Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5524
Peer-review started: August 8, 2014
First decision: August 27, 2014
Revised: September 16, 2014
Accepted: November 18, 2014
Article in press: November 19, 2014
Published online: May 14, 2015
AIM: To compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) in Asian and non-Asian chronic hepatitis B (CHB) patients.
METHODS: The efficacy and safety of the initial 48 wk of treatment with TDF was compared in a post-hoc analysis of combined data from 217 Asians and 299 non-Asians included in Studies 102 and 103 and a post-approval, open-label trial (Study 123). Patient groups were compared according to baseline hepatitis B e antigen (HBeAg) status and viral load. The main outcome measures included the proportion of patients who achieved a hepatitis B virus (HBV) DNA level < 400 copies/mL at Week 48 of treatment. Secondary measures included: HBV DNA and alanine aminotransaminase (ALT) levels over time; proportion of patients with normal ALT levels; proportion of patients with HBeAg loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion; changes in liver histology. Safety and tolerability were evaluated by the occurrence of adverse events (AEs), serious AEs, laboratory abnormalities, discontinuation of the study drug due to AEs, or death. The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug.
RESULTS: At week 48, similar proportions of Asians and non-Asians reached HBV DNA < 400 copies/mL (96% of Asian and 97% of non-Asian patients with HBeAg-negative CHB and 83% of Asian and 79% of non-Asian patients with HBeAg-positive CHB had HBV DNA) and normal ALT (78% of Asian and 81% of non-Asian patients with HBeAg-negative CHB and 71% of Asian and 74% of non-Asian patients with HBeAg-positive CHB had normal ALT). On-treatment HBV DNA decline rates were similar between Asians and non-Asians regardless of baseline HBeAg status and viral load. HBV DNA decline during the first four weeks was 2.9 log10 copies/mL in HBeAg-negative Asians and non-Asians, and in HBeAg-positive non-Asians, and 3.1 log10 copies/mL in HBeAg-positive Asians. HBeAg loss and seroconversion was achieved in 14% of Asians vs 26% and 24%, respectively, in non-Asians. Liver histology improved in 77.2% of Asians and 71.5% of non-Asians. No resistance to TDF developed. No renal safety signals were observed.
CONCLUSION: TDF demonstrated similar viral suppression, normalization of ALT, improvements in liver fibrosis, and no detectable resistance in Asian and non-Asian patients regardless of baseline HBeAg status.
Core tip: Although a substantial proportion of the worldwide hepatitis B virus-infected population is Asian, this is often not reflected in clinical trial populations. Comparison of data from Asian and non-Asian patients is important to provide a better understanding of treatment outcome in Asian populations. Our analysis is the first and largest to compare early (48 wk) response to tenofovir disoproxil fumarate (TDF) in Asian and non-Asian patients during large-scale clinical studies. Overall, TDF demonstrated similar viral suppression, normalization of alanine aminotransaminase and improvements in liver fibrosis, with no resistance, in all cohorts, irrespective of baseline hepatitis B e antigen status and viral load.