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Wu L, Li Z, Gao N, Deng H, Zhao Q, Hu Z, Chen J, Lei Z, Zhao J, Lin B, Gao Z. Interferon-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level. Heliyon 2024; 10:e32730. [PMID: 38975233 PMCID: PMC11226829 DOI: 10.1016/j.heliyon.2024.e32730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 06/07/2024] [Indexed: 07/09/2024] Open
Abstract
Background The correlation between metabolic syndrome (MetS) and hepatitis B surface antigen (HBsAg) loss remains to be further elucidated, particularly in patients receiving pegylated interferon-α (PEG-IFN) treatment. Methods 758 patients with low HBsAg quantification who had received nucleos(t)ide analog (NUC) therapy for at least one year and subsequently switched to or add on PEG-IFN therapy over an unfixed course were enrolled. 412 patients were obtained with baseline data matched. A total of 206 patients achieved HBsAg loss (cured group) within 48 weeks. Demographic and biochemical data associated with MetS were gathered for analysis. HepG2.2.15 cell line was used in vitro experiments to validate the efficacy of interferon-α (IFN-α). Results The proportion of patients with diabetes or hypertension in the uncured group was significantly higher than in the cured group. The levels of fasting blood glucose (FBG) and glycated albumin remained elevated in the uncured group over the 48 weeks. In contrast, the levels of blood lipids and uric acid remained higher in the cured group within 48 weeks. Triglycerides levels and liver steatosis of all patients increased after PEG-IFN therapy. Baseline elevated uric acid levels and hepatic steatosis may be beneficial for HBsAg loss. IFN-α could induce hepatic steatosis and indirectly promote HBsAg loss by increasing triglyceride level through upregulation of acyl-CoA synthetase long-chain family member 1(ACSL1). Conclusions IFN-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level through upregulation of ACSL1. Comorbid diabetes may be detrimental to obtaining HBsAg loss with PEG-IFN therapy in CHB patients.
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Affiliation(s)
- Lili Wu
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhihui Li
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Na Gao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hong Deng
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiyi Zhao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhaoxia Hu
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Junfeng Chen
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ziying Lei
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jinhua Zhao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bingliang Lin
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhiliang Gao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, 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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Lin KW, Kumar R, Shen F, Chan HLY, Wong GLH, Kumar R, Chow WC, Lin S, Wong VWS, Fan JG, Goh GBB. The utility of non-invasive tests to assess advanced fibrosis in Asian subjects with chronic hepatitis B and concomitant hepatic steatosis. Liver Int 2023; 43:1008-1014. [PMID: 36855842 DOI: 10.1111/liv.15541] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 01/11/2023] [Accepted: 02/07/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver-related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non-invasive tests (NITs) including FIB-4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. AIM To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. METHODOLOGY This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. RESULTS 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62-0.69) for FIB-4 and 0.63 (95% CI 0.60-0.66) for APRI. The specificities were 0.94 for FIB-4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63-0.71) for FIB-4, 0.60 (95% CI 0.56-0.64) for APRI and 0.65 (95% CI 0.61-0.69) for NFS. The specificities were 0.95 for FIB-4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. CONCLUSION The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB-4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects.
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Affiliation(s)
- Kenneth W Lin
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Academic Medical Centre, Singapore, Singapore
| | - Feng Shen
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Henry L-Y Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Department of Internal Medicine, Union Hospital, Hong Kong, Hong Kong
| | - Grace L-H Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
- Duke-NUS Academic Medical Centre, Singapore, Singapore
| | - Wan Cheng Chow
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Academic Medical Centre, Singapore, Singapore
| | - Su Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Clinical Research Center for Liver and Intestinal Diseases of Fujian Province, Fuzhou, China
| | - Vincent W-S Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - George B-B Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
- Duke-NUS Academic Medical Centre, Singapore, Singapore
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Tan YW, Wang JM, Zhou XB. Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease. World J Hepatol 2023; 15:237-254. [PMID: 36926239 PMCID: PMC10011903 DOI: 10.4254/wjh.v15.i2.237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/14/2022] [Accepted: 01/17/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) on liver disease, few have investigated the relationship between nonalcoholic steatohepatitis (NASH) defined by liver pathology and the prognosis of chronic HBV infection. Most patients were followed up for a short time. This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection. AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events [cirrhosis, hepatocellular carcinoma (HCC), and death] in patients with chronic hepatitis B (CHB) virus infection. METHODS We enrolled patients with chronic hepatitis B virus (HBV) infection who underwent liver biopsy at the Third People's Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020. Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected. Propensity score matching (PSM) was used to balance baseline parameters, Kaplan-Meier (K-M) survival analysis was used to evaluate the risk of clinical events, and Cox regression was used to analyze the risk factors of events. RESULTS Overall, 456 patients with chronic HBV infection were included in the study, of whom 152 (33.3%) had histologically confirmed NAFLD. The median follow-up time of the entire cohort was 70.5 mo. Thirty-four patients developed cirrhosis, which was diagnosed using ultrasound during the follow-up period. K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis (log-rank test, P > 0.05). Patients with CHB with fibrosis at baseline were more prone to cirrhosis (log-rank test, P = 0.046). After PSM, multivariate analysis showed that diabetes mellitus, ballooning deformation (BD), and platelet (PLT) were independent risk factors for cirrhosis diagnosed using ultrasound (P < 0.05). A total of 10 patients (2.2%) developed HCC, and six of these patients were in the combined NAFLD group. K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher (log-rank test, P < 0.05). Hepatocyte ballooning, and severe liver fibrosis were also associated with an increased risk of HCC (log-rank test, all P < 0.05). Cox multivariate analysis revealed that hepatocyte ballooning, liver fibrosis, and diabetes mellitus were independent risk factors for HCC. CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD. Diabetes mellitus, BD, and PLT were independent risk factors for liver cirrhosis. Patients with chronic HBV infection and NASH have an increased risk of HCC. BD, liver fibrosis, and diabetes mellitus are independent risk factors for HCC.
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Affiliation(s)
- You-Wen Tan
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China.
| | - Jia-Min Wang
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Xing-Bei Zhou
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
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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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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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High Rates of Liver Cirrhosis and Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Metabolic and Cardiovascular Comorbidities. Microorganisms 2021; 9:microorganisms9050968. [PMID: 33946154 PMCID: PMC8146494 DOI: 10.3390/microorganisms9050968] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/24/2021] [Accepted: 04/26/2021] [Indexed: 12/12/2022] Open
Abstract
Background: The prevalence of metabolic and cardiovascular diseases is rising worldwide. However, little is known about the impact of such disorders on hepatic disease progression in chronic hepatitis B (CHB) during the era of potent nucleo(s)tide analogues (NAs). Methods: We retrospectively analyzed a single-center cohort of 602 CHB patients, comparing the frequency of liver cirrhosis at baseline and incidences of liver-related events during follow-up (hepatocellular carcinoma, liver transplantation and liver-related death) between CHB patients with a history of diabetes, obesity, hypertension or coronary heart disease (CHD). Results: Rates of cirrhosis at baseline and liver-related events during follow-up (median follow-up time: 2.51 years; NA-treated: 37%) were substantially higher in CHB patients with diabetes (11/23; 3/23), obesity (6/13; 2/13), CHD (7/11; 2/11) or hypertension (15/43; 4/43) compared to CHB patients without the indicated comorbidities (26/509; 6/509). Multivariate analysis identified diabetes as the most significant predictor for cirrhosis (p = 0.0105), while comorbidities did not correlate with liver-related events in pre-existing cirrhosis. Conclusion: The combination of metabolic diseases and CHB is associated with substantially increased rates of liver cirrhosis and secondary liver-related events compared to CHB alone, indicating that hepatitis B patients with metabolic comorbidities warrant particular attention in disease surveillance and evaluation of treatment indication.
