title: Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: results of a pilot study.
abstract: Sustained viral suppression using monotherapy with interferon alfa (IFN-alpha) or lamivudine can only be achieved in a small percentage of patients with chronic hepatitis B. The concomitant administration of lamivudine and IFN-alpha does not enhance efficacy. We postulated that the optimal timing of therapy might be sequential treatment with lamivudine and IFN-alpha. The aim of this study was therefore to assess the efficacy of sequential treatment in patients resistant to IFN-alpha alone. Fourteen male patients, with a median age of 40 years, nonresponders to IFN-alpha with hepatitis B virus (HBV) DNA > 100 pg/mL (branched DNA [bDNA] Chiron) and positive hepatitis B e antigen (HBeAg) in 11 of 14 patients, were treated with lamivudine 100 mg/d alone for 20 weeks, then with both IFN-alpha2b 5 MU 3 times per week and lamivudine for 4 weeks, and lastly with IFN-alpha alone for 24 weeks. At the end of lamivudine therapy, all patients had undetectable serum HBV DNA, and none exhibited an emergence of HBV polymerase mutant or breakthrough. Sustained serum HBV-DNA clearance 6 months after the end of sequential treatment was achieved in 8 of 14 patients, HBeAg-to-anti-HBe seroconversion in 5 of 11 patients, and HBeAg and hepatitis B surface antigen (HBsAg) seroconversions in 3 of 14 patients (anti-HBs > 100 IU/mL). All sustained responders had normalized their alanine transaminase (ALT) values and exhibited histologic improvements. In conclusion, the results of this pilot study suggest that sequential treatment with lamivudine and IFN-alpha can induce a sustained virologic response, including HBs seroconversion, in patients with chronic hepatitis B not responding to IFN-alpha alone, without the selection of drug-resistant mutants. This therapeutic schedule warrants further evaluation in clinical trials.
authors.affiliation: Service d'Hépato-gastroenterologie, Hôpital Saint-Antoine, Paris, France. lawrence.serfaty@sat.ap-hop-paris.fr
authors.forename: L
authors.initials: L
authors.lastname: Serfaty
authors.forename: D
authors.initials: D
authors.lastname: Thabut
authors.forename: F
authors.initials: F
authors.lastname: Zoulim
authors.forename: T
authors.initials: T
authors.lastname: Andreani
authors.forename: O
authors.initials: O
authors.lastname: Chazouillères
authors.forename: N
authors.initials: N
authors.lastname: Carbonell
authors.forename: A
authors.initials: A
authors.lastname: Loria
authors.forename: R
authors.initials: R
authors.lastname: Poupon
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D015684:Gene Products, pol / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019233:Retreatment
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D019259:Lamivudine; D007372:Interferons; D000410:Alanine Transaminase