Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice

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Hepatology. 2011 Jun;53(6):1854-63. doi: 10.1002/hep.24318.

Virological breakthrough and resistance in patients with chronic hepatitis B

receiving nucleos(t)ide analogues in clinical practice.

Hongthanakorn C, Chotiyaputta W, Oberhelman K, Fontana RJ, Marrero JA, Licari T,

Lok AS.

Source

Division of Gastroenterology, Department of Internal Medicine, University of

Michigan Health System, Ann Arbor, MI.

Abstract

Virological breakthrough (VBT) is the first manifestation of antiviral drug

resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B

(CHB), but not all VBTs are due to drug resistance. This study sought to

determine the incidence of VBT and genotypic resistance (GR) in patients with

CHB who were receiving NUCs in clinical practice. Records of patients with CHB

who were receiving NUCs were reviewed. All patients with VBT were tested for

drug resistance mutations. Of 148 patients included, 73% were men and mean age

was 44.9 years. During a mean follow-up of 37.5 ± 20.1 months, 39 (26%) patients

had at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have

VBT on retesting, and 10 of these 15 had no evidence of GR. The cumulative

probability of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and

33.9%, respectively. In multivariate analysis, failure to achieve undetectable

hepatitis B virus (HBV) DNA was the only factor significantly associated with

VBT. Among the 10 patients who had VBT but no confirmed VBT or GR and who were

maintained on the same medications, serum HBV DNA decreased in all 10, and nine

had undetectable HBV DNA at a mean of 6.8 months after the VBT. Four patients

had persistently undetectable HBV DNA, six had transient increase in HBV DNA

during follow-up, and none had GR. Conclusion: VBT was common in patients with

CHB receiving NUCs in clinical practice, but nearly 40% of the VBTs were not

related to antiviral drug resistance. Counseling of patients with CHB on

medication adherence and confirmation of VBT and/or GR can avoid unnecessary

changes in antiviral medications.

(HEPATOLOGY 2011;).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21618260 [PubMed - in process]

[Guest guest]

Hepatology. 2011 Jun;53(6):1854-63. doi: 10.1002/hep.24318.

Virological breakthrough and resistance in patients with chronic hepatitis B

receiving nucleos(t)ide analogues in clinical practice.

Hongthanakorn C, Chotiyaputta W, Oberhelman K, Fontana RJ, Marrero JA, Licari T,

Lok AS.

Source

Division of Gastroenterology, Department of Internal Medicine, University of

Michigan Health System, Ann Arbor, MI.

Abstract

Virological breakthrough (VBT) is the first manifestation of antiviral drug

resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B

(CHB), but not all VBTs are due to drug resistance. This study sought to

determine the incidence of VBT and genotypic resistance (GR) in patients with

CHB who were receiving NUCs in clinical practice. Records of patients with CHB

who were receiving NUCs were reviewed. All patients with VBT were tested for

drug resistance mutations. Of 148 patients included, 73% were men and mean age

was 44.9 years. During a mean follow-up of 37.5 ± 20.1 months, 39 (26%) patients

had at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have

VBT on retesting, and 10 of these 15 had no evidence of GR. The cumulative

probability of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and

33.9%, respectively. In multivariate analysis, failure to achieve undetectable

hepatitis B virus (HBV) DNA was the only factor significantly associated with

VBT. Among the 10 patients who had VBT but no confirmed VBT or GR and who were

maintained on the same medications, serum HBV DNA decreased in all 10, and nine

had undetectable HBV DNA at a mean of 6.8 months after the VBT. Four patients

had persistently undetectable HBV DNA, six had transient increase in HBV DNA

during follow-up, and none had GR. Conclusion: VBT was common in patients with

CHB receiving NUCs in clinical practice, but nearly 40% of the VBTs were not

related to antiviral drug resistance. Counseling of patients with CHB on

medication adherence and confirmation of VBT and/or GR can avoid unnecessary

changes in antiviral medications.

(HEPATOLOGY 2011;).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21618260 [PubMed - in process]