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Yoon JS, Lee HY, Chung SW, Kim SW, Chang Y, Lee YB, Cho EJ, Lee JH, Yu SJ, Kim H, Yoon JH, Kim YJ. Prognostic impact of concurrent nonalcoholic fatty liver disease in patients with chronic hepatitis B-related hepatocellular carcinoma. J Gastroenterol Hepatol 2020; 35:1960-1968. [PMID: 32128882 DOI: 10.1111/jgh.15026] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 02/24/2020] [Accepted: 03/01/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM As the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing globally, patients with both NAFLD and chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is also frequently found. This study aimed to investigate the clinical impact of concurrent NAFLD on the prognosis of patients with CHB-related HCC. METHODS Patients with CHB-related HCC who underwent surgical resection were consecutively selected from August 2009 to December 2013. The association between histologically proven concurrent NAFLD and clinical outcomes were analyzed. Propensity score (PS) matching was adapted to adjust for baseline characteristics. We also investigated the presence of nonalcoholic steatohepatitis (NASH) among patients with NAFLD and its association with clinical outcomes. RESULTS Among 338 CHB-related HCC patients selected, 196 patients (58.0%) were diagnosed with concurrent NAFLD. The median follow-up duration was 74.9 months. The patients with NAFLD tended to have better recurrence-free survival (RFS; log-rank, P = 0.16) and had significantly better overall survival (OS; log-rank, P = 0.004) than those without NAFLD. However, the survival benefit of the concurrent NAFLD was not significant in a multivariable Cox analysis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73, P = 0.84) or an analysis after PS matching (log-rank, P = 0.57). Regarding the presence or absence of NASH, no differences in the RFS (log-rank, P = 0.61) and OS (log-rank, P = 0.26) were found. CONCLUSIONS Concurrent NAFLD was not associated with both RFS and OS in patients with CHB-related HCC after adjusting for baseline characteristics. Moreover, NAFLD patients with NASH did not have significantly different clinical outcomes compared with NAFLD patients without NASH.
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Affiliation(s)
- Jun Sik Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
| | - Hyo Young Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Eulji General Hospital, Eulji University School of Medicine, Seoul, South Korea
| | - Sung Won Chung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sun Woong Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Chang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.,Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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Li ZM, Kong CY, Zhang SL, Han B, Zhang ZY, Wang LS. Alcohol and HBV synergistically promote hepatic steatosis. Ann Hepatol 2020; 18:913-917. [PMID: 31147179 DOI: 10.1016/j.aohep.2019.04.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 03/28/2019] [Accepted: 04/24/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Hepatitis virus and alcohol are the main factors leading to liver damage. Synergy between hepatitis B virus (HBV) and alcohol in promoting liver cell damage and disease progression has been reported. However, the interaction of HBV and ethanol in hepatic steatosis development has not been fully elucidated. METHODS Eight-week-old male C57BL/6 mice were treated with or without HBV, ethanol, or the combination of HBV and ethanol (HBV+EtOH), followed by a three-week high-fat diet (HFD) regimen. Liver histology, serum biomarkers, and liver triglyceride levels were analysed. Furthermore, a meta-analysis of the effects of alcohol and HBV on hepatic steatosis in populations was performed. RESULTS Hepatic steatosis was significantly more severe in the HBV+EtOH group than in the other groups. The serum alanine aminotransferase, aspartate aminotransferase and liver triglyceride levels in the HBV+EtOH group were also significantly higher than those in the other groups. The HBeAg and HBsAg levels in the HBV+EtOH group were significantly higher than those in the pair-fed HBV-infected mice. In addition, the meta-analysis showed that alcohol consumption increased the risk of hepatic steatosis by 43% in HBV-infected patients (pooled risk ratio (RR)=1.43, P<0.01). CONCLUSIONS Alcohol and HBV synergistically promote high-fat diet-induced hepatic steatosis in mice. In addition, alcohol consumption increases the risk of hepatic steatosis in HBV-infected patients.
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Affiliation(s)
- Zhan-Ming Li
- Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Chao-Yue Kong
- Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Shi-Long Zhang
- Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Bing Han
- Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Zheng-Yan Zhang
- Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Li-Shun Wang
- Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
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Chen YC, Jeng WJ, Hsu CW, Lin CY. Impact of hepatic steatosis on treatment response in nuclesos(t)ide analogue-treated HBeAg-positive chronic hepatitis B: a retrospective study. BMC Gastroenterol 2020; 20:146. [PMID: 32397963 PMCID: PMC7216492 DOI: 10.1186/s12876-020-01289-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 04/30/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The impact of hepatic steatosis (HS) on treatment response following nucleos(t)ide analogue (NA) treatment for chronic hepatitis B (CHB) patients has not been clearly elucidated. We aimed to investigate the difference in HBeAg seroclearance between NA-treated HBeAg-positive CHB patients with and without HS. METHODS We retrospectively recruited HBeAg-positive CHB patients receiving liver biopsy and NA monotherapy. The baseline clinical characteristics and cumulative incidence of HBeAg seroclearance were compared between patients with and without HS and age/gender-matched subgroup analysis was performed. RESULTS A total of 196 patients were enrolled from 2003 April to 2016 October. The mean age was 39.6 ± 11.2 years, 142 (72.4%) were males and 94 (48%) had histological evidence of HS. Median treatment duration and follow-up period were 24.3 months and 54.9 months, respectively. HBeAg seroclearance was achieved in 56/102 (54.9%) and 54/94 (57.4%) patients with and without HS, respectively (p = 0.830). The 5-year cumulative incidence of HBeAg seroclearance in patients with and without HS was 62.8 and 67.7% in overall population (p = 0.398) and 62.4 and 66.9% in age/gender-matched subgroups (p = 0.395), respectively. The rate of HBeAg seroclearance was comparable between patients with or without HS in different NA monotherapy (all p > 0.05). CONCLUSIONS HS had no significant impact on HBeAg seroclearance in HBeAg-positive CHB patients with NA monotherapy during long-term follow-up.
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Affiliation(s)
- Yi-Cheng Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China. .,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China
| | - Chao-Wei Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, and University, Linkou, No 5, Fu Hsing Street, Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China.,College of Medicine, Chang Gung University, No.259, Wen Hua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan, Republic of China
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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: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 12/16/2019] [Accepted: 01/02/2020] [Indexed: 02/06/2023]
Abstract
Despite the widespread use of vaccines and antiviral drugs, approximately 350-400 million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB is commonly observed, especially in Asian CHB populations; however, little is known regarding the relationship between these two diseases as comorbidities. In this review, we summarize recent advances in clinical and basic researches related to the underlying mutual interactions, as well as potential animal models to facilitate further investigation.
