Korean J Med.  2015 Nov;89(5):527-536. 10.3904/kjm.2015.89.5.527.

Entecavir Resistance at rtS202, rtM250 May Cause Poor Viral Response to Tenofovir-based Rescue Therapy in Chronic Hepatitis B

• Kim SE
• Park JW
• Kim HS
• Suk KT
• Jang MK
• Park SH
• Lee MS
• Kim DJ
• Park CK

• KMID: 2268953
• DOI: http://doi.org/10.3904/kjm.2015.89.5.527

Abstract

BACKGROUND/AIMS
Long-term use of nucleos(t)ide analogues (NA) may lead to genotypic and/or phenotypic resistance of the hepatitis B virus (HBV). We investigated the efficacy of tenofovir-based rescue therapy in chronic hepatitis B (CHB) patients with newly developed genotypic resistance to prior NAs or partial virologic response to sequential rescue therapies.
METHODS
Fifty-four CHB patients were included retrospectively. The patients were treated with tenofovir alone or combined with lamivudine or entecavir.
RESULTS
There were 26 forms of genotypic resistance at enrollment. The median amount of serum HBV-DNA was 18,438 IU/mL and 83% of samples were positive for hepatitis B e antigen (HBeAg). Serum HBV-DNA was undetectable in 50%, 61%, and 76% of the patients at 3, 6, and 12 months, respectively. In multivariate analysis, HBV-DNA < 20,000 IU/mL and negative HBeAg at baseline were independent predictors of negativity for serum HBV-DNA. Interestingly, the rtS202 mutation tended to be associated with an unfavorable response. Other clinical variables and viral resistance genotypes showed non-significant viral response.
CONCLUSIONS
Lower serum HBV-DNA, negative HBeAg and lack of rtS202G mutations at baseline may predict a favorable response to tenofovir-based rescue therapies in CHB patients with newly developed genotypic resistance to prior NAs or a partial virologic response to sequential rescue therapies.

Keyword

Hepatitis B; Partialvirologicalresponse; Drug resistance; Tenofovir

MeSH Terms

Drug Resistance
Genotype
Hepatitis B
Hepatitis B e Antigens
Hepatitis B virus
Hepatitis B, Chronic*
Hepatitis, Chronic*
Humans
Lamivudine
Multivariate Analysis
Retrospective Studies
Tenofovir
Hepatitis B e Antigens
Lamivudine