Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies

Hyoung Su Kim, Hyung Joon Yim, Myoung Kuk Jang, Ji Won Park, Sang Jun Suh, Yeon Seok Seo, Ji Hoon Kim, Bo Hyun Kim, Sang Jong Park, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Jung Il Lee, Jin Woo Lee, In Hee Kim, Tae Yeob Kim, Jin Wook Kim, Sook Hyang Jeong, Young Kul Jung, Hana ParkSeong Gyu Hwang

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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 realtime 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 logrank 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.

Original languageEnglish
Pages (from-to)10874-10882
Number of pages9
JournalWorld journal of gastroenterology
Volume21
Issue number38
DOIs
Publication statusPublished - 2015 Oct 14

Keywords

  • Adefovir
  • Chronic hepatitis B
  • Entecavir
  • Lamivudine
  • Resistance

ASJC Scopus subject areas

  • Gastroenterology

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    Kim, H. S., Yim, H. J., Jang, M. K., Park, J. W., Suh, S. J., Seo, Y. S., Kim, J. H., Kim, B. H., Park, S. J., Lee, S. H., Kim, S. G., Kim, Y. S., Lee, J. I., Lee, J. W., Kim, I. H., Kim, T. Y., Kim, J. W., Jeong, S. H., Jung, Y. K., ... Hwang, S. G. (2015). Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies. World journal of gastroenterology, 21(38), 10874-10882. https://doi.org/10.3748/wjg.v21.i38.10874