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Entecavir plus tenofovir combination therapy in patients with multidrug‐resistant chronic hepatitis B : results of a multicentre, prospective study
Author(s) -
Park Jun Yong,
Kim Chang Wook,
Bae Si Hyun,
Jung Kyu Sik,
Kim Hee Yeon,
Yoon Seung Kew,
Han KwangHyub,
Ahn Sang Hoon
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13059
Subject(s) - entecavir , tenofovir , medicine , prospective cohort study , chronic hepatitis , multiple drug resistance , hepatitis b , virology , lamivudine , gastroenterology , drug resistance , human immunodeficiency virus (hiv) , virus , biology , microbiology and biotechnology
Background & Aims Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B ( CHB ) treatment. We evaluated the antiviral efficacy and safety of entecavir ( ETV ) plus tenofovir ( TDF ) combination therapy in multidrug‐resistant ( MDR ) CHB patients. Methods In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks. Results A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2–6) were included. At baseline, median age was 47.0 years, 89.1% were HB eAg(+), and median HBV DNA was 4.24 (range, 2.11–6.73) log 10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log 10 IU/ml and 2.38 log 10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients. Conclusions In difficult‐to‐treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.