Abstract
Background
Few studies have investigated the efficacy of long-term tenofovir disoproxil fumarate (TDF)-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs.
Methods
We retrospectively analyzed 40 Japanese patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs who received TDF-based rescue therapy [TDF monotherapy, TDF plus lamivudine (LAM) combination therapy, or TDF plus entecavir (ETV) combination therapy] followed up for a median of 45 months (range 14–99 months). Viral response, changes in hepatitis B surface antigen levels from the baseline, and viral breakthrough during therapy were analyzed.
Results
The proportion of patients with undetectable serum hepatitis B virus (HBV) DNA levels (less than 2.1 log copies per milliliter) (viral response) during TDF-based rescue therapy was 68, 78, 85, 88, 83, 81, 88, and 100 % at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, and 4 years respectively. There were no differences in the viral response rate between the TDF plus LAM group and the TDF plus ETV group. The mean reduction from the baseline in hepatitis B surface antigen levels in patients with LAM-resistant HBV was greater than the reductions in patients with adefovir dipivoxil (ADV)-resistant or ETV-resistant HBV at 2 and 3 years (P = 0.024, and P = 0.025 respectively). However, two patients with ADV- or ETV-resistant HBV at the baseline developed viral breakthrough during TDF-based rescue therapy.
Conclusions
Long-term therapy with a TDF-based rescue regimen demonstrated high viral suppression in patients in whom LAM plus ADV combination therapy, ETV plus ADV combination therapy, or ETV monotherapy had failed. However, patients with ADV- or ETV-resistant HBV at the baseline may develop viral breakthrough and resistance, and careful follow-up is advised.
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Abbreviations
- ADV:
-
Adefovir dipivoxil
- ALT:
-
Alanine aminotransferase
- CHB:
-
Chronic hepatitis B
- ETV:
-
Entecavir
- HIV:
-
Human immunodeficiency virus
- HBV:
-
Hepatitis B virus
- LAM:
-
Lamivudine
- NA:
-
Nucleoside/nucleotide analog
- PCR:
-
Polymerase chain reaction
- TDF:
-
Tenofovir disoproxil fumarate
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Acknowledgments
This study was supported in part by Grants-in-Aid for Scientific Research (C) (grant no. 24590999) from the Japan Society for the Promotion of Science, for Okinaka Memorial Institute for Medical Research, and by grants from the Ministry of Health, Labor and Welfare of Japan and the Japan Agency for Medical Research and Development.
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Fumitaka Suzuki and Yoshiyuki Suzuki have received investigator and lecture fees from Bristol-Myers KK. Hiromitsu Kumada has received investigator, lecture, and consulting fees from Bristol-Myers KK and GlaxoSmithKline KK. The other authors declare that they have no conflict of interest.
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Suzuki, F., Suzuki, Y., Hosaka, T. et al. Efficacy of long-term tenofovir-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs. J Gastroenterol 52, 641–651 (2017). https://doi.org/10.1007/s00535-016-1270-5
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DOI: https://doi.org/10.1007/s00535-016-1270-5