Successful treatment with peginterferon alfa-2b of HBeAg-positive HBV non-responders to standard interferon or lamivudine.
OBJECTIVE
Antiviral therapy leads to HBeAg seroconversion in 10-40% of the patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in progression of liver disease and increased risk of hepatocellular carcinoma. As part of a global randomized controlled trial we investigated the efficacy (i.e., loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b) in patients who failed to respond to previous courses of standard interferon (IFN) or lamivudine.


METHODS
We analyzed a total of 76 previous nonresponders: 37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and 22 were nonresponders to both therapies. All patients received a 52-wks course of 100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or a placebo. After therapy patients were followed for 26 wks.


RESULTS
Thirteen (35%) nonresponders to previous IFN, five (29%) nonresponders to previous lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to treatment with Peg-IFN alpha2b. No difference in response was found for those treated with Peg-IFN alpha2b alone or in combination with lamivudine. Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) > 4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those with ALT levels <or= 4 x ULN (53%vs 20%, respectively, p= 0.036).


CONCLUSIONS
Peg-IFN alpha2b is effective in approximately one-third of patients who failed to respond to previous treatment with standard IFN or lamivudine. High serum ALT level at baseline of Peg-IFN alpha2b therapy was the best predictor for response in these patients.
Flink
Hajo J
HJ
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Hansen
Bettina E
BE
Heathcote
E Jenny
EJ
Feinman
S Victor
SV
Simsek
Halis
H
Karayalcin
Selim
S
Mach
Tomasz
T
Leemans
Wim F
WF
de Man
Robert A
RA
Verhey
Elke
E
Schalm
Solko W
SW
Janssen
Harry L A
HL
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007372:Interferons / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; D007372:Interferons; C417083:peginterferon alfa-2b