Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10874
Peer-review started: February 5, 2015
First decision: March 26, 2015
Revised: May 13, 2015
Accepted: July 18, 2015
Article in press: July 18, 2015
Published online: October 14, 2015
AIM: To evaluate the long-term efficacy adefovir (ADV)-based combination therapies in entecavir (ETV)-resistant chronic hepatitis B (CHB) patients.
METHODS: Fifty CHB patients with genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV (ADV/ETV, n = 23) or ADV plus lamivudine (LMV) (ADV/LMV, n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by real-time PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA < 20 IU/mL) were calculated using the Kaplan-Meier method, and the difference was determined by a log-rank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR, respectively.
RESULTS: Baseline median HBV DNA levels were 5.53 (2.81-7.63) log10 IU/mL. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27 (12-45) mo. Overall, cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates (35%, 43%, 65%, and 76%, respectively) than those with the ADV/LAM combination (18%, 30%, 30%, and 62%, respectively; P = 0.048). In the multivariate analysis, low baseline HBV DNA levels (< 5.2 log10 IU/mL) and initial virologic response at 3 mo (IVR-3; HBV DNA < 3.3 log10 IU/mL after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors.
CONCLUSION: If tenofovir is not available, ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may be continued if IVR-3 is achieved.
Core tip: Studies regarding optimal treatment strategies for entecavir-resistant chronic hepatitis B are sparse. Tenofovir may be the best option, but it is still not available in many countries. Where tenofovir is not available, adefovir plus entecavir can be considered an alternative treatment option in patients with favorable predictive factors. These factors included lower baseline hepatitis B virus (HBV) DNA levels (< 5.2 log10 IU/mL) and reduction of HBV DNA < 3.3 log10 IU/mL after 3 mo of treatment in our study. The present study will guide the treatment of entecavir-resistant chronic hepatitis B.