Elsevier

Infection, Genetics and Evolution

Volume 53, September 2017, Pages 195-198
Infection, Genetics and Evolution

Short communication
Role of IL28B genotype in the liver stiffness increase in untreated patients with chronic hepatitis C

https://doi.org/10.1016/j.meegid.2017.05.026Get rights and content

Highlights

  • The role of IL28B in the fibrosis progression has been demonstrated in previous studies with discrepant results.

  • The IL28B variants associated with a poor virological response are related to slower fibrosis progression.

  • The TT/CC genotype was strongly related to liver stiffness increase after 5 years in untreated patients.

Abstract

The role of interleukin (IL)28B has been deepened in the treatment response to pegylated-interferon in patients affected by chronic hepatitis C (CHC). However, recently the IL28B genotypes were also related to hepatic fibrosis progression in untreated patients, using the liver biopsy. The aim of this prospective and longitudinal study was to assess the role of different IL28B genotypes in the liver stiffness progression in a cohort of untreated subjects affected by CHC.

We included in this analysis all untreated patients affected by CHC and followed for at least 5 years with the annual evaluation of liver stiffness using Fibroscan®. All enrolled subjects were genotyped for rs8099917 and rs12979860 IL28B polymorphisms.

In the study period, 266 patients were considered. After 5 years we observed the following median stiffness increases: 6.7 kPa [5.1–7.8] in TT/CC, 4.9 kPa [4.1–5.0] in TT/TC, 3.4 kPa [3.2–3.8] in TG/TC and 1.7 kPa [1.2–1.9] in GG/TT. These values were statistically significant in all groups (p < 0.001). In the multivariate analysis resulted as predictive factors of liver stiffness progression the following: IL28B TT/CC genotype (OR = 4.571; 95%IC = 2.381–12.994; p < 0.001) and IL28B GG/TT genotype (OR = 0.510; 95%IC = 0.289–0.712; p = 0.007). In this study we evidenced that IL28B genotypes were associated with a different level of liver stiffness increase after 5 years and could be used to select the patients who should be treated with priority.

Introduction

Chronic hepatitis C (CHC) is a global health problem, related to progressive fibrosis, cirrhosis and end stage liver disease (Thomas and Seeff 2005); some studies examined the role of different factors on the fibrosis progression (Poynard et al. 2001) such as male gender (Poynard et al. 1998), geographical origin (Pearlman 2006), age (Horsmans 2010), insulin resistance and diabetes (Grasso et al. 2009). The fibrosis progression is an important medical reason to encourage the treatment of patients, however in the era of dual therapy with pegylated (PEG)-interferon (IFN) and ribavirin (RBV) not all subjects were eligible to this treatment for the related side-effects, the need of good adherence and other specific conditions as well as older age, psychiatric disorders or risk of anemia (Clark et al., 2012, Roomer et al., 2010, Schaefer et al., 2007). Therefore, a large part of patients affected by CHC were not treated with dual therapy, but the fibrosis progression was different in these subjects (Leandro et al. 2006).

Recently, was observed the role of interleukin (IL) 28B genotype in the spontaneous clearance of HCV infection (Thomas et al. 2009), during antiviral treatment (Suppiah et al. 2009) and as predictive tool used for the optimization of PEG-IFN therapy (Boglione et al., 2015, Boglione et al., 2014); furthermore, the role of IL28B has also been related to fibrosis progression in untreated patients (Bochud et al., 2012, Fabris et al., 2011, Falleti et al., 2011); in details, the GG genotype at rs809917 was associated with a slower progression of fibrosis, while the CC genotype at rs12979860 was related to enhanced immunity and increased necroinflammation (Noureddin et al. 2013).

The aim of this study was to investigate whether the IL28B genotypes (rs12979860 and rs809917) were associated with the liver stiffness variation in a cohort of untreated patients affected by CHC.

Section snippets

Study design

This longitudinal and prospective analysis included all untreated patients followed at our centre of Infectious Disease “Amedeo di Savoia”, Turin, Italy, from 2010 to 2015.

Inclusion criteria were: diagnosis of CHC with positive HCV-RNA, naïve, not eligible for dual therapy or treatment refusal, follow-up of at least 5 years with annual transient elastography evaluation (Fibroscan®).

Genetic evaluation

Genomic DNA was isolated from blood samples. Patients who agreed to undergo genetic analyses and for whom blood

Results

In the study period, 266 patients were considered. The baseline features of the population were reported in the Table 1. Male were 158 (59.3%), with median age of 56 years; most of patients were Italians (66.5%); F1 Metavir score was prevalent (62.4%). The most common HCV genotype was 1b (38.7%). IL28B genotypes (rs8099917 T > G/rs12979860 C > T) were as following: 102 with TT/CC (38.3%), 88 with TT/TC (33%), 40 with TG/TC (15%), and 36 with GG/TT (13.5%). The reasons of delayed treatment with

Discussion

Several studies examined the role of IL28B polymorphisms in the progression of hepatic fibrosis and necroinflammation with different results; although in most cases was reported an association between the rs12979860 CC genotype or rs809917 TT genotype and fibrosis progression (Abe et al., 2010, Bochud et al., 2012), in other studies no relationship was assessed (Marabita et al. 2011) but the heterogeneity of the populations was higher and the method of estimation of fibrosis progression

Conflicts of interest

The authors disclose no conflicts.

Ethical approval

Approved by our local Ethic Committee.

Funding

This study was not supported.

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    Both authors contributed equally to this paper.

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