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Wang Z, Xu Q, Wang M, Xiao Q, Xu Y, Wang X, Shi Y, Yang R, Fan JG. Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients and Mice with Wilson Disease. THE AMERICAN JOURNAL OF PATHOLOGY 2025:S0002-9440(25)00191-9. [PMID: 40499780 DOI: 10.1016/j.ajpath.2025.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 04/29/2025] [Accepted: 05/23/2025] [Indexed: 06/22/2025]
Abstract
Wilson disease (WD) is a copper metabolism disorder caused by ATP7B gene mutations, and hepatic steatosis is not uncommon in WD. We therefore investigated the effects of ATP7B (ATPase copper-transporting beta) deficiency and/or a high-fat diet (HFD) on the development of steatohepatitis in mouse models and examined the relationship of hepatic steatosis with cardiometabolic factors in WD patients. A retrospective analysis of data was conducted on adults with WD. Atp7b gene knockout (KO) was achieved by CRISPR/Cas9 technology, followed by a comprehensive phenotypic analysis. An HFD was administered to induce steatohepatitis, allowing for analysis of lipid metabolism and hepatic injuries in KO mice subjected to overnutrition. Of 61 WD patients, 11.5% had evidence of hepatic steatosis, significantly linked to cardiometabolic factors. Although ATP7B KO mice under normal diets exhibited significant copper metabolism disorders without overt hepatic or neurologic injury, steatohepatitis was successfully induced in both wild-type and KO mice after 24 weeks of an HFD. Compared with a normal diet, an HFD resulted in markedly decreased hepatic copper levels with obvious liver injury in KO mice. Moreover, HFD-fed KO mice exhibited significantly higher severity of hepatic steatosis, inflammation, and fibrosis than wild-type control mice. Results suggest that hepatic steatosis in WD relates more to acquired metabolic dysfunction than excess copper accumulation, underscoring the influence of nutritional excess on WD phenotypes.
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Affiliation(s)
- Zixuan Wang
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingyang Xu
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengyu Wang
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianqian Xiao
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanhuang Xu
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoying Wang
- Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yiwen Shi
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruixu Yang
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
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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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3
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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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Wang SW, Chang YW, Wang C, Cheng YM, Hsieh TH, Wang CC, Kao JH. Clinical profiles and their interaction of concurrent metabolic associated steatotic liver disease and hepatitis B virus infection. World J Hepatol 2024; 16:1429-1440. [DOI: 10.4254/wjh.v16.i12.1429] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/23/2024] [Accepted: 07/30/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND A new nomenclature of metabolic associated steatotic liver disease (MASLD) was proposed in 2023, thus expanding the diagnostic name of “MASLD combined with other etiologies”.
AIM To investigate the clinical profiles of patients with concurrent MASLD and chronic hepatitis B virus (HBV) infection.
METHODS This study included participants from the Taiwan Bio-bank. The diagnostic criteria of MASLD encompassed hepatic steatosis and any cardio-metabolic risk factors. Positive hepatitis B surface antigen was considered indicative of chronic HBV infection. Dual etiology was defined as MASLD combined with chronic HBV infection (MASLD-HBV). Fibrosis 4 (FIB-4) score determined the severity of liver fibrosis, and atherosclerosis was diagnosed by the presence of carotid plaques on duplex ultrasound.
RESULTS In a total of 18980 participants (mean age, 55.18 ± 10.35 years; males, 30.42%), there were 7654 (40.3%) MASLD patients and 2128 (11.2%) HBV carriers. After propensity score matching for age and gender, HBV carriers had a lower percentage of MASLD than healthy controls. Those with dual etiology had higher aspartate aminotransferase, alanine aminotransferase (ALT), and FIB-4 levels, but lower gamma glutamyl transferase (GGT) levels than MASLD patients. In contrast, those with dual etiology had higher ALT and GGT levels, but lower FIB-4 than “HBV alone” patients. The risk of atherosclerosis was similar among these three groups.
CONCLUSION MASLD-HBV patients have worse liver fibrosis severity than MASLD patients, but better liver fibrosis stage than “HBV alone” patients, suggesting a complex interaction between MASLD and chronic HBV infection.
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Affiliation(s)
- Shao-Wen Wang
- Department of Education, Taipei Medical University-Shuang Ho Hospital, Taipei 235, Taiwan
| | - Yu-Wen Chang
- Department of Gastroenterology and Hepatology, Taipei Tzu Chi Hospital, Taipei 231, Taiwan
| | - Ching Wang
- Department of Education, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan
| | - Yu-Ming Cheng
- Department of Gastroenterology and Hepatology, Tung’s Taichung MetroHarbor Hospital, Taichung 43503, Taiwan
| | | | - Chia-Chi Wang
- Department of Hepatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan
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Huang SC, Su TH, Tseng TC, Hsu SJ, Hong CM, Lan TY, Liu CH, Yang HC, Liu CJ, Kao JH. All-cause and cause-specific mortality in patients with chronic hepatitis B and concurrent steatotic liver disease. J Hepatol 2024:S0168-8278(24)02763-6. [PMID: 39675434 DOI: 10.1016/j.jhep.2024.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 11/15/2024] [Accepted: 12/03/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND & AIMS Steatotic liver disease (SLD) is prevalent among patients with chronic hepatitis B (CHB). However, the effects of metabolic dysfunction-associated SLD (MASLD) on the long-term survival of such patients remain unknown. Accordingly, this study investigated the mortality risks in patients with CHB and concurrent SLD. METHODS Consecutive patients with CHB and concurrent SLD were retrospectively recruited at National Taiwan University Hospital. MASLD was defined by the presence of cardiometabolic risk factors. The cumulative incidences of all-cause and cause-specific mortality were compared. RESULTS A total of 8,718 patients with CHB and concurrent SLD were included from 2006 to 2021. At baseline, the MASLD group (n = 6,562) was older and had a lower proportion of HBeAg positivity and lower HBV DNA levels compared with the non-MASLD group (n = 2,156). After a median follow-up period of 9.1 years, the MASLD group exhibited a higher risk of all-cause mortality compared with the non-MASLD group (adjusted hazard ratio 1.79, 95% CI 1.24-2.58, p = 0.002). Furthermore, cumulative cardiometabolic risk factors dose-dependently elevated the risks of all-cause, liver-related, and cardiovascular mortality (all p <0.05). During the follow-up period, new-onset diabetes mellitus, hypertension, and significant weight gain further increased the risks of all-cause and liver-related mortality (all p <0.05). However, patients with SLD had a lower mortality risk than those without SLD after propensity score matching (hazard ratio 0.62, 95% CI 0.53-0.74, p <0.001). CONCLUSIONS Among patients with CHB and SLD, metabolic burden dose-dependently increases all-cause, liver-related, and cardiovascular mortality risks. Patients with SLD have a lower mortality risk than those without SLD. Identifying these metabolic dysfunctions is crucial for stratifying the level of risk in daily care. IMPACT AND IMPLICATIONS Concurrent steatotic liver disease (SLD) is prevalent among patients with chronic hepatitis B (CHB); however, the effects of the associated cardiometabolic risk factors on all-cause and cause-specific mortality remain unknown. This study demonstrated that cumulative metabolic burden dose-dependently increased the risks of all-cause, liver-related, and cardiovascular mortality in patients with CHB and SLD. Moreover, new-onset diabetes mellitus, hypertension, and weight gain during the follow-up period further exacerbated these risks. However, patients with SLD had a lower risk of mortality than those without SLD. Thus, routine screening and monitoring of metabolic dysfunctions constitute a key element of daily care for patients with CHB.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yuan Lan
- Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Bae J, Han E, Lee HW, Park CY, Chung CH, Lee DH, Cho EH, Rhee EJ, Yu JH, Park JH, Bae JC, Park JH, Choi KM, Kim KS, Seo MH, Lee M, Kim NH, Kim SH, Lee WY, Lee WJ, Choi YK, Lee YH, Hwang YC, Lyu YS, Lee BW, Cha BS, on Behalf of the Fatty Liver Research Group of the Korean Diabetes Association. Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association. Diabetes Metab J 2024; 48:1015-1028. [PMID: 39610131 PMCID: PMC11621661 DOI: 10.4093/dmj.2024.0541] [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: 09/06/2024] [Accepted: 10/23/2024] [Indexed: 11/30/2024] Open
Abstract
Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist's perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.
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Affiliation(s)
- Jaehyun Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
| | - Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hye Won Lee
- Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
| | - Cheol-Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hee Chung
- Department of Internal Medicine and Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dae Ho Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Eun-Hee Cho
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Eun-Jung Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Ji-Cheol Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Jung Hwan Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kyung-Soo Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Mi Hae Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea
| | - Minyoung Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Nan-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - So Hun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Won-Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yeon-Kyung Choi
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yong-ho Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - You-Cheol Hwang
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Young Sang Lyu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - on Behalf of the Fatty Liver Research Group of the Korean Diabetes Association
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Internal Medicine and Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
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Choudhury A, Rajaram R, Sarin SK. Acute-on-chronic liver failure in metabolic dysfunction-associated fatty liver disease patients: a disease multiplier. Hepatol Int 2024; 18:941-958. [PMID: 39107615 DOI: 10.1007/s12072-024-10711-4] [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: 02/22/2024] [Accepted: 06/30/2024] [Indexed: 10/05/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome of liver failure due to an acute hepatic insult leading to liver failure with or without extra-hepatic organ failure in a patient of chronic liver disease (CLD) with or without cirrhosis presenting for the first time. The definition is still with controversy; hence, homogeneity and clarity of the case is an unmet need. There is a paradigm shift noted as far as the etiology of CLD is concerned with rise in metabolic dysfunction-associated fatty liver disease (MAFLD) and ethanol as the dominant cause even in developing countries. MAFLD is the change in nomenclature from NAFLD to justify the metabolic derangement in these group of patients. The shift from an exclusion-based criteria to one that has evolved to a diagnosis that requires positive criteria has profound significance. Clearly there is a difference in terms of its prevalence, disease progression, and liver-related events, as well as management of metabolic risk factors and MAFLD itself which requires further understanding. In tandem with the global rise in MAFLD, the incidence of MAFLD-ACLF is increasing. Excessive alcohol consumption causes metabolic and toxic injury to the liver resulting in nearly similar pathway of fatty liver, hepatitis, and cirrhosis. The interaction of MAFLD as an additional underlying chronic liver injury in ACLF patients is complex due to the presence of metabolic risk factors that are unique to MAFLD. There is lack of clarity on how MAFLD affects the clinical course of ACLF due to scarcity of this specific data. This narrative review aims to understand the unique effects, consequences, and management of MAFLD as the chronic liver injury component in ACLF.
