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

• Published in: Alimentary pharmacology & therapeutics Vol. 20; no. 3; pp. 281 - 287
• Main Authors: Gaia, S., Marzano, A., Smedile, A., Barbon, V., Abate, M. L., Olivero, A., Lagget, M., Paganin, S., Fadda, M., Niro, G., Rizzetto, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2004; Blackwell
• Subjects: Antiviral Agents - therapeutic use; Biological and medical sciences; Carcinoma, Hepatocellular - etiology; Digestive system; Drug Evaluation; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis B e Antigens - analysis; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Humans; Lamivudine - therapeutic use; Liver Neoplasms - etiology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - therapeutic use; Treatment Outcome; RNA-directed DNA polymerase; Enzyme; Transferases; Enzyme inhibitor; Hepatic disease; Lamivudine; Infection; Viral hepatitis B; Nucleotidyltransferases; Treatment; Dideoxynucleoside; Reverse transcriptase inhibitor; Viral disease; Digestive diseases; Antiviral; Nucleosidic analog; Pyrimidine nucleoside
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2004.02073.x

Summary 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.