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Qin Z, Liu Y, Liu Y, Yang A, Zhang R, Zhang K, Zhang S. Association between resolved hepatitis B virus infection and depression in American adults : a cross-sectional study. Sci Rep 2025; 15:16141. [PMID: 40341244 PMCID: PMC12062217 DOI: 10.1038/s41598-025-99864-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 04/23/2025] [Indexed: 05/10/2025] Open
Abstract
Hepatitis B virus (HBV) infection is a global health concern, and it can potentially affect mental health like depression. Resolved HBV infection, often perceived as a milder form of HBV infection, are often overlooked, and the association between it and depression remains unclear. This study aims to investigate the association between resolved HBV infection and depression. A cross-sectional analysis was conducted using the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018, including 20,655 adult Americans. Resolved HBV infection was defined as HBV surface antigen (HBsAg) negative and HBV core antibody (HBcAb) positive. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) score. Propensity score matching (PSM) was performed to balance baseline characteristics. Algorithms such as inverse probability of treatment weighting (IPTW) were also applied. Among the participants, 1,551 (7.5%) were reported to have resolved HBV infection. Depression was reported by 1,796 participants (8.7%), with a higher prevalence among those with resolved HBV infection (10.6%) compared to those without HBV infection(8.5%). PSM and IPTW revealed a significantly positive association between resolved HBV infection and depression (PSM: OR = 1.40, 95%CI 1.09-1.79, p = 0.008; IPTW: OR = 1.48, 95%CI 1.26-1.74, p < 0.001). Subgroup and sensitivity analyses supported the robustness of the findings. The results suggest a complex relationship between resolved chronic viral infections and mental health. Based on this finding, it is advisable to conduct psychological monitoring and offer support to individuals who have achieved a functional cure for HBV. Further prospective studies are still needed to reveal the potential mechanism.
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Affiliation(s)
- Zihan Qin
- Hebei Medical University, Shijiazhuang, 050017, China
| | - Yizhuo Liu
- Hebei Medical University, Shijiazhuang, 050017, China
| | - Yifei Liu
- Hebei Medical University, Shijiazhuang, 050017, China
| | - Anqi Yang
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China
| | - Ruoyi Zhang
- Hebei Medical University, Shijiazhuang, 050017, China.
| | - Kun Zhang
- Hebei Medical University, Shijiazhuang, 050017, China.
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
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Jespersen S, Bollerup S, Madsbad S, Krogh-Madsen R, Byberg S, Weis N. Cardiometabolic Comorbidities in Patients With Chronic Hepatitis B and Impact on Incidence of Liver Complications. A Danish Nationwide Cohort Study. Int J Gen Med 2025; 18:1591-1604. [PMID: 40123812 PMCID: PMC11930244 DOI: 10.2147/ijgm.s471083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 12/21/2024] [Indexed: 03/25/2025] Open
Abstract
Purpose To evaluate liver complications in patients with chronic hepatitis B, both with and without cardiometabolic comorbidities, and to compare the incidence of cardiometabolic comorbidities in these patients with that of the general population. Study Population and Methods This nationwide registry-based cohort study included data from 2002-2020. In the primary analysis, we used multivariate Poisson regression to estimate the incidence rate and incidence rate ratio of liver complications in patients with chronic hepatitis B, stratified by the presence of cardiometabolic comorbidities. In the secondary analysis, we compared the incidence rate of developing cardiometabolic comorbidities in patients with chronic hepatitis B to those of the general population. Both analyses were adjusted for sex, age, and country of origin, while the primary analysis was additionally adjusted for time since cardiometabolic comorbidity diagnosis and calendar year. Results The primary analysis included 4731 patients with chronic hepatitis B, of whom 532 (11%) had at least one cardiometabolic comorbidity. The unadjusted overall incidence rate of liver complications in patients with cardiometabolic comorbidities was 1.0 per 100 person-years (95% confidence intervals: 0.84-1.30) compared to 0.4 per 100 person-years (95% confidence intervals: 0.30-0.42) in those without. The incidence rate ratio for liver complications was highest in the first year following the diagnosis of cardiometabolic comorbidity. The incidence rate ratio for developing cardiometabolic comorbidities in the chronic hepatitis B cohort compared to the general population, was 1.10 (95% confidence intervals: 1.02-1.19). Sensitivity analyses revealed a higher incidence rate ratio for type 2 diabetes and hypertension but a lower incidence rate ratio for hypercholesterolemia. Conclusion Patients with chronic hepatitis B and cardiometabolic comorbidities exhibit a higher incidence of liver complications, particularly in the first year following comorbidity diagnosis compared to those without comorbidities. Furthermore, patients with chronic hepatitis B have a higher incidence of cardiometabolic comorbidities than the general population.
