Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses.
OBJECTIVE
The relative efficacies of licensed antiviral therapies for treatment-naive chronic hepatitis B (CHB) infection in randomized controlled trials have not been determined. We evaluated the relative efficacies of the first 12 months of CHB treatments.


METHODS
Drugs evaluated were lamivudine, pegylated interferon, adefovir, entecavir, telbivudine, and tenofovir, as monotherapies and combination therapies, in treatment-naive individuals. Databases were searched for randomized controlled trials of the first 12 months of therapy in hepatitis B e antigen (HBeAg)-positive and/or HBeAg-negative patients with CHB published in English before October 31, 2009. Bayesian mixed treatment comparisons were used to calculate the odds ratios, including 95% credible intervals and predicted probabilities of surrogate outcomes to determine the relative effects of each treatment.


RESULTS
In HBeAg-positive patients, tenofovir was most effective in inducing undetectable levels of HBV DNA (predicted probability, 88%), normalization of alanine aminotransferase (ALT) levels (66%), HBeAg seroconversion (20%), and hepatitis B surface antigen loss (5%); it ranked third in histologic improvement of the liver (53%). Entecavir was most effective in improving liver histology (56%), second for inducing undetectable levels of HBV DNA (61%) and normalization of ALT levels (70%), and third in loss of hepatitis B surface antigen (1%). In HBeAg-negative patients, tenofovir was the most effective in inducing undetectable levels of HBV DNA (94%) and improving liver histology (65%); it ranked second for normalization of ALT levels (73%).


CONCLUSIONS
In the first year of treatment for CHB, tenofovir and entecavir are the most potent oral antiviral agents for HBeAg-positive patients; tenofovir is most effective for HBeAg-negative patients.
Woo
Gloria
G
Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada. gloria.woo@theta.utoronto.ca
Tomlinson
George
G
Nishikawa
Yasunori
Y
Kowgier
Matthew
M
Sherman
Morris
M
Wong
David K H
DK
Pham
Ba
B
Ungar
Wendy J
WJ
Einarson
Thomas R
TR
Heathcote
E Jenny
EJ
Krahn
Murray
M
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use*; D000068698:Tenofovir
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D000225:Adenine