Background and aims: Hepatitis B e Antigen (HBeAg) seroconversion and Hepatitis B surface Antigen (HBsAg) seroclearance confer an improved prognosis. Both endpoints are more often achieved with one year peginterferon (PEG-IFN) compared to one year of nucleos(t)ide analogues (NA), but prolonged NA therapy may result in serological response rates similar to those achieved with PEG-IFN.
Materials and methods: A total of 266 HBeAg-positive CHB patients were treated with PEG-IFN±lamivudine for one year and 91 NA-naïve patients were treated with prolonged entecavir (ETV). Follow-up was terminated in patients retreated with NA after PEG-IFN.
Results: Median follow-up was 92 weeks (IQR 78-198) for PEG-IFN patients, and 92 (IQR 50-132) for ETV patients. Groups were balanced for HBV genotype, age, sex and previous IFN therapy. Baseline HBV DNA and ALT were higher in PEG-IFN patients (9.1 vs. 8.0 log copies/mL (p< 0.001) and 4.3 vs. 3.1xULN (p=0.004)). One-hundred-fourteen (32%) patients achieved HBeAg seroconversion after 78 weeks (IQR 52-120). The cumulative probability of HBeAg seroconversion was higher in PEG-IFN treated patients (p=0.007). PEG-IFN was an independent determinant of HBeAg seroconversion in a Cox model; hazard rate (HR) for PEG-IFN versus ETV was 3.16 (95%CI: 1.57-6.36, p< 0.001), adjusted for HBV genotype, age, ALT and HBV DNA. Thirty (8%) patients cleared HBsAg in 92 (78-170) weeks. The cumulative probability of HBsAg loss was higher in patients receiving PEG-IFN (p=0.032). PEG-IFN therapy was independently associated with HBsAg clearance, with a HR of 5.66 (95%CI: 0.76-42.40, p=0.027) after adjustment for genotype, age and previous IFN. However, HBV DNA undetectability (HBV DNA < 80 IU/mL) at week 78 (6 months post-treatment in patients treated with PEG-IFN) was only achieved in 8% of patients treated with PEG-IFN versus 77% for ETV (p< 0.001). At last follow-up evaluation (≥ week 78) HBV DNA undetectability was achieved in 15% of PEG-IFN treated patients versus 92% of patients on ETV (p< 0.001).
Conclusions: PEG-IFN results in higher rates of HBsAg clearance, and thus sustained remission of CHB, than prolonged ETV therapy, also after adjustment for baseline factors. However, continuous ETV results in higher rates of virological suppression compared with PEG-IFN. |