Efficacy and Safety of <i>Xiaochaihu decoction</i> in the Treatment of Chronic Hepatitis B: A Systematic Review and Meta-Analysis

Abstract

Background: Chronic hepatitis B (CHB) remains a major cause of cirrhosis and hepatocellular carcinoma. Xiaochaihu decoction (XCHD) is frequently used in China as an adjunct to Western medicine (WM), but its incremental benefit remains uncertain. This review evaluated the efficacy and safety of XCHD added to WM in patients with CHB. Methods: Eight databases were searched from inception to October 5, 2025, for randomized controlled trials comparing XCHD + WM with the same background WM alone. Full search strategies are provided in Supplementary Material A. Primary outcomes were virological response (HBV-DNA, HBeAg, and HBsAg negativity) and liver biochemical indices (ALT and AST). Secondary outcomes included total clinical efficacy, TBil, HA, LN, PCIII, IV-C, and adverse events. Risk of bias was assessed with RoB 2, certainty of evidence was assessed with GRADE, and trial sequential analysis (TSA) was used as a supplementary assessment of random error. Results: Forty-nine trials (n = 4,768) were included. Compared with WM alone, XCHD + WM was associated with higher HBV-DNA, HBeAg, and HBsAg negativity rates and lower ALT, AST, TBil, HA, LN, PCIII, and IV-C values. Total clinical efficacy was higher, and the reported incidence of adverse events was not increased. However, most continuous outcomes showed substantial heterogeneity, several outcomes were affected by suspected publication bias, and certainty was low or very low for most biochemical and fibrosis-related outcomes. Discussion: Current evidence suggests that XCHD may offer short-term adjunctive benefits for surrogate virological and biochemical outcomes when added to WM for CHB, without an apparent increase in reported adverse events. While these preliminary findings are promising, due to methodological limitations and heterogeneity, future large-scale and high-quality RCTs are warranted to confirm their long-term clinical benefits and establish definitive evidence.