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Affiliation(s)
- Ashok Choudhury
- Dept of Hepatology and Liver Transplantation. Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ruveena Rajaram
- Consultant, Gastroenterology and Hepatology Unit, Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Shiv Kumar Sarin
- Department of Hepatology and Liver TransplantChancellor, Chancellor . Institute of Liver and Biliary Sciences, Senior Proffesor, New Delhi, 110070, India.
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Liu CJ, Seto WK, Yu ML. Dual-etiology MAFLD: the interactions between viral hepatitis B, viral hepatitis C, alcohol, and MAFLD. Hepatol Int 2024; 18:897-908. [PMID: 39115632 DOI: 10.1007/s12072-024-10699-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 05/03/2024] [Indexed: 10/05/2024]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) and viral hepatitis due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are common liver diseases worldwide. Excessive alcohol consumption and alcoholic liver disease (ALD) are also emerging health problems. Therefore, in clinical practice, we may encounter subjects with dual etiology of liver diseases such as coexisting MAFLD/HBV, MAFLD/HCV, and MAFLD/ALD. In this review, we summarize the epidemiology, clinical features, and mutual interactions of MAFLD with coexisting HBV, HCV, or ALD. The impact of MAFLD on the progression of liver diseases and treatment outcomes in patients with chronic viral hepatitis and the clinical questions to be addressed regarding dual MAFLD and ALD are also discussed.
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Affiliation(s)
- Chun-Jen Liu
- Hepatitis Research Center, National Taiwan University College of Medicine and, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Wai Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Pok Fu Lam, China.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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Pagheh AS, Alemzadeh E, Nazar E, Moodi M, Sharifi F, Miri-Moghaddam E, Rahimi MT, Mohammadi S, Ziaee M. Monitoring of hepatitis B infection in the elderly population of eastern Iran. VACUNAS 2024. [DOI: 10.1016/j.vacun.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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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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11
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Zhang L, Wu HD, Qian YF, Xu HY. Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B: A meta-analysis. World J Clin Cases 2024; 12:5749-5760. [PMID: 39247728 PMCID: PMC11263053 DOI: 10.12998/wjcc.v12.i25.5749] [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: 05/21/2024] [Revised: 06/27/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has increased in recent clinical practice; however, the relationship between CHB and hepatic steatosis (HS) remains controversial. AIM To shed light on the potential association between NAFLD and hepatitis B virus (HBV) infection. METHODS We conducted a systematic literature search using multiple databases, including PubMed, the Cochrane Library, Web of Science, and EMBASE, to identify relevant studies. Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis. RESULTS Comprehensive meta-analysis software was used for statistical analysis, which covered 20 studies. The results indicated a lower NAFLD susceptibility in HBV-infected individuals (pooled OR = 0.87; 95%CI = 0.69-1.08; I 2 = 91.1%), with diabetes (P = 0.015), body mass index (BMI; P = 0.010), and possibly age (P = 0.061) as heterogeneity sources. Of note, in four studies (6197 HBV patients), HBV-infected individuals had a reduced NAFLD risk (OR = 0.68, 95%CI = 0.51-0.89, P = 0.006). A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients, along with specific biochemical indicators, including BMI, creatinine, uric acid, fasting blood glucose, and homeostasis model assessment of insulin resistance. CONCLUSION HBV infection may provide protection against HS; however, the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.
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Affiliation(s)
- Li Zhang
- Department of Infectious Diseases, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
| | - Hong-Di Wu
- Department of Infectious Diseases, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
| | - Yuan-Fang Qian
- Department of Nursing, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
| | - Hong-Yan Xu
- Department of Nursing, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
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Wutsdorff L, Mougnekabol J, Tang P, Reutzel-Selke A, Sauer IM, Haep N. Unveiling the Multifaceted Role of CIDEB: From Apoptosis to Lipid Metabolism and Liver Health. LIVERS 2024; 4:406-419. [DOI: 10.3390/livers4030030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Cell-death-inducing DNA fragmentation factor-alpha (DFFA)-like effector b (CIDEB) was first identified as an apoptosis-inducing protein. Further research revealed a pivotal role in lipid metabolism, regulating very-low-density lipoprotein (VLDL), lipid droplets (LD), sterol response element-binding protein (SREBP), and chylomicrons. Recent studies have uncovered that rare germline variants in CIDEB protect against liver diseases, including MAFLD, cirrhosis, and viral hepatitis. Furthermore, CIDEB influences steps of the hepatitis C virus (HCV) replication cycle. This review summarizes the current knowledge about CIDEB’s roles in apoptosis, lipid metabolism, and viral hepatitis, and highlights its critical role in liver diseases.
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Affiliation(s)
- Louise Wutsdorff
- Department of Surgery, CCM|CVK, Experimental Surgery, Charité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany
| | - Julienne Mougnekabol
- Department of Surgery, CCM|CVK, Experimental Surgery, Charité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany
| | - Peter Tang
- Department of Surgery, CCM|CVK, Experimental Surgery, Charité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany
| | - Anja Reutzel-Selke
- Department of Surgery, CCM|CVK, Experimental Surgery, Charité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany
| | - Igor M. Sauer
- Department of Surgery, CCM|CVK, Experimental Surgery, Charité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany
| | - Nils Haep
- Department of Surgery, CCM|CVK, Experimental Surgery, Charité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany
- Clinician Scientist Program, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, BIH Academy, 10178 Berlin, Germany
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Maung ST, Decharatanachart P, Treeprasertsuk S, Chaiteerakij R. Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy. J Clin Exp Hepatol 2024; 14:101388. [PMID: 38523735 PMCID: PMC10956063 DOI: 10.1016/j.jceh.2024.101388] [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: 09/13/2023] [Accepted: 02/24/2024] [Indexed: 03/26/2024] Open
Abstract
BACKGROUND AND AIMS Chronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in hepatitis B virus (HBV)-suppressed patients. METHODS We conducted a case-control study involving 120 noncirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and Fibrosis-4 (FIB-4)-matched controls. Clinical and laboratory data at viral suppression, including body mass index (BMI), comorbidities, pretreatment HBV viral load, HBe antigen status, hepatitis C virus (HCV) and HIV coinfections, liver chemistries, and AST to Platelets Ratio Index (APRI) values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. RESULTS Case and control groups had similar ages (51.4 ± 9.9 vs. 51.4 ± 10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, P = 0.01) and more diabetes prevalence (50.0% vs. 26.3%, P = 0.01), while other comorbidities and laboratory parameters were comparable (P > 0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46-6.13), 2.31 (1.23-4.36), and 2.71 (1.05-6.99), P = 0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, P = 0.006), while diabetes showed borderline significance (aHR: 1.99, P = 0.072). CONCLUSIONS In HBV-infected patients achieving viral suppression with therapy, a BMI >23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.
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Affiliation(s)
- Soe T. Maung
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | | | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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14
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Yu Y, Tong K, Hu G, Yang X, Wu J, Bai S, Yu R. Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study. Front Microbiol 2024; 15:1378311. [PMID: 38646627 PMCID: PMC11026703 DOI: 10.3389/fmicb.2024.1378311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/15/2024] [Indexed: 04/23/2024] Open
Abstract
Objective The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR). Methods Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran's Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis. Results MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962-0.989; p < 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007-1.036; p = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002-1.028; p = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust. Conclusion CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.
