Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients: A pilot study

• Published in: Digestive and liver disease 2007-09, Vol.39 (9), p.857-863
• Main Authors: Niro, G.A, Fontana, R, Gioffreda, D, Fiorella, S, Accadia, L, Iacobellis, A, Caruso, N, Conoscitore, P, Andriulli, A
• Format: Article
• Language: English
• Subjects: Adult; Antiviral Agents - administration & dosage; DNA, Viral - drug effects; Drug Administration Schedule; Drug Resistance, Multiple, Viral - genetics; Female; Gastroenterology and Hepatology; HBV; HBV-DNA polymerase; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Humans; Interferon; Interferon-alpha - administration & dosage; Lamivudine; Lamivudine - administration & dosage; Male; Middle Aged; Pilot Projects; Recombinant Proteins; Sequential therapy; Viral Load; Viral resistance; YMDD
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2007.06.002

Abstract Background In chronic hepatitis B, long-term use of alpha interferon is hampered by side effects, and long-term treatment with nucleos(t)ide analogues is burdened by drug-resistant mutants. We hypothesized that alternate rounds of lamivudine and alpha interferon might circumvent previous shortcomings. Aim To evaluate efficacy of sequential lamivudine or IFN-α2b monotherapies in preventing occurrence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants and achieving virological and biochemical response. Methods Fifteen patients with hepatitis B surface antigen, anti-HBe-positive chronic hepatitis received four consecutive rounds of monotherapy with lamivudine (100 mg/day), IFN-α2b (5 MU/tiw), lamivudine, IFN-α2b. Serum HBV-DNA levels were evaluated during and off treatment, HBV polymerase and pre-core/core regions sequenced. Results End-of-treatment response was achieved in 10 patients (67%). One patient did not respond, a second developed genotypic resistance at week 24. A rebound in viremia occurred in three patients at week 48. Six patients (40%) remained sustained responders. Triple promoter mutations at nucleotides 1762-1764-1896 prevailed in non-responders (60%) as compared to responders (20%). L180M/M204V mutations were identified during virological breakthrough. Conclusion Sequential approach of alternate rounds of lamivudine or interferon may help patients to tolerate a prolonged schedule of therapy and protect them from emergence of viral strains.