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Affiliation(s)
- Jianbin Zhang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shuangzhe Lin
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Daixi Jiang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Mengting Li
- Department of Gastroenterology, Yinzhou People's Hospital, Zhejiang, China
| | - Yuanwen Chen
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiangao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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14
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Liver Fibrosis is Associated with NAFLD Activity Score in Chronic Hepatitis B Patients with Liver Steatosis. HEPATITIS MONTHLY 2018. [DOI: 10.5812/hepatmon.84182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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15
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Chen Y, Fan C, Chen Y, Liu H, Wang S, Dong P, Li L, Ding H. Effect of hepatic steatosis on the progression of chronic hepatitis B: A prospective cohort and in vitro study. Oncotarget 2017; 8:58601-58610. [PMID: 28938582 PMCID: PMC5601678 DOI: 10.18632/oncotarget.17380] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 03/22/2017] [Indexed: 12/22/2022] Open
Abstract
AIM To characterize the effect of hepatic steatosis (HS) on the progression of chronic hepatitis B. METHODS A total of 162 chronic hepatitis B (CHB) patients confirmed by liver biopsy were involved in this study. All subjects were prospectively followed-up for 5 years in real-life clinical practice. Fibrosis stage was determined using aspartate aminotransferase-to-platelet ratio index (APRI). The end-point was cirrhosis, liver cancer or death. The effects of steatosis on the biological behavior of hepatocellular carcinoma cells were investigated using oleic acid-induced lipid accumulation in HepG2, HLE, PLC, and SMMC-7721 cells. RESULTS Mean age, body mass index, and serum cholesterol were significantly higher in CHB patients with HS than those without HS at baseline (p< 0.05). The APRI was lower in patients without HS at baseline (p<0.05). Compared to patients with HS, APRI of patients without HS decreased significantly during the follow-up period (p<0.05). The 5-year cumulative incidence of cirrhosis were 4.17% and 5.19% in patients without and with HS, respectively (p>0.05). The multivariate analysis showed that older (RR 1.07, 95% CI 0.996-1.149, p = 0.065) and S3 stage of liver fibrosis (RR 3.50, 95% CI 0.812-15.117, p=0.093) were risk factors for the progression to cirrhosis. In vitro, cell steatosis promoted proliferation and migration of HCC cells and conferred cell cycle at S phase. CONCLUSION The older and S3 stage of fibrosis may be risk factors for progression to cirrhosis in CHB patients with HS. HS may aggravate liver disease, promoting HCC progression.
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Affiliation(s)
- Yangqin Chen
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
| | - Chunlei Fan
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
| | - Yuhan Chen
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
| | - Hui Liu
- Department of Pathology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
| | - Shanshan Wang
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
- Beijing Institute of Hepatology, Beijing 100069, China
| | - Peiling Dong
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
| | - Lei Li
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
| | - Huiguo Ding
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
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16
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Chen J, Wang ML, Long Q, Bai L, Tang H. High value of controlled attenuation parameter predicts a poor antiviral response in patients with chronic hepatits B. Hepatobiliary Pancreat Dis Int 2017; 16:370-374. [PMID: 28823366 DOI: 10.1016/s1499-3872(16)60144-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Accepted: 09/05/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis based on vibration-controlled transient elastography. The objective of this study was to investigate the effect of high value of CAP on antiviral therapy in patients with chronic hepatitis B (CHB). METHODS Patients with CHB receiving enticavir for initial antiviral therapy were studied; they were divided into the high CAP group and normal CAP group at baseline according to the CAP values. The effect of the antiviral therapy between the two groups were compared at week 12, 24 and 48. Patients with high CAP value at baseline were divided into three subgroups, mild, moderate and severe elevation; the therapeutic response were compared among patients with normal CAP and subgroups of patients with elevated CAP. RESULTS A total of 153 patients were enrolled. Among them, 63 were in the high CAP group and 90 in the normal CAP group. Patients with high CAP had lower rates of ALT normalization and HBV DNA clearance in response to antiviral therapy compared with those with normal CAP at week 12, 24 and 48. Further analysis showed that the rate of ALT normalization in patients with mildly and moderately elevated CAP were significant lower than those with normal CAP at week 12 and 24; while the difference was not significant between the patients with normal CAP and those with severely elevated CAP. The rate of HBV DNA clearance was significantly lower in patients with severely elevated CAP compared with those with normal CAP at week 12, 24 and 48. CONCLUSION CHB patients with high CAP had poor response to antiviral therapy.
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Affiliation(s)
- Jing Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Meng-Lan Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Qin Long
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
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17
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Verdelho Machado M. Controlled Attenuation Parameter as a Noninvasive Method to Detect and Quantify Hepatic Steatosis in Chronic Liver Disease: What Is the Clinical Relevance? GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2017; 24:157-160. [PMID: 29255744 DOI: 10.1159/000478944] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 06/23/2017] [Indexed: 12/20/2022]
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18
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The Effect of Hepatosteatosis on Response to Antiviral Treatment in Patients with Chronic Hepatitis B: A Meta-Analysis. Gastroenterol Res Pract 2017; 2017:1096406. [PMID: 28421108 PMCID: PMC5379138 DOI: 10.1155/2017/1096406] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Accepted: 02/08/2017] [Indexed: 12/23/2022] Open
Abstract
Background. This study is to systematically analyze the effects of hepatosteatosis on the response to antiviral treatment in patients with chronic hepatitis B (CHB) and hepatosteatosis. Methods. Systematic search was performed in PubMed, Embase, Web of Science, Elsevier, and the Chinese BioMedical literature databases for relevant studies published until February 2016. Treatment outcomes were compared between patients with CHB plus concomitant hepatosteatosis and those without hepatosteatosis. Results. A total of 8 prospective cohort studies (399 patients with CHB plus hepatosteatosis and 688 patients with only CHB) were included. Biochemical and virological response at both 48 and 96 weeks were significantly lower in patients with CHB plus hepatosteatosis as compared to that in patients with only CHB. Subgroup analysis based on methods used for diagnosis of hepatosteatosis and treatment regimens showed that when hepatosteatosis was diagnosed on Doppler ultrasound and treated with nucleotide analogues, patients with CHB plus hepatosteatosis showed lower biochemical (62.7% versus 75.8%, P = 0.002) and virological response (66.2% versus 72.3%, P = 0.006) as compared to that in patients with CHB. Conclusion. Hepatosteatosis lowers the efficacy of antiviral treatment in patients with CHB, especially when hepatosteatosis was diagnosed on ultrasound findings and treated with nucleotide analogues.
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19
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Lim CT, Kumar R. Hepatitis B and concomitant hepatic steatosis. ANNALS OF TRANSLATIONAL MEDICINE 2017; 5:38. [PMID: 28251117 DOI: 10.21037/atm.2016.12.04] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hepatic steatosis is becoming more common in Asia with prevalence becoming as common as Western countries. Concomitant Hepatitis B and hepatic steatosis is increasingly encountered in clinical practice. The interaction between the two concomitant conditions at both molecular level and clinical outcome remains to be explored. The present review is aimed at summarizing the existing literature on the complex interaction of the two-concomitant disease.
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Affiliation(s)
- Chong Teik Lim
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
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20
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Kumar R, Boon-Bee Goh G. Chronic hepatitis B and fatty liver: Issues in clinical management. Clin Res Hepatol Gastroenterol 2016; 40:755-759. [PMID: 26850361 DOI: 10.1016/j.clinre.2015.12.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 11/19/2015] [Accepted: 12/25/2015] [Indexed: 02/08/2023]
Abstract
With an increasing incidence of non-alcoholic fatty livers, the existence of concomitant hepatitis B and fatty liver is becoming more common in clinical practice. In clinical practice, the concomitant existence of hepatitis B and fatty livers raises practical issues in clinical management. It becomes more difficult for the clinician to decide on the mode of treatment in the case of elevated Alanine aminotransferase (ALT) and in deciding potential causes, whether they are related to chronic hepatitis B or to non-alcoholic steatohepatitis (NASH). With evolving changes in the practice and knowledge of non-alcoholic fatty liver disease and chronic hepatitis B, clinical judgment on the predominant disease becomes essential for their coexistence. This short review is aimed at reviewing the evidence available on the frequency of the two diseases existing concomitantly, possible ways of differentiating the two, the prognosis, outcomes of treatment and a possible common pathway.
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Affiliation(s)
- Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore; Cancer research centre of Lyon (CRCL), INSERM U1052, Lyon, France.
