The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection.
OBJECTIVE
To determine the response to pegylated interferon-alpha treatment of HBeAg-positive hepatitis B patients with proven lamivudine resistance.


METHODS
Sixteen HBeAg-positive HBV patients with YMDD mutations were treated with pegylated interferon. Median treatment duration was 52 weeks (range 20-53), with a 26-week follow-up.


RESULTS
Two of 16 (12.5%) patients seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA levels below 10log 5 copies/ml) together with biochemical (normalization of serum ALT levels) responses. Compared with the strong signal in all other patients, only these two patients had a faint signal in the lamivudine resistance assay. For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml (P = 0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml after treatment cessation. Similarly, elevated median ALT levels at baseline decreased with treatment but rebounded after the end of treatment.


CONCLUSIONS
In the largest cohort study to date, pegylated interferon-alpha therapy showed marginal efficacy in the presence of lamivudine resistance but such therapy may be beneficial in patients with only small amounts of mutant virus. In our opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should be included in all future studies of pegylated interferon-alpha in chronic hepatitis B.
Leemans
Wilhelmus F
WF
Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Flink
Hajo J
HJ
Janssen
Harry L A
HL
Niesters
Hubert G M
HG
Schalm
Solko W
SW
de Man
Robert A
RA
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D004337:Drug Carriers; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D004337:Drug Carriers; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b