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Affiliation(s)
- Sofie Jespersen
- Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark
- Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Signe Bollerup
- Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark
| | - Sten Madsbad
- Department of Endocrinology, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rikke Krogh-Madsen
- Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark
- Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Stine Byberg
- Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - On behalf of The DANHEP group
- Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark
- Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Endocrinology, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, Herlev, Denmark
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Zheng J, Yang Q, Huang J, Chen H, Shen J, Tang S. Hospital-treated infectious diseases, genetic susceptibility and risk of type 2 diabetes: A population-based longitudinal study. Diabetes Metab Syndr 2024; 18:103063. [PMID: 38917709 DOI: 10.1016/j.dsx.2024.103063] [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: 01/28/2024] [Revised: 06/11/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024]
Abstract
BACKGROUND The longitudinal association between infectious diseases and the risk of type 2 diabetes (T2D) remains unclear. METHODS Based on the UK Biobank, the prospective cohort study included a total of 396,080 participants without diabetes at baseline. We determined the types and sites of infectious diseases and incident T2D using the International Classification of Diseases 10th Revision codes (ICD-10). Time-varying Cox proportional hazard model was used to assess the association. Infection burden was defined as the number of infection episodes over time and the number of co-occurring infections. Genetic risk score (GRS) for T2D consisted of 424 single nucleotide polymorphisms. RESULTS During a median of 9.04 [IQR, 8.3-9.7] years of follow-up, hospital-treated infectious diseases were associated with a greater risk of T2D (adjusted HR [aHR] 1.54 [95 % CI 1.46-1.61]), with risk difference per 10,000 individuals equal to 154.1 [95 % CI 140.7-168.2]. The heightened risk persisted after 5 years following the index infection. Bacterial infection with sepsis had the strongest risk of T2D (aHR 2.95 [95 % CI 2.53-3.44]) among different infection types. For site-specific analysis, bloodstream infections posed the greatest risk (3.01 [95 % CI 2.60-3.48]). A dose-response association was observed between infection burden and T2D risk within each GRS tertile (p-trend <0.001). High genetic risk and infection synergistically increased the T2D risk. CONCLUSION Infectious diseases were associated with an increased risk of subsequent T2D. The risk showed specificity according to types, sites, severity of infection and the period since infection occurred. A potential accumulative effect of infection was revealed.
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Affiliation(s)
- Jiazhen Zheng
- Bioscience and Biomedical Engineering Thrust, Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong, China
| | - Quan Yang
- Cardiac and Vascular Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jinghan Huang
- Biomedical Genetics Section, School of Medicine, Boston University, China; Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, China
| | - Hengying Chen
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Junchun Shen
- Bioscience and Biomedical Engineering Thrust, Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong, China
| | - Shaojun Tang
- Bioscience and Biomedical Engineering Thrust, Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong, China; Division of Emerging Interdisciplinary Areas, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.
