S2065 Combination Therapy Improves Outcomes in Chronic Hepatitis B: A Systematic Review

Introduction: Chronic hepatitis B (CHB) virus affects over 250 million individuals globally and remains a leading cause of liver-related morbidity and mortality, including cirrhosis and hepatocellular carcinoma (HCC). The primary goal of antiviral treatment is sustained viral suppression to prevent disease progression. This systematic review compares the efficacy and safety of monotherapy versus combination therapy in CHB, focusing on virological and serological outcomes. Methods: A systematic literature search was conducted using PubMed, EMBASE, and Cochrane databases for peer-reviewed studies published from 2013 to 2023. Eligible studies included randomized controlled trials (RCTs), cohort studies, and meta-analyses evaluating nucleoside/nucleotide analogues or biologics, either as monotherapy or in combination, in adult patients with CHB. Study selection followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of 965 records screened, 33 studies met inclusion criteria. Data were extracted on HBsAg clearance, Hepatitis B virus DNA suppression, alanine aminotransferase normalization, and adverse events. Results: Combination therapy—most commonly involving pegylated interferon (PEG-IFN) with tenofovir or entecavir—demonstrated superior efficacy compared to monotherapy. HBsAg seroclearance was observed in 12%–28% of patients receiving combination therapy, compared to 2%–10% in monotherapy groups. HBV DNA suppression to undetectable levels was achieved in 78%–95% of patients on combination therapy, versus 60%–80% on monotherapy. Combination regimens also correlated with a lower incidence of HCC over long-term follow-up. Adverse event rates were similar across both treatment groups in over 90% of studies. Conclusion: The synergistic effects of combination therapy enhance immune-mediated viral control and reduce disease progression. Given its superior efficacy and similar safety profile, it should be considered a frontline option, especially for patients at higher risk of HCC or with suboptimal response to monotherapy. This systematic review provides strong evidence supporting the adoption of combination regimens in individualized CHB management.