, Republic of China
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan, Republic of China
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Tsung-Hui Hu
- Department of Gastroenterology and Hepatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China.
- Translational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
- Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China.
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46
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Liu J, Wang J, Yan X, Xue R, Zhan J, Jiang S, Geng Y, Liu Y, Mao M, Xia J, Yin S, Tong X, Chen Y, Ding W, Huang R, Wu C. Presence of Liver Inflammation in Asian Patients With Chronic Hepatitis B With Normal ALT and Detectable HBV DNA in Absence of Liver Fibrosis. Hepatol Commun 2021; 6:855-866. [PMID: 34783181 PMCID: PMC8948668 DOI: 10.1002/hep4.1859] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 10/16/2021] [Accepted: 10/26/2021] [Indexed: 02/06/2023] Open
Abstract
Liver biopsies are recommended to exclude significant liver inflammation in patients with chronic hepatitis B (CHB) with elevated HBV DNA but without other indications for antiviral treatment. We aimed to investigate the proportions and determinants of significant inflammation in Asian patients with CHB with detectable HBV DNA. We conducted a cross‐sectional study that retrospectively included 581 patients with CHB with detectable HBV DNA who had undergone liver biopsy. Liver inflammation and fibrosis were staged by Scheuer’s classification. Significant inflammation and significant fibrosis were defined as G ≥ 2 and S ≥ 2, respectively. There were 179 (30.8%) patients with alanine aminotransferase (ALT) < 1 × upper limit of normal (ULN), 205 (35.3%) patients with ALT 1‐2 × ULN, and 197 (33.9%) patients with ALT > 2 × ULN. A total of 397 (68.3%) patients had significant inflammation, and 340 (58.5%) patients had significant fibrosis. Significant inflammation was found in 85% of patients with significant fibrosis and in 44.8% of patients without significant fibrosis. Furthermore, 28.7% of patients with CHB with detectable HBV DNA and normal ALT in the absence of significant fibrosis had significant inflammation. Moderate HBV DNA (5‐7 log10 IU/mL) was a risk factor for significant inflammation (odds ratio [OR] 6.929, 95% confidence interval [CI] 2.830‐16.966, P < 0.001) in patients with CHB with detectable HBV DNA, especially for patients with detectable HBV DNA and normal ALT in the absence of significant fibrosis (adjusted OR 13.161, 95% CI 1.026‐168.889, P = 0.048). Conclusion: A high proportion of CHB patients with detectable HBV DNA and normal ALT in the absence of significant fibrosis have significant liver inflammation. Liver biopsies are recommended to evaluate liver inflammation in such patients, especially for those with moderate HBV DNA.
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Affiliation(s)
- Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jie Zhan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Suling Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yu Geng
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yilin Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Minxin Mao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.,Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
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Zhang C, Li JW, Wu Z, Zhao H, Wang GQ. Significant Histologic Changes Are Not Rare in Treatment-naive Hepatitis B Patients with Normal Alanine Aminotransferase Level: A Meta-analysis. J Clin Transl Hepatol 2021; 9:615-625. [PMID: 34722176 PMCID: PMC8516830 DOI: 10.14218/jcth.2020.00136] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 03/19/2021] [Accepted: 03/22/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis B is the main cause of liver cancer. However, the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase (ALT). People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment. However, the truth is not as optimistic as we thought. We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients. METHODS Medline, Embase, and Cochrane Library were searched up to January 10th 2020, to identify studies of these patients with liver biopsy. The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis. Potential heterogeneity was explored by subgroup analysis and meta-regression. Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis. The secondary outcome was to find the risk factors of significant histological changes. RESULTS Nineteen eligible studies, with 2,771 participants, were included. The pooled proportion of significant inflammation or fibrosis was 35% [95% confidence interval (CI): 27 to 43] and 30% (95% CI: 25 to 36), respectively. The pooled proportion of cirrhosis was 3% [95% CI: 1 to 5, (12 studies; 1,755 participants)]. In subgroup analysis, old age [vs. young (<40 years-old), 44% vs. 26%, p=0.012] was significantly associated with higher fibrosis stage as well as cirrhosis [vs. young (<40 years-old), 4.8% vs. 1.8%, p<0.001]. CONCLUSIONS About 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes, and some even have cirrhosis.
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Affiliation(s)
- Chi Zhang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Xicheng District, Beijing, China
| | - Jia-Wen Li
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Xicheng District, Beijing, China
| | - Zhao Wu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Xicheng District, Beijing, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Xicheng District, Beijing, China
- Peking University International Hospital, Beijing, China
- Correspondence to: Gui-Qiang Wang and Hong Zhao, Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China. Tel: +86-13911405123, Fax: +86-10-66551680, E-mail: , (GQW); Tel: +86-13810765943, Fax: +86-10-66551680, E-mail: (HZ)
| | - Gui-Qiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Xicheng District, Beijing, China
- The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China
- Peking University International Hospital, Beijing, China
- Correspondence to: Gui-Qiang Wang and Hong Zhao, Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China. Tel: +86-13911405123, Fax: +86-10-66551680, E-mail: , (GQW); Tel: +86-13810765943, Fax: +86-10-66551680, E-mail: (HZ)
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Xie X, Lv H, Liu C, Su X, Yu Z, Song S, Bian H, Tian M, Qin C, Qi J, Zhu Q. HBeAg mediates inflammatory functions of macrophages by TLR2 contributing to hepatic fibrosis. BMC Med 2021; 19:247. [PMID: 34649530 PMCID: PMC8518250 DOI: 10.1186/s12916-021-02085-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 08/03/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND We and others have confirmed activation of macrophages plays a critical role in liver injury and fibrogenesis during HBV infection. And we have also proved HBeAg can obviously induce the production of macrophage inflammatory cytokines compared with HBsAg and HBcAg. However, the receptor and functional domain of HBeAg in macrophage activation and its effects and mechanisms on hepatic fibrosis remain elusive. METHODS The potentially direct binding receptors of HBeAg were screened and verified by Co-IP assay. Meanwhile, the function domain and accessible peptides of HBeAg for macrophage activation were analyzed by prediction of surface accessible peptide, construction, and synthesis of truncated fragments. Furthermore, effects and mechanisms of the activation of hepatic stellate cells induced by HBeAg-treated macrophages were investigated by Transwell, CCK-8, Gel contraction assay, Phospho Explorer antibody microarray, and Luminex assay. Finally, the effect of HBeAg in hepatic inflammation and fibrosis was evaluated in both human and murine tissues by immunohistochemistry, immunofluorescence, ELISA, and detection of liver enzymes. RESULTS Herein, we verified TLR-2 was the direct binding receptor of HBeAg. Meanwhile, C-terminal peptide (122-143 aa.) of core domain in HBeAg was critical for macrophage activation. But arginine-rich domain of HBcAg hided this function, although HBcAg and HBeAg shared the same core domain. Furthermore, HBeAg promoted the proliferation, motility, and contraction of hepatic stellate cells (HSCs) in a macrophage-dependent manner, but not alone. PI3K-AKT-mTOR and p38 MAPK signaling pathway were responsible for motility phenotype of HSCs, while the Smad-dependent TGF-β signaling pathway for proliferation and contraction of them. Additionally, multiple chemokines and cytokines, such as CCL2, CCL5, CXCL10, and TNF-α, might be key mediators of HSC activation. Consistently, HBeAg induced transient inflammation response and promoted early fibrogenesis via TLR-2 in mice. Finally, clinical investigations suggested that the level of HBeAg is associated with inflammation and fibrosis degrees in patients infected with HBV. CONCLUSIONS HBeAg activated macrophages via the TLR-2/NF-κB signal pathway and further exacerbated hepatic fibrosis by facilitating motility, proliferation, and contraction of HSCs with the help of macrophages.
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Affiliation(s)
- Xiaoyu Xie
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China.,Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China.,Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, Shandong, 250021, People's Republic of China
| | - Huanran Lv
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China
| | - Chenxi Liu
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China
| | - Xiaonan Su
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China
| | - Zhen Yu
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China
| | - Shouyang Song
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China
| | - Hongjun Bian
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China.,Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China
| | - Miaomiao Tian
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China.,Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, Shandong, 250021, People's Republic of China
| | - Chengyong Qin
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China.,Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China.,Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, Shandong, 250021, People's Republic of China
| | - Jianni Qi
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China. .,Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China. .,Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, Shandong, 250021, People's Republic of China.
| | - Qiang Zhu
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People's Republic of China. .,Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People's Republic of China. .,Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, Shandong, 250021, People's Republic of China. .,The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China.
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Zhu L, Fang Z, Jin Y, Chang W, Huang M, He L, Chen Y, Yao Y. Association between serum alanine and aspartate aminotransferase and blood pressure: a cross-sectional study of Chinese freshmen. BMC Cardiovasc Disord 2021; 21:472. [PMID: 34598675 PMCID: PMC8485510 DOI: 10.1186/s12872-021-02282-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 09/24/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND High blood pressure is a well-recognized risk factor for cardiovascular events, and the incidence of hypertension is increasing among young people. This study investigated the relationship between ALT and AST levels and hypertension among freshmen in China. METHODS This cross-sectional study was conducted in the Anhui Province from September to November 2018. A total of 3114 freshmen underwent a physical examination including testing of biochemical indicators and a standardized questionnaire. RESULTS The overall prevalence of elevated ALT and AST were 6.8% and 2.3% among freshmen. The mean ALT and AST levels were higher in males (22.59 ± 21.98 vs.12.62 ± 10.30 U/L; 23.55 ± 12.24 vs. 20.02 ± 5.75 U/L, respectively). The prevalence of hypertension was significantly higher in men (16.1%) than in women (1.9%). The mean values of BMI, SBP, DBP, TC, TG, and LDL-C were found to be increased with elevated levels of serum ALT and AST in the quartiles (P for trend < 0.05). After adjusting for covariates, the risk of hypertension was significantly higher in the highest ALT quartile than in the lowest quartile (OR (95% CI) of 1.681 (1.028, 2.751) in males; 2.802 (1.102, 7.124) in females). A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders only in total population and females (P for trend < 0.05). CONCLUSIONS These findings suggest that ALT level is significantly associated with hypertension both in male and female freshmen.
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Affiliation(s)
- Lijun Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
- Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
| | - Zhengmei Fang
- Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
- Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
| | - Yuelong Jin
- Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
- Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
| | - Weiwei Chang
- Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
- Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
| | - Mengyun Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
- Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China
| | - Lianping He
- School of Medicine, Taizhou University, Taizhou, 318000, China
| | - Yan Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China.
- Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China.
| | - Yingshui Yao
- Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China.
- Institute of Chronic Disease Prevention and Control, Wannan Medical College, No. 22, Wenchang Road, Wuhu, 241002, Anhui, China.
- Department of Medicine, Anhui College of Traditional Chinese Medicine, No.18, Wuxia Shanxi Road, Wuhu, 241002, Anhui, China.
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50
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Yao K, Wang J, Wang L, Xia J, Yan X, Wu W, Liu J, Wang L, Yin S, Tong X, Ding W, Huang R, Wu C. Association of anti-HBc and liver inflammation in HBeAg-negative chronic hepatitis B virus-infected patients with normal ALT and detectable HBV DNA. J Med Virol 2021; 94:659-666. [PMID: 34499353 DOI: 10.1002/jmv.27327] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/07/2021] [Indexed: 12/11/2022]
Abstract
Serum hepatitis B core antibody (anti-HBc) is associated with liver inflammation in chronic hepatitis B patients. This study aimed to investigate whether anti-HBc could serve as a predictor of significant liver inflammation in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infected patients with normal alanine aminotransferase (ALT) and detectable HBV DNA. Treatment-naïve HBeAg-negative chronic HBV infected patients with normal ALT and detectable HBV DNA who underwent liver biopsy were retrospectively included from two medical centers. Liver inflammation grade was evaluated using the Scheuer scoring system and significant liver inflammation was defined as ≥G2. Serum anti-HBc levels were measured by commercial immunoassays (Abbott GmbH & Co. KG). A total of 117 patients were included and 50 (42.7%) patients showed significant liver inflammation. Serum anti-HBc levels in patients with significant liver inflammation were significantly higher than patients with no or mild liver inflammation (<G2) (p < 0.001). High serum anti-HBc (odds ratio 1.562, 95% confidential interval 1.157-2.110, p = 0.004) was an independent risk factor of significant liver inflammation. The area under the receiver operating characteristic curve of serum anti-HBc in predicting significant liver inflammation was 0.769 and the optimal cut-off value was 10.87 S/CO, with a sensitivity of 59.2% and a specificity of 87.9%. Our data revealed that a substantial of HBeAg-negative chronic infection patients with normal ALT and detectable HBV DNA showed significant liver inflammation. Serum anti-HBc can predict significant liver inflammation in these patients.
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Affiliation(s)
- Kefang Yao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Lijuan Wang
- Department of Laboratory Medicine, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weihua Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Li Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
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