Single Nucleotide Polymorphism of Interferon Lambda-4 Gene is not Associated with Treatment Response to Pegylated Interferon in Thai Patients with Chronic Hepatitis B.

Umaporn Limothai,Pisit Tangkijvanich,Rujipat Wasitthankasem,Yong Poovorawan

doi:10.7314/apjcp.2015.16.13.5515

Single Nucleotide Polymorphism of Interferon Lambda-4 Gene is not Associated with Treatment Response to Pegylated Interferon in Thai Patients with Chronic Hepatitis B.

Umaporn Limothai, Pisit Tangkijvanich + Show 2 more

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https://doi.org/10.7314/apjcp.2015.16.13.5515

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Abstract

The single nucleotide polymorphism (SNP) ss469415590 in the interferon lambda-4 (IFNL4) gene has recently been reported to have an association with treatment response in chronic hepatitis C. However, any importance of the SNP in association with response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B (CHB) is unclear. We retrospectively analyzed data for Thai patients with CHB treated with PEG-IFN for 48 weeks. Virological response (VR) for HBeAg-positive CHB was defined as HBeAg seroconversion plus HBV DNA level<2,000 IU/mL at 24 weeks post-treatment. VR for HBeAg-negative CHB was defined as an HBV DNA level<2,000 IU/mL at 48 weeks. The SNP was identified by real time PCR using the TaqMan genotyping assay with MGB probes. A total 254 patients (107 HBeAg-positive and 147 HBeAg-negative) were enrolled in the study. The distribution of TT/TT, ΔG/TT and ΔG/ΔG genotypes was 221 (87.0%), 32 (12.6%) and 1 (0.4%), respectively. Patients with non-TT/TT genotypes had significantly higher baseline HBV DNA levels than patients with the TT/TT genotype. In HBeAg-positive CHB, 41.2% of patients with TT/TT genotype versus 50.0% with non-TT/TT genotype achieved VR (P=0.593). In HBeAg-negative CHB, the corresponding figures were 40.3% and 43.5%, respectively (P=0.777). There was no significant correlation between the SNP genotypes and HBsAg clearance in both groups of patients. In summary, ss469415590 genotypes were not associated with response to PEG-IFN in Thai patients with HBeAg-positive and HBeAg-negative CHB.

Highlights

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) worldwide (Gao et al, 2012)
Increasing data have suggested that host genetic variations may play an important role in the natural history and treatment outcome of patients with chronic viral hepatitis (Stattermayer et al, 2014)
In patients with chronic hepatitis C (CHC), ss469415590 polymorphism has been shown to be the best predictor of response to pegylated interferon (PEG-IFN)/RBV treatment and the best marker of spontaneous hepatitis C virus (HCV) clearance (Bibert et al, 2013; Prokunina-Olsson et al, 2013)

Summary

Introduction

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) worldwide (Gao et al, 2012). Pegylated interferon alfa (PEG-IFN), which has an immunomodulatory and antiviral effects, is one of the approved agents for treatment of patients with chronic hepatitis B (CHB) (Hoofnagle et al, 2007). The long-term therapeutic effect of PEG-IFN is durable and patients who achieve treatment response have a reduced risk of cirrhosis and HCC (Sung et al, 2008). The overall sustained response rate to PEG-IFN can be achieved in approximately 30-40% of patients with HBeAg-positive CHB and 20-30% of patients with HBeAg-negative CHB (Hoofnagle et al, 2007). PEG-IFN treatment is expensive and has potential side effects. Selection of patients with a high probability of treatment response to PEG-IFN is important

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