Steatohepatitis in Chronic Hepatitis B

March 30, 2022 updated by: Phunchai Charatcharoenwitthaya, Mahidol University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

408

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
    • Bangkok
      • Bangkoknoi, Bangkok, Thailand, 10700
        • Faculty of Medicine Siriraj Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Chronic hepatitis B patients who underwent liver biopsy during 2002-2008 and then received antiviral therapy. The studied patients 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. According to Brunt's classification, patients will be categorized into three groups, including non-steatosis, steatosis but no steatohepatitis, and steatohepatitis groups based on the histological features of the liver specimens.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Chronic hepatitis B patients without hepatic steatosis
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
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.
Other Names:
  • Nucleotide analogue
  • Peginterferon
  • Nucleoside analogue
Chronic hepatitis B with steatosis but no steatohepatitis
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
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.
Other Names:
  • Nucleotide analogue
  • Peginterferon
  • Nucleoside analogue
Chronic hepatitis B patients with steatohepatitis
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
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.
Other Names:
  • Nucleotide analogue
  • Peginterferon
  • Nucleoside analogue

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall mortality
Time Frame: 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
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
Time Frame: From date of liver biopsy until the date of first documented liver-related complications, whichever came first, assessed up to 22 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mahidol University

Investigators

  • Principal Investigator: Phunchai Charatcharoenwitthaya, MD., Faculty of Medicine Siriraj Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2002

Primary Completion (Actual)

December 31, 2020

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

March 11, 2022

First Submitted That Met QC Criteria

March 30, 2022

First Posted (Actual)

April 7, 2022

Study Record Updates

Last Update Posted (Actual)

April 7, 2022

Last Update Submitted That Met QC Criteria

March 30, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 043/2560(EC2)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The datasets generated and analyzed during the current study are not publicly available due to our University's institutional review boards (IRB) and the health insurance portability and accountability act (HIPAA) privacy rule but are available from the corresponding author on reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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