RESUMO
BACKGROUND/AIMS: Alpha-interferon (alpha-IFN) and lamivudine are the two licensed drugs for patients with chronic hepatitis B, however, their efficacy in precore mutant chronic hepatitis B is limited. The aim of this study was to investigate the efficacy of 1 year alpha-IFN-lamivudine combination therapy for anti-HBe/hepatitis B virus- (HBV)-DNA positive patients. METHODS: Between 1997 and 1999, 29 consecutive anti-HBe/HBV-DNA positive patients entered this prospective pilot study. Patients received 100mg lamivudine orally daily and alpha-IFN 6 million units (MU) three times weekly for 52 weeks. All patients were followed-up for 12 months after stopping therapy. Primary end points were loss of serum HBV-DNA and alanine transaminase normalization at week 52. RESULTS: Overall, the end-treatment biochemical and virological response was 93% while the sustained response at week 104 was 14%. HBV-DNA negative patients did not experience a viral breakthrough during treatment; no tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase (YMDD) variant emerged. At week 52, 46% of patients with paired liver biopsies slides available, showed an histological improvement (histological activity index > or =2). CONCLUSIONS: Combination of lamivudine and interferon for 1 year is followed by high end-treatment virological and biochemical response rates, by improvement of liver histology and by the prevention of the emergence of YMDD mutation; however, the sustained response rate remains low.
Assuntos
Antivirais/uso terapêutico , Produtos do Gene pol/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Mutação , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Alanina Transaminase/sangue , Motivos de Aminoácidos/genética , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Variação Genética , Antígenos E da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Projetos Piloto , Estudos Prospectivos , Análise de SobrevidaRESUMO
In a study of 37 patients with hepatitis C (proved histologically) positive chronic hepatitis, a correlation was seen between clinical efficacy and histological improvement after treatment with interferon alfa-2b (3 million units (MU) three times a week for six months plus six months' follow up). Alanine aminotransferase activities became normal in 18 (48%) patients during treatment; at the end of follow up eight (45%) had a continued response to the treatment. Paired liver biopsy specimens showed marked improvements in Knodell index score and portal inflammation in these patients.