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
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21
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Lee J, Yoo SH, Sohn W, Kim HW, Choi YS, Won JH, Heo JY, Park SJ, Park YM. Obesity and hepatocellular carcinoma in patients receiving entecavir for chronic hepatitis B. Clin Mol Hepatol 2016; 22:339-349. [PMID: 27729627 PMCID: PMC5066372 DOI: 10.3350/cmh.2016.0021] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 06/13/2016] [Accepted: 06/29/2016] [Indexed: 12/11/2022] Open
Abstract
Background/Aims This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. Methods This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). Results The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm2 (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m2 (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm2 (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). Conclusion HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.
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Affiliation(s)
- Jaemin Lee
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Sun Hong Yoo
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Won Sohn
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Yong Sun Choi
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Jung Ho Won
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Jin Young Heo
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Sang Jong Park
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Young Min Park
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
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22
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Gong L, Liu J, Wang J, Lou GQ, Shi JP. Hepatic Steatosis as a Predictive Factor of Antiviral Effect of Pegylated Interferon Therapy in Patients With Hepatitis B. Transplant Proc 2016; 47:2886-91. [PMID: 26707308 DOI: 10.1016/j.transproceed.2015.10.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 10/08/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS This study sought to evaluate the impact of hepatic steatosis, a common hepatocyte change in nonalcoholic fatty liver disease, upon response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B (CHB). METHODS Eighty-nine consecutive CHB patients from the Affiliated Hospital of Hangzhou Normal University receiving 48 weeks of PEG-IFN therapy were enrolled in this study, and 56 patients were followed up for 48 weeks among subjects with completed therapy. Baseline characteristics, end-of-treatment response (ETR), and sustained viral response (SVR) to PEG-IFN therapy were evaluated. Univariate analysis and multivariate logistic regression were applied to find independent factors of hepatic steatosis and PEG-IFN treatment failure. RESULTS Steatosis was present in 34.5% (31 of 89) of liver biopsy samples. ETR to PEG-IFN therapy was 56.17% (50 of 89) at 48 weeks, and SVR to PEG-IFN therapy was 57.6% (32 of 56) at 96 weeks. There was no significant difference in ETR between the patients with hepatic steatosis and those without hepatic steatosis at 48 weeks (P > .05), whereas SVR was higher in patients without hepatic steatosis than in those with hepatic steatosis at 96 weeks (P < .05). Multivariate analysis showed that the sustained response rate was independently associated with steatosis, fibrosis, aspartate aminotransferase, C-reactive protein, and ferritin. Hepatic steatosis was a prediction factor with the sustained response. CONCLUSIONS Hepatic steatosis may be a predictive factor of response to PEG-IFN therapy in patients with CHB.
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Affiliation(s)
- L Gong
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China
| | - J Liu
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China
| | - J Wang
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China
| | - G Q Lou
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China
| | - J P Shi
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China.
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23
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Liu X, Shen Z, Zhang H, Liang J, Lin H. Interleukin-21 Is Associated with Early Antiviral Response in Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease. J Interferon Cytokine Res 2016; 36:367-373. [PMID: 26840345 DOI: 10.1089/jir.2015.0129] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) becomes a characteristic of liver disease. Interleukin-21 (IL-21) plays an important role in the control of chronic hepatitis B (CHB). We aimed to investigate the relationship between IL-21 and early (24 weeks) viral response (EVR) to antiviral therapy in patients with coexistence of CHB and NAFLD (CHB + NAFLD). A prospective study was carried out in hepatitis B e antigen (HBeAg)-positive CHB + NAFLD and CHB patients receiving Entecavir for initial antiviral therapy, by recording demographic, anthropometric, and clinical data at baseline 12 and 24 weeks. Univariate analysis, correlation analysis, and receiver operating characteristic curve (ROC) were applied to find related factors with EVR. Forty CHB + NAFLD patients and 20 CHB patients entered final analysis. At baseline, IL-21, triglyceride (TG), cholesterol (CHOL), glutanyltransferase (GGT), body mass index (BMI), and computed tomography (CT) ratio of liver/spleen showed significant difference between the 2 groups. Although no significant difference was found, EVR rates was lower in CHB + NAFLD than CHB (75% vs. 90%, P = 0.053). Baseline IL-21 was associated with BMI, CT ratio of liver/spleen, TG, CHOL, and HBeAg level in CHB + NAFLD patients, whose IL-21, alanine aminotransferase, aspartate aminotransferase, CHOL, BMI, and CT ratio of liver/spleen at baseline was associated with EVR. Only the level of IL-21 exhibited significant increase from 0 to 12 weeks, while the change line of other associated factors was nearly parallel between EVR group and non-EVR group. ROC discovered the level of IL-21 at 12 weeks implied a strong predictive value for EVR. We deduced that IL-21 was associated with EVR, and the elevated level of IL-21 at treatment week 12 can predict EVR in CHB + NAFLD patients.
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Affiliation(s)
- Xudong Liu
- 1 Department of Liver Disease, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine , Nanning, China
| | - Zhen Shen
- 2 Department of Liver Disease, Huangshi Traditional Chinese Medicine , Huangshi, China
| | - Hongxing Zhang
- 1 Department of Liver Disease, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine , Nanning, China
| | - Jian Liang
- 1 Department of Liver Disease, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine , Nanning, China
| | - Hai Lin
- 1 Department of Liver Disease, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine , Nanning, China
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24
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Jin LX, Hong MZ. Influence of hepatic steatosis on chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2016; 24:1366-1371. [DOI: 10.11569/wcjd.v24.i9.1366] [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] [Indexed: 02/06/2023] Open
Abstract
Worldwide, nonalcoholic fatty liver disease (NAFLD) has a high prevalence with the rising rates of overweight and/or obesity. Chronic hepatitis B (CHB) virus infection is another common cause of infectious liver diseases. In practice, the overlap between NAFLD and CHB is rather common. In this review, we summarize the relationship between NAFLD and CHB, the influence of NAFLD on CHB, and the role of the metabolic syndrome in the development of hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Recent advances in understanding the reason CHB is prone to overlap NAFLD will be discussed. The adverse effects caused by NAFLD on the treatment and progression of CHB will be also elucidated. NAFLD overlapping CHB often raises a great challenge to the clinicians, in terms of diagnosis or treatment. Therefore, appropriate management of this complex situation is needed.
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25
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Haga Y, Kanda T, Sasaki R, Nakamura M, Nakamoto S, Yokosuka O. Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis. World J Gastroenterol 2015; 21:12989-12995. [PMID: 26675364 PMCID: PMC4674717 DOI: 10.3748/wjg.v21.i46.12989] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Revised: 09/07/2015] [Accepted: 10/17/2015] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.
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Interactions of Hepatitis B Virus Infection with Nonalcoholic Fatty Liver Disease: Possible Mechanisms and Clinical Impact. Dig Dis Sci 2015; 60:3513-24. [PMID: 26112990 DOI: 10.1007/s10620-015-3772-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Accepted: 06/17/2015] [Indexed: 12/19/2022]
Abstract
Hepatitis B virus (HBV) infection is a major etiology of chronic liver disease worldwide. In the past decade, nonalcoholic fatty liver disease (NAFLD) has emerged as a common liver disorder in general population. Accordingly, the patient number of chronic hepatitis B (CHB) concomitant with NAFLD grows rapidly. The present article reviewed the recent studies aiming to explore the relationship between CHB and NAFLD from different aspects, including the relevant pathogenesis of CHB and NAFLD, the intracellular molecular mechanisms overlaying HBV infection and hepatic steatosis, and the observational studies with animal models and clinical cohorts for analyzing the coincidence of the two diseases. It is concluded that although numerous cross-links have been suggested between the molecular pathways in HBV infection and NAFLD pathogenesis, regarding whether HBV infection can substantially interfere with the occurrence of NAFLD or vice versa in the patients, there is still far from a conclusive agreement.