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Huang SC, Kao JH. The interplay between chronic hepatitis B and diabetes mellitus: A narrative and concise review. Kaohsiung J Med Sci 2024; 40:6-10. [PMID: 37732697 DOI: 10.1002/kjm2.12762] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/02/2023] [Accepted: 09/05/2023] [Indexed: 09/22/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder among individuals with chronic hepatitis B (CHB), contributing to additional adverse impacts on both hepatic and extrahepatic systems. Existing evidence suggests a potential positive association between CHB and the development of insulin resistance and T2DM. The presence of T2DM in CHB patients is associated with an increased risk of liver fibrosis, cirrhosis, decompensation, and hepatocellular carcinoma (HCC) occurrence. Moreover, it elevates the risk of non-liver cancers and all-cause mortality in this population. T2DM also serves as the key element in metabolic dysfunction-associated steatotic liver disease, which is prevalent in the CHB population. Although specific guidelines for managing T2DM in CHB patients have not been proposed, some studies indicated that intensive glycemic control may benefit the prognosis of these patients. Additionally, specific antidiabetic agents, such as metformin and thiazolidinediones, promise to reduce HCC risk. However, unresolved questions, including the optimal glycemic control target and the selection of antidiabetic agents for CHB patients, remain and thus warrant further investigations through well-designed prospective trials. Implementing a standardized protocol encompassing regular monitoring, risk stratification, and early intervention using a multidisciplinary framework may improve the outcomes of diabetic CHB patients.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Zhou G, Chen C, Han G, Jiang H, Cao M. Relationship between different hepatitis B virus infection status and gestational diabetes mellitus prevalence among pregnant women with chronic HBV infection: A retrospective study. J Viral Hepat 2022; 29:596-603. [PMID: 35582862 DOI: 10.1111/jvh.13700] [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: 11/24/2021] [Accepted: 03/18/2022] [Indexed: 12/09/2022]
Abstract
To investigate the relationships between different hepatitis B virus (HBV) infection status and gestational diabetes mellitus (GDM) and analyse the potential risk factors, we conducted an observational retrospective study in HBV-infected pregnant women to compare the differences of GDM prevalence and clinical outcomes between groups divided by HBV infection status. Spearman's correlation coefficient was used to evaluate the correlations among hepatitis B e antigen (HBeAg), HBV DNA and liver function. Logistic regression model was used to analyse the risk factors. In all, 1390 HBsAg-positive pregnant women were enrolled. HBeAg titre and HBV DNA, ALT and AST were correlated (r = 0.743, p < 0.001; r = 0.813, p < 0.001). Overall GDM prevalence was 21%. GDM prevalence of HBV-infected women with abnormal liver function was higher than those with normal liver function (26.8% vs. 20%, p = 0.027). Age over 35 years and abnormal liver function over 5 times ULN and 1-2 times ULN were independent risk factors for GDM prevalence with odds ratio (OR) of 1.858 (95% CI 1.227-2.815), 1.589 (95% CI 1.023-2.468) and 2.203 (95% CI 1.029-4.718), respectively. GDM prevalence in HBV-infected pregnancies with abnormal liver function was higher than those with normal liver function. Age over 35 years and abnormal liver function were independent risk factors for GDM in HBV-infected women.
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Affiliation(s)
- Guanlun Zhou
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chao Chen
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guorong Han
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongxiu Jiang
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Minkai Cao
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
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Cui XY, Wu X, Lu D, Wang D. Network pharmacology-based strategy for predicting therapy targets of Sanqi and Huangjing in diabetes mellitus. World J Clin Cases 2022; 10:6900-6914. [PMID: 36051114 PMCID: PMC9297423 DOI: 10.12998/wjcc.v10.i20.6900] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/02/2022] [Accepted: 04/15/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A comprehensive literature search shows that Sanqi and Huangjing (SQHJ) can improve diabetes treatment in vivo and in vitro, respectively. However, the combined effects of SQHJ on diabetes mellitus (DM) are still unclear.
AIM To explore the potential mechanism of Panax notoginseng (Sanqi in Chinese) and Polygonati Rhizoma (Huangjing in Chinese) for the treatment of DM using network pharmacology.
METHODS The active components of SQHJ and targets were predicted and screened by network pharmacology through oral bioavailability and drug-likeness filtration using the Traditional Chinese Medicine Systems Pharmacology Analysis Platform database. The potential targets for the treatment of DM were identified according to the DisGeNET database. A comparative analysis was performed to investigate the overlapping genes between active component targets and DM treatment-related targets. We constructed networks of the active component-target and target pathways of SQHJ using Cytoscape software and then analyzed the gene functions. Using the STRING database to perform an interaction analysis among overlapping genes and a topological analysis, the interactions between potential targets were identified. Gene Ontology (GO) function analyses and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in DAVID.
