Discovery of critical host factor, IL‐28B, associated with response to hepatitis C virus treatment

Abstract

Chronic hepatitis C affects 2.2-3.0% of the world population (130 million-170 million). Pegylated interferon-a (PEG-IFN-a) in combination with ribavirin (RBV), the approved and standard therapy, leads to viral eradication in about 50% of treated patients. In 2009, genome-wide association studies (GWAS) identified host genetic variation to be critical for predicting treatment response and spontaneous clearance in patients infected with hepatitis C virus (HCV). A correlated set of polymorphisms in the region of the interleukin-28B (IL-28B) gene on chromosome 19, coding for interferon (IFN)-l3 were associated with clearance of genotype 1 hepatitis C virus (HCV) in patients treated with PEG-IFN-a and RBV. The same polymorphisms were subsequently associated with spontaneous clearance of HCV in untreated patients. In addition, prediction of viral response to PEG-IFN-a and RBV therapy of patients with recurrent HCV infection after orthotopic liver transplantation depends on the IL-28B genotype of both recipient and donor tissues. Diagnosis of a patient's IL-28B genotype is likely to aid in clinical decision making with standard-of-care regimens. Future studies will investigate the possibility of individualizing treatment duration and novel regimens according to IL-28B genotype. As GWAS yield unexpected data, this approach could lead to the development of novel drug therapy, such as already appears promising with IFN-l. In this Okuda lecture, I present the current understanding in regard to the relationship between host variations and clinical outcome of hepatitis C.

The Impact of IFN‐γ Gene Polymorphisms on Spontaneous Clearance of HCV Infection in Fars Province, Southern of Iran

“…Although sex and age have been reported as the factors that influence the outcome of HCV infection, in this study statistical analysis did not show any association between sex ( P = 0.6), age ( P = 0.47) and outcome of HCV infection .…”

Endoscopic Resection Versus Surgical Resection for Early Gastric Cancer

“…The 3 and 5-year DFS was reported for EGC in three 8 – 10 and four 8 – 10 , 22 studies, respectively. The meta-analysis of the 3 and 5-year DFS of ER versus SR showed no statistically significant difference, with pooled RRs of 0.92 (95% CI 0.84–1.01, P = 0.07) and 0.95 (95% CI 0.86–1.05, P = 0.30), based on a random-effects model due to significant interstudy heterogeneity ( P = 0.004, I 2 = 82%; P < 0.0001, I 2 = 88%, respectively) (Figure 4 ).…”

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran

“…It has also been reported that demographic factors such as gender and age could influence the outcome of therapy in patients with HCV infection (5, 42). Although in this study no association was found between gender and response to therapy, the frequency of females who did not respond to therapy was higher than responders (10% versus 20%).…”