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Yilmaz B, Koklu S, Buyukbayram H, Yalçin K, Korkmaz U, Posul E, Can G, Kurt M. Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis. Afr Health Sci 2015; 15:714-718. [PMID: 26957957 PMCID: PMC4765474 DOI: 10.4314/ahs.v15i3.3] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The effect of hepatitis B virus (HBV) infection on fatty liver disease is unclear. OBJECTIVES The aim of this study was to investigate the viral and host causes of fatty liver in chronic hepatitis B (CHB) patients. This study included 88 CHB patients of which 17 were not treated. Liver biopsy was performed in each patient. Group 1 included those with hepatic steatosis (n=28) and group 2 those without hepatic steatosis. The groups were compared in terms of age, body mass index (BMI), Homeostasis Model Assessment- Insulin Resistance (HOMA-IR), viral load, biochemical parameters and histological findings. Patients in group 1 were subdivided according to the degree of steatosis as follows: grade 1 (15 patients, 53.6%), grade 2 (6 patients, 21.4%), and grade 3 (7 patients, 25%). RESULTS In group 1 (n=28), mean age, BMI, cholesterol, and HOMA-IR were found to be significantly higher than in group 2 (n=60). There were no significant differences in the positivity of viral load, HbeAg, treatment, fibrosis and other laboratory parameters between the two groups. HOMA-IR was the only independent predictive factor of liver steatosis in patients with CHB in logistic regression analysis. CONCLUSION Hepatic steatosis in CHB patients was associated with host metabolic factors.
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Affiliation(s)
- Bulent Yilmaz
- Department of Internal Medicine, Dicle University School of Medicine, Ankara, Turkey
| | - Seyfettin Koklu
- Department of Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
| | - Huseyin Buyukbayram
- Department of Pathology, Dicle University School of Medicine, Ankara, Turkey
| | - Kendal Yalçin
- Department of Gastroenterology, Dicle University School of Medicine, Ankara, Turkey
| | - Ugur Korkmaz
- Department of Gastroenterology, Bolu Izzet Baysal State Hospital, Bolu, Turkey
| | - Emrah Posul
- Department of Gastroenterology, Abant Izzet Baysal University, Faculty of Medicine, Bolu, Turkey
| | - Guray Can
- Department of Gastroenterology, Abant Izzet Baysal University, Faculty of Medicine, Bolu, Turkey
| | - Mevlut Kurt
- Department of Gastroenterology, Abant Izzet Baysal University, Faculty of Medicine, Bolu, Turkey
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Hsiang JC, Wong GLH, Chan HLY, Chan AWH, Chim AML, Wong VWS. Metabolic syndrome delays HBeAg seroclearance in Chinese patients with hepatitis B. Aliment Pharmacol Ther 2014; 40:716-26. [PMID: 25039861 DOI: 10.1111/apt.12874] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Revised: 04/19/2014] [Accepted: 06/22/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Delayed hepatitis B e antigen (HBeAg) seroclearance increases the risk of cirrhosis and hepatocellular carcinoma (HCC). The effect of metabolic syndrome (MetS) on HBeAg seroclearance in chronic hepatitis B (CHB) patients remains unclear. AIMS To examine the effect of MetS on HBeAg seroclearance. METHODS A prospective cohort of 413 treatment-naïve HBeAg-positive CHB patients from 2005 to 2012 was studied. Clinical, virological and histological parameters were evaluated. The patients were classified into three groups according to the metabolic characteristics; normal, pre-MetS and MetS based on the International Diabetes Federation criteria. The primary outcome was age at HBeAg seroclearance. RESULTS The overall HBeAg seroclearance rate was 11.4% per annum during 19 351 patient-months of follow-up with no difference in HBeAg seroclearance rates between 162 treatment-free and 251 patients receiving nucleos(t)ide analogues. Patients with pre-MetS and MetS were older when HBeAg seroclearance occurred (44 ± 12 and 53 ± 7 years, respectively) than the normal patients (37 ± 9 years, all P < 0.01). Patients with pre-MetS and MetS had more advanced liver fibrosis (33.0% and 53.1%, respectively) than the normal patients (18.4%, all P < 0.05). By the age of 50, 59.3% of the metabolic normal patients, 42.1% of the pre-MetS and 18.7% of the MetS patients had achieved HBeAg seroclearance (all P < 0.05, except P = 0.07 for pre-MetS vs. MetS). In multivariate analysis, MetS and type II diabetes at baseline were predictors of delayed HBeAg seroclearance after adjusting for viral load, anti-viral therapy and necroinflammatiom. CONCLUSION Chinese patients with chronic hepatitis B and with pre-metabolic syndrome or metabolic syndrome have delayed HBeAg seroclearance.
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Affiliation(s)
- J C Hsiang
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong , Hong Kong, China
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Pais R, Rusu E, Ratziu V. The impact of obesity and metabolic syndrome on chronic hepatitis B and drug-induced liver disease. Clin Liver Dis 2014; 18:165-78. [PMID: 24274872 DOI: 10.1016/j.cld.2013.09.015] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Steatosis and insulin resistance (IR) are no more frequent in chronic hepatitis B (CHB) than in the general population. Although experimental studies suggest that the HBx protein induces liver fat, human studies have shown that steatosis and IR are related to coexistent metabolic risk factors, thus epidemiologically linked rather than virally induced. Diabetes and obesity are associated with advanced fibrosis and increased risk of hepatocellular carcinoma in CHB. Despite abundant experimental data showing that fatty liver is more susceptible to liver injury, drug-induced liver disease seems no more frequent in NAFLD patients, except, possibly, a higher incidence but not severity of acetaminophen hepatotoxicity.
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Affiliation(s)
- Raluca Pais
- Department of Hepatogastroenterology, Université Pierre et Marie Curie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Inserm UMR_S 938, Paris 75013, France
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Kumar M, Rastogi A, Singh T, Behari C, Gupta E, Garg H, Kumar R, Bhatia V, Sarin SK. Controlled attenuation parameter for non-invasive assessment of hepatic steatosis: does etiology affect performance? J Gastroenterol Hepatol 2013; 28:1194-1201. [PMID: 23425053 DOI: 10.1111/jgh.12134] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/23/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatic steatosis is an important parameter to assess in chronic liver disease patients. The controlled attenuation parameter (CAP) assesses liver steatosis using transient elastography. AIM To determine the accuracy of CAP for evaluation of hepatic steatosis in chronic hepatitis B virus (CHBV)-infected, chronic hepatitis C virus (CHCV)-infected, and non-alcoholic fatty liver disease (NAFLD) patients and to determine the influence of etiology on the diagnostic accuracy of CAP. METHODS One hundred forty-six CHBV patients, 108 CHCV-infected patients and 63 patients with NAFLD, who underwent both liver biopsy and successful CAP measurements within the study period, were assessed. Area under the receiver operating characteristics was used to evaluate performance of CAP for diagnosing steatosis compared with biopsy. RESULTS Multivariate analysis found that CAP correlated with body mass index (odds ratio, 95% confidence interval = 4.09 [1.2-6.8] for CHBV; 4.7 [1.1-8.4] for CHCV, and 16.2 [9.1-24.5] for NAFLD patients respectively) and hepatic steatosis score on biopsy (odds ratio, 95% confidence interval = 30.7 [19.2-42.2] for CHBV; 24.2 [11.5-37.3] for CHCV, and 21.8 [10.1-45.0] for NAFLD patients respectively). Area under the receiver operating characteristics for CAP was 0.683 (0.601-0.757) for steatosis (S) ≥ 6%, 0.793 (0.718-0.856) for S > 33%, and 0.841 (0.771-0.896) for S > 66% respectively for CHBV-infected patients. There was no difference in accuracy of CAP for assessing liver fat among CHBV, CHCV, and NAFLD patients. CONCLUSIONS CAP is a novel, non-invasive tool that can detect and quantify steatosis accurately among CHBV, CHCV, and NAFLD patients, the accuracy being similar for all the three groups of patients.
