Steatohepatitis in Chronic Hepatitis B

Study Overview
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Brief Summary
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Fatty liver disease is increasingly recognized in patients with chronic hepatitis B (CHB). Whether concurrent fatty liver disease affects the long-term outcomes of CHB is unclear. The investigators performed a longitudinal study to investigate the prognostic relevance of concurrent fatty liver disease for patients with CHB receiving antiviral therapy.

Detailed Description
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Chronic hepatitis B virus (HBV) infection is a global public health problem affecting more than 250 million people at high risk of death from cirrhosis and liver cancer. The goal of therapy for patients with chronic hepatitis B (CHB) is to improve survival and quality of life by preventing disease progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). This can be achieved by elimination of HBV or sustained suppression of viral replication with antiviral treatment. In recent years, accompanied by the growing prevalence of obesity, fatty liver disease is commonly observed in patients with CHB. The prevalence of the fatty liver disease is approximately 14-67% in Asian individuals with CHB, similar to Western countries. The coexistence of CHB and hepatic steatosis, particularly steatohepatitis, can aggravate liver damage and increase the risk of fibrosis. A recent histological study showed a significant association between steatohepatitis and advanced fibrosis in CHB patients. Fatty liver disease has been shown to increase the risk of fibrosis progression in patients with CHB receiving antiviral treatment. According to a follow-up study of cirrhotic patients treated with tenofovir disoproxil fumarate for CHB, patients with possible concurrent NAFLD were less likely to have fibrosis regression despite viral suppression. Likewise, another prospective study showed that lower body mass index was independently associated with fibrosis regression in CHB patients who achieved undetectable HBV viral load during long-term nucleoside analogue therapy. Hence, monitoring the development of unfavorable outcomes is recommended in this population. However, there are limited data on the impact of concurrent fatty liver disease on clinical outcomes (e.g., cirrhotic complications, HCC, and death) during comprehensive treatment for CHB. Therefore, this longitudinal cohort study aimed to determine the effect of concurrent fatty liver disease on overall survival and liver-related complications among CHB patients receiving antiviral therapy to improve our understanding of the prognostic value of concurrent fatty liver disease in these patients. METHODS The investigators conduct a retrospective analysis of a prospectively collected database of patients with chronic HBV infection who underwent a liver biopsy between 2002 and 2008 at the Faculty of Medicine Siriraj Hospital in Bangkok, Thailand. This cohort includes only patients who had at least moderate necroinflammation and/or liver fibrosis stage 2 or higher according to the METAVIR system and have been treated with antiviral agents. Patients will be excluded from analysis if they had co-infection with hepatitis C virus or human immunodeficiency virus; had the presence of alcohol dependence; had follow-up data less than six months in our clinic; had no available liver histology for review; had intermittent or persistent HBV DNA >2000 IU/ml after stopping antiviral agents during follow-up.

Official Title
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Prognostic Relevance of Fatty Liver Disease for Patients With Chronic Hepatitis B

Conditions
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Fatty Liver, Chronic Hepatitis b

Intervention / Treatment
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* Drug: Antiviral Agents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All CHB patients who had significant histologic features, defined as at least moderate necroinflammation and/or liver fibrosis stage 2 or higher according to the METAVIR system, required antiviral therapy and have been managed in our institution. HBV-treated patients who had achieved undetectable HBV DNA or hepatitis B surface antigen (HBsAg) loss during antiviral therapy, and those who had hepatitis B e antigen (HBeAg) seroconversion with serum HBV DNA persistently <2,000 IU/ml and normalization of aminotransferase levels after discontinuing antiviral therapy. Exclusion Criteria: Patients who had viremia >2000 IU/ml after stopping antiviral agents will be excluded. Patients with a history of alcohol dependence or co-infections with hepatitis C virus or human immunodeficiency virus before liver biopsy will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic hepatitis B patients without hepatic steatosis<br>Patients with chronic hepatitis B will be defined as the non-steatosis group if they had histological evidence of visible lipid droplets in hepatocytes less than 5%. | Drug: Antiviral Agents<br>* The type of antiviral agents for the individual patient was selected by physicians based on a policy to reimburse a patient's health and comorbidity.<br>* Other names: Peginterferon;|
| Chronic hepatitis B with steatosis but no steatohepatitis<br>Patients with chronic hepatitis B will be categorized as the steatosis but not steatohepatitis group if they had histological evidence of visible lipid droplets in hepatocytes more than 5% in the absence of steatohepatitis feature. | Drug: Antiviral Agents<br>* The type of antiviral agents for the individual patient was selected by physicians based on a policy to reimburse a patient's health and comorbidity.<br>* Other names: Peginterferon;|
| Chronic hepatitis B patients with steatohepatitis<br>Patients with chronic hepatitis B will be classified as the steatohepatitis group if they had histological evidence of steatosis, hepatocyte ballooning, mixed lobular acute and chronic inflammation, and intra-acinar perisinusoidal fibrosis according to Brunt's classification. | Drug: Antiviral Agents<br>* The type of antiviral agents for the individual patient was selected by physicians based on a policy to reimburse a patient's health and comorbidity.<br>* Other names: Peginterferon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall mortality | Death from any cause | From date of liver biopsy until the date of liver transplantation or date of death from any cause, whichever came first, assessed up to 22 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver-related complications | Liver-related complications such as hepatocellular carcinoma, spontaneous bacterial peritonitis, variceal hemorrhage, portosystemic encephalopathy, and hepatorenal syndrome | From date of liver biopsy until the date of first documented liver-related complications, whichever came first, assessed up to 22 years |