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He MW, Cui L, Chen DD, Zhao Y, Luo WZ, Jia YF, Zhou J, He QJ, Dai Y, Zhang WH, Yu ZX, Wang WC, Guo C, Fu YM, Yang WC, Li XY, Guo YF, Wang CY, Wang JJ, Li P, Qiao B, Ji D, Li ZB. Efficacy and safety of switching from entecavir to tenofovir alafenamide in chronic hepatitis B patients with low-level viremia: a real-world 48-week extension study. Antimicrob Agents Chemother 2025:e0182724. [PMID: 39902928 DOI: 10.1128/aac.01827-24] [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: 12/06/2024] [Accepted: 01/11/2025] [Indexed: 02/06/2025] Open
Abstract
Chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment might develop low-level viremia (LLV), which is proven to be associated with worse clinical outcomes, such as risk of drug-related mutations, progression to cirrhosis, and even hepatocellular carcinoma. This real-world prospective study evaluated the efficacy and safety of switching from ETV to tenofovir alafenamide fumarate (TAF) in CHB patients with LLV. From August 2020 to August 2023, 351 ETV-experienced CHB patients with LLV were enrolled from eight hospitals. Patients either continued ETV or switched to TAF. The primary efficacy endpoint was the complete virological response (CVR) at week 48; the safety endpoint was the first occurrence of any clinical adverse event during the treatment; and the renal safety and change in blood lipids were also assessed. Inverse probability treatment weighting (IPTW) generated 350.9 cases in the ETV group and 351.4 cases in the TAF group. After the 48-week treatment, the CVR and ALT normalization rates in the TAF group were 75.3% and 67.8%, which were significantly higher than 11.4% and 17.1% in the ETV group (P < 0.001). The two strategies showed comparable impact on renal function and lipid profiles, regarding low-density lipoprotein (LDL) cholesterol and the total cholesterol to high-density lipoprotein (TC/HDL) ratio. Therefore, for ETV-treated patients with LLV, switching to TAF is superior compared with continuing ETV treatment in terms of virological and biochemical response, with non-inferior renal safety and lipid profiles.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2400089257.
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Affiliation(s)
- Meng-Wen He
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Li Cui
- Department of Emergency, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Dan-Dan Chen
- Department II of Infectious Diseases (Hepatology), The Second People's Hospital of Jingzhou City, Jingzhou, China
| | - Yun Zhao
- Department of Interventional Radiology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Wen-Zhao Luo
- Department of Hepatobiliary & Gastrointestinal Diseases, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Yun-Fei Jia
- Department of Hepatobiliary & Gastrointestinal Diseases, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Jie Zhou
- Department of Infectious Diseases, Xinjiang Uygur Autonomous Region Infectious Disease Hospital, Xinjiang, China
| | - Qing-Juan He
- Department II of Gastroenterology, The Eighth People's Hospital of Qingdao, Qingdao, China
| | - Ying Dai
- Department of Gastroenterology, Qiqihar Seventh Hospital, Qiqihar, China
| | - Wei-Hua Zhang
- The Second ward, Qian 'an Infectious Disease Hospital, Tangshan, China
| | - Zhao-Xia Yu
- Liver Oncology Department, The Sixth People's Hospital of Qingdao, Qingdao, China
| | | | - Chang Guo
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yi-Ming Fu
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Wu-Cai Yang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xu-Yang Li
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yi-Fan Guo
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Chun-Yan Wang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jian-Jun Wang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Ping Li
- Integrated TCM & Western Medicine Department, Tianjin Second People's Hospital, Tianjin, China
| | - Bing Qiao
- Liver Oncology Department, The Sixth People's Hospital of Qingdao, Qingdao, China
| | - Dong Ji
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
- Chinese PLA Medical School, Beijing, Beijing, China
| | - Zhong-Bin Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
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Zhao W, Liu Y, Zhang M, Cui Z, Qu Z, Li Y, Wan M, Wang W, Chen Y, Shi L, Li J, Ye F. Lipid safety of tenofovir alafenamide during 96-week treatment in treatment-naive chronic hepatitis B patients. Front Med (Lausanne) 2024; 11:1399665. [PMID: 38895186 PMCID: PMC11183333 DOI: 10.3389/fmed.2024.1399665] [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: 03/12/2024] [Accepted: 05/15/2024] [Indexed: 06/21/2024] Open
Abstract
Background This study was aimed at investigating the dynamics of lipids and the effect of TAF on the lipid profile of patients including fatty liver disease in CHB patients. Methods The data of TC, LDL-c, HDL-c, TG, and TC/HDL ratio were collected at baseline, 24 weeks, 48 weeks, 72 weeks, and 96 weeks. CHB patients with fatty liver at baseline were further analyzed in a subgroup. Results A total of 137 CHB patients treated with TAF were enrolled in this study. During 96 weeks of TAF treatment, there was no significant change in TC, LDL-c, HDL-c, and TG level (P > 0.05). The TC/HDL-c ratio was increased with no significant change (+0.24, P > 0.05). In CHB patients with fatty liver (n = 48), TC, LDL-c, and TC/HDL-c ratio increased gradually during TAF treatment, TG levels increased to 146.63 mg/dL at 48 weeks (P = 0.057) and then decreased, but there was still no significant change compared with the baseline level by 96 weeks (P > 0.05). Conclusion TAF treatment had a low effect on the lipid profile of CHB patients over the course of 96 weeks, and it was safe even in patients with fatty liver. Clinical trial registration [https://www.chictr.org.cn/showproj.html?proj=65123], identifier [ChiCTR2000041005].