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Affiliation(s)
- Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Price JK, Srivastava R, Bai C, Diao G, Gerber LH, Younossi ZM. Comparison of activity level among patients with chronic liver disease. Disabil Rehabil 2012; 35:907-12. [PMID: 22931359 DOI: 10.3109/09638288.2012.712601] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
PURPOSE To determine whether self-reported maximal and daily activity levels are impaired among patients with nonalcoholic fatty liver disease (NAFLD), hepatitis C (HCV) and hepatitis B (HBV). METHODS Clinicodemographic, diagnostic, self-report and standard laboratory data were obtained. Univariate, multivariate and regression analyses were performed comparing group maximal (Maximum Activity Score [MAS]) and daily activity scores (Adjusted Activity Score [AAS]), adjusted for age and gender. RESULTS Two hundred twenty-two patients completed activity-level self-reports (mean age [52.4 ± 10.0 years], BMI [28.3 ± 6.58], 31.2% NAFLD, 48.3% HCV, 20.3% HBV). On multivariate analysis, significantly higher MAS (p < 0.05) and AAS in HBV patients correlated with absence of cirrhosis, younger age, male gender (higher MAS) and lower BMI (higher AAS). Lowest activity levels were found primarily in obese patients (p < 0.009). Compared with population norms, NAFLD and HCV cohorts scored mildly disabled on MAS; the HBV cohort scored low normal. Mild disability on AAS was observed in patients with HBV; moderate disability in those with NAFLD, HCV. CONCLUSIONS All groups had significantly lower activity levels than population norms. Nonobese patients showed significantly less disability than obese patients. Patients with NAFLD and HCV are likely to have lower levels than those with HBV without cirrhosis. This presents an additional risk factor for disability and mortality. IMPLICATIONS FOR REHABILITATION • Hepatitis B (HBV), hepatitis C (HCV), and nonalcoholic fatty liver disease (NAFLD) patients had significantly lower activity levels than expected for their age and gender, as measured by the Human Activity Profile (HAP). • Overweight and normal weight chronic liver disease (CLD) patients showed significantly less disability than obese chronic liver disease patients. • Patients with NAFLD and HCV are likely to participate in low levels of activity that require fewer metabolic equivalents for completion, adding an additional risk factor for disability and mortality. • Targeting low activity level in CLD patients, and decreasing BMI below the obesity threshold, may reduce disability and risk of mortality.
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Chung WG, Kim HJ, Choe YG, Seok HS, Chon CW, Cho YK, Kim BI, Koh YY. Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naïve patients with chronic hepatitis B infection. Clin Mol Hepatol 2012; 18:195-202. [PMID: 22893870 PMCID: PMC3415882 DOI: 10.3350/cmh.2012.18.2.195] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Revised: 04/11/2012] [Accepted: 04/12/2012] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND/AIMS The aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV) therapy in chronic hepatitis B (CHB) patients. METHODS The medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI) values and Alcohol Use Disorders Identification Test (AUDIT) scores were obtained at 6 months after the initiation of ETV (0.5 mg daily) treatment. RESULTS A BMI of 25 kg/m(2) or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3%) were obese and 17 (19.3%) were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT) normalization, and hepatitis B virus (HBV)-DNA negativity (<300 copies/mL) at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033). CONCLUSIONS Obesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users.
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Affiliation(s)
- Won Gil Chung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hong Joo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Gil Choe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyo Sun Seok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chang Wook Chon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung Ik Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Yool Koh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bundang Jaesaeng Hospital, Seongnam, Korea
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Association between hepatic steatosis and entecavir treatment failure in Chinese patients with chronic hepatitis B. PLoS One 2012; 7:e34198. [PMID: 22479562 PMCID: PMC3316632 DOI: 10.1371/journal.pone.0034198] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2011] [Accepted: 02/23/2012] [Indexed: 12/16/2022] Open
Abstract
Background The coexistence of HBV infection and nonalcoholic fatty liver disease (NAFLD) becomes characteristic of liver disease in China, with unknown bilateral influence. We aimed to investigate the effect of hepatic steatosis, a common hepatocyte change in NAFLD, on antiviral therapy in patients with chronic hepatitis B (CHB). Methods and Findings We carried out a prospective nested case control study in CHB patients receiving Entecavir for initial antiviral therapy, by recording demographic, anthropometric and clinical data at baseline, 24wk, 48wk and 96wk. Univariate analysis and multivariate logistic regression were applied to find out independent factors of hepatic steatosis and Entecavir treatment failure. The rates of HBV-DNA clearance, HBeAg seroconversion and ALT normalization were compared between CHB patients with and without steatosis by post hoc analysis. A total of 267 Chinese patients with CHB entered final analysis, with overall percentages of hepatic steatosis and HBeAg positive as 30.5% and 62.4%. Multivariate analysis showed waist circumference, serum TG and uric acid levels were independent factors of hepatic steatosis. The response rates to Entecavir were 54.9%, 63.8%, 74.2% at 24wk, 48wk and 96wk. Hepatic steatosis was revealed as an independent factor of Entecavir treatment failure by multivariate logistic regression at 24wk, 48wk and 96wk. In CHB patients with hepatic steatosis, HBV-DNA clearance and HBeAg seroconversion were both lower throughout the follow-up, but only the former reached statistical significance. Besides, ALT normalization was also significantly lower at 24wk and 48wk. Conclusion Hepatic steatosis is significantly associated with Entecavir treatment failure and metabolic factors are independent factors of hepatic steatosis in CHB patients, which called for a specified antiviral strategy in CHB patients with NAFLD.
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Wong VWS, Wong GLH, Chu WCW, Chim AML, Ong A, Yeung DKW, Yiu KKL, Chu SHT, Chan HY, Woo J, Chan FKL, Chan HLY. Hepatitis B virus infection and fatty liver in the general population. J Hepatol 2012; 56:533-40. [PMID: 22027575 DOI: 10.1016/j.jhep.2011.09.013] [Citation(s) in RCA: 191] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2011] [Revised: 08/23/2011] [Accepted: 09/21/2011] [Indexed: 02/09/2023]
Abstract
BACKGROUND & AIMS In animal studies, expression of hepatitis B virus (HBV) proteins causes hepatic steatosis. We aimed to study the prevalence of fatty liver in people with and without HBV infection in the general population. METHODS We performed a cross-sectional population study in Hong Kong Chinese. Intrahepatic triglyceride content (IHTG) was measured by proton-magnetic resonance spectroscopy. RESULTS One thousand and thirteen subjects (91 HBV patients and 922 controls) were recruited. The median IHTG was 1.3% (0.2-33.3) in HBV patients and 2.1% (0-44.2) in controls (p <0.001). Excluding subjects with significant alcohol consumption, the prevalence of nonalcoholic fatty liver disease was 13.5% (95% confidence interval [CI] 6.4%, 20.6%) in HBV patients and 28.3% (95% CI 25.3%, 31.2%) in controls (p=0.003). The fatty liver prevalence differed in HBV patients and controls aged 40-59 years but was similar in those aged 60 years or above. After adjusting for demographic and metabolic factors, HBV infection remained an independent factor associated with lower risk of fatty liver (adjusted odds ratio 0.42; 95% CI 0.20, 0.88; p=0.022). HBV patients also had a lower prevalence of metabolic syndrome (11.0% vs. 20.2%; p=0.034), but the difference was mainly attributed to lower triglyceride levels. Among HBV patients, viral genotypes, HBV DNA level and hepatitis B e antigen status were not associated with fatty liver. CONCLUSIONS HBV infection is associated with a lower prevalence of fatty liver, hypertriglyceridemia and metabolic syndrome. Viral replication may affect lipid metabolism and this warrants further studies.
