title: Combination of alpha-interferon with lamivudine reduces viral breakthrough during long-term therapy.
abstract: OBJECTIVE
  Viral breakthrough is frequently encountered during long-term lamivudine therapy, mostly associated with YMDD mutants. In this study, we investigated the effects of alpha-interferon (IFN-alpha) combined with lamivudine on the occurrence of viral breakthrough during long-term lamivudine therapy.
  
  
  METHODS
  Eighty-three patients with biopsy-proven chronic hepatitis B were randomly allocated to a combination of lamivudine and IFN-alpha (LAM/IFN; n = 41) or lamivudine only (LAM; n = 42), and then followed up for >12 months. We calculated the cumulative rate of undetectable serum HBV-DNA and hepatitis B e antigen (HBeAg) loss, as well as the cumulative occurrence rate of viral breakthrough. We also evaluated the relationship between YMDD mutants and the occurrence of viral breakthrough.
  
  
  RESULTS
  There was no difference in cumulative rates of undetectable serum HBV-DNA (100%vs 100% at 24 months, P = 0.13) and cumulative rates of serum HBeAg loss between the LAM/IFN group and the LAM group (49%, 61% and 67%vs 31%, 39% and 42%, respectively, at 12, 24 and 36 months; P = 0.07). The cumulative occurrence rate of viral breakthrough, however, was significantly lower in the LAM/IFN group compared with the LAM group (5%, 20% and 30%vs 10%, 55% and 58%, respectively, at 12, 24 and 36 months; P = 0.006). From the patients with viral breakthrough, YMDD mutants were detected in 82% (18 of 22) of the LAM group in contrast with 56% (five of nine) of the LAM/IFN group in their sera.
  
  
  CONCLUSIONS
  IFN-alpha combined with lamivudine may reduce viral breakthrough during long-term lamivudine therapy, probably by suppressing the appearance of YMDD mutants.
authors.affiliation: Department of Internal Medicine, Research Institute for Digestive Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Myoung Kuk
authors.initials: MK
authors.lastname: Jang
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Choi
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Kim
authors.forename: Soo Hyung
authors.initials: SH
authors.lastname: Ryu
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Shin
authors.forename: In Sook
authors.initials: IS
authors.lastname: Kim
authors.forename: Neung Hwa
authors.initials: NH
authors.lastname: Park
authors.forename: Han Chu
authors.initials: HC
authors.lastname: Lee
authors.forename: Yung Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Suh
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine