Impact of IL28B, ITPA and PNPLA3 Genetic Variants on Therapeutic Outcome and Progression of Hepatitis C Virus Infection

Abstract

Chronic HCV infection comprises a broad spectrum of liver disease, ranging from no or minimal activity to active hepatitis that in time may progress to severe liver fibrosis, cirrhosis and hepatocellular carcinoma if left untreated. This review describes the impact of genetic variants of interleukin 28B (IL28B; also known as interferon-lambda 3), inosine triphosphate pyrophosphatase (ITPA) and patatin-like phospholipase domain-containing 3 (PNPLA3) on therapeutic outcome and liver disease severity in HCV-infected patients.

Treatment of hepatitis C virus infection for adults and children: Updated Swedish consensus recommendations

“…Other factors that may impact the likelihood of achieving SVR following therapy with direct-acting antiviral agents (DAAs), especially if treatment duration is sub-optimal, include male gender (lower chance for SVR), baseline plasma viral load (greater likelihood of SVR at lower levels), indicators of more advanced cirrhosis (e.g. low platelets and low albumin) and host genetic factors,[ 12–14 ] e.g. IL28B genotype (higher likelihood of SVR among patients with IL28B CC than CT/TT).…”

A facile PCR‐RFLP method for genotyping of ITPA rs1127354 and rs7270101 polymorphisms

“…ITPase promotes the hydrolysis of inosine triphosphate (ITP) and deoxy inosine triphosphate (dITP) to monophosphate and diphosphate nucleotides (IMP and IDP) . The ITPA rs1127354 and rs7270101 polymorphisms may result in reducing the activity of the ITPase enzyme and subsequent accumulation of ITP and protecting against adenosine triphosphate (ATP) reduction in erythrocytes …”

Interleukin‐ 28B: a prognostic marker in interferon based therapy of chronic HCV patients of the Pakistan with variable treatment response

“…The genetic polymorphism of IL28B is also found in the study on Western population and in Chinese population which significantly associated with varied treatment response to the HCV therapy . The strongest association, among a predominantly caucasian population, was noted for the rs12979860 SNP where the CCrs12979860, had 2‐fold increased likelihood of achieving SVR as compared to the TT variant . However, in a recently published study from Pakistan, a significant association of HCV genotypes and genetic variants of IFNL (IL28B) have been shown with IFN α + Rib treatment of HCV infection .…”