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Affiliation(s)
- Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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Ateş F, Yalnız M, Alan S. Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B. World J Gastroenterol 2011; 17:4517-22. [PMID: 22110283 PMCID: PMC3218143 DOI: 10.3748/wjg.v17.i40.4517] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2011] [Revised: 02/21/2011] [Accepted: 02/28/2011] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the impact of liver steatosis upon response to given therapy in chronic hepatitis B (CHB) patients. METHODS 84 consecutive CHB patients treated with 48-wk PEGylated interferon (PEG-IFN) therapy were enrolled. Baseline characteristics and sustained viral response (SVR) to PEG-IFN therapy were evaluated. RESULTS Mean body mass index (BMI) was 27.36 ± 4.4 kg/m². Six (7.1%) had hypertension and three (3.5%) had diabetes mellitus. Steatosis was present in 22.6% (19/84) of liver biopsy samples. Age, BMI, and triglyceride levels of the patients with hepatic steatosis were significantly higher than those without hepatic steatosis (P < 0.05). SVR to PEG-IFN therapy was 21.4% (18/84). Sixteen of these 18 CHB patients with SVR (88.9%) did not have any histopathologically determined steatosis. On the other hand, only two of the 19 CHB patients with hepatic steatosis had SVR (10.5%). Although the SVR rate observed in patients without steatosis (16/65, 24.6%) was higher compared to those with steatosis (2/19, 10.5%), the difference was not statistically significant (P > 0.05). CONCLUSION Occurrence of hepatic steatosis is significantly high in CHB patients and this association leads to a trend of decreased, but statistically insignificant, SVR rates to PEG-IFN treatment.
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Lim JK, Nguyen MH. The Role of Hepatic Steatosis in Chronic Hepatitis B Infection. CURRENT HEPATITIS REPORTS 2011; 10:134-141. [DOI: 10.1007/s11901-011-0090-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/22/2025]
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Petta S, Cammà C, Di Marco V, Macaluso FS, Maida M, Pizzolanti G, Belmonte B, Cabibi D, Di Stefano R, Ferraro D, Guarnotta C, Venezia G, Craxì A. Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int 2011; 31:507-515. [PMID: 21382161 DOI: 10.1111/j.1478-3231.2011.02453.x] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. MATERIAL AND METHODS One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was defined if HOMA-IR>2.7. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was considered significant if ≥ 10%. RESULTS The prevalence of significant steatosis was similar in both CHB and CHC patients (31 vs. 38%; P=0.14). IR rate was significantly higher in CHC than in CHB patients (42 vs. 26%; P=0.002). Severe fibrosis (F3-F4), at multivariate analysis, was independently associated with older age (OR 1.050, 95% CI 1.009-1.093), steatosis >10% (OR 4.375, 95% CI 1.749-10.943), and moderate-severe necroinflammatory activity (OR 8.187, 95% CI 2.103-31.875), regardless of HBeAg status, in CHB patients, and with older age (OR 1.080, 95% CI 1.028-1.136), IR (OR 2.640, 95% CI 1.110-6.281), steatosis >10% (OR 3.375, 95% CI 1.394-8.171), and moderate-severe necroinflammatory activity (OR 8.988, 95% CI 1.853-43.593) in CHC patients. CONCLUSIONS CHB patients had high steatosis prevalence, similar to CHC controls, but lower IR rate. Both steatosis and IR in CHC, and only steatosis in CHB, are independently associated with fibrosis severity.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia, University of Palermo, Palermo, Italy.
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Shamliyan TA, Johnson JR, MacDonald R, Shaukat A, Yuan JM, Kane RL, Wilt TJ. Systematic review of the literature on comparative effectiveness of antiviral treatments for chronic hepatitis B infection. J Gen Intern Med 2011; 26:326-39. [PMID: 21203860 PMCID: PMC3043173 DOI: 10.1007/s11606-010-1569-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2010] [Revised: 10/07/2010] [Accepted: 10/20/2010] [Indexed: 12/19/2022]
Abstract
OBJECTIVES To evaluate the comparative effectiveness of antiviral drugs in adults with chronic hepatitis B monoinfection for evidence-based decision-making. METHODS A systematic review of randomized controlled clinical trials (RCTs) published in English. Results after interferon and nucleos(t)ides analog therapies were synthesized with random-effects meta-analyses and number needed to treat (NNT). RESULTS Despite sustained improvements in selected biomarkers, no one drug regimen improved all intermediate outcomes. In 16 underpowered RCTs, drug treatments did not reduce mortality, liver cancer, or cirrhosis. Sustained HBV DNA clearance was achieved in one patient when two were treated with adefovir (NNT from 1 RCT=2 95%CI 1;2) or interferon alpha-2b (NNT from 2 RCTs=2 95%CI 2;4), 13 with lamivudine (NNT from 1 RCT=13 95%CI 7;1000), and 11 with peginterferon alpha-2a vs. lamivudine (NNT from 1 RCT=11 95%CI 7;25). Sustained HBeAg seroconversion was achieved in one patient when eight were treated with interferon alpha-2b (NNT from 2 RCTs=8 95%CI 5;33) or 10--with peginterferon alpha-2b vs. interferon alpha-2b (NNT from 1 RCT=10 95%CI 5;1000). Greater benefits and safety after entecavir vs. lamivudine or pegylated interferon alpha-2b vs. interferon alpha-2b require future investigation of clinical outcomes. Adverse events were common and more frequent after interferon. Treatment utilization for adverse effects is unknown. CONCLUSIONS Individual clinical decisions should rely on comparative effectiveness and absolute rates of intermediate outcomes and adverse events. Future research should clarify the relationship of intermediate and clinical outcomes and cost-effectiveness of drugs for evidence-based policy and clinical decisions.
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Affiliation(s)
- Tatyana A Shamliyan
- Division of Health Policy and Management, Minnesota Evidence-based Practice Center, University of Minnesota School of Public Health, 420 Delaware Street SE, D330-5 Mayo (MMC 729), Minneapolis, MN 55455, USA.
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Wang YY, Lin SY, Sheu WHH, Liu PH, Tung KC. Obesity and diabetic hyperglycemia were associated with serum alanine aminotransferase activity in patients with hepatitis B infection. Metabolism 2010; 59:486-91. [PMID: 19846182 DOI: 10.1016/j.metabol.2009.07.038] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2008] [Accepted: 07/13/2009] [Indexed: 01/05/2023]
Abstract
Several studies have reported that obesity and diabetes are important risk factors for elevated blood aminotransferase activity in individuals with no underlying causes of liver disease. The aim of this study was to determine whether obesity and fasting glucose level were associated with hepatic dysfunction in patients with hepatitis B infection. A total of 934 patients with hepatitis B infection were enrolled, among whom increased alanine aminotransferase (ALT) activity (> or =40 IU/L) was observed in 25.1%. By univariate analysis, factors associated with increased ALT activity among patients with hepatitis B infection included body mass index (BMI), fasting blood glucose level, and blood triglyceride and high-density cholesterol levels. By multivariate logistic regression analysis, BMI and fasting blood glucose level were independent predictors of elevated ALT activity, with odds ratios of 1.73 (95% confidence interval, 1.17-2.56) for subjects with a BMI greater than or equal to 25 kg/m2 and 1.88 (95% confidence interval, 1.06-3.33) for subjects with a fasting blood glucose greater than or equal to 126 mg/dL. Even in subjects with ALT activity within the reference range, ALT activity was found to be associated with BMI. In conclusion, a BMI greater than or equal to 25 kg/m2 and a fasting blood glucose level greater than or equal to 126 mg/dL were risk factors for increased ALT activity in subjects with hepatitis B infection, suggesting that obesity and diabetic fasting hyperglycemia may aggravate liver injury in this population.
