Liver Fibrosis in the Natural Course of Chronic Hepatitis B Viral Infection: A Systematic Review with Meta-Analysis

Area of Science:

• Hepatology and Viral Hepatitis Research
• Fibrosis and Cirrhosis Pathogenesis
• Epidemiology of Chronic Liver Disease

Background:

• Limited quantitative data exist on the natural progression of liver fibrosis in patients with chronic hepatitis B virus (CHB) infection.
• Understanding fibrosis prevalence across different CHB phases is crucial for patient management and prognosis.
• Existing knowledge gaps hinder accurate risk stratification and the development of effective noninvasive diagnostic tools.

Purpose of the Study:

• To estimate the prevalence of liver fibrosis stages, including non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis, during the natural course of CHB.
• To provide a comprehensive overview of fibrosis status across distinct phases of CHB infection.
• To establish a data-driven foundation for improved clinical risk assessment and the validation of noninvasive fibrosis detection methods.

Main Methods:

• A systematic literature search was conducted across major databases (Cochrane, EMBASE, PubMed, SCOPUS, Web of Science, ScienceDirect) from January 1993 to November 2019.
• Studies included had histologic data on liver fibrosis in the natural course of CHB, categorized by international guidelines into HBeAg-positive immune-tolerant, HBeAg-positive immune-active, HBeAg-negative immune-inactive, HBeAg-negative immune-reactive, and HBsAg-negative phases.
• Random-effect meta-analyses were employed to pool the prevalence rates of different fibrosis statuses within each identified CHB phase.

Main Results:

• Thirty-three studies encompassing 9,377 adult participants were analyzed.
• Prevalence of advanced fibrosis and cirrhosis varied significantly across CHB phases, notably higher in the HBeAg-positive immune-active (32.1% advanced fibrosis, 12.8% cirrhosis) and HBeAg-negative immune-reactive (30.3% advanced fibrosis, 10.0% cirrhosis) phases.
• Non-fibrosis was most prevalent in the HBeAg-negative immune-inactive phase (32.4%), while significant fibrosis was common in immune-active and immune-reactive phases (over 50% combined).

Conclusions:

• The risk of liver fibrosis persists throughout the natural course of chronic hepatitis B infection.
• The findings underscore the importance of continuous monitoring and risk stratification in CHB patients.
• This meta-analysis provides valuable quantitative data to support clinical risk estimation and guide the development of noninvasive diagnostic strategies for liver fibrosis.