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1
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Li MP, Luo KZ. The outcomes and mechanisms of chronic hepatitis B complicated by metabolic dysfunction-associated steatotic liver disease. Hepatobiliary Pancreat Dis Int 2025:S1499-3872(25)00087-6. [PMID: 40355317 DOI: 10.1016/j.hbpd.2025.04.007] [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: 11/29/2024] [Accepted: 04/24/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND In recent years, the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, given the substantial global prevalence of chronic hepatitis B (CHB), instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios. Both conditions can lead to liver fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). However, the intricacies of the dual etiology, consequential outcomes, and associated risks of CHB concurrent with MASLD are still not fully understood. DATA SOURCES A literature search was conducted on PubMed for articles published up to March 2024. The search keywords included nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic hepatitis B, liver fibrosis, hepatocellular carcinoma, nuclear factor erythroid 2-related factor 2, and oxidative stress. RESULTS This review examined recent studies on the interplay between MASLD and CHB. The coexistence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus (HBV) replication. Conversely, individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD. Nevertheless, these observations do not necessarily indicate universally positive outcomes. Indeed, MASLD and CHB may synergistically act as "co-conspirators" to exacerbate clinical manifestations, particularly liver fibrosis and HCC. CONCLUSIONS As our understanding of the interaction between steatosis and HBV infection becomes clearer, we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD. These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.
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Affiliation(s)
- Mao-Ping Li
- Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha 410011, China; Institute of Hepatology, Central South University, Changsha 410011, China; Furong Laboratory, Changsha 410078, China
| | - Kai-Zhong Luo
- Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha 410011, China; Institute of Hepatology, Central South University, Changsha 410011, China; Furong Laboratory, Changsha 410078, China.
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Huang X, Huang S, Dong C, Chen N, Wang Y, Wang C, Zhang Y, Feng C. Study on Ultrasound-Assisted Diagnosis of CHB Complicated with NAFLD Hepatic Fibrosis Based on Deep Learning. JOURNAL OF IMAGING INFORMATICS IN MEDICINE 2025:10.1007/s10278-024-01331-3. [PMID: 40234347 DOI: 10.1007/s10278-024-01331-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 10/20/2024] [Accepted: 11/02/2024] [Indexed: 04/17/2025]
Abstract
This study aimed to develop and evaluate an automated classification model for diagnosing chronic hepatitis B (CHB) complicated with non-alcoholic fatty liver disease (NAFLD) using deep learning techniques applied to two-dimensional liver imaging. We retrospectively analyzed data from 2803 patients diagnosed with CHB and NAFLD via two-dimensional ultrasound and FibroScan at our hospital between June 2019 and December 2022. These patients contributed a total of 20,540 two-dimensional liver images. An additional 150 patients with CHB complicated with NAFLD, who had liver biopsy results, were selected (with a total of 922 liver 2D ultrasound images) for validation of the deep learning model. The diagnostic performance was assessed using sensitivity, specificity, and accuracy metrics for independent diagnoses made by clinicians or with AI assistance. Diagnostic performance was assessed under blinded conditions by physicians of varying expertise, primary, intermediate, and senior clinicians, either independently or assisted by the AI model. We then conducted a statistical analysis of the results, focusing on sensitivity, specificity, and accuracy metrics. The sensitivity, specificity, and accuracy for independent diagnoses made by primary, intermediate, and senior physicians were 24.3%, 29.1%, and 33.8% for sensitivity; 100% for specificity; and 25.3%, 30.0%, and 34.7% for accuracy, respectively. The AI model alone achieved 68.9% sensitivity, 100% specificity, and 69.3% accuracy. When diagnoses were AI-assisted, the sensitivity increased significantly to 73.7% for primary physicians, 73.7% for intermediate physicians, and 75.7% for senior physicians, while specificity remained at 100%, and accuracy was 74.0%, 74.0%, and 76.0%, respectively. The area under the receiver operating characteristic curve (AUC) for AI-independent diagnosis (0.845) was significantly higher than that for primary, intermediate, and senior physicians (0.622, 0.645, and 0.669, respectively;P < 0.001 ). Similarly, AI-assisted diagnosis AUC values (0.868, 0.868, and 0.878, respectively) surpassed those for independent diagnosis by physicians at each level of expertise (P < 0.001 ). In conclusion, the deep learning model based on two-dimensional liver imaging demonstrated feasibility for assisting in the identification of liver fibrosis in patients with CHB and NAFLD. Our results suggest that integrating AI models into the diagnostic process can significantly improve the accuracy of diagnosing liver conditions in this patient population.
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Affiliation(s)
- Xiuling Huang
- Guangdong Medical University, Zhanjiang, Guangdong, People's Republic of China
| | - Shan Huang
- Shenzhen Research Institute of Big Data, Shenzhen, Guangdong, People's Republic of China
| | - Changfeng Dong
- The Third People's Hospital of Shenzhen, Shenzhen, Guangdong, People's Republic of China
| | - Nuo Chen
- Zhejiang University of Finance and Economics, Hangzhou, Zhejiang, People's Republic of China
| | - Yuxuan Wang
- Zhejiang University of Finance and Economics, Hangzhou, Zhejiang, People's Republic of China
| | - Changmiao Wang
- Shenzhen Research Institute of Big Data, Shenzhen, Guangdong, People's Republic of China
| | - Yongquan Zhang
- Zhejiang University of Finance and Economics, Hangzhou, Zhejiang, People's Republic of China
| | - Cheng Feng
- The Third People's Hospital of Shenzhen, Shenzhen, Guangdong, People's Republic of China.
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Eslam M, Fan JG, Yu ML, Wong VWS, Cua IH, Liu CJ, Tanwandee T, Gani R, Seto WK, Alam S, Young DY, Hamid S, Zheng MH, Kawaguchi T, Chan WK, Payawal D, Tan SS, Goh GBB, Strasser SI, Viet HD, Kao JH, Kim W, Kim SU, Keating SE, Yilmaz Y, Kamani L, Wang CC, Fouad Y, Abbas Z, Treeprasertsuk S, Thanapirom K, Al Mahtab M, Lkhagvaa U, Baatarkhuu O, Choudhury AK, Stedman CAM, Chowdhury A, Dokmeci AK, Wang FS, Lin HC, Huang JF, Howell J, Jia J, Alboraie M, Roberts SK, Yoneda M, Ghazinian H, Mirijanyan A, Nan Y, Lesmana CRA, Adams LA, Shiha G, Kumar M, Örmeci N, Wei L, Lau G, Omata M, Sarin SK, George J. The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease. Hepatol Int 2025; 19:261-301. [PMID: 40016576 DOI: 10.1007/s12072-024-10774-3] [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: 09/06/2024] [Accepted: 12/28/2024] [Indexed: 03/01/2025]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.
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Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia.
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal MedicineCollege of Medicine and Center for Liquid Biopsy and Cohort ResearchFaculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of MedicineSchool of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, Kaohsiung Medical University, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong, China
| | - Ian Homer Cua
- Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Global City, Philippines
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal MedicineHepatitis Research CenterGraduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tawesak Tanwandee
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Rino Gani
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Pangeran Diponegoro Road No. 71St, Central Jakarta, 10430, Indonesia
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Shahinul Alam
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh
| | - Dan Yock Young
- Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Saeed Hamid
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Diana Payawal
- Department of Medicine, Cardinal Santos Medical Center, Mandaluyong, Philippines
| | - Soek-Siam Tan
- Department of Hepatology, Selayang Hospital, Batu Caves, Malaysia
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
- Medicine Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Hang Dao Viet
- Internal Medicine Faculty, Hanoi Medical University, Hanoi, Vietnam
| | - Jia-Horng Kao
- Graduate Institute of Clinical MedicineDepartment of Internal MedicineHepatitis Research CenterDepartment of Medical Research, National Taiwan University College of Medicine, National Taiwan University, National Taiwan University Hospital, 1 Chang-Te Street, 10002, Taipei, Taiwan
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1, Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - Shelley E Keating
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
| | | | - Chia-Chi Wang
- Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Taipei, Taiwan
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Cairo, Egypt
| | - Zaigham Abbas
- Department of Hepatogastroenterology, Dr.Ziauddin University Hospital, Clifton, Karachi, Pakistan
| | | | | | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Undram Lkhagvaa
- Department of Health Policy, School of Public Health, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Oidov Baatarkhuu
- Department of Infectious Diseases, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Ashok Kumar Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Abhijit Chowdhury
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - A Kadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Fu-Sheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Chinese PLA Medical School, Chinese PLA General Hospital, Beijing, 100039, China
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Institute of Clinical Medicine, School of Medicine, Taipei Veterans General Hospital, National Yang-Ming Chiao Tung University, No. 201, Section 2, Shipai RdNo. 155, Section 2, Linong St, Beitou District, Taipei City, 112, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal MedicineCollege of Medicine and Center for Liquid Biopsy and Cohort ResearchFaculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jess Howell
- Burnet Institute, Melbourne, VIC, 3004, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Clayton, VIC, 3008, Australia
- Department of Medicine, The University of Melbourne, Parkville, VIC, 3050, Australia
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, VIC, 3165, Australia
| | - Jidong Jia
- Liver Research Center, Beijing Key Laboratory of Translational Medicine On Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, 11884, Egypt
| | - Stuart K Roberts
- Department of Gastroenterology and Hepatology, Central Clinical School, The Alfred, Monash University, Melbourne, Australia
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan
| | - Hasmik Ghazinian
- Gastroenterology and Hepatology Department, Yerevan Medical Scientific Center, Yerevan, Armenia
| | - Aram Mirijanyan
- Gastroenterology and Hepatology Department, Yerevan Medical Scientific Center, Yerevan, Armenia
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China
| | | | - Leon A Adams
- Medical School, Faculty of Medicine and Health Sciences, The University of Western Australia, Nedlands, WA, Australia
| | - Gamal Shiha
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansoura, Egypt
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Necati Örmeci
- Department of Gastroenterohepatology, Istanbul Health and Technology University, Istanbul, Turkey
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - George Lau
- Humanity and Health Medical Group, Humanity and Health Clinical Trial Center, Hong Kong SAR, China
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Tokyo, Japan
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia
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Yan P, Yu X, Chen Z, Lan L, Kang J, Zhao B, Liu D. Assessing the consistency of FIB-4, APRI, and GPR in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with concurrent liver diseases. BMC Gastroenterol 2025; 25:191. [PMID: 40114058 PMCID: PMC11927168 DOI: 10.1186/s12876-025-03770-w] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 03/07/2025] [Indexed: 03/22/2025] Open
Abstract
OBJECTIVE This study investigated the consistency of the FIB-4, APRI, and GPR indices in assessing significant liver fibrosis and cirrhosis in patients with Coronavirus Disease 2019(COVID-19) who also suffer from various liver diseases, providing references for the clinical selection and application for non-invasive assessment methods. METHODS The study evaluated 744 COVID-19 patients with coexisting liver diseases: 508 cases with non-alcoholic fatty liver disease (NAFLD), 158 cases with chronic hepatitis B (CHB), and 78 cases with a combination of both ailments. FIB-4, APRI, and GPR were employed to assess significant liver fibrosis and cirrhosis. Concordance among the methods was determined using Kappa analysis, and receiver operating characteristic (ROC) curves helped identify the optimal cutoff values for each index. RESULTS For COVID-19 patients with NAFLD, Kappa values for significant liver fibrosis were 0.81, 0.90, 0.80, and 0.79, and for cirrhosis, they were 0.88, 0.97,0.88, and 0.88, respectively (all p < 0.05). Among those with CHB, Kappa values were 0.81, 0.81, 0.83, and 0.75 for fibrosis, and0.87, 0.91, 0.88, and 0.92 for cirrhosis (all p < 0.05). In patients with coexisting liver diseases, the values were 0.87, 0.86, 0.86, and 0.78 for fibrosis, and 0.67, 0.69, 0.54, and 0.81for cirrhosis (all p < 0.05). Linear trend analysis revealed significant relationships between FIB-4 values, APRI values, GPR values, and the severity of COVID-19 (χ2 trend: 15.205,35.114, and 13.973, respectively, all p < 0.001), between FIB-4 values and APRI values and the coronavirus negative conversion time (all p < 0.05) in COVID-19 with NAFLD, and between FIB-4 values and GPR values and the coronavirus negative conversion time in patients with COVID-19 with CHB(all p < 0.05). CONCLUSION Using the current cutoff values, the non-invasive assessments demonstrated almost perfect consistency in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with liver diseases, though FIB-4 and GPR showed moderate consistency in cirrhosis evaluation in patients with coexisting liver conditions. Moreover, it also indicated that increased liver fibrosis correlates with more severe COVID-19 and prolonged coronavirus negative conversion time.