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Affiliation(s)
- Ya-Yu Wang
- Division of Family Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan
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Abstract
BACKGROUND Liver steatosis (LS) and chronic infection with hepatitis B virus (HBV) are two common causes of chronic liver disease in Iran. LS is also a common histopathological feature of chronic hepatitis B (CHB). Association of chronic HBV infection and LS has not been extensively studied. AIM We investigated the prevalence of histological evidence of LS in a group of patients with chronic HBV infection undergoing liver biopsy and compared clinical data, laboratory features, and severity of hepatic fibrosis between patients both with and without steatosis. METHODS A total of 132 patients with CHB, undergoing liver biopsy for diagnostic purposes over a 2-year period were enrolled in this study. Clinical, biochemical, and histological factors that might have any kind of association with the presence of steatosis were evaluated. RESULTS Of the 132 patients with a liver biopsy, steatosis was present in 56 (42.4%) of the patients, of whom 36 (64%) had grade 1, 14 (25%) grade 2, and six (10.7%) grade 3. Our data showed that LS is not associated with age, sex, HBeAg, viral load, amount of fibrosis, serum cholesterol level, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Although body mass index, serum triglyceride, fasting blood glucose, and gamma-glutamyl transpeptidase showed significant correlation with LS in univariate analysis, in multivariate analysis only the serum triglyceride level was significantly correlated with LS. CONCLUSION Steatosis is a relatively common finding in CHB and metabolic host factors rather than viral factors responsible for the presence of steatosis in these patients.
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Hepatitis B virus X protein induces lipogenic transcription factor SREBP1 and fatty acid synthase through the activation of nuclear receptor LXRalpha. Biochem J 2008; 416:219-30. [PMID: 18782084 DOI: 10.1042/bj20081336] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
HBV (hepatitis B virus) is a primary cause of chronic liver disease, which frequently results in hepatitis, cirrhosis and ultimately HCC (hepatocellular carcinoma). Recently, we showed that HBx (HBV protein X) expression induces lipid accumulation in hepatic cells mediated by the induction of SREBP1 (sterol-regulatory-element-binding protein 1), a key regulator of lipogenic genes in the liver. However, the molecular mechanisms by which HBx increases SREBP1 expression and transactivation remain to be clearly elucidated. In the present study, we demonstrated that HBx interacts with LXRalpha (liver X receptor alpha) and enhances the binding of LXRalpha to LXRE (LXR-response element), thereby resulting in the up-regulation of SREBP1 and FAS (fatty acid synthase) in the presence or absence of the LXR agonist T0901317 in the hepatic cells and HBx-transgenic mice. Furthermore, HBx also augments the ability to recruit ASC2 (activating signal co-integrator 2), a transcriptional co-activator that controls liver lipid metabolic pathways, to the LXRE with LXRalpha. These studies place LXRalpha in a key position within the HBx-induced lipogenic pathways, and suggest a molecular mechanism through which HBV infection can stimulate the SREBP1-mediated control of hepatic lipid accumulation.
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Abstract
Treatment predictors are important tools for the management of therapy in patients with chronic hepatitis B and C virus (HBV, HCV) infection. In chronic hepatitis B, several pretreatment parameters have been identified for prediction of virologic response to interferon alfa-based antiviral therapies or treatment with polymerase inhibitors. In interferon alfa and pegylated interferon alfa-treated patients, low baseline HBV DNA concentrations, HBV genotype A (B), and high baseline ALT levels are significantly associated with treatment response. In patients treated with nucleos(t)ide analogues, low baseline HBV DNA but not viral genotype is positively associated with virologic response. During treatment the best predictor of response is HBV DNA kinetics. Early viral suppression is associated with favourable virologic response and reduced risk for subsequent resistance mutations. For the current standard treatment with pegylated interferon alfa and ribavirin in patients with chronic hepatitis C, infection with HCV genotypes 2 and 3, baseline viral load below 400,000-800,000 IU/ml, Asian and Caucasian ethnicity, younger age, low GGT levels, absence of advanced fibrosis/cirrhosis, and absence of steatosis in the liver have been identified as independent pretreatment predictors of a sustained virologic response. After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of sustained virologic response independent of HCV genotype.
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Affiliation(s)
- Annika Kau
- Zentrum der Inneren Medizin, Medizinische Klinik 1, Klinikum der JW Goethe-Universität, Frankfurt am Main, Germany
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Shi JP, Fan JG, Wu R, Gao XQ, Zhang L, Wang H, Farrell GC. Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection. J Gastroenterol Hepatol 2008; 23:1419-1425. [PMID: 18853998 DOI: 10.1111/j.1440-1746.2008.05531.x] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIMS The clinical significance of hepatic steatosis in chronic hepatitis B infection (CHB) is unclear. The aims of this study were thus to investigate the prevalence and risk factors for hepatic steatosis in patients with CHB and its relationship with liver injury. METHODS Consecutive patients with biopsy-proven CHB at Hangzhou Sixth People's Hospital between January 2005 and June 2007 were included. Patients co-infected with other viruses or suffering from liver disease of any other cause were excluded. Liver steatosis, necroinflammation and fibrosis were assessed by both Brunt and Scheuer classifications. RESULTS A total of 1915 patients (1497 men) with a mean age of 31 +/- 9.5 years were analyzed. Hepatic steatosis was present in 260 (14%) patients. The steatosis involved < 33% of hepatocytes in 90% of cases, and was more frequent among men than women (15% vs 8%, P < 0.001). Two-thirds (178 of 260) of patients with steatosis were hepatitis B e antigen (HBeAg)-positive, but there was no correlation with either serum HBeAg status or hepatitis B virus DNA titer. Degree of inflammation and fibrosis were more mild among those with steatosis than those without. Multivariate analysis showed that steatosis was independently associated with body mass index, serum triglyceride, apolipoprotein B, uric acid, and fasting blood glucose. However, fibrosis was only independently associated with age and inflammatory grade, and the latter associated with viral load and fibrosis stage. CONCLUSIONS Hepatic steatosis is common in CHB, it is associated with metabolic factors not viral ones, and does not appear to affect the severity of liver disease.
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Affiliation(s)
- Jun-ping Shi
- Center for Fatty Liver Disease, Shanghai First People's Hospital, Jiaotong University, Shanghai, China
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Li YR, Fan XL. Influence of metabolic syndrome on the response of chronic hepatitis C to anti-viral therapy and its possible mechanism. Shijie Huaren Xiaohua Zazhi 2008; 16:2321-2324. [DOI: 10.11569/wcjd.v16.i21.2321] [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] [Indexed: 02/06/2023] Open
Abstract
Genotype and viral load have been found as the most important viral factors influencing antiviral response. Host factors include metabolic syndrome such as diabetes type 2, hepatocyte steatosis, and insulin resistance. Diabetes type 2 decreases the sustained response to interferon α, and hepatocyte steatosis impairs the sustained response rate in patients with HCV genotype 1, but not in genotype 3. Insulin resistance emerges as the most important host factors in the prediction of response in chronic hepatitis C patients with interferon plus ribavirin. Most studies showed that insulin resistance may induce interferon resistance by blocking intracellular signal pathway of interferon.
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