Thymosin-ɑ1 Meta-Analysis Aims to Clarify Benefits, Harms for Chronic Hepatitis B

Chronic hepatitis B (HBV) infection remains a significant global public health challenge, affecting millions and leading to severe liver pathologies. Untreated, it can progress to chronic hepatitis, cirrhosis, hepatic decompensation, liver failure, and hepatocellular carcinoma (HCC), ultimately increasing mortality. Current standard-of-care treatments aim to suppress viral replication but often fall short in achieving functional cure or preventing long-term complications, highlighting a critical need for effective immunomodulatory or antiviral strategies. Thymosin-ɑ1, an endogenous immunomodulatory peptide, has demonstrated antiviral properties and immune-enhancing effects, making it a candidate for HBV treatment. However, individual randomized clinical trials (RCTs) investigating its efficacy have yielded inconsistent and often contradictory results, necessitating a comprehensive, high-quality synthesis of the evidence.

This systematic review and meta-analysis, conducted according to Cochrane methods, aimed to evaluate the benefits and harms of Thymosin-ɑ1 in individuals with chronic hepatitis B. Researchers performed an exhaustive search across the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, four other databases, and six trials registers, supplemented by reference checking, citation searching, and direct author contact, with the latest search on 10 June 2026. Eligibility criteria included all randomized controlled trials (RCTs) assessing Thymosin-ɑ1 at any dose, route of administration, or formulation type, administered as monotherapy, in combination, or as an adjunct to standard treatment. Comparators included placebo, no intervention, or standard medical treatment. Critical outcomes assessed were all-cause mortality, serious adverse events, and health-related quality of life. Important outcomes included HBV-related morbidity, HBV-related mortality, non-serious adverse events, and the proportion of people without histological improvements. Risk of bias was rigorously assessed using the Cochrane Risk of bias 2 tool (RoB 2).