title: Three-phase sequential combined treatment with lamivudine and interferon in young patients with chronic hepatitis B.
abstract: Alpha-interferon (IFN) or lamivudine monotherapy are ineffective in treating chronic HBeAg positive patients with high viral load and low alanine aminotransferase (ALT) levels. We investigated whether priming lamivudine treatment might enhance the antiviral and immunostimulant action of lamivudine/IFN combination in young tolerant patients. Eleven chronic HBeAg positive patients received: 100 mg/day lamivudine for 3 months followed by IFN 5 MU/m2/tiw with lamivudine 100 mg/day for 6 months and then lamivudine alone 100 mg/day for 9 months. Quantitative hepatitis B virus (HBV)-DNA was evaluated during treatment and core-promoter, precore and polymerase HBV mutants were detected by direct sequencing at the end of therapy. Serum HBV-DNA levels dropped during lamivudine monotherapy and in combination with IFN. After IFN withdrawal, viraemia transiently increased to high levels in five of 11 (45%) patients who showed rt M204V/I lamivudine mutant resistant. Two patients cleared HBeAg without anti-HBe seroconversion. One patient presented core-promoter (A1762T/G1764A) and precore stop codon mutations. Hence, three-phase sequential combined lamivudine/IFN treatment reduced HBV-DNA serum level, but did not lead to HBeAg and HBV-DNA clearance in these highly viraemic, normal ALT patients. Lamivudine/IFN combination did not prevent the emergence of YMDD lamivudine resistance. New schedules of antiviral treatments must be evaluated in this population at risk of disease progression.
authors.affiliation: Internal Medicine and Hepatology, Second University of Naples, Naples, Italy. aldo.marrone@unina2.it
authors.forename: A
authors.initials: A
authors.lastname: Marrone
authors.forename: R
authors.initials: R
authors.lastname: Zampino
authors.forename: G
authors.initials: G
authors.lastname: Portella
authors.forename: M
authors.initials: M
authors.lastname: Grimaldi
authors.forename: E
authors.initials: E
authors.lastname: Durante-Mangoni
authors.forename: E D
authors.initials: ED
authors.lastname: Mangoni
authors.forename: L
authors.initials: L
authors.lastname: Santarpia
authors.forename: G
authors.initials: G
authors.lastname: Ruggiero
authors.forename: R
authors.initials: R
authors.lastname: Utili
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D011336:Probability; D011446:Prospective Studies; D011994:Recombinant Proteins; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine