HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B.
The aims of this study were to evaluate the usefulness of quantitative hepatitis B e antigen (HBeAg) values for predicting HBeAg seroconversion in patients treated with peginterferon alfa-2a and to assess the dynamic changes in quantitative HBeAg during therapy, compared with conventional measures of serum hepatitis B virus DNA. Data were analyzed from a large, randomized, multinational phase III registration trial involving 271 HBV-infected HBeAg-positive patients who received peginterferon alfa-2a plus oral placebo for 48 weeks. HBeAg levels were measured serially during therapy using a microparticle enzyme immunoassay validated with in-house reference standards obtained from the Paul Ehrlich Institute (PEIU/mL). In patients who achieved HBeAg seroconversion, levels of HBeAg consistently decreased during treatment and remained at their lowest level during the 24 weeks of posttreatment follow-up. After 24 weeks of treatment, 4% of patients with the highest levels of HBeAg (>or=100 PEIU/mL) achieved HBeAg seroconversion, yielding a negative predictive value of 96%, which was greater than that obtained for levels of HBV DNA (86%). Late responders to peginterferon alfa-2a could also be differentiated from nonresponders by continued decrease in HBeAg values, which were not evident by changes in HBV DNA.


CONCLUSIONS
These analyses suggest quantitative HBeAg is a useful adjunctive measurement for predicting HBeAg seroconversion in patients treated with peginterferon when considering both sensitivity and specificity compared with serum HBV DNA.
Fried
Michael W
MW
University of North Carolina, Chapel Hill, NC 27599-7584, USA. mfried@med.unc.edu
Piratvisuth
Teerha
T
Lau
George K K
GK
Marcellin
Patrick
P
Chow
Wan-Cheng
WC
Cooksley
Graham
G
Luo
Kang-Xian
KX
Paik
Seung Woon
SW
Liaw
Yun-Fan
YF
Button
Peter
P
Popescu
Matei
M
D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a