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Affiliation(s)
- Wenjuan Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Yi Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Mengdi Zhang
- Department of Nutrition, Xian Jiaotong University, Xi’an, China
| | - Zixin Cui
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Zhan Qu
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Yiyang Li
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Meijuan Wan
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Wen Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Yunru Chen
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Lei Shi
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Jianzhou Li
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
| | - Feng Ye
- Department of Infectious Diseases, The First Affiliated Hospital of Xian Jiaotong University, Xi’an, China
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Yeh ML, Huang JF, Yu ML. Fatty liver and viral hepatitis: Prevalence, risk factors, natural course, pathogenesis, and management. METABOLIC STEATOTIC LIVER DISEASE 2024:261-275. [DOI: 10.1016/b978-0-323-99649-5.00008-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Wu Q, Pan C, Jia W, Li C, Sun C, Niu J, Hou J. 96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients. J Clin Transl Hepatol 2023; 11:649-660. [PMID: 36969889 PMCID: PMC10037506 DOI: 10.14218/jcth.2022.00058] [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: 10/11/2022] [Revised: 10/28/2022] [Accepted: 10/29/2022] [Indexed: 03/29/2023] Open
Abstract
Background and Aims Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results. Methods Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters. Results Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group (p=0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend. Conclusions TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796).
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Affiliation(s)
- Zhihong Liu
- Department of Infectious Diseases and Hepatology Unit, Institutes of Liver Diseases Research of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qinglong Jin
- The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yuexin Zhang
- The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Guozhong Gong
- The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Guicheng Wu
- Chongqing University Three Gorges Hospital, Chongqing, China
| | - Lvfeng Yao
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Xiaofeng Wen
- Liuzhou People’s Hospital, Liuzhou, Guangxi, China
| | - Zhiliang Gao
- The Third Affiliated Hospital of Zhongshan University, Guangzhou, Guangdong, China
| | - Yan Huang
- Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Daokun Yang
- The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
| | - Enqiang Chen
- West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Qing Mao
- The Southwest Hospital of AMU, Chongqing, China
| | - Shide Lin
- Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Jia Shang
- Henan Provincial People’s Hospital, Zhengzhou, Henan, China
| | - Huanyu Gong
- The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Lihua Zhong
- The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Huafa Yin
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | | | - Peng Hu
- The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qiong Wu
- Jiangsu Hansoh Pharmaceutical Group Co., Ltd, Lianyungang, Jiangsu, China
| | - Chao Pan
- Jiangsu Hansoh Pharmaceutical Group Co., Ltd, Lianyungang, Jiangsu, China
| | - Wen Jia
- Jiangsu Hansoh Pharmaceutical Group Co., Ltd, Lianyungang, Jiangsu, China
| | - Chuan Li
- Jiangsu Hansoh Pharmaceutical Group Co., Ltd, Lianyungang, Jiangsu, China
| | - Chang’an Sun
- Jiangsu Hansoh Pharmaceutical Group Co., Ltd, Lianyungang, Jiangsu, China
| | - Junqi Niu
- The First Hospital of Jilin University, Changchun, Jilin, China
| | - Jinlin Hou
- Department of Infectious Diseases and Hepatology Unit, Institutes of Liver Diseases Research of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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Jespersen S, Plomgaard P, Madsbad S, Hansen AE, Bandholm T, Pedersen BK, Ritz C, Weis N, Krogh-Madsen R. Effect of aerobic exercise training on the fat fraction of the liver in persons with chronic hepatitis B and hepatic steatosis: Trial protocol for a randomized controlled intervention trial- The FitLiver study. Trials 2023; 24:398. [PMID: 37312098 DOI: 10.1186/s13063-023-07385-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/17/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND The global prevalence of chronic hepatitis B is more than 300 million people, and in Denmark, 17,000 people are estimated to have chronic hepatitis B. Untreated, chronic hepatitis B can lead to the development of liver cirrhosis and liver cancer. There is no curable therapy. In persons with obesity and chronic hepatitis B infection, the development of hepatic steatosis imposes a double burden on the liver, leading to an increased risk of cirrhosis and liver cancer. In patients without chronic hepatitis B, exercise interventions have shown beneficial effects on hepatic steatosis through improvements in fat fraction of the liver, insulin resistance, fatty acid metabolism, and