RESULTS We screened 18 active components from 157 SQHJ components, 187 potential targets for active components and 115 overlapping genes for active components and DM. The network pharmacology analysis revealed that quercetin, beta-sitosterol, baicalein, etc. were the major active components. The mechanism underlying the SQHJ intervention effects in DM may involve nine core targets (TP53, AKT1, CASP3, TNF, interleukin-6, PTGS2, MMP9, JUN, and MAPK1). The screening and enrichment analysis revealed that the treatment of DM using SQHJ primarily involved 16 GO enriched terms and 13 related pathways.
CONCLUSION SQHJ treatment for DM targets TP53, AKT1, CASP3, and TNF and participates in pathways in leishmaniasis and cancer.
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Affiliation(s)
- Xiao-Yan Cui
- Hebei Institute for Drug and Medical Device Control, Shijiazhuang 050011, Hebei Province, China
| | - Xiao Wu
- Department of Basic Medical, HE’s University, Shenyang 110163, Liaoning Province, China
| | - Dan Lu
- College of Clinical, HE’s University, Shenyang 110163, Liaoning Province, China
| | - Dan Wang
- College of Human Kinesiology, Shenyang Sport University, Shenyang 110102, Liaoning Province, China
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Farshadpour F, Taherkhani R, Saberi F. Molecular evaluation of hepatitis B virus infection and predominant mutations of pre-core, basal core promoter and S regions in an Iranian population with type 2 diabetes mellitus: a case-control study. BMC Infect Dis 2022; 22:553. [PMID: 35715756 PMCID: PMC9206294 DOI: 10.1186/s12879-022-07528-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/06/2022] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND This study was designed to evaluate the prevalence, genotypic patterns, and predominant mutations of hepatitis B virus (HBV) infection among diabetic patients. METHODS Serum samples were obtained from 733 patients with type 2 diabetes mellitus and 782 non-diabetic controls. The presence of HBsAg and HBcAb was determined by ELISA. Nested PCR, targeting S and pre-core regions of the HBV genome, followed by sequencing was carried out to determine HBV genotypes and predominant mutations in the S, basal core promoter (BCP), and pre-core regions of the HBV genome. RESULTS Of 733 diabetic patients, 94 cases (12.82%) were positive for HBcAb, 28 cases (3.82%) were positive for HBsAg, and 19 cases (2.59%) had HBV-DNA with genotype D, sub-genotype D1/D3 and subtype ayw2. An occult HBV infection was found in one of the HBV DNA-positive samples, which was positive for HBcAb but negative for HBsAg. P120T/G145R, G1896A/G1899A, and A1762T/G1764T were the most frequent point substitution mutations detected in the S, pre-core, and BCP regions of the HBV genome, respectively. P120T and G145R mutations were associated with low levels or undetectable levels of HBsAg in serum. Therefore, routine tests based on HBsAg detection cannot detect HBsAg-negative infected patients. CONCLUSIONS Relatively high prevalence of HBV infection was found in diabetic patients, while all of the HBV-infected patients were unaware of their infection. Therefore, screening for HBV infection should be included in the management program of diabetes for timely diagnosis and treatment of infected but asymptomatic patients.
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Affiliation(s)
- Fatemeh Farshadpour
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran
| | - Reza Taherkhani
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran.
| | - Fatemeh Saberi
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran
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Shi YW, Yang RX, Fan JG. Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion. World J Gastroenterol 2021; 27:3971-3983. [PMID: 34326608 PMCID: PMC8311534 DOI: 10.3748/wjg.v27.i26.3971] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 04/28/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
With the increasing incidence of obesity and metabolic syndrome worldwide, concomitant nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has become highly prevalent. The risk of dual etiologies, outcome, and mechanism of CHB with concomitant NAFLD have not been fully characterized. In this review, we assessed the overlapping prevalence of metabolic disorders and CHB, assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD, and discussed the remaining clinical issues to be addressed in the outcome of such patients. We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation. For CHB patients, it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses. The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.
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Affiliation(s)
- Yi-Wen Shi
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Rui-Xu Yang
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
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