Meta-analysis of the clinical efficacy of combination therapy with traditional Chinese medicine and nucleoside analogue antiviral drugs for chronic hepatitis B

Objective To investigate whether the collected randomized controlled trials (RCTs) published to date have shown that supplemental application of traditional Chinese medicine (TCM) improves the outcome of chronic hepatitis B (CHB) patients treated with nucleoside analogue antiviral drugs.Methods Literature collections on the Chinese Biomedical Literature Database, the Chinese Academic Journal Full-text Database, the Chinese Scientific Journals Database, PubMed, and Embase were searched from inception to July 2012 to identify publications of RCTs comparing the therapeutic efficacy of TCM combined with nucleoside analogues lamivudine (LDM) , adefovir (ADV) , entecavir (ETV) ) to treat CHB.Inclusion criteria included: patients with CHB for more than six months, serum HbsAg-positivity, 2 × upper normal limit (ULN) ≤alanine aminotransferase (ALT) ≤10 × ULN, hepatitis B virus (HBV) DNA-positivity, and no previous antiviral therapy for six months prior to study;a control group receiving a single nucleoside analogue;study treatment time of at least three months.The methodological quality of included RCTs was assessed using the Jadad scale.The meta-analysis was carried out with RevMan 5.0 software.Heterogeneity was examined by Chi-squared test.Pooled data was analyzed by the fixed effects model or random effects model, according to presence of heterogeneity.Publication bias was assessed by funnel plot asymmetry.Results A total of 14 RCTs were included in the analysis and comprised 1386 CHB patients with 703 in the trial groups and 683 in the control groups.Only one study had moderate-high methodological quality (Jadad score: 3) , and the remaining studies had low methodological quality (Jadad score: 2, n = 1;1, n = 12) .The outcome measures included: ALT normalization rate, aspartate aminotransferase (AST) normalization rate, hepatitis B e antigen (HbeAg) -negativity rate, HBeAg seroconversion rate, HBV DNA-negativity rate, and incidence of the LAM-resistance YMDD mutation.Meta-analysis indicated that the combined treatment strategy produced significantly better outcome in ALT normalization, AST normalization, HBeAg-negativity, and HBV DNA-negativity compared to the single nucleoside analogue alone treatment strategy after treating for 24 and 48 weeks (all P < 0.05) .The YMDD mutation rates were not significantly different between the groups after 24 weeks of treatment, but were significantly better in the combined treatment strategy group then in the single nucleoside analogue alone treatment strategy group after 48 weeks of treatment (P < 0.05) .Conclusion RCTs examining the benefit of supplementing nucleoside analogue antiviral drugs with TCM treatment show an improved therapeutic efficacy for chronic hepatitis B patients, especially when administered for 48 weeks.