Combination of alpha-interferon with lamivudine reduces viral breakthrough during long-term therapy.
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.
Jang
Myoung Kuk
MK
Department of Internal Medicine, Research Institute for Digestive Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Chung
Young-Hwa
YH
Choi
Min Hee
MH
Kim
Jeong A
JA
Ryu
Soo Hyung
SH
Shin
Jung Woo
JW
Kim
In Sook
IS
Park
Neung Hwa
NH
Lee
Han Chu
HC
Lee
Yung Sang
YS
Suh
Dong Jin
DJ
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
D000998:Antiviral Agents; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine