Korean J Intern Med.  2015 Jan;30(1):32-41. 10.3904/kjim.2015.30.1.32.

Long-term efficacy of tenofovir disoproxil fumarate therapy after multiple nucleos(t)ide analogue failure in chronic hepatitis B patients

• Kim HJ
• Cho JY
• Kim YJ
• Gwak GY
• Paik YH
• Choi MS
• Koh KC
• Paik SW
• Yoo BC
• Lee JH

• KMID: 2129661
• DOI: http://doi.org/10.3904/kjim.2015.30.1.32

Abstract

BACKGROUND/AIMS
The efficacy of tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B (CHB) patients following prior treatment failure with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in Asian populations. In this study we investigated the efficacy and safety of TDF rescue therapy in CHB patients after multiple NA treatment failure.
METHODS
The study retrospectively analyzed 52 CHB patients who experienced failure with two or more NAs and who were switched to regimens containing TDF. The efficacy and safety assessments included hepatitis B virus (HBV) DNA undetectability, hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT) normalization and changes in serum creatinine and phosphorus levels.
RESULTS
The mean HBV DNA level at baseline was 5.4 +/- 1.76 log10 IU/mL. At a median duration of 34.5 months of TDF treatment, the cumulative probabilities of achieving complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12, 24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48 patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly associated with increased CVR rates (p < 0.001). However, CVR rates did not differ between TDF monotherapy or combination therapy with other NAs, and were not affected by mutations associated with resistance to NAs. No significant adverse events were observed.
CONCLUSIONS
TDF is an efficient and safe rescue therapy for CHB patients after treatment failure with multiple NAs.

Keyword

Tenofovir; Hepatitis B, chronic; Treatment failure; Resistance

MeSH Terms

Adenine/adverse effects/*analogs & derivatives/therapeutic use
Adult
Aged
Alanine Transaminase/blood
Antiviral Agents/adverse effects/*therapeutic use
Biological Markers/blood
Creatinine/blood
DNA, Viral/blood
Drug Resistance, Viral/genetics
Drug Substitution
Female
Genotype
Hepatitis B e Antigens/blood
Hepatitis B virus/*drug effects/genetics/immunology/pathogenicity
Hepatitis B, Chronic/blood/diagnosis/*drug therapy
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mutation
Phosphorous Acids/adverse effects/*therapeutic use
Phosphorus/blood
Retrospective Studies
Time Factors
Treatment Failure
Viral Load
Young Adult
Adenine
Alanine Transaminase
Antiviral Agents
Biological Markers
Creatinine
DNA, Viral
Hepatitis B e Antigens
Phosphorous Acids
Phosphorus