Mixed Treatment Comparison Meta-Analysis Evaluating the Relative Efficacy of Nucleos(t)ides for Treatment of Nucleos(t)ide-Naive Patients with Chronic Hepatitis B

Background/aims: Five nucleoside/nucleotide treatments are now available for chronic hepatitis B (CHB). This meta-analysis aimed to assess the relative efficacy of adefovir, entecavir, lamivudine, telbivudine, tenofovir disoproxil fumarate (TDF), and nucleos(t)ide combinations in the treatment of CHB. Methods: A systematic review of MEDLINE and the Cochrane library was conducted to identify all studies evaluating these nucleos(t)ides in adults with CHB. Randomized controlled trials were included in the meta-analysis if they reported the proportion of patients with undetectable hepatitis B virus (HBV) DNA or hepatitis B e antigen (HBeAg) loss/seroconversion at 1 year. Bayesian mixed treatment comparison meta-analyses were conducted in WinBUGS to assess relative efficacy. Results: A random-effects meta-analysis of trials on treatment-naive patients with HBeAg-positive CHB demonstrated that 94% of patients will achieve HBV DNA < 300 copies/ml after 1 year with TDF, compared with 73% for entecavir, 50% for adefovir, and 38% for lamivudine. There was a 97.7% probability that TDF enabled a greater proportion of patients to achieve HBV DNA < 300 copies/ml at 1 year than all other treatments considered in the analysis. TDF was significantly superior to all nucleos(t)ides for this outcome at the 0.05 level. There were no statistically significant differences between nucleos(t)ides in HBeAg seroconversion at 1 year, based on a fixed-effects meta-analysis in the same population. More trials on HBeAg-negative and drug-resistant patients are required to facilitate meta-analyses for these subgroups. Conclusions: In nucleos(t)ide-naive patients with HBeAg-positive CHB, TDF is associated with the highest probability of achieving undetectable HBV DNA at 1 year of all nucleos(t)ides considered.