Potential and limitations of lamivudine monotherapy in chronic hepatitis B: evidence from genotyping


Prof. Geoffrey Dusheiko, Centre for Hepatology, Royal Free and University College School of Medicine, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
Tel: +44 207 433 2885
Fax: +44 207 433 2884
email: g.dusheiko@medsch.ucl.ac.uk


Background: Current oral therapy for hepatitis B virus (HBV) is limited by the presence of resistance leading to resumption of higher levels of HBV replication. Therefore, there is a need for a better definition of the potential role and limitations of lamivudine or similar therapies, used alone.

Aims: To examine the viability of lamivudine and similar monotherapies as a treatment strategy in chronic HBV in the face of the worldwide burden of disease.

Methods: We have reviewed the role of lamivudine monotherapy in the treatment of chronic HBV in a single tertiary referral liver centre over a 9-year period. We analysed the outcome in 90 patients where lamivudine has apparently conferred long-term viral suppression and investigated the development of genotypic resistance in the absence of ostensible phenotypic resistance. Patients were subdivided into hepatitis B e antigen (HBeAg)-positive and anti-HBe-positive groups.

Results: Virtually all HBeAg-positive patients who failed to seroconvert have progressed to combination antiviral therapy. Only 19%(7/36) of HBeAg-negative patients have continued suppression without detectable genotypic change after 4 years of therapy.

Conclusions: These data demonstrate that despite a relatively low level of viraemia in HBeAg-negative patients, we could detect resistance mutations by direct sequencing in all patients with amplifiable HBV DNA. Our results suggest that for patients with ongoing replication at ‘amplifiable’ levels of HBV DNA, but <105 copies/ml, genotypic selection is readily detectable. Lamivudine monotherapy has not sufficed for the overwhelming majority of patients.