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Affiliation(s)
- Yunfeng Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Keke Tong
- The Hospital of Hunan University of Traditional Chinese Medicine, Changde, China
| | - Gang Hu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xinyu Yang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Jingyi Wu
- The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Siyang Bai
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Rong Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
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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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Yi S, Ren G, Zhu Y, Cong Q. Correlation analysis of hepatic steatosis and hepatitis B virus: a cross-sectional study. Virol J 2024; 21:22. [PMID: 38243304 PMCID: PMC10799397 DOI: 10.1186/s12985-023-02277-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 12/24/2023] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND The co-occurrence of chronic hepatitis B (CHB) and metabolic dysfunction-associated fatty liver disease (MAFLD) has drawn considerable attention due to its impact on disease outcomes. This study aimed to investigate the association between hepatic steatosis and hepatitis B virus (HBV) and analyzed the influence of hepatic steatosis on hepatitis B virology in patients with CHB. METHODS In this cross-sectional study, 272 patients infected with HBV who were treatment-naïve or had ceased antiviral treatment for > 6 months were categorized into the CHB group (n = 128) and CHB + MAFLD group (n = 144). Furthermore, based on whether HBV DNA was higher than 2000 IU/mL, patients were categorized into the high-level HBV DNA group (n = 129) and the low-level HBV DNA group (n = 143). The impact of hepatic steatosis on hepatitis B virology was analyzed within the CHB cohort. Multivariate logistic regression analysis was employed to identify independent factors influencing pre-genomic RNA (pgRNA) levels below the lower limit of detection (LLD) in patients with CHB. RESULTS Among the 272 patients, compared with CHB group, HBV DNA levels (4.11 vs. 3.62 log10 IU/mL, P = 0.045), hepatitis B surface antigen (HBsAg) levels (3.52 vs. 3.20 log10 IU/mL, P = 0.008) and the hepatitis B e antigen (HBeAg) positive rate (33.6% vs. 22.2%, P = 0.036) were significantly decreased in the CHB + MAFLD group; In 143 low-level HBV DNA patients, the CHB + MAFLD group exhibited decreased levels of pgRNA and HBsAg compared to the CHB group. However, in 129 high-level HBV DNA patients, a more significant decrease was observed in pgRNA (3.85 vs 3.35 log10 copies/mL, P = 0.044) and HBsAg (3.85 vs 3.59 log10 IU/mL, P = 0.033); Spearman correlation analysis revealed a negative correlation between hepatic steatosis and pgRNA (r = - 0.529, P < 0.001), HBV DNA (r = - 0.456, P < 0.001), HBsAg (r = - 0.465, P < 0.001) and HBeAg (r = - 0.339, P < 0.001) levels; Multivariate logistic regression analysis identified HBV DNA (odds ratio [OR] = 0.283, P < 0.001), HBsAg (OR = 0.300, P < 0.001), and controlled attenuation parameter (CAP) values (OR = 1.013, P = 0.038) as independent factors influencing pgRNA levels below the LLD in patients with CHB. CONCLUSIONS This study establishes a negative correlation between hepatic steatosis and hepatitis B virology, demonstrating decreased HBV expression in patients with CHB + MAFLD.
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Affiliation(s)
- Sitong Yi
- Department of Infectious Disease and Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Guanghui Ren
- Department of Infectious Disease and Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Ying Zhu
- Department of Infectious Disease and Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
| | - Qingwei Cong
- Department of Infectious Disease and Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
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Cheng PN, Liu CJ. Editorial: Tenofovir disoproxil fumarate more than an antiviral drug-Another piece of the puzzle. Authors' reply. Aliment Pharmacol Ther 2024; 59:289-290. [PMID: 38153280 DOI: 10.1111/apt.17807] [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] [Indexed: 12/29/2023]
Abstract
LINKED CONTENTThis article is linked to Cheng et al papers. To view these articles, visit https://doi.org/10.1111/apt.17765 and https://doi.org/10.1111/apt.17793
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Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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18
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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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19
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Cheng PN, Feng IC, Chen JJ, Kuo HT, Lee PL, Yu ML, Chiu YC, Chiu HC, Chien SC, Chen PJ, Liu CJ. Body weight increase and metabolic derangements after tenofovir disoproxil fumarate switch to tenofovir alafenamide in patients with chronic hepatitis B. Aliment Pharmacol Ther 2024; 59:230-238. [PMID: 37845815 DOI: 10.1111/apt.17765] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/30/2023] [Accepted: 10/04/2023] [Indexed: 10/18/2023]
Abstract
BACKGROUND Lipid-lowering effect was observed during treatment with tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB). However, the metabolic features in patients switching from TDF to tenofovir alafenamide (TAF) remain unclear. AIMS To compare the impacts of switching from TDF to TAF or from entecavir to TAF on body weight and metabolic features in patients with CHB. METHODS This was a multi-centre, prospective, observational study in patients with CHB on TDF or entecavir who switched to TAF. Baseline characteristics, lipid profile and sugar profile were determined. This study received IRB approval from each hospital. RESULTS We enrolled 177 patients on TDF (99) or entecavir (78) and followed them for 48 weeks after the switch to TAF. At baseline, TDF-experienced patients had lower serum triglyceride, total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol than entecavir-experienced patients. The switch from TDF to TAF significantly increased body weight, triglyceride, total cholesterol, HDL, LDL, fasting glucose, glycaemic haemoglobin, insulin and insulin resistance. The switch from entecavir to TAF did not affect these measures. There was no significant difference in atherosclerotic cardiovascular disease risk scores between groups. CONCLUSIONS The switch from TDF to TAF was associated with weight gain, derangements of lipid profile, and increased insulin resistance in patients with CHB. Long-term effects on these metabolic features need further investigation.
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Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Cher Feng
- Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Hsing-Tao Kuo
- Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Center for Liquid Biopsy and Cohort Research, College of Medicine, Kaohsiung, Taiwan
- Center of Excellence for Metabolic Associated Fatty Liver, School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Yen-Cheng Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chieh Chien
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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20
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Wang C, Gao XY, Han M, Jiang MC, Shi XY, Pu CW, Du X. Perilipin2 inhibits the replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions. World J Virol 2023; 12:296-308. [PMID: 38187502 PMCID: PMC10768386 DOI: 10.5501/wjv.v12.i5.296] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 10/19/2023] [Accepted: 11/30/2023] [Indexed: 12/25/2023] Open
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection is often associated with increased lipid deposition in hepatocytes. However, when combined with non-alcoholic fatty liver disease or hyperlipidemia, it tends to have a lower HBV deoxyribonucleic acid (DNA) load. The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood. AIM To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms. METHODS 1603 HBsAg-seropositive patients were included in the study. We first explored the relationship between patients' lipid levels, hepatic steatosis, and HBV DNA load. Also, we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro. By knocking down and overexpressing Plin2, we observed whether Plin2 regulates autophagy and HBV replication. By inhibiting both Plin2 and cellular autophagy under high lipid stimulation, we examined whether the Plin2-autophagy pathway regulates HBV replication. RESULTS The results revealed that serum triglyceride levels, high-density lipoprotein levels, and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group. Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load. Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAg-positive and HBeAg-negative groups. An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism. The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg, HBeAg, and HBV DNA load. Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins. Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy. Knocking down Plin2 and blocking autophagy with 3-methyladenine (3-MA) inhibited HBV DNA replication. CONCLUSION In conclusion, lipid metabolism is a significant factor affecting HBV load in patients with HBV infection. The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.
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Affiliation(s)
- Chuang Wang
- Graduate School, Graduate School of Dalian Medical University, Dalian 116000, Liaoning Province, China
| | - Xiao-Yun Gao
- Department of Geriatric, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
| | - Mei Han
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
| | - Meng-Chun Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
| | - Xiao-Yi Shi
- Graduate School, Graduate School of Dalian Medical University, Dalian 116000, Liaoning Province, China
| | - Chun-Wen Pu
- Dalian Public Health Clinical Center, Dalian Municipal Research Institute for Public Health, Dalian 116001, Liaoning Province, China
| | - Xuan Du
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
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21
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Du X, Shi X, Han M, Gao X, Wang C, Jiang C, Pu C. SCD1 inhibits HBV replication by regulating autophagy under high lipid conditions. Virus Genes 2023; 59:801-816. [PMID: 37644346 DOI: 10.1007/s11262-023-02028-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 08/20/2023] [Indexed: 08/31/2023]
Abstract
Chronic hepatitis B virus (HBV) infection remains a significant public health concern worldwide. Several metabolic processes regulate HBV DNA replication, including autophagy and lipid metabolism. In this study, we clarified the effect of lipids on HBV replication and elucidated possible mechanisms. We discovered that lipid metabolic gene expression levels were negatively correlated with the HBV DNA in plasma. Our data showed that fatty acid stimulation significantly reduced HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) levels in HepG2.2.15 cells, which are human hepatoma cell cultures transfected with HBV DNA. The Stearoyl coenzyme A desaturase 1 (SCD1)-autophagy pathway has also been implicated in inhibiting HBV replication by fatty acids stimulation. SCD1 knockdown deregulates the inhibitory effect of fatty acids on HBV by enhancing autophagy. When 3 methyladenine (3MA) was added, the inhibitory effects of specific autophagy inhibitors eliminated the positive effects of SCD1 knockdown on HBV replication. Our results indicate that SCD1 participates in the regulation of inhibition of HBV replication by fatty acids stimulation through regulating autophagy.
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Affiliation(s)
- Xuan Du
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China
| | - Xiaoyi Shi
- Graduate School of Dalian Medical University, Dalian, 116000, China
| | - Mei Han
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China
| | - Xiaoyun Gao
- Department of Geriatric, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, China
| | - Chuang Wang
- Graduate School of Dalian Medical University, Dalian, 116000, China
| | - Chunmeng Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
| | - Chunwen Pu
- Department of Biobank, The Affiliated Sixth People's Hospital of Dalian Medical University, Dalian, 116000, China.
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22
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Keeshan A, da Silva CF, Vachon A, Giles E, Osiowy C, Coffin C, Cooper CL. Hepatitis B Virus Genotype Influence on Virological and Enzymatic Measures over Time-A Retrospective Longitudinal Cohort Study. J Clin Med 2023; 12:6807. [PMID: 37959272 PMCID: PMC10649073 DOI: 10.3390/jcm12216807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/12/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
HBV is a hepatotropic virus with multiple genotypes. It is uncertain if specific genotype(s) influence virological measures and/or liver markers over time. It is unclear whether nucleos(t)ide analogue therapy response is influenced by genotype. In this retrospective longitudinal study, we utilized data from The Ottawa Hospital Viral Hepatitis Program (TOHVHP) to evaluate the role of HBV genotype on viral load, liver enzymatic levels, fibrosis progression, and parenchymal inflammation and steatosis over time. HBV DNA, ALT, and AST levels, as well as transient elastography scores for fibrosis (E) and inflammation/steatosis (CAP), were modeled using mixed-effects linear regression. Interaction terms between HBV genotype and time were included to investigate if there was a difference in trends between genotypes. A total of 393 HBV patients infected with genotypes A-E were included. The mean age was 44.4 years, and 56% were male. Asian (50.5%), Black (29.1%), and White (6.4%) patients were well-represented. By multivariate analysis, we found no evidence that the trajectories of these commonly measured viral or liver measures varied over time by HBV genotype in those receiving HBV nucleos(t)ides and in those not on antiviral therapy.
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Affiliation(s)
- Alexa Keeshan
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1N 6N5, Canada
| | | | - Alicia Vachon
- Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada
- Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada
| | - Elizabeth Giles
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R2C 3A9, Canada
| | - Carla Osiowy
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R2C 3A9, Canada
| | - Carla Coffin
- Department of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Curtis L. Cooper
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1N 6N5, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada
- Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada
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23
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Cheng YM, Hsieh TH, Wang CC, Kao JH. Impact of HBV infection on clinical outcomes in patients with metabolic dysfunction-associated fatty liver disease. JHEP Rep 2023; 5:100836. [PMID: 37600956 PMCID: PMC10432217 DOI: 10.1016/j.jhepr.2023.100836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 05/28/2023] [Accepted: 06/05/2023] [Indexed: 08/22/2023] Open
Abstract
Background & Aims The new name and diagnostic criteria of metabolic-associated fatty liver disease (MAFLD) was proposed in 2020. Although chronic HBV infection has protective effects on lipid profiles and hepatic steatosis, the impact of chronic HBV infection on clinical outcomes of MAFLD requires further investigation. Methods The participants from a Taiwan bio-bank cohort were included. MAFLD is defined as the presence of hepatic steatosis plus any of the following three conditions: overweight/obesity, type 2 diabetes mellitus, and metabolic dysfunction. The patients with positive glycated haemoglobin were considered as having chronic HBV infection. Atherosclerosis was determined as having carotid plaques on duplex ultrasound. Advanced liver fibrosis was defined as Fibrosis-4 >2.67. Based on the status of MAFLD and HBV infection, the participants were distributed into four groups: 'dual aetiology', 'MAFLD alone', 'HBV alone', and 'healthy controls'. Results A total of 20,460 participants (age 55.51 ± 10.37; males 32.67%) were included for final analysis. The prevalence of MAFLD and chronic HBV infections were 38.8% and 10.3%, respectively. According to univariate analysis, 'HBV alone' group had lower levels of glycated haemoglobin, lipid profiles, and intima media thickness than healthy controls. The 'dual aetiology' group had lower levels of triglycerides, cholesterol, γ-glutamyl transferase, intima media thickness, and percentage of carotid plaques than 'MAFLD alone' group. Using binary logistic regression, chronic HBV infection increased the overall risk of advanced liver fibrosis; and had a lower probability of carotid plaques in MAFLD patients, but not in those without MAFLD. Conclusions The large population-based study revealed chronic HBV infection increases the overall risk of liver fibrosis, but protects from atherosclerosis in patients with MAFLD. Impact and implications Patients with metabolic-associated fatty liver disease can also be coinfected with chronic HBV. Concomitant HBV infection increases the overall risk of liver fibrosis, but protects from atherosclerosis in patients with MAFLD.
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Affiliation(s)
- Yu-Ming Cheng
- Tung’s Taichung MetroHarbor Hospital, Taichung, Taiwan
| | - Tsung-Han Hsieh
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan
| | - Chia-Chi Wang
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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24
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Hsu YC, Huang DQ, Nguyen MH. Global burden of hepatitis B virus: current status, missed opportunities and a call for action. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00760-9. [PMID: 37024566 DOI: 10.1038/s41575-023-00760-9] [Citation(s) in RCA: 226] [Impact Index Per Article: 113.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/24/2023] [Indexed: 04/08/2023]
Abstract
Chronic hepatitis B virus (HBV) infection affects about 296 million people worldwide and is the leading aetiology of cirrhosis and liver cancer globally. Major medical complications also include acute flares and extrahepatic manifestations. In addition, people living with HBV infection also experience stigma. HBV-related cirrhosis resulted in an estimated 331,000 deaths in 2019, and it is estimated that the number of deaths from HBV-related liver cancer in 2019 was 192,000, an increase from 156,000 in 2010. Meanwhile, HBV remains severely underdiagnosed and effective measures that can prevent infection and disease progression are underutilized. Birth dose coverage for HBV vaccines remains low, particularly in low-income countries or regions where HBV burden is high. Patients with HBV infection are inadequately evaluated and linked to care and are undertreated worldwide, even in high-income countries or regions. Despite the goal of the World Health Organization to eliminate viral hepatitis as a public health problem by 2030, the annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains. In this Review, we discuss the current status and future projections of the global burden of HBV infection. We also discuss gaps in the current care cascade and propose future directions.
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Affiliation(s)
- Yao-Chun Hsu
- Center for Liver Diseases, E-Da Hospital, Kaohsiung, Taiwan.
- School of Medicine, I-Shou University, Kaohsiung, Taiwan.
- Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, New Taipei, Taiwan.
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
- Department of Medicine, National University of Singapore, Singapore, Singapore
| | - Mindie H Nguyen
- Department of Medicine, Stanford University Medical Centre, Palo Alto, CA, USA.
- Department of Epidemiology and Population Health, Stanford University Medical Centre, Palo Alto, CA, USA.
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25
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Yip TCF, Vilar-Gomez E, Petta S, Yilmaz Y, Wong GLH, Adams LA, de Lédinghen V, Sookoian S, Wong VWS. Geographical similarity and differences in the burden and genetic predisposition of NAFLD. Hepatology 2023; 77:1404-1427. [PMID: 36062393 DOI: 10.1002/hep.32774] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/28/2022] [Accepted: 09/01/2022] [Indexed: 12/13/2022]
Abstract
NAFLD has become a major public health problem for more than 2 decades with a growing prevalence in parallel with the epidemic of obesity and type 2 diabetes (T2D). The disease burden of NAFLD differs across geographical regions and ethnicities. Variations in prevalence of metabolic diseases, extent of urban-rural divide, dietary habits, lifestyles, and the prevalence of NAFLD risk and protective alleles can contribute to such differences. The rise in NAFLD has led to a remarkable increase in the number of cases of cirrhosis, hepatocellular carcinoma, hepatic decompensation, and liver-related mortality related to NAFLD. Moreover, NAFLD is associated with multiple extrahepatic manifestations. Most of them are risk factors for the progression of liver fibrosis and thus worsen the prognosis of NAFLD. All these comorbidities and complications affect the quality of life in subjects with NAFLD. Given the huge and growing size of the population with NAFLD, it is expected that patients, healthcare systems, and the economy will suffer from the ongoing burden related to NAFLD. In this review, we examine the disease burden of NAFLD across geographical areas and ethnicities, together with the distribution of some well-known genetic variants for NAFLD. We also describe some special populations including patients with T2D, lean patients, the pediatric population, and patients with concomitant liver diseases. We discuss extrahepatic outcomes, patient-reported outcomes, and economic burden related to NAFLD.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Medical Data Analytics Center, Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong
- State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Department of Medicine , Indiana University School of Medicine , Indianapolis , Indiana , USA
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE) , University of Palermo , Palermo , Italy
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine , Recep Tayyip Erdogan University , Rize , Turkey
- Liver Research Unit , Institute of Gastroenterology , Marmara University , Istanbul , Turkey
| | - Grace Lai-Hung Wong
- Medical Data Analytics Center, Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong
- State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong
| | - Leon A Adams
- Department of Hepatology , Sir Charles Gairdner Hospital , Perth , Australia
- Medical School , University of Western Australia , Perth , Australia
| | - Victor de Lédinghen
- Hepatology Unit , Hôpital Haut Lévêque, Bordeaux University Hospital , Bordeaux , France
- INSERM U1312 , Bordeaux University , Bordeaux , France
| | - Silvia Sookoian
- School of Medicine, Institute of Medical Research A Lanari , University of Buenos Aires , Ciudad Autónoma de Buenos Aires , Argentina
- Department of Clinical and Molecular Hepatology, Institute of Medical Research (IDIM) , National Scientific and Technical Research Council (CONICET), University of Buenos Aires , Ciudad Autónoma de Buenos Aires , Argentina
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Center, Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong
- State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong
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26
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Leow YW, Chan WK, Goh GBB, Wong VWS, Fan JG, Kim YS, Kim SU, Nakajima A, Seto WK, Lee IC, Huang YH, Kim YJ, Young JJ, Chow WC. Hepatic steatosis and metabolic risk factors among patients with chronic hepatitis B: The multicentre, prospective CAP-Asia study. J Viral Hepat 2023; 30:319-326. [PMID: 36606597 DOI: 10.1111/jvh.13796] [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: 08/17/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023]
Abstract
We aimed to compare the severity of liver disease, metabolic profile and cardiovascular disease (CVD) risk of chronic hepatitis B (CHB) patients with and without hepatic steatosis and patients with non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD and CHB were prospectively enrolled from 10 Asian centres. Fibroscan was performed for all patients and hepatic steatosis was defined based on controlled attenuation parameter >248 dB/m. CVD risk was assessed using the Framingham risk score. The data for 1080 patients were analysed (67% NAFLD, 33% CHB). A high proportion (59%) of CHB patients had hepatic steatosis. There was a significant stepwise increase in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, controlled attenuation parameter and liver stiffness measurement, from CHB patients without hepatic steatosis to CHB patients with hepatic steatosis to NAFLD patients (p < 0.001 for all comparisons). There was a significant stepwise increase in the proportion of patients with metabolic syndrome and in CVD risk, with very high or extreme CVD risk seen in 20%, 48% and 61%, across the groups (p < 0.001 between CHB patients with and without hepatic steatosis and p < 0.05 between CHB patients with hepatic steatosis and NAFLD patients). In conclusion, there was a high proportion of CHB patients with hepatic steatosis, which should be diagnosed, as they may have more severe liver disease, so that this and their metabolic risk factors can be assessed and managed accordingly for a better long-term outcome.
