Host and viral factors influencing disease progression and treatment response in chronic HBV infection

Abstract

Hepatitis B virus (HBV) infection represents a major risk factor of developing chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). The clinical outcome of HBV infection depends on complex of host and virus interactions. In this study, we found that serum HBV RNA levels has emerged as a potential viral marker for active HBV infection and may be used to evaluate response to antiviral therapy and disease progression. Serum HBV RNA levels varied among different phases of chronic HBV infection (CHB). There was a correlation between serum HBV RNA levels and amount of intrahepatic covalently closed circular DNA (cccDNA), suggesting that serum HBV RNA quantification represents a useful non-invasive marker for disease monitoring in patients with CHB. In addition, the measurement of serum HBV RNA prior to pegylated interferon (PEG-IFN)-based therapy could identify patients with high probability of sustained response (SR, HBV DNA <2,000 IU/mL). Moreover, early HBV RNA kinetics identified subgroup of patients who had a minimal chance of achieving favorable outcome, which could allow response guided therapy. Host genetic factors can also affect the outcome of HBV infection. We investigated the influence of single nucleotide polymorphisms (SNPs) in vitamin D-related genes including 25-Hydroxyvitamin D-1 alpha-hydroxylase (CYP27B1), vitamin D binding protein (DBP) and vitamin D receptor (VDR) and genetic variation in signal transducer and activator of transcription 4 (STAT4) on HBV infection outcomes. The results of this study showed that variations of both rs4646536 in the CYP27B1 gene and rs7574865 in the STAT4 gene might contribute to increased susceptibility to HBV-related HCC in the Thai population but did not correlate with HBV susceptibility and HBV natural clearance. In addition, both SNPs were predictive factors of response to PEG-IFN therapy in Thai patients with CHB. Thus, the determination of these SNPs could maximize cost-effectiveness of PEG-IFN in patients with CHB.