Korean J Gastroenterol.  2015 Jan;65(1):35-42. 10.4166/kjg.2015.65.1.35.

Efficacy of Tenofovir-based Rescue Therapy for Patients with Drug-resistant Chronic Hepatitis B

• Choi K
• Lee HM
• Jun BG
• Lee SH
• Kim HS
• Kim SG
• Kim YS
• Kim BS
• Jeong SW
• Jang JY
• Kim YD
• Cheon GJ

• KMID: 2373178
• DOI: http://doi.org/10.4166/kjg.2015.65.1.35

Abstract

BACKGROUND/AIMS
Tenofovir disoproxil fumarate (TDF) plays a pivotal role in the management of drug-resistant chronic hepatitis B. However, it remains unclear whether TDF-nucleoside analogue combination therapy provides better outcomes than TDF monotherapy. This study aimed to compare the efficacy of TDF monotherapy with that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.
METHODS
This retrospective cohort study included 76 patients receiving TDF-based rescue therapy for more than 12 months. Suboptimal response was defined as serum HBV-DNA level of >60 IU/mL during prior rescue therapy. Multi-drug resistance was defined as the presence of two or more drug resistance-related mutations confirmed by mutation detection assay. The relationship between baseline characteristics and virologic response (HBV DNA <20 IU/mL) at 12 months were evaluated using logistic regression analysis.
RESULTS
Fifty-five patients (72.4%) were suboptimal responders to prior rescue therapy, and 26 (34.2%) had multi-drug resistance. Forty-two patients (55.3%) received combination therapy with nucleoside analogues. Virologic response at 12 months was not significantly different between the TDF monotherapy group and TDF-nucleoside analogue combination therapy group (p=0.098). The serum HBV DNA level was reduced to -4.49+/-1.67 log10 IU/mL in the TDF monotherapy group and to -3.97+/-1.69 log10 IU/mL in the TDF-nucleoside analogue combination therapy group at 12 months (p=0.18). In multivariate analysis, female sex (p=0.032), low baseline HBV-DNA level (p=0.013), and TDF monotherapy (p=0.046) were predictive factors for virologic response at 12 months.
CONCLUSIONS
TDF monotherapy showed similar efficacy to that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.

Keyword

Hepatitis B; Drug resistance; Tenofovir; Virologic response

MeSH Terms

Adult
Aged
Antiviral Agents/pharmacology/*therapeutic use
Cohort Studies
DNA, Viral/blood
Drug Resistance, Viral
Drug Therapy, Combination
Female
Hepatitis B virus/drug effects/genetics/isolation & purification
Hepatitis B, Chronic/*drug therapy/virology
Humans
Logistic Models
Male
Middle Aged
Multivariate Analysis
Nucleosides/chemistry/therapeutic use
Retrospective Studies
Sex Factors
Tenofovir/*therapeutic use
Treatment Outcome
Young Adult
Antiviral Agents
DNA, Viral
Nucleosides
Tenofovir

Figure

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  Fig. 1. Mean (95% CI) changes in serum HBV DNA levels between TDF monotherapy group and TDF-nucleoside analogue combination therapy group.

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  Fig. 2. Mean (95% CI) changes in serum HBV DNA levels according to adefovir dipivoxil resistance-associated mutations. ADV-R, adefovir dipivoxil resistance-associate mutation.

Reference

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