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

Chanunta Hongthanakorn, Watcharasak Chotiyaputta, Kelly Oberhelman, Robert J. Fontana, Jorge A. Marrero, Tracy Licari, Anna S F Lok

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1854-1863
Number of pages10
JournalHepatology
Volume53
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Chronic Hepatitis B
Hepatitis B virus
Viral Drug Resistance
DNA
Drug Resistance
Medication Adherence
Antiviral Agents
Counseling
Multivariate Analysis
Mutation
Incidence

ASJC Scopus subject areas

  • Hepatology

Cite this

Hongthanakorn, C., Chotiyaputta, W., Oberhelman, K., Fontana, R. J., Marrero, J. A., Licari, T., & Lok, A. S. F. (2011). Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. Hepatology, 53(6), 1854-1863. https://doi.org/10.1002/hep.24318

Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. / Hongthanakorn, Chanunta; Chotiyaputta, Watcharasak; Oberhelman, Kelly; Fontana, Robert J.; Marrero, Jorge A.; Licari, Tracy; Lok, Anna S F.

In: Hepatology, Vol. 53, No. 6, 06.2011, p. 1854-1863.

Research output: Contribution to journalArticle

Hongthanakorn, C, Chotiyaputta, W, Oberhelman, K, Fontana, RJ, Marrero, JA, Licari, T & Lok, ASF 2011, 'Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice', Hepatology, vol. 53, no. 6, pp. 1854-1863. https://doi.org/10.1002/hep.24318
Hongthanakorn, Chanunta ; Chotiyaputta, Watcharasak ; Oberhelman, Kelly ; Fontana, Robert J. ; Marrero, Jorge A. ; Licari, Tracy ; Lok, Anna S F. / Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. In: Hepatology. 2011 ; Vol. 53, No. 6. pp. 1854-1863.
@article{e79ec37635714ce9b03f105ae3df59a3,
title = "Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice",
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.",
author = "Chanunta Hongthanakorn and Watcharasak Chotiyaputta and Kelly Oberhelman and Fontana, {Robert J.} and Marrero, {Jorge A.} and Tracy Licari and Lok, {Anna S F}",
year = "2011",
month = "6",
doi = "10.1002/hep.24318",
language = "English (US)",
volume = "53",
pages = "1854--1863",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice

AU - Hongthanakorn, Chanunta

AU - Chotiyaputta, Watcharasak

AU - Oberhelman, Kelly

AU - Fontana, Robert J.

AU - Marrero, Jorge A.

AU - Licari, Tracy

AU - Lok, Anna S F

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79957481330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957481330&partnerID=8YFLogxK

U2 - 10.1002/hep.24318

DO - 10.1002/hep.24318

M3 - Article

C2 - 21618260

AN - SCOPUS:79957481330

VL - 53

SP - 1854

EP - 1863

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 6

ER -