glucose metabolism, as well as activation of liver-induced regulatory protein secretion (hepatokines) after the exercise intervention. OBJECTIVE To investigate in persons with chronic hepatitis B and hepatic steatosis: Primary: Whether exercise will decrease the fat fraction of the liver. Secondary: If exercise will affect hepatokine secretion and if it will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure. METHODS A randomized, controlled, clinical intervention trial consisting of 12 weeks of aerobic exercise training or no intervention. Thirty persons with chronic hepatitis B and hepatic steatosis will be randomized 1:1. Before and after the intervention, participants will undergo an MRI scan of the liver, blood sampling, oral glucose tolerance test, fibroscan, VO2max test, DXA scan, blood pressure measurements, and optional liver biopsy. Lastly, a hormone infusion test with somatostatin and glucagon to increase the glucagon/insulin ratio for stimulating secretion of circulating hepatokines will be performed. The training program includes three weekly training sessions of 40 min/session over 12 weeks. DISCUSSION This trial, investigating high-intensity interval training in persons with chronic hepatitis B and hepatic steatosis, is the first exercise intervention trial performed on this group of patients. If exercise reduces hepatic steatosis and induces other beneficial effects of clinical markers in this group of patients, there might be an indication to recommend exercise as part of treatment. Furthermore, the investigation of the effect of exercise on hepatokine secretion will provide more knowledge on the effects of exercise on the liver. TRIAL REGISTRATION Danish Capital Regions committee on health research ethics reference: H-21034236 (version 1.4 date: 19-07-2022) and ClinicalTrials.gov: NCT05265026.
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Affiliation(s)
- Sofie Jespersen
- The Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- The Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
| | - Peter Plomgaard
- The Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- The Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Sten Madsbad
- The Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- The Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark
| | - Adam Espe Hansen
- The Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- The Department of Radiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Thomas Bandholm
- The Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- The Department of Physical and Occupational Therapy, Copenhagen University Hospital, Hvidovre, Denmark
- The Department of Clinical Research, Copenhagen University Hospital, Hvidovre, Denmark
| | - Bente Klarlund Pedersen
- The Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- The Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christian Ritz
- The National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
| | - Nina Weis
- The Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
- The Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rikke Krogh-Madsen
- The Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- The Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
- The Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Lu R, Liu Y, Hong T. Epidemiological characteristics and management of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis in China: A narrative review. Diabetes Obes Metab 2023; 25 Suppl 1:13-26. [PMID: 36775938 DOI: 10.1111/dom.15014] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/27/2023] [Accepted: 02/08/2023] [Indexed: 02/14/2023]
Abstract
AIM With industrialization and spread of the westernized lifestyle, the number of people affected by non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is growing rapidly in China; this has become a major public health concern. To better understand the burden and characteristics of NAFLD/NASH in China, we aim to perform a narrative review of the literature published in this field. MATERIALS AND METHODS We carried out a comprehensive electronic search of five English-language and three Chinese-language databases, to identify studies regarding NAFLD or NASH published from inception to November 30, 2022. Epidemiological studies of NAFLD/NASH in China were particularly noticed and summarized. We also searched the www. CLINICALTRIALS gov and www.chictr.org.cn websites for the registered trials on the treatment of the disease led by Chinese investigators or located in China. RESULTS The increasing rate of NAFLD prevalence in China is strikingly high, reaching more than twice that in western countries. The prevalence of NAFLD is nearly 30% of the general Chinese population, making it the leading cause of chronic liver diseases. The prevalence of NAFLD/NASH varies between provinces/regions, age groups, sexes, and individuals with different metabolic profiles. NAFLD co-exists in many Chinese patients with chronic hepatitis B. Since 2020, more Chinese studies have used the term metabolic-associated fatty liver disease (MAFLD), emphasizing the underlying metabolic disorders that occur concurrently with this disease. Several clinical trials involving lifestyle interventions, antidiabetic drugs, or traditional Chinese medicines, registered by Chinese investigators, have been completed or are ongoing. Moreover, several innovative targeted therapies developed in China are revolutionizing the treatment of NAFLD/NASH. CONCLUSIONS NAFLD has cast a heavy burden on the Chinese healthcare system. Chinese scholars are making efforts to achieve the optimal management of this disease.
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Affiliation(s)
- Ran Lu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Ye Liu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Tianpei Hong
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, 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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Zhang Q, Liang J, Yin J, Jiang Y, Yu N, Liao X, Zhao S, Wu L, Fan R. Real-life impact of tenofovir disoproxil fumarate and entecavir therapy on lipid profile, glucose, and uric acid in chronic hepatitis B patients. J Med Virol 2022; 94:5465-5474. [PMID: 35794065 DOI: 10.1002/jmv.27977] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 06/16/2022] [Accepted: 07/05/2022] [Indexed: 12/15/2022]
Abstract
The impact of long-term nucleos(t)ide analogs treatment on host metabolism is a concern. Hence, we conducted this study to compare the effect of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on metabolic parameters among chronic hepatitis B (CHB) patients. In this real-life retrospective study, 2030 CHB outpatients treated with ETV or TDF at Nanfang Hospital, China, were included. For treatment-naïve patients, pretreatment and semiannual metabolic parameters were collected. For treatment-experienced patients, metabolic parameters were collected at the first visit. Propensity score matching (PSM) was used to balance the effects of potential confounding factors. Among 122 treatment-naïve patients and 1908 treatment-experienced patients, ETV-treated patients were older with a higher percentage of metabolic syndrome. After PSM, the characteristics were comparable between the two groups. For treatment-naïve patients, four lipid parameters, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein, and triglyceride levels showed a decreasing trend during the 42-month TDF treatment, while they remained relatively stable or increased during ETV treatment. At Month 30, the levels of TC and LDL among TDF-treated patients were significantly lower than those among ETV-treated patients (TC: 4.7 mmol/L vs. 3.9 mmol/L, p = 0.004; LDL: 3.0 mmol/L vs. 2.4 mmol/L, p = 0.009). For treatment-experienced patients, we also observed lower levels of lipid parameters in patients with different durations of TDF treatment. The levels of glucose and uric acid were similar among ETV- and TDF-treated patients. TDF has a lipid-lowering effect in CHB patients, which provides a basis for the selection of antiviral drugs for aging CHB patients.
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Affiliation(s)
- Qi Zhang
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlin Liang
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junhua Yin
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yiyue Jiang
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ning Yu
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xingmei Liao
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Siru Zhao
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Leyuan Wu
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Rong Fan
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Santos CMDL, Brito MD, Castro PASVD, Vries TPD, Viana NL, Coelho MPP, Malheiro OB, Bering T, Gonzalez MC, Teixeira R, Cambraia RD, Rocha GA, Silva LD. Metabolic-associated fatty liver disease is associated with low muscle mass and strength in patients with chronic hepatitis B. World J Hepatol 2022; 14:1652-1666. [PMID: 36157867 PMCID: PMC9453457 DOI: 10.4254/wjh.v14.i8.1652] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 07/04/2022] [Accepted: 08/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although the prognostic relevance of sarcopenia has been increasingly recognised in the context of liver disease, there is a paucity of data evaluating body composition in patients with chronic hepatitis B (CHB). Beyond virus-related factors, nutritional and metabolic aspects can be associated with skeletal muscle abnormalities in these patients and should not be disregarded.
AIM To evaluate the association between components of sarcopenia and demographic, clinical, lifestyle, nutritional, and biochemical variables in CHB patients.
METHODS Dual-energy X-ray absorptiometry (DXA) was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for body mass index (ALMBMI). Muscle function was evaluated by hand grip strength (HGS) and the timed up and go test. Metabolic-associated fatty liver disease (MAFLD) was defined according to the criteria proposed by an international expert panel. A body shape index and the International Physical Activity Questionnaire were used to assess central obesity and physical activity level, respectively.
RESULTS This cross-sectional study included 105 CHB outpatients followed at the tertiary care ambulatory centre (mean age, 48.5 ± 12.0 years; 58.1% males; 76.2% without cirrhosis; 23.8% with compensated cirrhosis). The DXA-derived fat mass percentage was inversely correlated with the ALMBMI (r = - 0.87) and HGS (r = - 0.63). In the multivariable analysis, MAFLD, sedentarism and central obesity were positively and independently associated with low ALMBMI. MAFLD and central obesity were independently associated with low HGS.
CONCLUSION MAFLD and central obesity were associated with low muscle mass and strength in patients with chronic hepatitis B, independent of the liver disease stage.
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Affiliation(s)
- Cecy Maria de Lima Santos
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Matheus Duarte Brito
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Pedro Alves Soares Vaz de Castro
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Thais Pontello de Vries
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Nataly Lopes Viana
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Marta Paula Pereira Coelho
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Olívio Brito Malheiro
- Department of Locomotor System, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Tatiana Bering
- Department of Food and Nutrition, Universidade Federal de Mato Grosso, Cuiabá 78060-900, Mato Grosso, Brazil
| | - Maria Cristina Gonzalez
- Postgraduate Program in Health and Behaviour, Catholic University of Pelotas, Pelotas 96015-560, Rio Grande do Sul, Brazil
| | - Rosângela Teixeira
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Rodrigo Dias Cambraia
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Luciana Diniz Silva
- Sciences Applied to Adult Health Care Post-Graduate Programme Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
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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: 4] [Impact Index Per Article: 1.3] [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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11
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Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Xiao L, Li C, Wu Q, Sun C, Niu J, Hou J. Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B. Aliment Pharmacol Ther 2021; 54:1134-1149. [PMID: 34587302 PMCID: PMC9292801 DOI: 10.1111/apt.16611] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/10/2021] [Accepted: 09/07/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). AIM To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). METHODS We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. RESULTS We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. CONCLUSION TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).
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12
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Shi YW, Yang RX, Fan JG. Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion. World J Gastroenterol 2021; 27:3971-3983. [PMID: 34326608 PMCID: PMC8311534 DOI: 10.3748/wjg.v27.i26.3971] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 04/28/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
With the increasing incidence of obesity and metabolic syndrome worldwide, concomitant nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has become highly prevalent. The risk of dual etiologies, outcome, and mechanism of CHB with concomitant NAFLD have not been fully characterized. In this review, we assessed the overlapping prevalence of metabolic disorders and CHB, assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD, and discussed the remaining clinical issues to be addressed in the outcome of such patients. We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation. For CHB patients, it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses. The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.
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Affiliation(s)
- Yi-Wen Shi
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Rui-Xu Yang
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
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13
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Zhang J, Lin S, Jiang D, Li M, Chen Y, Li J, Fan J. Chronic hepatitis B and non-alcoholic fatty liver disease: Conspirators or competitors? Liver Int 2020; 40:496-508. [PMID: 31903714 DOI: 10.1111/liv.14369] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 12/16/2019] [Accepted: 01/02/2020] [Indexed: 02/06/2023]
Abstract
Despite the widespread use of vaccines and antiviral drugs, approximately 350-400 million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB is commonly observed, especially in Asian CHB populations; however, little is known regarding the relationship between these two diseases as comorbidities. In this review, we summarize recent advances in clinical and basic researches related to the underlying mutual interactions, as well as potential animal models to facilitate further investigation.
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Affiliation(s)
- Jianbin Zhang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shuangzhe Lin
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Daixi Jiang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Mengting Li
- Department of Gastroenterology, Yinzhou People's Hospital, Zhejiang, China
| | - Yuanwen Chen
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiangao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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