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.

Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B

GAIA, Silvia;SMEDILE, Antonina;ABATE, Maria Lorena;OLIVERO, Antonella;RIZZETTO, Mario
2004

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.
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S. Gaia; A. Marzano; A. Smedile; V. Barbon; M. L. Abate; A. Olivero; M. Lagget; S. Paganin; M. Fadda; G. Niro; M. Rizzetto
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/57572
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