Four years of treatment with lamivudine

Clinical and virological evaluations in HBe antigen-negative chronic hepatitis B

S. Gaia, A. Marzano, A. Smedile, V. Barbon, M. L. Abate, A. Olivero, M. Lagget, S. Paganin, M. Fadda, G. Niro, M. Rizzetto

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Aim: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. Methods: Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively. Results: The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma. Conclusion: Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.

Original languageEnglish
Pages (from-to)281-287
Number of pages7
JournalAlimentary Pharmacology and Therapeutics
Volume20
Issue number3
DOIs
Publication statusPublished - Aug 1 2004

Fingerprint

Lamivudine
Chronic Hepatitis B
Antigens
Drug Resistance
Therapeutics
Hepatocellular Carcinoma
Mutation
Genes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Four years of treatment with lamivudine : Clinical and virological evaluations in HBe antigen-negative chronic hepatitis B. / Gaia, S.; Marzano, A.; Smedile, A.; Barbon, V.; Abate, M. L.; Olivero, A.; Lagget, M.; Paganin, S.; Fadda, M.; Niro, G.; Rizzetto, M.

In: Alimentary Pharmacology and Therapeutics, Vol. 20, No. 3, 01.08.2004, p. 281-287.

Research output: Contribution to journalArticle

Gaia, S, Marzano, A, Smedile, A, Barbon, V, Abate, ML, Olivero, A, Lagget, M, Paganin, S, Fadda, M, Niro, G & Rizzetto, M 2004, 'Four years of treatment with lamivudine: Clinical and virological evaluations in HBe antigen-negative chronic hepatitis B', Alimentary Pharmacology and Therapeutics, vol. 20, no. 3, pp. 281-287. https://doi.org/10.1111/j.1365-2036.2004.02073.x
Gaia, S. ; Marzano, A. ; Smedile, A. ; Barbon, V. ; Abate, M. L. ; Olivero, A. ; Lagget, M. ; Paganin, S. ; Fadda, M. ; Niro, G. ; Rizzetto, M. / Four years of treatment with lamivudine : Clinical and virological evaluations in HBe antigen-negative chronic hepatitis B. In: Alimentary Pharmacology and Therapeutics. 2004 ; Vol. 20, No. 3. pp. 281-287.
@article{31be7d568e8043e78565255c172fea93,
title = "Four years of treatment with lamivudine: Clinical and virological evaluations in HBe antigen-negative chronic hepatitis B",
abstract = "Aim: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. Methods: Initial virological and biochemical responses were obtained in 84 (89{\%}) and in 83 (88{\%}) patients respectively. Results: The virological response peaked within the first 12 months, but diminished to 39{\%} at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4{\%}). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15{\%} at 24 months and 0{\%} at 29 months. There was no response in 10.6{\%}. Polymerase gene mutations were observed in 82.5{\%} of virological breakthroughs but also in 75{\%} of the non-responders. Overall 7.4{\%} of patients developed a hepatocellular carcinoma. Conclusion: Almost 90{\%} of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39{\%} at the fourth year of therapy. YMDD mutants explained the 75{\%} of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12{\%} of cases.",
author = "S. Gaia and A. Marzano and A. Smedile and V. Barbon and Abate, {M. L.} and A. Olivero and M. Lagget and S. Paganin and M. Fadda and G. Niro and M. Rizzetto",
year = "2004",
month = "8",
day = "1",
doi = "10.1111/j.1365-2036.2004.02073.x",
language = "English",
volume = "20",
pages = "281--287",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",

}

TY - JOUR

T1 - Four years of treatment with lamivudine

T2 - Clinical and virological evaluations in HBe antigen-negative chronic hepatitis B

AU - Gaia, S.

AU - Marzano, A.

AU - Smedile, A.

AU - Barbon, V.

AU - Abate, M. L.

AU - Olivero, A.

AU - Lagget, M.

AU - Paganin, S.

AU - Fadda, M.

AU - Niro, G.

AU - Rizzetto, M.

PY - 2004/8/1

Y1 - 2004/8/1

N2 - Aim: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. Methods: Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively. Results: The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma. Conclusion: Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.

AB - Aim: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. Methods: Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively. Results: The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma. Conclusion: Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.

UR - http://www.scopus.com/inward/record.url?scp=4043178381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4043178381&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2036.2004.02073.x

DO - 10.1111/j.1365-2036.2004.02073.x

M3 - Article

VL - 20

SP - 281

EP - 287

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

IS - 3

ER -