Relapse Of Hepatitis B E Antigen-positive Patients After Standardized Interferon α Regimen: A Five-year Follow-up Study

Objectives Interferon α(IFN-α) is considered as a first-line treatment option for hepatitis B e antigen(HBe Ag)-positive chronic hepatitis B(CHB). We aimed to estimate relapse of hepatitis B in HBe Ag-positive chronic hepatitis B patients who accept standardized interferon-alpha α(IFN-α) regimen during 5-year follow-up observation and evaluate the factors influencing relapse of hepatitis B.Methods We retrospectively analyzed 169 initial responders to standardized IFN-α therapy during 5-year follow-up. The clinical data and laboratory data, treatment regimen and relapse of the illness were recorded. Age, gender, pretreatment levels of serum alanine aminotransferase(ALT), hepatitis B virus(HBV) DNA, HBe Ag and hepatitis B surface antigen(HBs Ag), liver histology at baseline, HBs Ag level, decline in HBs Ag and absence of hepatitis B e antibody(Anti-HBe) at the end of treatment, HBV genotype, type, dose and duration of IFN therapy were evaluated as potential risk factors for relapse. The Kaplan-Meier method was used to calculate cumulative relapse rate; The χ2 test, student’s t test and Cox proportional hazards regression model were used to analyze the correlation between the potential risk factors and relapse.Results The cumulative relapse rates at 1, 2, 3, 4, and 5 year posttreatment were 21.9%, 28.4%, 32.0%, 33.1% and 34.3% respectively; Relapse was related to age, serum hepatitis B virus deoxyribonucleic acid(HBV DNA) and hepatitis B surface antigen(HBs Ag) levels, decline in serum HBs Ag levels at the end of treatment, HBV genotype and duration of IFN-α therapy by univariate analysis; According to COX regression,duration of IFN-α therapy and serum HBs Ag levels at the end of treatment were two main indicators for relapse of hepatitis B; The relative risk(RR) were 0.640(95% CI:0.413 ~ 0.991) and 1.789(95% CI:1.218 ~ 2.629) respectively. The positive predictive value(PPV) and negative predictive value(NPV) of serum HBs Ag being 2 lg IU/ml or greater at end of treatment was 49.5% and 90.6% for prediction of relapse. The PPV and NPV of decline in serum HBs Ag compared with the baseline being 1.7 lg IU/ml or less at end of treatment was 43.8% and 84.2% for prediction of relapse.Conclusions Shorter duration of IFN-α therapy and higher serum HBs Ag levels at the end of treatment are risk factors for relapse of hepatitis B, prolongation of IFN-α therapy might reduce risk of relapse, and serum HBs Ag quantification may be useful in determining course of individualized IFN-α treatment.