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Efficacy and safety of tenofovir disoproxil fumarate rescue therapy for chronic hepatitis B patients who failed other nucleos(t)ide analogs
Author(s) -
Kumada Hiromitsu,
Koike Kazuhiko,
Suyama Kazuaki,
Ito Hiroshi,
Itoh Hiroshi,
Sugiura Wataru
Publication year - 2017
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12842
Subject(s) - medicine , adefovir , entecavir , hbsag , seroconversion , hepatitis b , adverse effect , lamivudine , hepatitis b virus , gastroenterology , hbeag , antibody , immunology , virus
Aim Acquisition of nucleos(t)ide analog (NA) inhibitor resistance is critical in successful chronic hepatitis B treatment. As the pattern of tenofovir disoproxil fumarate (TDF) resistance mutations differs from that of other antiviral drugs, we sought to clarify the salvaging potential of TDF in patients with hepatitis B virus (HBV) infection who are poor responders or resistant to other NAs. Methods A prospective, multicenter, single‐arm, open‐label study was carried out from December 2011 to October 2014. Poor responders defined as subjects with serum HBV‐DNA levels >4 log 10 copies/mL were enrolled. Subjects receiving lamivudine (LAM) + adefovir pivoxil (ADV) before the initiation of the study were switched to LAM + TDF. Subjects on entecavir hydrate (ETV) with or without ADV were switched to ETV + TDF. The primary efficacy end‐point was the proportion of subjects achieving HBV‐DNA <2.1 log 10 copies/mL (LLQ) at week 24. The secondary efficacy end‐points were the proportion of subjects with LLQ at weeks 48 and 96, serum alanine aminotransferase normalization, hepatitis B envelope antigen/antibody and hepatitis B surface antigen/antibody seroconversion. Results Thirty‐four subjects were enrolled, 21 subjects were switched to ETV + TDF, and 13 subjects were switched to LAM + TDF. Drug resistance mutations were determined in 85% of the subjects at the time of the enrolment. The proportion of subjects who achieved LLQ was 59%, 62%, and 71% at weeks 24, 48, and 96, respectively. No serious adverse event related to TDF was reported. Conclusion Our study clearly showed that TDF containing regimens were effective in salvaging poor responders and/or those who are drug‐resistant to other NAs. This study is registered with ClinicalTrials.gov (NCT01475851) and the GSK Clinical Study Register (GSK LOC115912).