Kim HS, Yim HJ, Jang MK, Park JW, Suh SJ, Seo YS, Kim JH, Kim BH, Park SJ, Lee SH, Kim SG, Kim YS, Lee JI, Lee JW, Kim IH, Kim TY, Kim JW, Jeong SH, Jung YK, Park H, Group SGHOBOARS. Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies.
World J Gastroenterol 2015;
21:10874-10882. [PMID:
26478678 PMCID:
PMC4600588 DOI:
10.3748/wjg.v21.i38.10874]
[Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 05/13/2015] [Accepted: 07/18/2015] [Indexed: 02/06/2023] Open
Abstract
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.
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