Clin Mol Hepatol.  2013 Mar;19(1):29-35. 10.3350/cmh.2013.19.1.29.

Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B

• Park MS
• Kim BK
• Kim KS
• Kim JK
• Kim SU
• Park JY
• Kim DY
• Baartarkhuu O
• Han KH
• Chon CY
• Ahn SH

• KMID: 1493572
• DOI: http://doi.org/10.3350/cmh.2013.19.1.29

Abstract

BACKGROUND/AIMS
The incidence of multidrug-resistant (MDR) chronic hepatitis B (CHB) during sequential lamivudine (LAM) and adefovir dipivoxil (ADV) treatment is increasing. We investigated the antiviral efficacies of various rescue regimens in patients who failed sequential LAM-ADV treatment.
METHODS
Forty-eight patients (83.3% of whom were HBeAg-positive) who failed sequential LAM-ADV treatment were treated with one of the following regimens: entecavir (ETV) (1 mg) monotherapy (n=16), LAM+ADV combination therapy (n=20), or ETV (1 mg)+ADV combination therapy (n=12). All patients had confirmed genotypic resistance to both LAM and ADV and were evaluated every 12 weeks.
RESULTS
The baseline characteristics and treatment duration did not differ significantly among the study groups. During the treatment period (median duration: 100 weeks), the decline of serum HBV DNA from baseline tended to be greatest in the ETV+ADV group at all-time points (week 48: -2.55 log10 IU/mL, week 96: -4.27 log10 IU/mL), but the difference was not statistically significant. The ETV+ADV group also tended to have higher virologic response rates at 96 weeks compared to the ETV monotherapy or LAM+ADV groups (40.0% vs. 20.0% or 20.0%, P=0.656), and less virologic breakthrough was observed compared to the ETV monotherapy or LAM+ADV groups (8.3% vs. 37.5% or 30.0%; P=0.219), but again, the differences were not statistically significant. HBeAg loss occurred in one patient in the ETV+ADV group, in two in the ETV monotherapy group, and in none of the LAM+ADV group. The safety profiles were similar in each arm.
CONCLUSIONS
There was a nonsignificant tendency toward better antiviral efficacy with ETV+ADV combination therapy compared to LAM+ADV combination therapy and ETV monotherapy for MDR CHB in Korea, where tenofovir is not yet available.

Keyword

Hepatitis B virus; Multidrug resistance; Hepatitis B; Entecavir; Adefovir

MeSH Terms

Adenine/analogs & derivatives/therapeutic use
Adult
Aged
Antiviral Agents/*therapeutic use
DNA, Viral/blood
Drug Resistance, Viral
Drug Therapy, Combination
Female
Follow-Up Studies
Genotype
Guanine/analogs & derivatives/therapeutic use
Hepatitis B e Antigens/blood
Hepatitis B virus/genetics
Hepatitis B, Chronic/*drug therapy
Humans
Lamivudine/therapeutic use
Male
Middle Aged
Organophosphonates/therapeutic use
Treatment Outcome
Antiviral Agents
DNA, Viral
Hepatitis B e Antigens
Organophosphonates
Lamivudine
Adenine
Guanine