A Lower PBMC Estrogen Receptor a Gene Expression in Chronic Hepatitis B Is Associated with a Sustained Virological Response to Pegylated Interferon

The aim of this study was to investigate possible involvement of estrogen receptor (ESR1) in responding to pegylated interferon alpha-2a (PEG IFN-2a) therapy in chronic hepatitis B (CHB) patients. A total of 106 HBeAg-positive patients and 52 healthy controls were enrolled into this study. ESR1 messenger RNA (mRNA) expression in peripheral blood mononuclear cells was quantified at the baseline, during treatment (weeks 4 and 12), and at the end of treatment (week 48) by real-time reverse transcriptase-polymerase chain reaction assay (RT-PCR). The sequence polymorphism of ESR1 (rs2077647, rs2234693, rs9340799, and rs9322354) was analyzed using the Sequenom MassARRAY Analyzer. Our results suggested that the most accurate prediction of nonresponder in female patients was the baseline alanine aminotransferase (ALT) in combination with ESR1 expression at week 4 of treatment (area under the receiver operating characteristic curve [AUC]=0.908). Combining the baseline ALT with ESR1 mRNA expression at the end of treatment showed the best prediction of sustained virological response in male patients (AUC=0.818). Internal validation was assessed by bootstrap cross-validation. These results may have clinical relevance and warrant future validation in studies with larger cohorts.