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Affiliation(s)
- Yong-Wen Leow
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Jian Gao Fan
- Department of Gastroenterology and Hepatology, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China
| | - Young Seok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, SoonChunHyang University, Bucheon Hospital, Bucheon-si, Korea
| | - Seung Up Kim
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Seoul, Korea
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yoon Jun Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | | | - Wan Cheng Chow
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
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27
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Wang J, Huang R, Liu J, Lai R, Liu Y, Zhu C, Qiu Y, He Z, Yin S, Chen Y, Yan X, Ding W, Zheng Q, Li J, Wu C. A novel non-invasive model for the prediction of advanced liver fibrosis in chronic hepatitis B patients with NAFLD. J Viral Hepat 2023; 30:287-296. [PMID: 36696366 DOI: 10.1111/jvh.13808] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/26/2023]
Abstract
There are still lack of non-invasive models to evaluate liver fibrosis in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). We aimed to establish a predictive model for advanced fibrosis in these patients. A total of 504 treatment-naive CHB patients with NAFLD who underwent liver biopsy were enrolled and randomly divided into a training set (n = 336) and a validation set (n = 168). Receiver operating characteristic (ROC) curve was used to compare predicting accuracy for the different models. One hundred fifty-six patients (31.0%) had advanced fibrosis. In the training set, platelet, prothrombin time, type 2 diabetes, HBeAg positivity and globulin were significantly associated with advanced fibrosis by multivariable analysis. A predictive model namely PPDHG for advanced fibrosis was developed based on these parameters. The areas under the ROC curve (AUROC) of PPDHG with an optimal cut-off value of -0.980 in predicting advanced fibrosis was 0.817 (95% confidence interval 0.772 to 0.862), with a sensitivity of 81.82% and a specificity of 66.81%. The predicting accuracy of PPDHG for advanced fibrosis was significantly superior to AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS). Further analysis revealed that the AUROC of PPDHG remained significantly higher than FIB-4 and NFS indexes, while it was comparable with APRI for predicting advanced fibrosis in the validation set. PPDHG had a better predicting performance than established models for advanced fibrosis in CHB patients with NAFLD. The application of PPDHG can reduce the necessary for liver biopsy in these patients.
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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
| | - 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
| | - 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
| | - Ruimin Lai
- Department of Hepatology, Hepatology Research institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 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
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, China
| | - Zebao He
- Department of Infectious Diseases, Taizhou Enze Medical Center (Group) Enze Hospital, Taizhou, 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
| | - 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
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Weimao Ding
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, China
| | - Qi Zheng
- Department of Hepatology, Hepatology Research institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 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
| | - 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
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28
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Liu CH, Jiang W, Wu DB, Zeng QM, Wang YJ, Tang H. Concomitant Diseases and Co-contribution on Progression of Liver Stiffness in Patients with Hepatitis B Virus Infection. Dig Dis Sci 2023; 68:1605-1614. [PMID: 36227429 DOI: 10.1007/s10620-022-07695-2] [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: 02/13/2022] [Accepted: 09/05/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. AIM The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. METHODS A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. RESULTS The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65-0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67-0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02-1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01-1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69-2.83, p < 0.001 vs OR 1.59, 95% CI 1.51-1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98-3.65, p < 0.001 vs OR 1.89, 95% CI 1.76-2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35-7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41-13.20, p = 0.010). CONCLUSION Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients.
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Affiliation(s)
- Chang-Hai Liu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China
| | - Wei Jiang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China
| | - Dong-Bo Wu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China
| | - Qing-Min Zeng
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China
| | - You-Juan Wang
- Health Management Center, West China Hospital of Sichuan University, Chengdu, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
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29
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Lu MC, Wu YH, Chung CH, Lin HH, Hsieh TY, Chen PJ, Chien WC, Chen HW. Association of Hepatitis B and C Virus with the Risk of Coronary Artery Disease and Cerebrovascular Disease in Patients with Hepatocellular Carcinoma. J Clin Med 2023; 12:jcm12072602. [PMID: 37048685 PMCID: PMC10095061 DOI: 10.3390/jcm12072602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/14/2023] [Accepted: 03/28/2023] [Indexed: 03/31/2023] Open
Abstract
Background: Hepatocellular carcinoma accounts for approximately 90% of primary liver cancers and hepatitis virus was believed to have the potential for altering the pathogenesis of arteriosclerosis. However, the influence of the hepatitis virus on coronary artery disease or cerebral vascular disease remains unclear. This study used the Taiwan National Health Insurance Research Database to clarify the virus-associated risk of coronary artery disease and cerebral vascular disease in patients with hepatocellular carcinoma (HCC). Methods: A total of 188,039 HCC individuals, age 20 years or older, were enrolled from the Longitudinal Health Insurance Database between 2000 and 2017 for cohort analysis. A total of 109,348 with hepatitis B virus (HBV) infection, 37,506 with hepatitis C virus (HCV) infection, 34,110 without HBV or HCV, and 7075 with both HBV and HCV were recorded. Statistically, propensity score matched by sex, age, and index year at a ratio of 15:5:5:1 and a sensitivity test using multivariable Cox regression were used. Results: The risk of coronary artery disease in the HCV-related HCC group was 1.516-fold (95% CI: 1.328–2.034, p < 0.001) higher than in the HBV-related HCC group, followed by the HBV/HCV-related HCC group and the non-B/C HCC group; the cerebral vascular disease risk in the HCV-related HCC group was 1.467-fold higher than in the HBV-related HCC group (95% CI: 1.335 to 1.786, p < 0.001), followed by the HBV/HCV-related HCC group and the non-B/C HCC group. Conclusion: Hepatitis C virus infection was found to have a higher risk of developing coronary artery disease or cerebral vascular disease in patients with hepatocellular carcinoma. For patients with hepatocellular carcinoma, our findings warrant the importance in preventing artherosclerotic disease in the setting of hepatitis C virus infection.
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30
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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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31
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Han CL, Tian BW, Yang CC, Yang YF, Ma YL, Ding ZN, Yan LJ, Liu H, Dong ZR, Chen ZQ, Hong JG, Wang DX, Li T. The association of fatty liver and risk of hepatocellular carcinoma in HBV or HCV infected individuals: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2023; 17:189-198. [PMID: 36625022 DOI: 10.1080/17474124.2023.2166930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Fatty liver (FL) is reportedly a risk factor for hepatocellular carcinoma (HCC) in individuals affected with Hepatitis C (HCV) or B (HBV) virus. However, the results are contradictory, necessitating a meta-analysis. RESEARCH DESIGN AND METHODS Sixteen relevant studies involving 88,618 individuals were retrieved from the Cochrane Library, PubMed, MEDLINE, Embase, and Scopus databases from their inception to 10 December 2022. The hazard ratios (HR) and 95% confidence intervals (CI) were analyzed. RESULTS Liver biopsy-proven FL may be a significant risk factor for HCC in individuals affected with HBV (univariate analyses: HR = 3.13, 95% CI = 1.69-5.79; multivariate analyses: HR = 3.42, 95% CI = 0.83-14.09) as well as HCV (univariate analyses: HR = 1.64, 95% CI = 0.93-2.90; multivariate analyses: HR = 1.75, 95% CI = 1.02-3.00). However, the presence of FL confirmed using reasonable methods other than liver biopsy may not indicate a risk for HCC in HBV-infected individuals (univariate analyses: HR = 0.90, 95% CI = 0.44-1.81; multivariate analyses: HR = 0.69, 95% CI = 0.45-1.08). CONCLUSIONS Biopsy-proven FL may be a significant risk factor for HCC in HCV/HBV-infected individuals. Thus, such individuals should receive suitable interventions to prevent HCC formation or at least attenuate the risk of HCC.
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Affiliation(s)
- Cheng-Long Han
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Chun-Cheng Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Ya-Fei Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yun-Long Ma
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China.,Department of Hepatobiliary Surgery, the Second Hospital of Shandong University, Jinan, P.R. China
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32
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Tang Y, Fan R, Lan Z, Xie Q, Zhang J, Liang X, Wang H, Tan D, Cheng J, Chen S, Ning Q, Bai X, Xu M, Chen X, Niu J, Shi J, Ren H, Gao Z, Wang M, Dou X, Hou J, Sun J. Impact of nonalcoholic fatty liver disease status change on antiviral efficacy of nucleos(t)ide analogues in HBeAg-positive chronic hepatitis B. J Med Virol 2023; 95:e28501. [PMID: 36655747 DOI: 10.1002/jmv.28501] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/29/2022] [Accepted: 01/16/2023] [Indexed: 01/20/2023]
Abstract
Data on the dynamic changes in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD) during antiviral therapy are scarce. We aimed to investigate the evolution of NAFLD status change in CHB patients treated with nucleos(t)ide analogues (NAs) and its influence on therapeutic outcomes. This retrospective study included 164 HBeAg-positive CHB patients from a randomized controlled trial who were treated with NAs for 104 weeks and underwent paired liver biopsies. Histological evaluation was performed at baseline and Week 104. The patients were divided into four groups according to NAFLD status changes. From baseline to Week 104, the overall percentage of CHB patients with concurrent NAFLD increased from 17.1% to 26.2% (p = 0.044). Among them, 7 of 28 patients (25.0%) with NAFLD at baseline showed NAFLD remission at week 104, while 22 of 136 patients (16.2%) without NAFLD at baseline developed new-onset NAFLD. In subgroup analyses, the new-onset and sustained NAFLD groups showed significantly lower rates of biochemical response at week 104 as compared to the sustained non-NAFLD group (77.3% and 57.1% vs. 93.9%, respectively; all p < 0.05), as well as fibrosis improvement (31.8% and 42.9% vs. 69.3%, respectively; all p < 0.05). NAFLD status changes did not influence the virological response, HBeAg seroconversion, and necroinflammation improvement (all p > 0.05). In HBeAg-positive CHB patients receiving NAs therapy, new-onset and sustained NAFLD may counteract the benefits of antiviral therapy, reducing the rate of biochemical response and fibrosis improvement.
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Affiliation(s)
- Yanhua Tang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Rong Fan
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhixian Lan
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jiping Zhang
- Pathology Department of Guangzhou KingMed Center for Clinical Laboratory, Guangzhou, China
| | - Xieer Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hao Wang
- Hepatology Unit, Peking University People's Hospital, Beijing, China
| | - Deming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Jun Cheng
- Beijing Ditan Hospital, Beijing, China
| | - Shijun Chen
- Ji'nan Infectious Diseases Hospital, Ji'nan, China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuefan Bai
- Department of Infectious Diseases, Tangdu Hospital, Xi'an, China
| | - Min Xu
- 8th People's Hospital, Guangzhou, China
| | | | - Junqi Niu
- Department of Hepatology, The First Hospital, Jilin University, Changchun, China
| | | | - Hong Ren
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhiliang Gao
- Department of Infectious Diseases, Sun Yat-Sen University 3rd Affiliated Hospital, Guangzhou, China
| | - Maorong Wang
- Department of Infectious Diseases, 81st PLA Hospital, Nanjing, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jian Sun
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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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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Metabolic Syndrome, Nonalcoholic Fatty Liver Disease, and Chronic Hepatitis B: A Narrative Review. Infect Dis Ther 2023; 12:53-66. [PMID: 36441483 PMCID: PMC9868033 DOI: 10.1007/s40121-022-00725-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 11/03/2022] [Indexed: 11/29/2022] Open
Abstract
Chronic hepatitis B (CHB) remains a relatively major public health problem. Simultaneously, an unhealthy lifestyle causes a series of metabolic abnormalities, the most critical of which are metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). Therefore, it is increasingly common for MS and NAFLD to coexist with CHB. MS is a cluster of metabolic disorders, while NAFLD is always considered as the manifestation of MS in the liver. The aim of this article is to review recent advances to explain the complex relationship among MS, NAFLD, and hepatitis B virus (HBV) infection. MS and NAFLD both have obesity and insulin resistance as central factors and both can lead to adverse hepatic and extrahepatic outcomes. However, there is insufficient evidence to associate NAFLD with all components of MS, and genetically related NAFLD has little association with MS. Incidences of MS and NAFLD are inversely associated with HBV infection. However, the effect of HBV infection on the risk of insulin resistance and dyslipidemia is not well understood. Evidence from both clinical studies and animal experiments suggested that hepatic steatosis inhibits HBV replication. MS and NAFLD may have adverse effects on CHB disease progression and prognosis. Furthermore, in related studies of CHB with normal alanine aminotransferase (ALT), the roles of MS and NAFLD should also be emphasized. In conclusion, there are complicated interactions that are not yet fully defined among MS, NAFLD, and CHB. To control chronic liver disease effectively, the relationship among the three must be clarified.
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Chen JW, Cao XY, Qi X, Zhang JM. Effect of nucleos(t)ide analogues on blood lipid profiles in patients with chronic hepatitis B: A cross-sectional survey. Medicine (Baltimore) 2022; 101:e31980. [PMID: 36550809 PMCID: PMC9771272 DOI: 10.1097/md.0000000000031980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
This study aimed to explore the effects of the 3 nucleos(t)ide analogues (NAs) on lipid levels. We retrospectively included patients treated with NAs at 2 centers and collected their clinical data at their visiting points. Differences in blood lipid levels were analyzed by statistical methods, and factors related to hyperlipidemia were discussed. In these 2 centers, the prevalence rates of hypercholesterolemia were 12/181 (6.6%) for tenofovir alafenamide fumarate (TAF)-, 0/158 (0%) for tenofovir disoproxil fumarate (TDF)-, and 13/182 (7.1%) for entecavir (ETV)-treated individuals (P = .003). The prevalence rates of hypertriglyceridemia were 30/181 (16.6%) for TAF-, 11/158 (7.0%) for TDF-, and 26/182 (14.3%) for ETV-treated individuals (P = .025). In TAF (n = 181, 10 [6, 15] months), TDF (n = 158, 18 [7.5, 45] months), and ETV (n = 182, 24 [10, 60] months) groups, total cholesterol (TC) levels were 4.63 ± 0.91 mmol/L, 3.86 ± 0.61 mmol/L, and 4.53 ± 0.87 mmol/L, respectively; triglyceride (TG) levels were 1.27 ± 0.76 mmol/L, 0.87 ± 0.51 mmol/L, and 1.14 ± 0.67 mmol/L, respectively (P < .001). In multivariate regression analysis, factors associated with hypercholesterolemia were age (adjusted hazard risk [HR] = 1.055 [1.018-1.094]; P = .003) and body mass index (BMI) (adjusted HR = 0.817 [0.669-0.998]; P = .048). Factors associated with hypertriglyceridemia were TAF group (vs. TDF group) (adjusted HR = 0.405 [0.167-0.980]; P = .045), age (adjusted HR = 1.028 [1.002-1.055]; P = .038), and sex (adjusted HR = 0.190 [0.079-0.456]; P < .001). Among the patients treated with TAF (10 [6, 15] months), TDF (18 [7.5, 45] months), and ETV (24 [10, 60] months), the blood lipid levels in the TDF group were lower than those in the TAF group and ETV group, and the occurrence of hyperlipidemia was associated with age, sex, BMI, and different treatment.
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Affiliation(s)
- Jing Wen Chen
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiong Yue Cao
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Ji Ming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
- * Correspondence: Ji Ming Zhang, MD, PhD, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China (e-mail: )
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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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Tai CM, Tu HP, Hwang JC, Yeh ML, Huang CF, Yu ML. HBV Reactivation After Bariatric Surgery for HBV-Infected Obese Patients. Obes Surg 2022; 32:3332-3339. [PMID: 35922612 DOI: 10.1007/s11695-022-05979-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/10/2022] [Accepted: 02/17/2022] [Indexed: 10/16/2022]
Abstract
BACKGROUND The association between non-alcoholic fatty liver disease and hepatitis B virus (HBV) infection is inconclusive. The aim of this study was to investigate the viral dynamic of HBV and its association with change of body mass index (BMI), aspartate transaminase (AST), and alanine transaminase (ALT) levels after bariatric surgery. METHODS Patients who underwent bariatric surgery between June 2011 and May 2014 were selected in this retrospective study. BMI, AST, ALT, and HBV DNA levels were calculated pre-operatively and at 1st, 3rd, and 6th postoperative months. RESULTS Two hundred and seventy-nine patients including 34 (12.2%) HBsAg-positive and 245 (87.8%) HBsAg-negative patients were enrolled. Eighteen HBsAg-positive and HBeAg-negative patients were matched with 36 HBsAg-negative patients. A significant decrease in BMI was found since 1st postoperative month in both groups. AST and ALT increased at 1st postoperative month, but decreased at 3rd and 6th postoperative months in both groups. However, a significant increase in HBV DNA level was observed in HBeAg-negative patients since 1st postoperative month with the highest peak at 3rd postoperative month. HBV reactivation occurred in 4 out of 17 (23.5%) patients, 8 out of 16 (50.0%) patients, and 4 out of 12 (33.3%) patients at 1st, 3rd, and 6th postoperative months, respectively. The change of HBV DNA was not associated with change of BMI, AST, or ALT after bariatric surgery. CONCLUSION Bariatric surgery can achieve significant weight loss and improvement of liver function tests. However, there existed significant risk of HBV reactivation after bariatric surgery for patients with obesity.
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Affiliation(s)
- Chi-Ming Tai
- Department of Medicine, Division of Gastroenterology and Hepatology, I-Shou University, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Hung-Pin Tu
- Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jau-Chung Hwang
- Department of Pathology, Lin Shin Hospital, Taichung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tz-You 1st road, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tz-You 1st road, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tz-You 1st road, Kaohsiung, Taiwan.
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
- National Pingtung University of Science and Technology, Pingtung, Taiwan.
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Association between HBV Infection and the Prevalence of Coronary Artery Disease in the US Population. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:5062798. [PMID: 35979042 PMCID: PMC9377945 DOI: 10.1155/2022/5062798] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/18/2022] [Accepted: 07/20/2022] [Indexed: 11/19/2022]
Abstract
Aims This study aims to investigate the association between HBV infection and coronary artery disease (CAD) prevalence in the US population. A nomogram was proposed to predict CAD based on HBV infection. Methods 25,749 individuals were collected from the 2001-2014 National Health and Nutrition Examination Survey. Participants with hepatitis B core antibody seropositivity were identified with HBV infection, including current and previous HBV infection status. We used adjusted logistic regression and performed sensitivity analysis to investigate the association between HBV infection and the prevalence of CAD. The effect size was evaluated by odds ratio (OR) with a 95% confidence interval (CI). Then, we created a nomogram to predict coronary artery disease. Additionally, we applied the Cox regression model to assess the association between HBV infection and all-cause mortality in those with baseline CAD. Results 1790 (6.95%) individuals were with HBV infection. In the adjusted model, individuals with HBV showed a decreased CAD risk than those without (OR, 0.81; 95% CI, 0.67-0.98). Consistently, reduced risk in self-reported angina (OR, 0.72; 95% CI, 0.52-0.98) and coronary heart disease (OR, 0.76; 95% CI, 0.58-0.98) was observed in the hepatitis B core antibody seropositivity group. The subgroup analysis showed a consistent trend in the subgroups of age (<45 or ≥45), gender (male or female), hypertension (no or yes), and diabetes (no or yes). In the testing set, the proposed predictive model showed good performance with an area under the curve of 0.85 (95% CI, 0.83-0.86). There was no significant association between HBV infection and all-cause mortality in CAD patients (adjusted P = 0.202). Conclusion Our study suggests that HBV infection was associated with lower CAD risk. The proposed nomogram showed good performance in predicting CAD. However, no significant association was observed between HBV and all-cause mortality in CAD patients.
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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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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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Risk factors for underlying comorbidities and complications in patients with hepatitis B virus-related acute-on-chronic liver failure. Epidemiol Infect 2022; 150:e147. [PMID: 35788251 PMCID: PMC9354478 DOI: 10.1017/s0950268822001169] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe and life-threatening complication, characterised by multi-organ failure and high short-term mortality. However, there is limited information on the impact of various comorbidities on HBV-ACLF in a large population. This study aimed to investigate the relationship between comorbidities, complications and mortality. In this retrospective observational study, we identified 2166 cases of HBV-ACLF hospitalised from January 2010 to March 2018. Demographic data from the patients, medical history, treatment, laboratory indices, comorbidities and complications were collected. The mortality rate in our study group was 47.37%. Type 2 diabetes mellitus was the most common comorbidity, followed by alcoholic liver disease. Spontaneous bacterial peritonitis, pneumonia and hepatic encephalopathy (HE) were common in these patients. Diabetes mellitus and hyperthyroidism are risk factors for death within 90 days, together with gastrointestinal bleeding and HE at admission, HE and hepatorenal syndrome during hospitalisation. Knowledge of risk factors can help identify HBV-ACLF patients with a poor prognosis for HBV-ACLF with comorbidities and complications.
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Zhou YG, Tian N, Xie WN. Total cholesterol to high-density lipoprotein ratio and nonalcoholic fatty liver disease in a population with chronic hepatitis B. World J Hepatol 2022; 14:791-801. [PMID: 35646261 PMCID: PMC9099113 DOI: 10.4254/wjh.v14.i4.791] [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: 10/20/2021] [Revised: 12/13/2021] [Accepted: 04/03/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is characterized by hypertriglyceridemia, increased low-density lipoprotein cholesterol levels, and reduced high-density lipoprotein cholesterol (HDL-C) particles. Previous studies have shown that the total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C) was superior to other lipid metabolism biomarkers for predicting NAFLD risk and could be a new indicator of NAFLD. However, the association between TC/HDL-C and NAFLD in patients with hepatitis B virus (HBV) has not yet been determined. AIM To investigate the association between TC/HDL-C and NAFLD in a population with chronic hepatitis B (CHB). METHODS In this study, 183 HBV-infected patients were enrolled. All participants underwent blood chemistry examinations and abdominal ultrasound. Univariate and multivariate logistic regression models, curve fitting analysis, and threshold calculation were used to assess the relationship between TC/HDL-C and NAFLD. RESULTS The overall prevalence of NAFLD was 17.49% (n = 32) in the 183 CHB participants. The TC/HDL-C of non-NAFLD and NAFLD patients were 3.83 ± 0.75 and 4.44 ± 0.77, respectively (P < 0.01). Logistic regression analysis showed that TC/HDL-C was not associated with NAFLD after adjusting for other pertinent clinical variables. However, at an optimal cutoff point of 4.9, a non-linear correlation between TC/HDL-C and NAFLD was detected. The effect size of the left and right sides of the inflection point were 5.4 (95% confidence interval: 2.3-12.6, P < 0.01) and 0.5 (95% confidence interval: 0.1-2.2, P = 0.39), respectively. On the left side of the inflection point, TC/HDL-C was positively associated with NAFLD. However, no significant association was observed on the right side of the inflection point. CONCLUSION This study demonstrated a non-linear correlation between TC/HDL-C and NAFLD in a population with CHB. TC/HDL-C was positively associated with NAFLD when TC/HDL-C was less than 4.9 but not when TC/HDL-C was more than 4.9.
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Affiliation(s)
- Yu-Ge Zhou
- Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Foshan 528200, Guangdong Province, China
| | - Ning Tian
- Preventive Healthcare Center, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan 528200, Guangdong Province, China
| | - Wei-Ning Xie
- Department of Scientific Research, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan 528200, Guangdong Province, China.
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Diao Y, Hu D, Hu X, Wang P, Wang X, Luo X, Wang H, Ning Q. The Role of Metabolic Factors and Steatosis in Treatment-Naïve Patients with Chronic Hepatitis B and Normal Alanine Aminotransferase. Infect Dis Ther 2022; 11:1133-1148. [PMID: 35397765 PMCID: PMC9124274 DOI: 10.1007/s40121-022-00629-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/18/2022] [Indexed: 11/30/2022] Open
Abstract
Introduction We aimed to elucidate the impact of metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) on treatment-naïve patients with chronic hepatitis B (CHB) and normal alanine aminotransferase (ALT). Methods We analyzed the clinical characteristics of a cross-sectional cohort of treatment-naïve patients with CHB and ALT in the upper limit of normal (ULN) from October 2018 to July 2021. ALT ≤ 0.5 ULN was stratified as low-normal ALT (LNALT) and 0.5 ULN < ALT ≤ ULN as high-normal ALT (HNALT). Transient elastography (TE) was used to evaluate liver steatosis and fibrosis. Results Among 733 patients with CHB enrolled, 23.1% of them had MS, 37.2% of them had NAFLD, and 5.9% of them had significant fibrosis. The proportions of patients with MS, steatosis, and significant fibrosis in the HNALT group were higher than those in the LNALT group (31.4% vs. 14.1%, p < 0.001; 48.7% vs. 25.2%, p < 0.001; and 8.0% vs. 3.6%, p = 0.013, respectively). Multiple linear regression showed that steatosis (beta = 0.098, p = 0.001) and MS (beta = 0.092, p = 0.002) were independently related to ALT levels in the normal range. Multivariate logistic regression showed that age (OR 1.049, 95% CI 1.012–1.087, p = 0.010), aspartate aminotransferase (AST) (OR 1.059, 95% CI 1.005–1.115, p = 0.030), and severe steatosis (OR 2.559, 95% CI 1.212–5.403, p = 0.014) were independently associated with significant fibrosis. When analyzed in the subgroup of CHB with NAFLD, age (OR 1.060, 95% CI 1.006–1.117, p = 0.029) and severe steatosis (OR 2.962, 95% CI 1.126–7.792, p = 0.028) were still statistically significant. Conclusion The accumulation of MS components exacerbated hepatic steatosis. Severe NAFLD was independently associated with significant fibrosis. This emphasizes the importance of screening for MS and NAFLD in patients with CHB and normal ALT, where a more active intervention may apply. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00629-5.
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Affiliation(s)
- Yuting Diao
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
- National Medical Center for Major Public Health Events, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
| | - Danqing Hu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
- National Medical Center for Major Public Health Events, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
| | - Xue Hu
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
- National Medical Center for Major Public Health Events, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
| | - Peng Wang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
- National Medical Center for Major Public Health Events, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
| | - Xiaojing Wang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
- National Medical Center for Major Public Health Events, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
| | - Xiaoping Luo
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China
| | - Hongwu Wang
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China.
- National Medical Center for Major Public Health Events, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China.
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China.
- National Medical Center for Major Public Health Events, 1095, Jiefang Avenue, Wuhan, 430030, Hubei Province, China.
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Liou JW, Mani H, Yen JH. Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds. Int J Mol Sci 2022; 23:ijms23073897. [PMID: 35409259 PMCID: PMC8999150 DOI: 10.3390/ijms23073897] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 03/27/2022] [Accepted: 03/30/2022] [Indexed: 11/24/2022] Open
Abstract
Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections. The most common causes of viral hepatitis are the five hepatitis viruses—hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). While HAV and HEV rarely (or do not) cause chronic hepatitis, a considerable proportion of acute hepatitis cases caused by HBV (sometimes co-infected with HDV) and HCV infections become chronic. Thus, many medical researchers have focused on the treatment of HBV and HCV. It has been documented that host lipid metabolism, particularly cholesterol metabolism, is required for the hepatitis viral infection and life cycle. Thus, manipulating host cholesterol metabolism-related genes and proteins is a strategy used in fighting the viral infections. Efforts have been made to evaluate the efficacy of cholesterol-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the treatment of hepatitis viral infections; promising results have been obtained. This review provides information on the relationships between hepatitis viruses and host cholesterol metabolism/homeostasis, as well as the discovery/development of cholesterol-lowering natural phytochemicals that could potentially be applied in the treatment of viral hepatitis.
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Affiliation(s)
- Je-Wen Liou
- Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan;
- Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan;
| | - Hemalatha Mani
- Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan;
| | - Jui-Hung Yen
- Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan;
- Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan
- Correspondence: or ; Tel.: +886-3-856-5301 (ext. 2683)
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Liu J, Ayada I, Zhang X, Wang L, Li Y, Wen T, Ma Z, Bruno MJ, de Knegt RJ, Cao W, Peppelenbosch MP, Ghanbari M, Li Z, Pan Q. Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults. Clin Gastroenterol Hepatol 2022; 20:e573-e582. [PMID: 33618024 DOI: 10.1016/j.cgh.2021.02.030] [Citation(s) in RCA: 126] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 02/10/2021] [Accepted: 02/17/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease. METHODS We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity. RESULTS We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively. CONCLUSIONS MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.
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Affiliation(s)
- Jiaye Liu
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Ibrahim Ayada
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Xiaofang Zhang
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Ling Wang
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yang Li
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhongren Ma
- Biomedical Research Center, Northwest Minzu University, Lanzhou, China
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Wanlu Cao
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Mohsen Ghanbari
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Zhihui Li
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
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46
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Wang X, Xie Q. Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) and Viral Hepatitis. J Clin Transl Hepatol 2022; 10:128-133. [PMID: 35233381 PMCID: PMC8845159 DOI: 10.14218/jcth.2021.00200] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 08/19/2021] [Accepted: 09/07/2021] [Indexed: 12/04/2022] Open
Abstract
A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed in 2020. The change from nonalcoholic fatty liver disease (NAFLD) to MAFLD highlights the metabolic abnormalities that accompany fatty liver. The diagnosis of MAFLD does not require exclusion of secondary causes of liver diseases and alcohol consumption. Thus, MAFLD may coexist with other types of liver diseases, such as viral hepatitis, a disease that remains the most common cause of liver disease-related death. With the increasing prevalence of MAFLD, patients with coincidental MAFLD and viral hepatitis are frequently encountered in clinical practice. In this review, we mainly summarize the mutual relationship between hepatitis B/C and systematic metabolism dysfunction related to MAFLD. We discuss the impact of MAFLD on progression of viral hepatitis and the therapies. Some unaddressed clinical problems related to concomitant MAFLD and viral hepatitis are also identified.
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Affiliation(s)
- Xiaolin Wang
- 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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47
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Li H, Xu QY, Xie Y, Luo JJ, Cao HX, Pan Q. Effects of chronic HBV infection on lipid metabolism in non-alcoholic fatty liver disease: A lipidomic analysis. Ann Hepatol 2022; 24:100316. [PMID: 33515803 DOI: 10.1016/j.aohep.2021.100316] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/04/2021] [Accepted: 01/06/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Chronic hepatitis B virus (HBV) infection exerts an impact on lipid metabolism, but its interaction with dysmetabolism-based non-alcoholic fatty liver disease (NAFLD) remains uncertain. The purpose of the study was to investigate the effects of HBV infection on lipid metabolism, hepatic steatosis and related impairments of NAFLD patients. METHODS Biopsy-proven Chinese NAFLD patients with (NAFLD-HBV group, n = 21) or without chronic HBV infection (NAFLD group, n = 41) were enrolled in the case-control study. Their serum lipidomics was subjected to individual investigation by ultra-performance liquid chromatography-tandem mass spectrometry. Steatosis, activity, and fibrosis (SAF) scoring revealed the NAFLD-specific pathological characteristics. RESULTS Chronic HBV infection was associated with global alteration of serum lipidomics in NAFLD patients. Upregulation of phosphatidylcholine (PCs), choline plasmalogen (PC-Os) and downregulation of free fatty acids (FFAs), lysophosphatidylcholine (LPCs) dominated the HBV-related lipidomic characteristics. Compared to those of NAFLD group, the levels of serum hepatoxic lipids (FFA16:0, FFA16: 1, FFA18:1, FFA18:2) were significantly lowered in the NAFLD-HBV group. These low-level FFAs demonstrated correlation to statistical improvements in aspartate aminotransferase activity (FFA16:0, r = 0.33; FFA16:1, r = 0.37; FFA18:1, r = 0.32; FFA18:2, r = 0.42), hepatocyte steatosis (FFA16: 1, r = 0.39; FFA18:1, r = 0.39; FFA18:2, r = 0.32), and ballooning (FFA16:0, r = 0.30; FFA16:1, r = 0.45; FFA18:1, r = 0.36; FFA18:2, r = 0.30) (all P < 0.05). CONCLUSION Chronic HBV infection may impact on the serum lipidomics and steatosis-related pathological characteristics of NAFLD.
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Affiliation(s)
- Han Li
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Qing-Yang Xu
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yang Xie
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Ji-Jun Luo
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Hai-Xia Cao
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
| | - Qin Pan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
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Lin H, Zhang X, Li G, Wong GLH, Wong VWS. Epidemiology and Clinical Outcomes of Metabolic (Dysfunction)-associated Fatty Liver Disease. J Clin Transl Hepatol 2021; 9:972-982. [PMID: 34966660 PMCID: PMC8666360 DOI: 10.14218/jcth.2021.00201] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/24/2021] [Accepted: 08/13/2021] [Indexed: 12/13/2022] Open
Abstract
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease and affects at least a quarter of the global adult population. It has rapidly become one of the leading causes of hepatocellular carcinoma and cirrhosis in Western countries. In this review, we discuss the nomenclature and definition of MAFLD as well as its prevalence and incidence in different geographical regions. Although cardiovascular disease remains the leading cause of death in MAFLD patients, the proportion of patients dying from hepatic complications increases sharply as the disease progresses to advanced liver fibrosis and cirrhosis. In addition, patients with MAFLD are at increased risk of various extrahepatic cancers. Although a causal relationship between MAFLD and extrahepatic cancers has not been established, clinicians should recognize the association and consider cancer screening (e.g., for colorectal cancer) as appropriate.
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Affiliation(s)
| | | | | | | | - Vincent Wai-Sun Wong
- Correspondence to: Vincent Wai-Sun Wong, Department of Medicine and Therapeutics, 9/F, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China. ORCID: https://orcid.org/0000-0003-2215-9410. Tel: 852-3505-1205, Fax: 852-2637-3852, E-mail:
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Hsu YC, Yeh ML, Wong GLH, Chen CH, Peng CY, Buti M, Enomoto M, Xie Q, Trinh H, Preda C, Liu L, Cheung KS, Yeo YH, Hoang J, Huang CF, Riveiro-Barciela M, Kozuka R, Istratescu D, Tsai PC, Accarino EV, Lee DH, Wu JL, Huang JF, Dai CY, Cheung R, Chuang WL, Yuen MF, Wong VWS, Yu ML, Nguyen MH. Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B. J Infect Dis 2021; 224:1890-1899. [PMID: 33999179 DOI: 10.1093/infdis/jiab241] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 05/10/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood. METHODS This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression. RESULTS The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]). CONCLUSION HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.
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Affiliation(s)
- Yao-Chun Hsu
- Center for Liver Diseases and School of Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan
- Institute of Biomedical Informatics, National Yang-Ming University, New Taipei, Taiwan
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
| | - Ming-Lun Yeh
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Chien-Hung Chen
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huy Trinh
- San Jose Gastroenterology, San Jose, California, USA
| | - Carmen Preda
- Institutul Clinic Fundeni-Gastroenterologie si Hepatologie, Bucuresti, Romania
| | - Li Liu
- Department of Infection Disease, Third Hospital of Kumming City, Kumming, China
| | - Ka-Shing Cheung
- Department of Medicine, University of Hong Kong, Hong Kong SAR, China
| | - Yee Hui Yeo
- Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Joseph Hoang
- Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Chung-Feng Huang
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mar Riveiro-Barciela
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Ritsuzo Kozuka
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Doina Istratescu
- Institutul Clinic Fundeni-Gastroenterologie si Hepatologie, Bucuresti, Romania
| | - Pei-Chien Tsai
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Elena Vargas Accarino
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Dong-Hyun Lee
- Department of Gastroenterology, Good Gang-An Hospital, Busan, South Korea
| | - Jia-Ling Wu
- Department of Public Health, National Cheng Kung University, College of Medicine, Tainan, Taiwan
| | - Jee Fu Huang
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ramsey Cheung
- Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
| | - Wan-Long Chuang
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Man-Fung Yuen
- Department of Medicine, University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ming-Lung Yu
- Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mindie H Nguyen
- Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California, USA
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Bacaksız F, Gökcan H, Akdoğan M, Gökçe DT, Arı D, Gökbulut V, Ergün Y, Öztürk Ö, Kacar S. Role of hepatosteatosis in HBsAg seroconversion in HBeAg-negative chronic hepatitis B patients. Int J Clin Pract 2021; 75:e14899. [PMID: 34547163 DOI: 10.1111/ijcp.14899] [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: 02/02/2021] [Accepted: 09/19/2021] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND In chronic Hepatitis B virus (HBV) infection, certain individual and viral characteristics such as advanced age, presence of hepatic steatosis (HS), normal ALT levels, initially negative HBeAg and HBV DNA, and genotype of the virus are associated with HBsAg seroclearance and seroconversion. Herein, we report the results of our study evaluating the association between hepatosteatosis and HbsAg seroconversion. METHODS The clinical and biochemical data of patients with CHB and hepatosteatosis (HS) (HBsAg seroconversion, n:52, and non-HbsAg seroconversion, n:352), and the rate of development of HBsAg seroconversion were evaluated. RESULTS We collected data from 404 patients with HBeAg negative CBH (mean age ± SD: 36.2 ± 11 years; 223 [55.2%] men, 181 [44.8%] women). The mean age at diagnosis of disease was 36.2 ± 11 years. The mean duration of the disease was 10.6 ± 7 years. Seroconversion developed in 52 patients (12.8%) with serum HBsAg positive (mean ± SD: 12.7 ± 5.8). Elderly age and the duration of disease time were significantly associated with seroconversion (P < .001). The presence of serum HBsAg seroconversion was significantly associated with hepatosteatosis (OR: 3.06, 95% CI 1.64-5.71, P < .01). Serum HBsAg seroconversion was more frequent in patients with mild HS than patients with moderate-severe HS (P = .04). In multivariate regression analysis, the presence of HS was found to be an independent factor predicting the development of HBsAg seroconversion (OR: 2.07 95% GA:1.07-4.0 P = .03). CONCLUSION The presence of mild HS in HBeAg negative chronic hepatitis B patients contributes to HBsAg seroconversion. Further studies are required to better understand the relationship between steatosis and HBsAg seroconversion.
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Affiliation(s)
- Ferhat Bacaksız
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | - Hale Gökcan
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | - Meral Akdoğan
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | | | - Derya Arı
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | - Volkan Gökbulut
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | - Yakup Ergün
- Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey
| | - Ömer Öztürk
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | - Sabite Kacar
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
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