Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: Results ofa pilot study

Sustained viral suppression using monotherapy with interferon alfa (IFN-alp ha) or lamivudine can only be achieved in a small percentage of patients wi th chronic hepatitis B. The concomitant administration of lamivudine and IF N-alpha does not enhance efficacy. We postulated that the optimal timing of therapy might be sequential treatment with lamivudine and IFN-alpha. The a im of this study was therefore to assess the efficacy of sequential treatme nt 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 m g/d alone for 20 weeks, then with both IFN-alpha 2b 5 MU 3 times per week a nd 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 tre atment was achieved in 8 of 14 patients, HBeAg-to-anti-HBe seroconversion i n 5 of 11 patients, and HBeAg and hepatitis B surface antigen (HBsAg) seroc onversions in 3 of 14 patients (anti-HBs > 100 IU/mL). All sustained respon ders had normalized their alanine transaminase (ALT) values and exhibited h istologic improvements. In conclusion, the results of this pilot study sugg est that sequential treatment with lamivudine and IFN-alpha can induce a su stained virologic response, including HBs seroconversion, in patients with chronic hepatitis B not responding to IFN-alpha alone, without the selectio n of drug-resistant mutants. This therapeutic schedule warrants further eva luation in clinical trials.