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Affiliation(s)
- Pan Yan
- School of Public Health, Chengdu Medical College, Chengdu, Sichuan Province, 610500, China
| | - Xiaoping Yu
- School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan Province, 610106, China
| | - Zhu Chen
- Department of Drug Clinical Trial Center, Public Health Clinical Centre of Chengdu, Chengdu, Sichuan Province, 610060, China
| | - Lijuan Lan
- The First Ward of Internal Medicine, Public Health Clinical Centre of Chengdu, Chengdu, Sichuan Province, 610060, China
| | - Jun Kang
- The First Ward of Internal Medicine, Public Health Clinical Centre of Chengdu, Chengdu, Sichuan Province, 610060, China
| | - Bennan Zhao
- The First Ward of Internal Medicine, Public Health Clinical Centre of Chengdu, Chengdu, Sichuan Province, 610060, China
| | - Dafeng Liu
- The First Ward of Internal Medicine, Public Health Clinical Centre of Chengdu, Chengdu, Sichuan Province, 610060, China.
- , No.377 Jingming Road, Jinjiang District, Chengdu City, Sichuan Province Chengdu, 610060, China.
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Uman N, Kaewdech A, Sripongpun P, Chamroonkul N, Piratvisuth T. Coexisting steatotic liver disease is not associated with long-term liver-related events in patients with chronic hepatitis B. Gastroenterol Rep (Oxf) 2025; 13:goaf013. [PMID: 39944164 PMCID: PMC11821271 DOI: 10.1093/gastro/goaf013] [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: 07/23/2024] [Revised: 10/18/2024] [Accepted: 11/26/2024] [Indexed: 03/02/2025] Open
Abstract
Steatotic liver disease (SLD) is an emerging liver disease, whereas chronic viral hepatitis is the renowned cause of chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC). The impact of coexisting SLD in chronic hepatitis B (CHB) on liver-related events (LREs) in the long term is still debated. This study aims to compare all-cause mortality and LRE between CHB patients with and without SLD. This retrospective study included CHB patients who underwent transient elastography between 2014 and 2021 at a tertiary-care hospital. Exclusion criteria were those without controlled attenuated parameter (CAP) results, interquartile range/median of liver stiffness measurement (LSM) > 30%, follow-up time < 6 months, and without hepatitis B virus DNA data during follow-up. SLD was defined as CAP ≥ 248 dB/m, significant liver fibrosis (SF) as LSM ≥ 7 kPa, and cirrhosis as LSM ≥11 kPa or imaging evidence. LRE was defined as the development of HCC and/or cirrhosis complications. Among 532 patients (median follow-up 4.3 years), SLD was present in 161 (30.2%) patients, SF was found in 186 (34.5%) patients, and 104 (19.6%) patients had cirrhosis at baseline. SF was insignificantly more common in SLD patients (40.1% vs 32.4%, P = 0.068). Long-term outcomes showed SF, not SLD, was independently associated with higher LRE development with an adjusted HR of 13.85 (95% confidence interval [CI]: 3.06-62.76, P < 0.001), while the adjusted HR of SLD was 0.49 (95% CI: 0.16-1.53, P = 0.22). In conclusion, SLD commonly coexists with CHB patients. CHB patients with SLD were more likely to have SF at baseline, albeit not significantly. Long-term HCC and cirrhosis complications development are associated with SF but not SLD status.
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Affiliation(s)
- Navavee Uman
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
- Department of Internal Medicine, Pattani Hospital, Pattani, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
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Wu D, Kao JH, Piratvisuth T, Wang X, Kennedy PT, Otsuka M, Ahn SH, Tanaka Y, Wang G, Yuan Z, Li W, Lim YS, Niu J, Lu F, Zhang W, Gao Z, Kaewdech A, Han M, Yan W, Ren H, Hu P, Shu S, Kwo PY, Wang FS, Yuen MF, Ning Q. Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0. Clin Mol Hepatol 2025; 31:S134-S164. [PMID: 39838828 PMCID: PMC11925436 DOI: 10.3350/cmh.2024.0780] [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: 09/09/2024] [Revised: 01/18/2025] [Accepted: 01/21/2025] [Indexed: 01/23/2025] Open
Abstract
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
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Affiliation(s)
- Di Wu
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Xiaojing Wang
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Patrick T.F. Kennedy
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry, and Pharmaceutical Science, Okayama University, Okayama, Japan
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Wenhui Li
- National Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Junqi Niu
- Department of Hepatology, First Hospital of Jilin University, Jilin University, Jilin, China
| | - Fengmin Lu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiliang Gao
- Department of Infectious Diseases, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Meifang Han
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Weiming Yan
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Hong Ren
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Sainan Shu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Paul Yien Kwo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University School of Medicine, Stanford, CA, USA
| | - Fu-sheng Wang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine & State Key Laboratory of Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
| | - Qin Ning
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
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Li HD, Liu YN, Wu S, Quan XF, Wang XY, Xiang TD, Li SM, Xu L, Wang T, Wang H, Zheng X. Influence of nonalcoholic fatty liver disease on the therapeutic effect of nucleoside (acid) analogs for hepatitis B virus. World J Hepatol 2024; 16:1395-1406. [DOI: 10.4254/wjh.v16.i12.1395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 10/02/2024] [Accepted: 10/29/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The effect of nonalcoholic fatty liver disease (NAFLD) on the efficacy of nucleoside analogues (NAs) in antiviral therapy for patients with chronic hepatitis B (CHB) remains controversial.
AIM To investigate the influence of NAFLD on virological response in CHB patients undergoing NAs treatment.
METHODS Logistic regression analysis was conducted on a cohort of 465 CHB patients from two hospitals to determine whether NAFLD was a risk factor for adverse reactions to NAs. CHB patients were followed up for more than 28 months after initial antiviral treatment, and further validation was performed using different viral load populations.
RESULTS NAFLD was identified as an independent risk factor for partial virological response following antiviral therapy with NAs (odds ratio = 1.777, P = 0.017). In our subsequent analysis focusing on CHB patients with high viral load, the NAFLD group exhibited significantly longer virus shedding time and lower proportion of the complete virological response compared with the non-NAFLD group (16.8 ± 6.1 vs 13.0 ± 6.8, P < 0.05). During the 24-month period of antiviral treatment with NAs, hepatitis B virus (HBV) DNA levels decreased slowly in the NAFLD group, and the negative conversion rate of HBV was notably lower than that observed in non-NAFLD group (P = 0.001). Similar results were obtained when analyzing patients with low baseline HBV viral load within the NAFLD group.
CONCLUSION Coexistence of NAFLD may diminish virological response among CHB patients receiving antiviral treatment with NAs.
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Affiliation(s)
- Hua-Dong Li
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
- Department of Infectious Diseases, Wuhan Jinyintan Hospital, Wuhan 430023, Hubei Province, China
| | - Ya-Nan Liu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Shuang Wu
- Department of Infectious Diseases, Wuhan Jinyintan Hospital, Wuhan 430023, Hubei Province, China
| | - Xu-Feng Quan
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xiao-Yan Wang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Tian-Dan Xiang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Shu-Meng Li
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Ling Xu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Tong Wang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Hua Wang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xin Zheng
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Fouad Y, Alboraie M, Shiha G. Epidemiology and diagnosis of metabolic dysfunction-associated fatty liver disease. Hepatol Int 2024; 18:827-833. [PMID: 38967907 PMCID: PMC11450050 DOI: 10.1007/s12072-024-10704-3] [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: 02/08/2024] [Accepted: 06/01/2024] [Indexed: 07/06/2024]
Abstract
The most common chronic liver illness worldwide is metabolic dysfunction linked to fatty liver disease (MAFLD), which is poorly understood by doctors and patients. Many people with this disease develop steatohepatitis, cirrhosis and its consequences, as well as extrahepatic manifestations; these conditions are particularly common if they are linked to diabetes mellitus or obesity. A breakthrough with numerous benefits is the switch from NAFLD to MAFLD in terms of terminology and methodology. The diagnosis of MAFLD is based on affirmative criteria; unlike NAFLD, it is no longer based on exclusion. The diagnosis of MAFLD and the evaluation of steatosis and fibrosis is achieved using liver biopsy and non-invasive laboratory or radiographic techniques. We briefly address the most recent developments in MAFLD epidemiology and diagnosis.
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Affiliation(s)
- Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minia, Egypt.
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Gamal Shiha
- Egyptian Liver Research Institute and Hospital, Mansoura, Egypt
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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9
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Chen MY, Li SX, Du ZX, Xiong QF, Zhong YD, Liu DX, Yang YF. Liver biopsy-proven non-alcoholic fatty liver disease predicts no impact on antiviral response in patients with chronic hepatitis B. Clinics (Sao Paulo) 2024; 79:100493. [PMID: 39332149 PMCID: PMC11467630 DOI: 10.1016/j.clinsp.2024.100493] [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: 11/10/2023] [Revised: 05/31/2024] [Accepted: 08/25/2024] [Indexed: 09/29/2024] Open
Abstract
OBJECTIVE The role of Non-Alcoholic Fatty Liver Disease (NAFLD) on antiviral response in Chronic Hepatitis B (CHB) remains unclear. Previous studies mainly focus on the impact of the Non-Alcoholic Fatty Liver (NAFL) on antiviral efficacy, whereas the role of Non-Alcoholic Steatohepatitis (NASH) has not been highlighted. The authors aimed to investigate the association of NAFLD (NAFL and NASH), viral and histological characteristics with antiviral response. METHODS The authors collected data of treatment-naïve CHB patients who underwent liver biopsy. All these patients received antiviral monotherapy and 48-week follow-up. The antiviral response was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the variables associated with antiviral response. RESULTS Overall, 120 treatment-naïve CHB patients were enrolled, with 49.2 % (59/120) of them were complicated by NAFLD. Male (Odd Ratio [OR = 4.222], 95 % Confidence Interval [95 % CI 1.620-11.003]) and overweight (OR = 8.709, 95 % CI 3.355-22.606) were independent predictors for concurrent NAFLD. After 48-week follow-up, the authors found that the overall antiviral response did not differ between CHB patients with and without concomitant NAFL/NASH (p > 0.05). High viral load (Hazard Ratio [HR = 0.522], 95 % CI 0.286-0.952), advanced fibrosis (HR = 2.426, 95 % CI 1.256-4.686), and moderate-to-severe interface hepatitis (HR = 2.541, 95 % CI 1.406-4.592) were significantly correlated with antiviral response after 8-week follow-up. CONCLUSION Neither NAFL nor NASH had an impact on antiviral therapy for CHB. It was low hepatitis B load, advanced fibrosis, and moderate-to-severe interface hepatitis that contributed to the virological response.
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Affiliation(s)
- Miao-Yang Chen
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shun-Xin Li
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhi-Xiang Du
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Qing-Fang Xiong
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yan-Dan Zhong
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Du-Xian Liu
- Department of Pathology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yong-Feng Yang
- Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
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10
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Wang J, Lu H, Li Q. Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation. Front Immunol 2024; 15:1414594. [PMID: 39091506 PMCID: PMC11291371 DOI: 10.3389/fimmu.2024.1414594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 07/02/2024] [Indexed: 08/04/2024] Open
Abstract
Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV's exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.
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Affiliation(s)
- Jun Wang
- The Third People’s Hospital of Shenzhen (National Clinical Research Center for Infectious Diseases) and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
- Clinical Research Center, The Fifth People’s Hospital of Wuxi, Jiangnan University, Wuxi, Jiangsu, China
| | - Hongzhou Lu
- The Third People’s Hospital of Shenzhen (National Clinical Research Center for Infectious Diseases) and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Qian Li
- The Third People’s Hospital of Shenzhen (National Clinical Research Center for Infectious Diseases) and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
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11
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Rui F, Garcia E, Hu X, Ni W, Xue Q, Xu Y, Xu X, Shi J, Nguyen MH, Cheung RC, Li J. Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis. J Viral Hepat 2024; 31:372-382. [PMID: 38590002 DOI: 10.1111/jvh.13942] [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: 02/06/2024] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/10/2024]
Abstract
The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.
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Affiliation(s)
- Fajuan Rui
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | | | - Xinyu Hu
- Department of Infectious Disease, Shandong Provincial Hospital, Shandong University, Ji'nan, Shandong, China
| | - Wenjing Ni
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Qi Xue
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Yayun Xu
- Department of Infectious Disease, Shandong Provincial Hospital, Shandong University, Ji'nan, Shandong, China
| | - Xiaoming Xu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Junping Shi
- Department of Infectious Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, California, USA
| | - Ramsey C Cheung
- Department of Epidemiology and Population Health, Veterans Affairs Medical Center, Palo Alto, California, USA
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
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12
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Kaewdech A, Sripongpun P. Navigating the Nomenclature of Liver Steatosis: Transitioning from NAFLD to MAFLD and MASLD - Understanding Affinities and Differences. SIRIRAJ MEDICAL JOURNAL 2024; 76:234-243. [DOI: 10.33192/smj.v76i4.267556] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The escalating prevalence of non-alcoholic fatty liver disease (NAFLD) represents a significant challenge to public health, with an increasing impact observed across various demographics. This review delivers a comprehensive evaluation of the evolving terminology in steatotic liver disease (SLD), documenting the transition from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD), and progressing to the latest terms, metabolic dysfunction-associated fatty liver disease (MASLD) and MASLD with increased alcohol intake (MetALD). We conducted a comprehensive review of literature discussing the benefits and drawbacks of these nomenclatural changes. Clinical evidence supporting MASLD and MetALD, including the implications of alcohol consumption thresholds on disease classification and outcomes, was analyzed. The “MAFLD” and “MASLD” labels align with the pathophysiology of metabolic diseases, afford a positive disease connotation, and facilitate the identification of more severe diseases, such as significant fibrosis or advanced liver disease. However, the MAFLD criteria may underdiagnose lean, non-overweight, or non-obese individuals with MAFLD. The review underscores the understanding of liver diseases linked to metabolic dysfunction and alcohol use. The shift in terminology marks progress towards a clinical diagnosis that reflects underlying pathophysiology. However, additional studies are necessary to assess the longterm effects of these changes and their efficacy in enhancing patient care and health outcomes.
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13
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Luo J, Liu Z, Wang Q, Tan S. Liver iron overload and fat content analyzed by magnetic resonance contribute to evaluatingthe progression of chronic hepatitis B. Biomed Rep 2024; 20:23. [PMID: 38169881 PMCID: PMC10758915 DOI: 10.3892/br.2023.1711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 11/22/2023] [Indexed: 01/05/2024] Open
Abstract
Chronic hepatitis B (CHB) and its complications still have a major role in liver-related mortality. It has been indicated that hepatic iron and steatosis may influence liver fibrosis and carcinogenesis. The present study aimed to assess the liver iron and fat in patients with CHB by MRI in order to estimate the associations among liver iron, fat and the severity and progression of liver fibrosis. In the present retrospective study, consecutive patients with CHB examined from August 2018 to August 2020 were analyzed. Liver iron and fat content were assessed by MRI, which was measured as liver iron content (LIC) and proton density fat fraction (PDFF). A total of 340 patients were included in the current study. For LIC, the median value was 1.68 mg/g and elevated LIC was seen in 122 patients (35.9%). For liver fat content, the median value of PDFF was 3.1%, while only 15.0% of patients had liver steatosis (PDFF ≥5%). Age, total bilirubin and sex were independent predictive factors of liver iron overload [odds ratio (OR)=1.036, 1.005 and 8.834, respectively]. A higher platelet count (OR=1.005) and no portal hypertension (OR=0.381) independently predicted liver steatosis. The areas under the receiver operating characteristic curves of PDFF for the identification of liver cirrhosis estimated by different non-invasive tools ranged from 0.629 to 0.704. It was concluded that iron overload was common in patients with CHB, particularly in those with older age, male sex and high total bilirubin level, and liver steatosis was less common in CHB. Liver iron and fat content analyzed by MRI may contribute to the evaluation of the severity and progression of CHB.
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Affiliation(s)
- Jinni Luo
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Zhenzhen Liu
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Qian Wang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Siwei Tan
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
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14
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Fernandez CJ, Alkhalifah M, Afsar H, Pappachan JM. Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink. Pathogens 2024; 13:68. [PMID: 38251375 PMCID: PMC10821334 DOI: 10.3390/pathogens13010068] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/05/2024] [Accepted: 01/07/2024] [Indexed: 01/23/2024] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease.
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Affiliation(s)
- Cornelius J. Fernandez
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, UK;
| | - Mohammed Alkhalifah
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia
| | - Hafsa Afsar
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
| | - Joseph M. Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, UK
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PL, UK
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Lai RM, Yao LX, Lin S, Zhou JH, Liu BP, Liang ZY, Chen T, Jiang JJ, Zheng Q, Zhu Y. Influence of metabolic dysfunction-associated fatty liver disease on the prognosis of patients with HBV-related acute-on-chronic liver failure. Expert Rev Gastroenterol Hepatol 2024; 18:103-112. [PMID: 38164659 DOI: 10.1080/17474124.2023.2298261] [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: 09/10/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVES Metabolic-associated fatty liver disease (MAFLD) has clinical relevance in patients with acute-on-chronic liver failure (ACLF). We investigated the association between MAFLD and prognosis in patients with ACLF. METHODS We included patients with ACLF with available clinical data who visited our hospital for nearly 9 years. We compared the prognosis of patients in the different subgroups of ACLF and predicted the incidence of adverse outcomes. Moreover, a new model based on MAFLD was established. RESULTS Among 339 participants, 75 had MAFLD. The prognosis of patients with ACLF was significantly correlated with MAFLD. Patients with ACLF with concomitant MAFLD tended to have a lower cumulative survival rate (p = 0.026) and a higher incidence of hepatorenal syndrome (9.33% versus 3.40%, p = 0.033) than those without MAFLD. We developed an TIM2 model and the area under the ROC curve of the new model for 30-day and 60-day mortality (0.759 and 0.748) was higher than other predictive methods. CONCLUSION The presence of MAFLD in patients with HBV-related ACLF was associated with an increased risk of in-hospital mortality. Moreover, The TIM2 model is a high-performance prognostic score for HBV-related ACLF.
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Affiliation(s)
- Rui-Min Lai
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hosptial, Fujian Medical University, Fuzhou, China
| | - Li-Xi Yao
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Shan Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Jia-Hui Zhou
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Bing-Ping Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Zhao-Yi Liang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Tianbin Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jia-Ji Jiang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Qi Zheng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
| | - Yueyong Zhu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou, Fujian Province, China
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Yao R, Lu S, Xue R, Wang J, Qiu Y, Chen Y, Liu J, Zhu L, Zhan J, Jiang S, Yin S, Tong X, Ding W, Li J, Zhu C, Huang R, Wu C. NAFLD is associated with less severe liver fibrosis in chronic hepatitis B: A multi-center, retrospective study. Ann Hepatol 2024; 29:101155. [PMID: 37742745 DOI: 10.1016/j.aohep.2023.101155] [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: 06/12/2023] [Revised: 08/24/2023] [Accepted: 09/14/2023] [Indexed: 09/26/2023]
Abstract
INTRODUCTION AND OBJECTIVES Chronic hepatitis B (CHB) may progress to more serious liver diseases and it is often accompanied by non-alcoholic fatty liver disease (NAFLD). NAFLD and CHB share risk factors for liver fibrosis and cirrhosis, but the influence of NAFLD on fibrosis progression is controversial. This retrospective study evaluated the prevalence of NAFLD in patients with CHB and investigated associations between NAFLD and liver fibrosis in a large multi-center cohort of hepatitis B patients submitted to liver biopsy. PATIENTS AND METHODS Treatment-naïve patients with CHB who underwent liver biopsy were analyzed. Propensity score matching (PSM) was performed to adjust the confounders between patients with and without NAFLD. RESULTS A total of 1496 CHB patients were included. Two hundred and ninety (19.4%) patients were diagnosed with NAFLD by liver biopsy. The proportions of significant liver fibrosis (52.8% vs. 63.9%, P<0.001), advanced liver fibrosis (27.2% vs. 36.5%, P=0.003), and cirrhosis (13.4% vs. 19.7%, P=0.013) was considerably lower in CHB patients with NAFLD compared to those without NAFLD. 273 patients were included in each group after PSM adjusted for age, sex, hepatitis B envelope antigen status, and hepatitis B virus DNA. Liver fibrosis remained less severe in CHB patients with NAFLD than those without NAFLD (P<0.05) after PSM. The presence of NAFLD was considered an independent negative factor of significant liver fibrosis (odds ratio (OR) 0.692, P=0.013) and advanced liver fibrosis (OR 0.533, P = 0.002) in CHB patients. CONCLUSIONS NAFLD is not uncommon in CHB patients with the prevalence of 19.4%. The presence of NAFLD is associated with less severe liver fibrosis in CHB patients. REGISTRATION NO OF THE STUDY/TRIAL NCT03097952.
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Affiliation(s)
- Renling Yao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Sufang Lu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Yuxin Chen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, 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
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, 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
| | - Weimao Ding
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, 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, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China; Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China; Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
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17
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Yeh ML, Huang JF, Yu ML. Fatty liver and viral hepatitis: Prevalence, risk factors, natural course, pathogenesis, and management. METABOLIC STEATOTIC LIVER DISEASE 2024:261-275. [DOI: 10.1016/b978-0-323-99649-5.00008-x] [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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18
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Yang Y, Ge F, Qin S, Luo C, Xiao X, Bai Z, Tang C. Identification the shared pathogenesis between chronic hepatitis B and non-alcoholic fatty liver disease: Evidence from transcriptome data. GASTROENTEROLOGY & ENDOSCOPY 2023; 1:190-198. [DOI: 10.1016/j.gande.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/06/2024]
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19
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Zhang M, Chen S, Wu X, Zhou J, Wang T, Liu H, Zhao X, Wang B, Zhao X, Kong Y, Soon GST, Ou X, Jia J, Chen W, Sun Y, You H. Persistent steatosis correlates with decreased fibrosis regression during anti-HBV treatment in patients with chronic HBV infection. J Med Virol 2023; 95:e29156. [PMID: 37822064 DOI: 10.1002/jmv.29156] [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: 04/26/2023] [Revised: 08/23/2023] [Accepted: 09/25/2023] [Indexed: 10/13/2023]
Abstract
Despite the increasing prevalence of steatosis in patients with chronic hepatitis B (CHB), whether the changes in steatosis impact fibrosis regression during antiviral therapy remain unclear. We aimed to identify the association between histological changes of steatosis and fibrosis in patients undergone antiviral treatment. Patients with paired liver biopsies before and after 78 weeks of antiviral therapy were enrolled in this study. Liver fibrosis was assessed by the Ishak score combined with Beijing Classification predominantly progressive, indeterminate, and predominately regressive score. Steatosis was evaluated by the nonalcoholic fatty liver disease activity score. Collagen in each site was quantitated by second harmonic generation/two photon excitation fluorescence technology. Serum proteomic changes after treatment were characterized by mass-based spectrometry. A total of 239 CHB patients were included and divided into four groups according to the changes in steatosis: 162 (67.8%) had no steatosis throughout, 24 (10.0%) developed new-onset steatosis, 21 (8.8%) had initial steatosis which disappeared, and 32 (13.4%) had persistent steatosis. The persistent steatosis group showed the lowest rate of fibrosis regression (14/32, 43.8%). Persistent steatosis correlated with decreased fibrosis regression significantly after adjusting for age, sex, fibrosis stage, and metabolic factors at baseline, as well as the viral response (adjusted odds ratio = 0.380, 95% confidence interval 0.145-0.996, p = 0.049). This decreased fibrosis regression was associated with accumulated collagen in the perisinusoidal area. Patients with persistent steatosis showed unique changes in glycolipid metabolism according to the serum proteomic atlas. Persistent steatosis correlated with decreased fibrosis regression during antiviral therapy in patients with CHB.
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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, Beijing, China
| | - Shuyan Chen
- 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, Beijing, China
| | - Xiaoning Wu
- 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, Beijing, China
| | - Jialing Zhou
- 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, Beijing, China
| | - Tailing Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Hui Liu
- Department of Pathology, Beijing You-an Hospital, Capital Medical University, Beijing, China
| | - Xinyan Zhao
- 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, Beijing, China
| | - Bingqiong Wang
- 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, Beijing, China
| | - Xinyu Zhao
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China
| | | | - Xiaojuan Ou
- 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, 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, Beijing, China
| | - Wei Chen
- Experimental and Translational Research Center, 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, 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, Beijing, China
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20
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Wang Y, Li J, Wang S, Pang Y, Liu P, Xie B, Dou S, Yang T, Liu X, Shi Y, Chen D. The hepatitis B virus promotes the progression of non-alcoholic fatty liver disease through incomplete autophagy. Free Radic Biol Med 2023:S0891-5849(23)00436-7. [PMID: 37244371 DOI: 10.1016/j.freeradbiomed.2023.05.020] [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: 02/13/2023] [Revised: 05/09/2023] [Accepted: 05/18/2023] [Indexed: 05/29/2023]
Abstract
Hepatitis B virus (HBV) infection is still a serious public health problem. In recent years, with the increasing incidence of chronic hepatitis B (CHB) combined with nonalcoholic fatty liver disease (NAFLD), a more in-depth exploration of the pathogenesis of CHB combined with NAFLD is required. HBV can induce autophagy and use to increase replication. The removal of fat by autophagy, also known as lipophagy, is also currently considered an alternative pathway for lipid metabolism in liver cells. This degradation of autophagy prevents hepatotoxicity and steatosis. However, it is not known whether there is a correlation between HBV-related autophagy and the progression of NAFLD. We explored how HBV affects disease progression in NAFLD should be " and determined whether it is associated with HBV-associated autophagy. In this study, we constructed HBV-TG mouse high-fat diet (HFD) models and controls, and the results showed that the presence of HBV promoted the occurrence of NAFLD. We also demonstrated that HBV promotes lipid droplet accumulation in hepatocytes using HBV-stable expression cell lines HepG2.2.15 and AML12-HBV. In addition, this study also found that exogenous OA supplementation reduced HBV replication. We further studied the mechanism and found that HBV-related autophagy can promote the absorption of liver cells to lipid droplets. It can reduce the decomposition of lipid droplets by inhibiting the function of autophagolysosome, and eventually lead to the accumulation of lipid droplets in hepatocytes. In a word, HBV promotes the progression of NAFLD by increasing lipid accumulation in hepatocytes through incomplete autophagy.
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Affiliation(s)
- Yang Wang
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Jiaxi Li
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Shanshan Wang
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Yuheng Pang
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China; Harbin Medical University Cancer Hospital, Harbin, China
| | - Pengxiang Liu
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Bangxiang Xie
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Shuangshuang Dou
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Tongwang Yang
- Academician Workstation, Changsha Medical University, Changsha, China; Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China
| | - Xiaoni Liu
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Ying Shi
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
| | - Dexi Chen
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
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21
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Wang J, Liu J, Liu Y, Xue R, Zhan J, Jiang S, Wang L, Yan X, Xiong Y, Xia J, Yin S, Tong X, Chen Y, Li J, Huang R, Wu C. Clinical features of chronic hepatitis B patients with lean nonalcoholic fatty liver disease. Hepatol Res 2023; 53:184-195. [PMID: 36317959 DOI: 10.1111/hepr.13854] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 10/06/2022] [Accepted: 10/23/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND The clinical features have been well described in obese chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). However, little is known about the clinical features of lean CHB-NAFLD patients. METHODS The study retrospectively included treatment-naïve CHB patients who underwent ultrasound between 2015 and 2021. Liver fibrosis was assessed by aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis-4 score (FIB-4), NAFLD fibrosis score (NFS), and transient elastography. RESULTS Among 1226 CHB-NAFLD patients, 25.0% patients were lean. The age, gender, and platelet, alanine aminotransferase, AST, and albumin levels were comparable between lean CHB-NAFLD and nonlean patients. The levels of plasma glucose, triglycerides, total cholesterol, and uric acid, as well as proportions of concurrent hypertension and diabetes, were lower in lean patients. Lean patients presented higher hepatitis B surface antigen (HBsAg) levels (3.4 log10 IU/ml vs. 3.2 log10 IU/ml, p = 0.006), hepatitis B virus (HBV) DNA levels (4.1 log10 IU/ml vs. 3.2 log10 IU/ml, p < 0.001), and hepatitis B e antigen (HBeAg) positive proportions (40.4% vs. 30.2%, p = 0.002) than nonlean patients. The values of APRI, FIB-4, and liver stiffness were comparable between two groups. However, lean patients had lower NFS values (-3.0 vs. -2.6, p < 0.001) and lower proportions (12.6% vs. 21.1%, p = 0.003) of advanced fibrosis (NFS ≥ -1.5) than nonlean patients. Similar results were observed in HBeAg-positive and HBeAg-negative subgroups. CONCLUSIONS Nearly a quarter of CHB-NAFLD patients were lean. Lean patients had lower proportions of metabolic abnormalities and advanced liver fibrosis than nonlean patients. However, lean CHB-NAFLD patients had higher HBsAg levels, HBV DNA levels, and HBeAg-positive proportions. Registry and registration no. of the study/trial: Clinicaltrials.gov, Identifier: NCT03097952.
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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, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 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, China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Jie Zhan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Suling Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Li Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Yali Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China.,Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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22
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Liu Y, Chen M. Is nonalcoholic fatty liver disease a predictor of treatment response in chronic hepatitis B? J Med Virol 2023; 95:e28654. [PMID: 36897035 DOI: 10.1002/jmv.28654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/24/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023]
Affiliation(s)
- Yuanbin Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Mingkai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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23
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Rugivarodom M, Pongpaibul A, Chainuvati S, Nimanong S, Chotiyaputta W, Tanwandee T, Charatcharoenwitthaya P. Prognostic Relevance of Metabolic Dysfunction-associated Steatohepatitis for Patients with Chronic Hepatitis B. J Clin Transl Hepatol 2023; 11:76-87. [PMID: 36406326 PMCID: PMC9647119 DOI: 10.14218/jcth.2022.00055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/16/2022] [Accepted: 05/05/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) is prevalent in patients with chronic hepatitis B (CHB). The effect of the histologic MAFLD phenotype on long-term CHB outcomes is unknown. We performed a longitudinal study to determine the prognostic relevance of biopsy-proven hepatic steatosis and steatohepatitis for CHB patients. METHODS Clinical and laboratory data were obtained from CHB patients who underwent liver biopsy during 2002-2008 and were treated with antiviral drugs. A hepatopathologist reviewed the biopsy specimens. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (aHR) of outcomes, including all-cause mortality, liver transplantation, and liver-related events. RESULTS In accordance with Brunt's classification, 408 patients had steatohepatitis (n=34), "steatosis but not steatohepatitis" (n=118), or "non-steatosis" (n=256). All steatohepatitis patients had features of metabolic dysfunction. Over a mean follow-up of 13.8±3.1 years, 18 patients died or underwent liver transplantation. In multivariate-adjusted analysis, steatohepatitis (aHR, 6.37; 95% confidence interval [CI]: 1.59-25.5) compared with non-steatosis and advanced fibrosis (aHR, 11.3; 95% CI: 1.32-96.3) compared with no fibrosis were associated with overall mortality/liver transplantation. Thirty-five patients developed 43 liver-related events, among which 32 were hepatocellular carcinoma. These events were associated with steatohepatitis (aHR, 5.55; 95% CI: 2.01-15.3) compared with non-steatosis and advanced fibrosis (aHR, 6.23; 95% CI: 1.75-22.2) compared with no fibrosis. The steatosis but not steatohepatitis group had a non-significantly higher risk of overall mortality and liver-related events. CONCLUSIONS Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in CHB patients.
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Affiliation(s)
- Manus Rugivarodom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ananya Pongpaibul
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Siwaporn Chainuvati
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Supot Nimanong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Watcharasak Chotiyaputta
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Correspondence to: Phunchai Charatcharoenwitthaya, Division of Gastroenterology, Medicine Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Wang-Lang Road, Bangkok10700, Thailand. ORCID: https://orcid.org/0000-0002-8334-0267. Tel: +662-4197282, Fax: +662-4198435, E-mail:
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Tan YW, Wang JM, Zhou XB. Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease. World J Hepatol 2023; 15:237-254. [PMID: 36926239 PMCID: PMC10011903 DOI: 10.4254/wjh.v15.i2.237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/14/2022] [Accepted: 01/17/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) on liver disease, few have investigated the relationship between nonalcoholic steatohepatitis (NASH) defined by liver pathology and the prognosis of chronic HBV infection. Most patients were followed up for a short time. This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection. AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events [cirrhosis, hepatocellular carcinoma (HCC), and death] in patients with chronic hepatitis B (CHB) virus infection. METHODS We enrolled patients with chronic hepatitis B virus (HBV) infection who underwent liver biopsy at the Third People's Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020. Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected. Propensity score matching (PSM) was used to balance baseline parameters, Kaplan-Meier (K-M) survival analysis was used to evaluate the risk of clinical events, and Cox regression was used to analyze the risk factors of events. RESULTS Overall, 456 patients with chronic HBV infection were included in the study, of whom 152 (33.3%) had histologically confirmed NAFLD. The median follow-up time of the entire cohort was 70.5 mo. Thirty-four patients developed cirrhosis, which was diagnosed using ultrasound during the follow-up period. K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis (log-rank test, P > 0.05). Patients with CHB with fibrosis at baseline were more prone to cirrhosis (log-rank test, P = 0.046). After PSM, multivariate analysis showed that diabetes mellitus, ballooning deformation (BD), and platelet (PLT) were independent risk factors for cirrhosis diagnosed using ultrasound (P < 0.05). A total of 10 patients (2.2%) developed HCC, and six of these patients were in the combined NAFLD group. K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher (log-rank test, P < 0.05). Hepatocyte ballooning, and severe liver fibrosis were also associated with an increased risk of HCC (log-rank test, all P < 0.05). Cox multivariate analysis revealed that hepatocyte ballooning, liver fibrosis, and diabetes mellitus were independent risk factors for HCC. CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD. Diabetes mellitus, BD, and PLT were independent risk factors for liver cirrhosis. Patients with chronic HBV infection and NASH have an increased risk of HCC. BD, liver fibrosis, and diabetes mellitus are independent risk factors for HCC.
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Affiliation(s)
- You-Wen Tan
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China.
| | - Jia-Min Wang
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Xing-Bei Zhou
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
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25
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Hepatitis B virus infection combined with nonalcoholic fatty liver disease: Interaction and prognosis. Heliyon 2023; 9:e13113. [PMID: 36747946 PMCID: PMC9898750 DOI: 10.1016/j.heliyon.2023.e13113] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 01/07/2023] [Accepted: 01/18/2023] [Indexed: 01/22/2023] Open
Abstract
Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.
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Key Words
- AVT, antiviral therapy
- Antiviral efficacy
- BMI, body mass index
- CHB, chronic hepatitis B
- CI, confidence interval
- ETV, entecavir
- HBV infection
- HBV, hepatitis B virus
- HBeAg, hepatitis B e antigen
- HBsAg, hepatitis B surface antigen
- HCC, hepatocellular carcinoma
- HDL, high-density lipoprotein
- HDL-C, high-density lipoprotein-cholesterol
- HR, hazard ratio
- HS, hepatis steatosis
- Hepatocellular carcinoma
- LDL-C, low-density lipoprotein cholesterol
- Liver fibrosis
- NA, nucleos(t)ide analogue
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- NR, not reported
- Nonalcoholic fatty liver disease
- OR, odds ratio
- PEG-IFN, pegylated interferon
- TAF, tenofovir alafenamide
- TDF, tenofovir
- TLR4, Toll-Like Receptor 4
- aHR, adjusted hazard ratio
- non-HDL-C, non-high-density lipoprotein-cholesterol
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Chen F, Liu Y, Li Q, Wang F. Inhibition of hepatic NLRP3 inflammasome ameliorates non-alcoholic steatohepatitis/hepatitis B - induced hepatic injury. Clin Res Hepatol Gastroenterol 2023; 47:102056. [PMID: 36427780 DOI: 10.1016/j.clinre.2022.102056] [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: 10/18/2022] [Revised: 11/16/2022] [Accepted: 11/21/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND AIM Both chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) are the most common liver diseases over the world, but their underlying pathological mechanisms and interrelations are poorly understood. METHODS Histological analysis and NLRP3 protein expression were performed on 130 CHB patients with liver-biopsied. Wild-type or NLRP3 knockdown hepatitis B virus (HBV) -transgenic mice were fed with high-fat diet to induce steatosis, with or without co-administration with a novel NLRP3 inhibitor MCC950. RESULTS Hepatic NLRP3 inflammasome is markedly up-regulated in the CHB, NASH, superimposed NASH with CHB patients and their corresponding model mice. Hepatic knock-down of NLRP3 significantly inhibits HBV replication and surface antigen expression, as well as ameliorates NASH typical symptoms of HBV transgenic mice with or without high-fat diet consumption. In addition, administration of MCC950 successfully inhibits pathological features of both CHB and steatosis-induced liver damage without detectable adverse effects. CONCLUSIONS NLRP3 inflammasome is activated during the progression of both CHB and NASH and may play a critical role in their pathogenesis by regulating hepatic inflammation. Targeting this protein platform may represent an effective and novel strategy for the treatment of CHB, NASH and the superimposed patients.
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Affiliation(s)
- Feng Chen
- Division of Gastroenterology, Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Road, Shenzhen 518107, China; National Clinical Research Center for Infectious Diseases, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
| | - Yingxia Liu
- National Clinical Research Center for Infectious Diseases, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
| | - Qianhui Li
- Division of Gastroenterology, Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Road, Shenzhen 518107, China
| | - Fei Wang
- Division of Gastroenterology, Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Road, Shenzhen 518107, China.
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27
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Kim RG, Chu JN, Vittinghoff E, Deng J, Reaso JN, Grenert JP, Khalili M. Racial/ethnic differences in fibrosis prevalence and progression in biopsy-proven steatosis: A focus on the Asian American population. Hepatol Commun 2022; 6:3024-3035. [PMID: 36087033 PMCID: PMC9592793 DOI: 10.1002/hep4.2078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 06/10/2022] [Accepted: 08/01/2022] [Indexed: 12/14/2022] Open
Abstract
Fatty liver disease (FLD) is a leading cause of chronic liver disease (CLD) globally, and vulnerable populations are disproportionately affected. Prior studies have suggested racial/ethnic differences in FLD prevalence and severity; however, these studies often excluded Asian Americans. This study aims to evaluate racial/ethnic differences in the prevalence of, and predictors associated with steatohepatitis, advanced fibrosis, and fibrosis progression over time within a diverse population. Using descriptive analyses and multivariable modeling, we performed a longitudinal evaluation of 648 patients with histologic evidence of FLD (steatosis or steatohepatitis) from August 2009 to February 2020 within San Francisco's safety-net health care system. Overall demographics were median age of 53 years, 54% male, and 38% Asian (40% Hispanic, 14% White). On histology, 61% had steatohepatitis and 30% had advanced fibrosis (≥F3). The comparison between steatosis and steatohepatitis groups showed differences in sex, race/ethnicity, metabolic risk factors, and co-existing CLD (predominantly viral hepatitis); patients with steatosis were more likely to be Asian (50%), and those with steatohepatitis were more likely to be Hispanic (51%). On multivariable modeling, while Asian race (vs. non-Asian) was not associated with steatohepatitis or advanced fibrosis when models included all relevant clinical predictors, Asian race was associated with higher relative risk of fibrosis progression as defined by change in Fibrosis-4 category over time (relative risk ratio = 1.9; p = 0.047). Conclusion: In this vulnerable population with a large proportion of Asian Americans, Asian race was associated with progression of fibrosis. Given the relative paucity of data in this high-risk group, future studies should confirm these findings.
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Affiliation(s)
- Rebecca G. Kim
- Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of California, San FranciscoSan FranciscoCaliforniaUSA
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
| | - Janet N. Chu
- Division of General Internal MedicineDepartment of MedicineUniversity of California, San FranciscoSan FranciscoCaliforniaUSA
| | - Eric Vittinghoff
- Department of Epidemiology and BiostatisticsUniversity of California, San FranciscoSan FranciscoCaliforniaUSA
| | - Jasmine Deng
- David Geffen School of Medicine at University of California, Los AngelesLos AngelesCaliforniaUSA
| | - Jewel N. Reaso
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
| | - James P. Grenert
- Division of Surgical PathologyDepartment of Pathology and Laboratory MedicineUniversity of California, San FranciscoSan FranciscoCaliforniaUSA
- Liver CenterUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Mandana Khalili
- Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of California, San FranciscoSan FranciscoCaliforniaUSA
- Division of Gastroenterology and HepatologyZuckerberg San Francisco GeneralSan FranciscoCaliforniaUSA
- Liver CenterUniversity of California San FranciscoSan FranciscoCaliforniaUSA
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28
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Mao X, Cheung KS, Peng C, Mak LY, Cheng HM, Fung J, Peleg N, Leung HHW, Kumar R, Lee JH, Shlomai A, Yuen MF, Seto WK. Steatosis, HBV-related HCC, cirrhosis, and HBsAg seroclearance: A systematic review and meta-analysis. Hepatology 2022; 77:1735-1745. [PMID: 36111362 DOI: 10.1002/hep.32792] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/22/2022] [Accepted: 09/13/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIMS NAFLD and chronic hepatitis B (CHB) infection are common etiologies of HCC. The impact of hepatic steatosis on HCC in CHB, as well as its relationship with the development of cirrhosis, fibrosis, and HBsAg seroclearance, remains controversial. APPROACH AND RESULTS Data from observational studies were collected through PubMed, EMBASE, and the Cochrane Library from inception to February 1, 2022. Outcomes of interest included the association of hepatic steatosis with HCC, cirrhosis, advanced fibrosis, and HBsAg seroclearance, expressed in terms of pooled ORs. Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A total of 34 studies with 68,268 patients with CHB were included. Hepatic steatosis was associated with higher odds of HCC (OR, 1.59; 95% CI, 1.12-2.26; I2 = 72.5%), with the association remaining consistent in Asia (OR, 1.56; 95% CI, 1.08-2.25), studies with a median follow-up duration of ≥5 years (OR, 2.82; 95% CI, 1.57-5.08), exclusion of alcohol use (OR, 1.71; 95% CI, 1.01-2.91), and biopsy-proven steatosis (OR, 2.86; 95% CI, 1.61-5.06), although no significant association was noted among nucleos(t)ide analogue-treated patients (OR, 1.05; 95% CI, 0.62-1.77). Steatosis was associated with the development of cirrhosis (OR, 1.52; 95% CI, 1.07-2.16; I2 = 0%) and HBsAg seroclearance (OR, 2.22; 95% CI, 1.58-3.10; I2 = 49.0%). CONCLUSIONS Hepatic steatosis was associated with an increased risk of HCC and cirrhosis among patients with CHB but with a higher chance of achieving a functional cure, highlighting the importance of identifying concomitant steatosis in CHB.
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Affiliation(s)
- Xianhua Mao
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Ka Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Chengzhi Peng
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Ho Ming Cheng
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - James Fung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Noam Peleg
- Division of Gastroenterology, Rabin Medical Center, Petach Tikva, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Howard H-W Leung
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.,Duke-NUS Graduate Medical School, Singapore
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Amir Shlomai
- Department of Medicine D and The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tikva and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong
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29
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Yang M, Wei L. Impact of NAFLD on the outcome of patients with chronic hepatitis B in Asia. Liver Int 2022; 42:1981-1990. [PMID: 35373500 DOI: 10.1111/liv.15252] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 03/01/2022] [Accepted: 03/18/2022] [Indexed: 01/29/2023]
Abstract
Hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) are two major causes of chronic liver disease (CLD) that can cause liver cirrhosis and hepatocellular carcinoma (HCC). It is a trend to superimpose NAFLD on chronic HBV infection in Asia. This review presents the epidemiology of concurrent NAFLD in chronic hepatitis B (CHB) patients and focuses on the impact of concurrent NAFLD on the outcome of CHB patients in Asia. Although CHB patients tend to have a lower prevalence and incidence of NAFLD than the general population, concurrent NAFLD among CHB patients is still common and has an upward trend over time. Concurrent NAFLD can promote hepatitis B surface antigen (HBsAg) seroclearance and might inhibit HBV replication but exacerbate liver fibrosis. The impacts of concurrent NAFLD on HCC risk, all-cause mortality and antiviral treatment response in CHB patients remain controversial.
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Affiliation(s)
- Ming Yang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
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30
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Clinical impact and mechanisms of hepatitis B virus infection concurrent with non-alcoholic fatty liver disease. Chin Med J (Engl) 2022; 135:1653-1663. [PMID: 35940901 PMCID: PMC9509100 DOI: 10.1097/cm9.0000000000002310] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
ABSTRACT Chronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully elucidated. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes of treatments for CHB patients with NAFLD. This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.
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31
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Keikha M, Sahebkar A, Jamialahmadi T, Karbalaei M. Metabolic syndromes, hepatitis B virus (HBV), and hepatitis C virus as three factors involved in the development of hepatic steatosis: a systematic review and meta-analysis. REVIEWS AND RESEARCH IN MEDICAL MICROBIOLOGY 2022; 33:139-147. [DOI: 10.1097/mrm.0000000000000303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Background:
In recent years, the increase in prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with viral chronic hepatitis due to hepatitis B virus (HBV) and hepatitis C virus (HCV) has been alarming. The pattern of liver histological changes in patients with HBV and HCV infections resembles those of NAFLD, leading to potential misdiagnosis.
Methods:
Using global databases such as Scopus and PubMed, relevant studies were retrieved and those studies found to be eligible based on inclusion criteria were analyzed. Statistical analysis was done by comprehensive meta-analysis software.
Results:
The results suggested an inverse association between HBV and HCV infections and hepatic steatosis risk, but not significant. The risk of hepatic steatosis in patients with concurrent chronic viral hepatitis is significantly associated performed with metabolic syndrome and biochemical parameters particularly body mass index > 25 kg/m2, arterial hypertension, dyslipidemia, type 2 diabetes, hypertriglyceridemia, and hypercholesterolemia.
Conclusion:
According to the results of the present study, viral hepatitis (viral load) has a protective role against the development of hepatic steatosis. Nevertheless, hepatic steatosis in patients infected with HBV and HCV was associated with metabolic syndrome.
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Affiliation(s)
- Masoud Keikha
- Department of Microbiology and Virology, Faculty of Medicine
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad
| | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad
| | - Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
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32
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Yang Q, Tong Y, Pi B, Yu H, Lv F. Influence of Metabolic Risk Factors on the Risk of Bacterial Infections in Hepatitis B-Related Cirrhosis: A 10-Year Cohort Study. Front Med (Lausanne) 2022; 9:847091. [PMID: 35492332 PMCID: PMC9046983 DOI: 10.3389/fmed.2022.847091] [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: 01/01/2022] [Accepted: 02/21/2022] [Indexed: 11/13/2022] Open
Abstract
Aim The effect of metabolic factors on the risk of bacterial infections (BIs) in patients with hepatitis B virus (HBV)-related cirrhosis has not been demonstrated. This study aimed to explore specific metabolic factors associated with the BIs in these patients. Methods A population-based cohort of 471 patients with HBV-related cirrhosis was retrospectively enrolled between 2009 and 2019. The primary end point was the incidence of BIs during hospitalization, which were compared according to the metabolism-related indicators, namely, presence of diabetes, level of high-density lipoprotein cholesterol (HDLC) and triglyceride, and body mass index (BMI). The propensity score matching (PSM) was adopted to eliminate baseline discrepancies. Results Compared with the non-diabetic group, the incidences of BIs were higher in the diabetic group before and after PSM (p = 0.029 and p = 0.027). Similar results were found in the low HDLC group as compared with the normal HDLC group before and after PSM (p < 0.001 and p = 0.025). Further analysis showed that the incidences of BIs in patients with low HDLC alone were lower than patients with both low HDLC and diabetes before and after PSM (p = 0.003 and p = 0.022). Similarly, the incidence of BIs in patients with diabetes alone was lower than those in patients with both low HDLC and diabetes both before and after PSM (p = 0.002 and p = 0.018). However, neither triglyceride nor BMI level was related to BIs in our cohort. Conclusion In patients with HBV-related cirrhosis, the presence of diabetes and low level of HDLC were risk factors of BIs, showing a synergistic effect.
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Affiliation(s)
- Qiao Yang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yifan Tong
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Borui Pi
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Hong Yu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Fangfang Lv
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Fangfang Lv,
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33
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Huang Y, Gan Q, Lai R, Wang W, Guo S, Sheng Z, Chen L, Guo Q, Cai W, Wang H, Zhao G, Cao Z, Xie Q. Application of Fatty Liver Inhibition of Progression Algorithm and Steatosis, Activity, and Fibrosis Score to Assess the Impact of Non-Alcoholic Fatty Liver on Untreated Chronic Hepatitis B Patients. Front Cell Infect Microbiol 2022; 11:733348. [PMID: 35111690 PMCID: PMC8801606 DOI: 10.3389/fcimb.2021.733348] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 12/13/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUNDS AND PURPOSE Concurrent non-alcoholic fatty liver disease (NAFLD) in chronic hepatitis B (CHB) patients is a frequent and increasingly concerning problem because of the NAFLD pandemic. Admittedly, NAFLD can progress to non-alcoholic steatohepatitis (NASH) and severe fibrosis. Direct evidence of the fibrotic effect of NAFLD or NASH in chronic hepatitis B virus (HBV) infection remains lacking. We aimed to reveal the influence of concurrent histologically proven fatty liver diseases in fibrogenesis with chronic HBV infection. METHODS We performed a retrospective cross-sectional study on a liver biopsy population of CHB patients without excessive alcohol intake to evaluate the prevalence of concurrent histologically proven NAFLD or NASH according to the fatty liver inhibition of progression (FLIP) algorithm and its association with the liver fibrosis stage. RESULTS Among 1,081 CHB patients, concurrent NAFLD was found in 404 patients (37.4%), among whom 24.0% (97/404) have NASH. The presence of NASH was an independent predictor of significant fibrosis (odds ratio (OR), 2.53; 95% CI, 1.52-4.21; p < 0.001) and severe fibrosis (OR, 1.83; 95% CI, 1.09-3.09; p = 0.023) in all patients, as well as in patients with normal alanine aminotransferase (ALT) (predicting significant fibrosis, OR, 2.86, 95% CI, 1.34-6.10; p = 0.007). The presence of lobular inflammation (p < 0.001) or presence of cytological ballooning (p < 0.001), rather than presence of steatosis (p = 0.419), was related with severity of fibrosis in Spearman's correlation analysis. CONCLUSIONS Concurrent NAFLD is common in CHB patients, and NASH is an independent risk factor potentiating significant fibrosis by 2.53-fold and severe fibrosis by 1.83-fold. While coping with chronic HBV infection, routine assessment of co-existing NAFLD or NASH is also important.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Gangde Zhao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhujun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Kim MN, Han K, Yoo J, Hwang SG, Ahn SH. Increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis with concurrent fatty liver. Aliment Pharmacol Ther 2022; 55:97-107. [PMID: 34820871 DOI: 10.1111/apt.16706] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/13/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Population-based data are lacking regarding whether fatty liver is a risk factor for hepatocellular carcinoma (HCC) and mortality in patients with chronic viral hepatitis. AIM To investigate the association of fatty liver with HCC incidence and mortality in patients with chronic viral hepatitis using a nationwide cohort METHODS: We included 57,385 patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who underwent health examinations. The patients were divided into three groups: no fatty liver, fatty liver index (FLI) <30, grade 1 (G1) fatty liver: 30≤ FLI <60, and grade 2 (G2) fatty liver: FLI >60. RESULTS During a median 8.4-year follow-up, we documented 3496 HCC cases and 4146 deaths. Compared to patients with no fatty liver (n = 35,018), the risk of HCC was significantly higher in patients with G1 fatty liver (n = 14,544) (adjusted hazard ratio [aHR] = 1.50, 95% confidence interval [CI] = 1.38-1.64) and G2 fatty liver (n = 7,823) (aHR = 1.88, 95% CI = 1.67-2.12). The risk of mortality was significantly higher in patients with G1 fatty liver (aHR = 1.53, 95% CI = 1.41-1.66) and G2 fatty liver (aHR = 2.16, 95% CI = 1.94-2.42) compared to patients with no fatty liver. CONCLUSIONS Concurrent fatty liver was associated with a higher risk of HCC and mortality in patients with chronic viral hepatitis. Our results suggest the importance of management of fatty liver to reduce the risks of HCC and mortality in patients with chronic viral hepatitis.
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Affiliation(s)
- Mi Na Kim
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.,Clinical and Translational Hepatology Laboratory, Seongnam, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Juhwan Yoo
- Department of Biomedicine & Health Science, The Catholic University of Korea, Seoul, Korea
| | - Seong Gyu Hwang
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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35
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Chen X, Zhou J, Wu L, Zhu X, Deng H. MAFLD is Associated with the Risk of Liver Fibrosis and Inflammatory Activity in HBeAg-Negative CHB Patients. Diabetes Metab Syndr Obes 2022; 15:673-683. [PMID: 35256849 PMCID: PMC8898022 DOI: 10.2147/dmso.s351492] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 02/15/2022] [Indexed: 04/10/2023] Open
Abstract
PURPOSE Chronic hepatitis B (CHB) and metabolic associated fatty liver disease (MAFLD) are both important public health problems. The effect of concomitant MAFLD on patients with CHB is still unclear. This study aimed to explore the influence of MAFLD on liver fibrosis and inflammation in CHB patients with different hepatitis B e antigen (HBeAg) status. PATIENTS AND METHODS We retrospectively collected the clinical data of 399 treatment-naïve CHB patients who underwent liver biopsy. All patients were divided into two groups (HBeAg± group). Logistic regression analysis was used to identify factors associated with liver inflammatory activity and significant fibrosis in patients with CHB. Multivariable logistic regressions were repeated in subgroups stratified by HBeAg status. RESULTS In patients with CHB, MAFLD was independently associated with a risk of moderate-to-severe liver activity and significant fibrosis (P <0.05). In the HBeAg-negative group, patients with MAFLD had significantly higher levels of alanine aminotransferase (ALT) (P <0.05) and more severe liver inflammatory activity and fibrosis (P <0.05) compared to those without MAFLD. MAFLD was independently associated with a risk of moderate-to-severe liver activity (A ≥3: OR 3.97, 95% CI 1.71-9.22, P =0.001) and significant fibrosis (F ≥2: OR 2.02, 95% CI 1.09-3.73, P =0.026). In the HBeAg-positive group, MAFLD was found to be independently associated with moderate-to-severe liver activity (OR 2.44, 95% CI 1.03-5.79, P =0.044) but not fibrosis (P =0.618). CONCLUSION MAFLD is associated with the risk of liver fibrosis and inflammatory activity in HBeAg-negative CHB patients. Sufficient attention should be paid to the prevention and treatment of MAFLD in patients with CHB, especially in HBeAg-negative patients.
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Affiliation(s)
- Xiaoman Chen
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
- Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China
| | - Jing Zhou
- Department of Pathology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Lili Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Xiang Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Hong Deng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
- Correspondence: Hong Deng; Xiang Zhu, Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou, People’s Republic of China, Tel +86-2085252506, Fax +86-2085252063, Email ;
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Wang QX, Xue J, Shi MJ, Xie YB, Xiao HM, Li S, Lin M, Chi XL. Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and the Risk of Cirrhosis in Patients with Chronic Hepatitis B-A Retrospective Cohort Study. Diabetes Metab Syndr Obes 2022; 15:2311-2322. [PMID: 35942038 PMCID: PMC9356614 DOI: 10.2147/dmso.s369824] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 07/19/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel proposed concept that is being recognized worldwide. Both chronic hepatitis B (CHB) and MAFLD have been independently attributed to an increased risk of disease development to cirrhosis. However, it is still unclear whether MAFLD is associated with an increased risk of cirrhosis in CHB patients. AIM This study aimed to analyze the impact of MAFLD on the risk of cirrhosis in CHB patients. METHODS In this retrospective cohort study, consecutive CHB patients with or without MAFLD were enrolled from January 1st, 2007, to May 1st, 2020, in Guangdong Provincial Hospital of Chinese Medicine. Inverse probability treatment weighting (IPTW) was performed to balance the covariates across groups. The weighted Kaplan-Meier analysis and Cox regression analysis were used to compare both groups for the risk of cirrhosis. RESULTS A total of 1223 CHB patients were included in this study during the median follow-up of 5.25 years; of these patients, 355 were CHB-MAFLD patients. After IPTW, the weighted Kaplan-Meier analysis showed that the weighted cumulative incidence of cirrhosis was significantly higher in patients with MAFLD than that in patients without MAFLD (12.6% versus 7.1%, P=0.015). In the weighted multivariate Cox analysis, coexisting MAFLD was related to an increased risk of cirrhosis [adjusted weighted hazard ratio (HR) 1.790; P =0.020]. Age (>40 years, adjusted weighted HR, 1.950; P=0.015), diabetes mellitus (adjusted weighted HR, 1.883; P=0.041), non-antiviral treatment (adjusted weighted HR, 2.037; P=0.013), and baseline serum HBV DNA levels (>2.4 log10 IU/mL, adjusted weighted HR, 1.756; P=0.045) were significant risk factors for cirrhosis. CONCLUSION We found that MAFLD was associated with a higher risk of cirrhosis in CHB patients.
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Affiliation(s)
- Qing-Xia Wang
- The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Jiao Xue
- The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Mei-Jie Shi
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Yu-Bao Xie
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Huan-Ming Xiao
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Sheng Li
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Ming Lin
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Xiao-Ling Chi
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
- Correspondence: Xiao-Ling Chi, Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China, Tel +86+39318398, Fax +86-020-81867705, Email
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Chen YC, Hsu CW, Jeng WJ, Lin CY. Advanced Liver Fibrosis Is Associated with Necroinflammatory Grade but Not Hepatic Steatosis in Chronic Hepatitis B Patients. Dig Dis Sci 2021; 66:4492-4500. [PMID: 33569664 DOI: 10.1007/s10620-020-06761-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 12/06/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Patients with chronic hepatitis B (CHB) are at an increased risk of disease progression. The influence of hepatic steatosis (HS) to liver fibrosis was controversial. We aim to investigate the association between HS and liver fibrosis and explore the predicting factors for advanced fibrosis. METHODS CHB patients undergoing liver biopsy with complete assessments of HS, necroinflammation grade [histological activity index (HAI) score], and fibrosis stage were retrospectively recruited. Logistic regression analysis was performed to determine the factors associated with advanced liver fibrosis. RESULTS In this cohort of 672 patients, 342 (50.9%) had HS and 267 (39.4%) were of advanced liver fibrosis. Age [odds ratio (OR) 1.026, 95% confidence interval (CI) 1.007-1.046, p = 0.008], body mass index (BMI, OR 1.091, 95% CI 1.026-1.159, p = 0.005), genotype (C vs. B) (OR 2.790, 95% CI 1.847-4.214, p < 0.001), platelet (OR 0.986, 95% CI 0.982-0.991, p < 0.001), and HAI score (OR 1.197, 95% CI 1.114-1.285, p < 0.001) were independent factors for advanced liver fibrosis in multivariate logistic regression analysis. HAI score was also a significantly associated factor for significant liver fibrosis in non-cirrhotic subpopulation (OR 1.578, 95% CI 1.375-1.810, p < 0.001). HS was not related to advanced/significant liver fibrosis in overall/non-cirrhotic population (p > 0.05). CONCLUSIONS Significant or advanced liver fibrosis is associated with grade of necroinflammation but not with HS in CHB patients.
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Affiliation(s)
- Yi-Cheng Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and University, Linkou, No. 5, Fu Hsing Street, Guishan Dist., Taoyuan City, 33302, Taiwan, ROC. .,College of Medicine, Guishan Dist, Chang Gung University, No. 259, Wen Hua 1st Rd, Taoyuan City, 33302, Taiwan, Republic of China.
| | - Chao-Wei Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and University, Linkou, No. 5, Fu Hsing Street, Guishan Dist., Taoyuan City, 33302, Taiwan, ROC.,College of Medicine, Guishan Dist, Chang Gung University, No. 259, Wen Hua 1st Rd, Taoyuan City, 33302, Taiwan, Republic of China
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and University, Linkou, No. 5, Fu Hsing Street, Guishan Dist., Taoyuan City, 33302, Taiwan, ROC.,College of Medicine, Guishan Dist, Chang Gung University, No. 259, Wen Hua 1st Rd, Taoyuan City, 33302, Taiwan, Republic of China
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and University, Linkou, No. 5, Fu Hsing Street, Guishan Dist., Taoyuan City, 33302, Taiwan, ROC.,College of Medicine, Guishan Dist, Chang Gung University, No. 259, Wen Hua 1st Rd, Taoyuan City, 33302, Taiwan, Republic of China
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Zheng Q, Zou B, Wu Y, Yeo Y, Wu H, Stave CD, Cheung RC, Nguyen MH. Systematic review with meta-analysis: prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B. Aliment Pharmacol Ther 2021; 54:1100-1109. [PMID: 34469587 DOI: 10.1111/apt.16595] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/18/2021] [Accepted: 08/22/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND As the prevalence of hepatitis steatosis (HS) increases, the prevalence of HS among those with chronic hepatitis B (CHB) may also be increasing but data on the effect of HS on CHB disease progression are lacking. AIMS To determine the prevalence of HS in CHB and associated factors, prevalence of fibrosis and its association with HS. METHODS Two researchers independently searched the literature and extracted data. We included full-length original articles of adults with CHB that evaluated. Prevalence estimates were pooled using a random-effects model. Associations between HS and fibrosis were assessed by pooled odds ratios (ORs) or mean differences (MD). RESULTS Of the 2821 records screened, 54 eligible studies (28 648 patients) were analysed. The pooled prevalence of HS in CHB was 32.8% (95% CI, 28.9-37.0) with higher prevalence in men and obese patients. Older age, male sex and metabolic factors were associated with HS while an inverse association was observed between HS and HBeAg (OR 0.82, 95% CI, 0.75-0.91) and HBV DNA levels (MD -0.38, 95% CI -1.16--0.42). The pooled prevalence of significant fibrosis (≥F2 or ≥F3) was similar between patients with CHB with or without HS (40.1% vs 42.22%, P = 0.68). HS was not significantly associated with fibrosis (pooled OR 0.87, 95% CI 0.54-1.39, 20 studies, 6232 patients). CONCLUSIONS Approximately 30% of patients with CHB had HS, which was positively associated with male sex, diabetes and metabolic factors, and was negatively associated with HBeAg and HBV DNA. HS was not significantly associated with increased fibrosis.
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Affiliation(s)
- Qi Zheng
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA.,Department of Hepatology, Hepatology Research institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA.,Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA
| | - Yuankai Wu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA.,The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yeehui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Huizhen Wu
- Department of Hepatology, Hepatology Research institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Christopher D Stave
- Lane Medical Library, Stanford University School of Medicine, Stanford, California, USA
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA.,Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA.,Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA
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Chang XJ, Shi YW, Wang J, Liu HB, Chen Y, Zhu XN, Chen YP, Yu ZJ, Shang QH, Tan L, Li Q, Jiang L, Xiao GM, Chen L, Lu W, Hu XY, Long QH, An LJ, Zou ZY, Wong VWS, Yang YP, Fan JG. Influence of weight management on the prognosis of steatohepatitis in chronic hepatitis B patients during antiviral treatment. Hepatobiliary Pancreat Dis Int 2021; 20:416-425. [PMID: 34275749 DOI: 10.1016/j.hbpd.2021.06.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 06/25/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment. METHODS In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72. RESULTS A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P > 0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P < 0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/m2 (Asian criteria) [odds ratio (OR): 0.414; 95% confidence interval (95% CI): 0.190-0.899; P = 0.012] and weight gain (OR: 0.187; 95% CI: 0.050-0.693; P = 0.026) were less likely to have NASH resolution. Among patients without NASH at baseline, 22 (3.7%) developed NASH. Baseline BMI ≥ 23 kg/m2 (OR: 12.506; 95% CI: 2.813-55.606; P = 0.001) and weight gain (OR: 5.126; 95% CI: 1.674-15.694; P = 0.005) were predictors of incident NASH. CONCLUSIONS Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.
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Affiliation(s)
- Xiu-Juan Chang
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - 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
| | - Jing Wang
- Department of Liver Disease, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 610072, China
| | - Hua-Bao Liu
- Department of Liver Diseases, Traditional Chinese Medicine Hospital of Chongqing, Chongqing 400038, China
| | - Yan Chen
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xiao-Ning Zhu
- Department of Liver Disease, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 610072, China
| | - Yong-Ping Chen
- Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Zu-Jiang Yu
- Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Qing-Hua Shang
- Center of Therapeutic Liver Disease, the 960th Hospital of Chinese PLA, Taian 271000, China
| | - Lin Tan
- Liver Disease Department, Fuyang 2nd People's Hospital, Fuyang 236015, China
| | - Qin Li
- Department of Liver Diseases, Fuzhou Infectious Diseases Hospital, Fuzhou 350025, China
| | - Li Jiang
- Department of Infectious Diseases, Southwest Hospital, Army Military Medical University, Chongqing 400038, China
| | - Guang-Ming Xiao
- Department of Infectious Diseases, Guangzhou 8th People's Hospital, Guangzhou 510060, China
| | - Liang Chen
- Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai 201508, China
| | - Wei Lu
- Department of Liver Diseases, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin 300192, China
| | - Xiao-Yu Hu
- National Integrative Medicine Clinical Base for Infectious Diseases and Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610000, China
| | - Qing-Hua Long
- Department of Infection and Liver Disease, Yichun People's Hospital, Yichun 336028, China
| | - Lin-Jing An
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zi-Yuan Zou
- 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
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
| | - Yong-Ping Yang
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, 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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Hepatic Steatosis and Steatohepatitis in a Large North American Cohort of Adults With Chronic Hepatitis B. Am J Gastroenterol 2021; 116:1686-1697. [PMID: 33840726 PMCID: PMC8484018 DOI: 10.14309/ajg.0000000000001257] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 02/23/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Fatty liver disease (FLD) influences liver disease progression and liver cancer risk. We investigated the impact of FLD on liver disease severity in a large North American cohort with chronic hepatitis B virus (HBV). METHODS Liver biopsies from 420 hepatitis B surface antigen-positive adults enrolled in the Hepatitis B Research Network and who were not on HBV therapy in the previous month were evaluated for inflammation and fibrosis. Steatohepatitis was based on steatosis, hepatocyte ballooning ± Mallory-Denk bodies, and perisinusoidal fibrosis. Models evaluated factors associated with steatohepatitis, and the associations of steatohepatitis with fibrosis, and longitudinal alanine aminotransferase, aspartate aminotransferase, and Fibrosis-4. RESULTS The median age was 42 years, 62.5% were male, and 79.5% were Asian. One hundred thirty-two (31.4%) patients had FLD (77 [18.3%] steatosis only, 55 [13.1%] steatohepatitis). Older age, overweight/obesity, and diabetes were associated with steatohepatitis. Steatohepatitis (vs no FLD) was associated with 1.68 times higher risk of advanced fibrosis at baseline (95% confidence interval, 1.12-2.51), and there was an indication of higher incident cirrhosis rate during follow-up. Steatohepatitis vs no FLD was also independently associated with, on average, 1.39 times higher alanine aminotransferase (P < 0.01) and 1.25 times higher Fibrosis-4 (P = 0.04) across 4 years. DISCUSSION Coexisting steatosis occurred in nearly a third of adults (13% had steatohepatitis) with chronic HBV in this North American cohort who underwent liver biopsies. Steatohepatitis was associated with advanced fibrosis and higher biochemical measures of hepatic inflammation over time. Therefore, in addition to viral suppression, screening for and managing metabolic abnormalities is important to prevent disease progression in HBV.
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Li J, Yang HI, Yeh ML, Le MH, Le AK, Yeo YH, Dai CY, Barnett S, Zhang JQ, Huang JF, Trinh HN, Wong C, Wong C, Hoang JK, Cheung R, Yu ML, Nguyen MH. Association Between Fatty Liver and Cirrhosis, Hepatocellular Carcinoma, and Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B. J Infect Dis 2021; 224:294-302. [PMID: 33249474 DOI: 10.1093/infdis/jiaa739] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 11/25/2020] [Indexed: 09/12/2023] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance incidence in CHB patients. METHODS In a retrospective cohort study of 6786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups. RESULTS Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in the antiviral-treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (hazard ratio [HR], 0.19 [95% confidence interval {CI}, .12-.33], P < .001 and HR, 0.21 [95% CI, .09-.51], P = .001, respectively) in antiviral-treated patients but not in untreated patients. CONCLUSIONS FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.
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Affiliation(s)
- Jie Li
- Department of Infectious Disease, Shandong Provincial Hospital affiliated to Shandong University, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong, China
- Department of Infectious Disease, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Hepatitis Research Center, College of Medicine and Center for Cancer Research and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Michael H Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - An K Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - Chia-Yen Dai
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Hepatitis Research Center, College of Medicine and Center for Cancer Research and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Scott Barnett
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - Jian Q Zhang
- Chinese Hospital, San Francisco, California, USA
| | - Jee-Fu Huang
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Hepatitis Research Center, College of Medicine and Center for Cancer Research and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Huy N Trinh
- San Jose Gastroenterology, San Jose, California, USA
| | | | | | - Joseph K Hoang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Hepatitis Research Center, College of Medicine and Center for Cancer Research and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
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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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Zhang J, Ling N, Lei Y, Peng M, Hu P, Chen M. Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B. Front Microbiol 2021; 12:636897. [PMID: 33776969 PMCID: PMC7991784 DOI: 10.3389/fmicb.2021.636897] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 02/18/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatitis B virus (HBV) is considered a “metabolic virus” and affects many hepatic metabolic pathways. However, how HBV affects lipid metabolism in hepatocytes remains uncertain yet. Accumulating clinical studies suggested that compared to non-HBV-infected controls, chronic HBV infection was associated with lower levels of serum total cholesterol and triglycerides and a lower prevalence of hepatic steatosis. In patients with chronic HBV infection, high ALT level, high body mass index, male gender, or old age was found to be positively correlated with hepatic steatosis. Furthermore, mechanisms of how HBV infection affected hepatic lipid metabolism had also been explored in a number of studies based on cell lines and mouse models. These results demonstrated that HBV replication or expression induced extensive and diverse changes in hepatic lipid metabolism, by not only activating expression of some critical lipogenesis and cholesterolgenesis-related proteins but also upregulating fatty acid oxidation and bile acid synthesis. Moreover, increasing studies found some potential targets to inhibit HBV replication or expression by decreasing or enhancing certain lipid metabolism-related proteins or metabolites. Therefore, in this article, we comprehensively reviewed these publications and revealed the connections between clinical observations and experimental findings to better understand the interaction between hepatic lipid metabolism and HBV infection. However, the available data are far from conclusive, and there is still a long way to go before clarifying the complex interaction between HBV infection and hepatic lipid metabolism.
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Affiliation(s)
- Jiaxuan Zhang
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ning Ling
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu Lei
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingli Peng
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Chen
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Eslam M, Sarin SK, Wong VWS, Fan JG, Kawaguchi T, Ahn SH, Zheng MH, Shiha G, Yilmaz Y, Gani R, Alam S, Dan YY, Kao JH, Hamid S, Cua IH, Chan WK, Payawal D, Tan SS, Tanwandee T, Adams LA, Kumar M, Omata M, George J. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol Int 2020; 14:889-919. [PMID: 33006093 DOI: 10.1007/s12072-020-10094-2] [Citation(s) in RCA: 532] [Impact Index Per Article: 106.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 09/06/2020] [Indexed: 02/06/2023]
Abstract
Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
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Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia.
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Ming-Hua Zheng
- Department of Hepatology, MAFLD Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
| | - Gamal Shiha
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, El Mansoura, Egypt
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
- Institute of Gastroenterology, Marmara University, Istanbul, Turkey
| | - Rino Gani
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Pangeran Diponegoro Road No. 71st, Central Jakarta, 10430, Indonesia
| | - Shahinul Alam
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh
| | - Yock Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University, 1 Chang-Te Street, Taipei, 10002, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan
| | - Saeed Hamid
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Ian Homer Cua
- Institute of Digestive and Liver Diseases, St. Luke's Medical Center, Global City, Philippines
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Diana Payawal
- Department of Medicine, Cardinal Santos Medical Center, Mandaluyong, Philippines
| | - Soek-Siam Tan
- Department of Hepatology, Selayang Hospital, Batu Caves, Malaysia
| | - Tawesak Tanwandee
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Leon A Adams
- Medical School, Faculty of Medicine and Health Sciences, The University of Western Australia, Nedlands, WA, Australia
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Tokyo, Japan
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, 2145, Australia.
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Hanif H, Khan MM, Ali MJ, Shah PA, Satiya J, Lau DT, Aslam A. A New Endemic of Concomitant Nonalcoholic Fatty Liver Disease and Chronic Hepatitis B. Microorganisms 2020; 8:1526. [PMID: 33020450 PMCID: PMC7601829 DOI: 10.3390/microorganisms8101526] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 09/28/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) infection remains a global public problem despite the availability of an effective vaccine. In the past decades, nonalcoholic fatty liver disease (NAFLD) has surpassed HBV as the most common cause of chronic liver disease worldwide. The prevalence of concomitant chronic hepatitis B (CHB) and NAFLD thus reaches endemic proportions in geographic regions where both conditions are common. Patients with CHB and NAFLD are at increased risk of liver disease progression to cirrhosis and hepatocellular carcinoma. Due to the complexity of the pathogenesis, accurate diagnosis of NAFLD in CHB patients can be challenging. Liver biopsy is considered the gold standard for diagnosing and determining disease severity, but it is an invasive procedure with potential complications. There is a growing body of literature on the application of novel noninvasive serum biomarkers and advanced radiological modalities to diagnose and evaluate NAFLD, but most have not been adequately validated, especially for patients with CHB. Currently, there is no approved therapy for NAFLD, although many new agents are in different phases of development. This review provides a summary of the epidemiology, clinical features, diagnosis, and management of the NAFLD and highlights the unmet needs in the areas of CHB and NAFLD coexistence.
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Affiliation(s)
- Hira Hanif
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Muzammil M. Khan
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Mukarram J. Ali
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Pir A. Shah
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
- Department of Internal Medicine, University of Texas, San Antonio, TX 78229, USA
| | - Jinendra Satiya
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Daryl T.Y. Lau
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (H.H.); (M.M.K.); (M.J.A.); (P.A.S.); (J.S.)
| | - Aysha Aslam
- Department of Medicine, Louis A Weiss Memorial Hospital, Chicago, IL 60640, USA
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46
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Pathologic findings of patients with nonalcoholic fatty liver disease and the impact of concurrent hepatitis B virus infection in Taiwan. J Formos Med Assoc 2020; 119:1476-1482. [PMID: 32499209 DOI: 10.1016/j.jfma.2020.05.027] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 05/11/2020] [Accepted: 05/18/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND & AIMS Pathologic data of non-alcoholic fatty liver disease (NAFLD) was limited and the association between NAFLD and chronic hepatitis B remained unclear in Taiwan. This study aimed to determine the pathological manifestations of NAFLD and the impact of concurrent hepatitis B virus (HBV) infection in a medical center. METHODS Retrospective review of 104 consecutive random liver biopsies with the histologic diagnosis of NAFLD or cryptogenic cirrhosis from 2009 to 2018 was conducted. Clinical, biochemical and histological data were compared among various stages of NAFLD and between those with or without concurrent HBV infection. RESULTS Advanced fibrosis was documented in 39.42% of Taiwanese patients with NAFLD according to METAVIR scoring system and was associated with aging (odds ratio, 1.06; 95% CI, 1.03-1.10), hypertension (odds ratio, 2.97; 95% CI, 1.31-6.74), diabetes mellitus (odds ratio, 4.36; 95% CI, 1.78-10.70) and concurrent HBV infection (odds ratio, 3.55; 95% CI, 1.46-8.58) by multivariate analyses. Concurrent HBV was found in 28.57% of the NAFLD patients. Patients with concurrent HBV had lower platelet counts, longer prothrombin time/INR and higher fibrosis stage than those without CHB. CONCLUSION Advanced fibrosis in patients with NAFLD was common in the biopsy series, and was related to aging, hypertension, diabetes mellitus and concurrent HBV infection.
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47
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Chen YC, Jeng WJ, Hsu CW, Lin CY. Impact of hepatic steatosis on treatment response in nuclesos(t)ide analogue-treated HBeAg-positive chronic hepatitis B: a retrospective study. BMC Gastroenterol 2020; 20:146. [PMID: 32397963 PMCID: PMC7216492 DOI: 10.1186/s12876-020-01289-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 04/30/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The impact of hepatic steatosis (HS) on treatment response following nucleos(t)ide analogue (NA) treatment for chronic hepatitis B (CHB) patients has not been clearly elucidated. We aimed to investigate the difference in HBeAg seroclearance between NA-treated HBeAg-positive CHB patients with and without HS. METHODS We retrospectively recruited HBeAg-positive CHB patients receiving liver biopsy and NA monotherapy. The baseline clinical characteristics and cumulative incidence of HBeAg seroclearance were compared between patients with and without HS and age/gender-matched subgroup analysis was performed. RESULTS A total of 196 patients were enrolled from 2003 April to 2016 October. The mean age was 39.6 ± 11.2 years, 142 (72.4%) were males and 94 (48%) had histological evidence of HS. Median treatment duration and follow-up period were 24.3 months and 54.9 months, respectively. HBeAg seroclearance was achieved in 56/102 (54.9%) and 54/94 (57.4%) patients with and without HS, respectively (p = 0.830). The 5-year cumulative incidence of HBeAg seroclearance in patients with and without HS was 62.8 and 67.7% in overall population (p = 0.398) and 62.4 and 66.9% in age/gender-matched subgroups (p = 0.395), respectively. The rate of HBeAg seroclearance was comparable between patients with or without HS in different NA monotherapy (all p > 0.05). CONCLUSIONS HS had no significant impact on HBeAg seroclearance in HBeAg-positive CHB patients with NA monotherapy during long-term follow-up.
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Affiliation(s)
- Yi-Cheng Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China. .,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China
| | - Chao-Wei Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China
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48
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Li J, Le AK, Chaung KT, Henry L, Hoang JK, Cheung R, Nguyen MH. Fatty liver is not independently associated with the rates of complete response to oral antiviral therapy in chronic hepatitis B patients. Liver Int 2020; 40:1052-1061. [PMID: 32086988 DOI: 10.1111/liv.14415] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 01/31/2020] [Accepted: 02/19/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are common liver diseases. Concurrent NAFLD may affect antiviral treatment outcomes in CHB patients. The aim of this study is to investigate the impact of NAFLD on complete viral suppression ([CVS], HBV DNA <20-100 IU/mL) and/or biochemical response ([BR], ALT of ≤25 U/L for females; 35 U/L for males) in CHB patients who received oral antiviral therapy. METHODS A retrospective study of 555 treated CHB patients (187 NAFLD; 368 non-NAFLD) from 2000 to 2016 at a USA medical centre. NAFLD was diagnosed by imaging and/or histology after ruling out secondary causes of hepatic steatosis. RESULTS The majority of patients were male (60.7%), Asian (87.56%) and HBeAg-negative (66.7%). NAFLD patients compared to non-NAFLD were more likely HBeAg negative (74.3% vs 62.8%, P = .02), hypertensive (33.2% vs 22.8%, P = .009) and male (67.4% vs 57.3%, P = .02) with a higher mean BMI (25.4 ± 4.3 vs 23.8 ± 4.0 kg/m2 , P < .001). Both cohorts achieved similar rates of CVS (86% vs 88%) and BR (38% vs 41%) during the follow-up of up to 60 months (P > .05), but NAFLD had higher cumulative rates of CVS + BR, compared with non-NAFLD patients (32.5% vs 22.8%, P = .03). In multivariate analyses, NAFLD was not independently associated with CVS and/or BR outcomes. Receipt of entecavir or tenofovir (vs older therapies) and lower baseline HBV DNA or higher ALT were positively associated with achieving CVS or BR. CONCLUSION Concomitant NAFLD had no impact on the long-term rates of CVS and/or BR in treated CHB patients.
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Affiliation(s)
- Jie Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong, China.,Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA
| | - An K Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA
| | - Kevin T Chaung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA
| | - Joseph K Hoang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA.,Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA
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49
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Zhang J, Lin S, Jiang D, Li M, Chen Y, Li J, Fan J. Chronic hepatitis B and non-alcoholic fatty liver disease: Conspirators or competitors? Liver Int 2020; 40:496-508. [PMID: 31903714 DOI: 10.1111/liv.14369] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 12/16/2019] [Accepted: 01/02/2020] [Indexed: 02/06/2023]
Abstract
Despite the widespread use of vaccines and antiviral drugs, approximately 350-400 million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB is commonly observed, especially in Asian CHB populations; however, little is known regarding the relationship between these two diseases as comorbidities. In this review, we summarize recent advances in clinical and basic researches related to the underlying mutual interactions, as well as potential animal models to facilitate further investigation.
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Affiliation(s)
- Jianbin Zhang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shuangzhe Lin
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Daixi Jiang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Mengting Li
- Department of Gastroenterology, Yinzhou People's Hospital, Zhejiang, China
| | - Yuanwen Chen
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiangao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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50
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Choi HSJ, Brouwer WP, Zanjir WMR, de Man RA, Feld JJ, Hansen BE, Janssen HLA, Patel K. Nonalcoholic Steatohepatitis Is Associated With Liver-Related Outcomes and All-Cause Mortality in Chronic Hepatitis B. Hepatology 2020; 71:539-548. [PMID: 31309589 DOI: 10.1002/hep.30857] [Citation(s) in RCA: 150] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 07/27/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Chronic hepatitis B (CHB) and nonalcoholic fatty liver disease are increasingly observed together in clinical practice, and development of nonalcoholic steatohepatitis (NASH) represents another leading cause of liver-related morbidity and mortality. Our aims were to determine whether biopsy-proven NASH impacts clinical outcomes in CHB patients and assess prognostic risk factors. APPROACH AND RESULTS CHB patients attending two tertiary centers in North America and Europe over 13 years with available clinical and biopsy data were included. Patients were categorized as no-NASH or probable/definite NASH based on standardized histological assessment. Clinical events (death, decompensation, transplant, and hepatoma) were evaluated, and Kaplan-Meier survival estimates and Cox proportional hazards regression were used to analyze the incidence of events. There were 1,089 CHB patients, classified as no-NASH (n = 904, 83%) or NASH (n = 185, 17%), with 52 (6%) versus 27 (15%) experiencing outcome events during follow-up, respectively. In the multivariable analysis adjusting for age, sex, hepatitis B e antigen serostatus, and diabetes, the presence of NASH and concomitant advanced fibrosis (AF) was significantly associated with clinical outcomes (hazard ratio [95% confidence interval], 4.8 [2.6-9.0], P < 0.01) when compared to absence of NASH and AF (reference). NASH and AF were associated with a greater risk of outcomes compared to AF (P = 0.01) or NASH alone (P < 0.01). Of the three histological determinants of NASH, ballooning and inflammation, but not steatosis, were independently associated with clinical outcomes (P < 0.05) in place of NASH. NASH was significantly associated with increased risk of hepatocellular carcinoma and death (P < 0.01) but not decompensation (P = 0.33). CONCLUSIONS In our large combined tertiary center cohort, patients with concomitant NASH and CHB had more AF and shorter time to development of liver-related outcomes or death compared to patients with CHB alone. Among patients with AF, superimposed NASH predicted poorer clinical outcomes.
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Affiliation(s)
- Hannah S J Choi
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Willem P Brouwer
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Wayel M R Zanjir
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
| | - Robert A de Man
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
| | - Bettina E Hansen
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada.,Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.,Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
| | - Keyur Patel
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada
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