Influence of hepatitis C virus and IL28B genotypes on liver stiffness.

Lene Fogt Lundbo,Lene Rosenørn,Thomas Benfield,Louise Nygaard Clausen,Kristian Schønning,Peer Brehm Christensen,Nina Weis,Michael Alan Polis

doi:10.1371/journal.pone.0115882

Lene Fogt Lundbo, Lene Rosenørn + Show 6 more

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https://doi.org/10.1371/journal.pone.0115882

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Abstract

ObjectiveLiver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness.Patients and MethodsThis cross-sectional study consists of 369 patients with chronic hepatitis C (CHC). Liver stiffness was evaluated using transient elastograhy (TE). Factors associated with development of liver fibrosis were identified by logistic regression analysis.ResultsWe identified 369 patients with CHC. 235 were male, 297 Caucasians, and 223 had been exposed to HCV through intravenous drug use. The overall median TE value was 7.4 kPa (interquartile range (IQR) 5.7–12.1). HCV replication was enhanced in patients carrying the IL28B CC genotype compared to TT and TC (5.8 vs. 5.4 log10 IU/mL, p = 0.03). Patients infected with HCV genotype 3 had significantly higher TE values (8.2 kPa; IQR, 5.9–14.5) compared to genotype 1 (6.9 kPa; IQR, 5.4–10.9) and 2 (6.7 kPa; IQR, 4.9–8.8) (p = 0.02). Within patients with genotype 3, IL28B CC genotype had the highest TE values (p = 0.04). However, in multivariate logistic regression, using various cut-off values for fibrosis and cirrhosis, only increasing age (odds ratio (OR) 1.09 (95% confidence interval (CI), 1.05–1.14 per year increment)), ALT (OR 1.01 (95% CI, 1.002–1.011), per unit increment) and HCV genotype 3 compared to genotype 1 (OR 2.40 (95% CI, 1.19–4.81), were consistently associated with cirrhosis (TE>17.1 kPa).ConclusionsAge, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by TE. However, IL28B genotype was not an independent predictor of fibrosis in our study.

Highlights

It is estimated that about 170 million people are infected with hepatitis C virus (HCV) world-wide, and that more than 350.000 people die annually from chronic hepatitis C (CHC) related end-stage liver disease [1].The influence of HCV genotypes in development of liver fibrosis is not well established
Age, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by transient elastography (TE)
HCV genotype 1 has been associated with higher mortality, AIDS in HIV/HCV coinfected, and hepatocellular carcinoma [3,4,5], whereas HCV genotype 3 has been associated with development of hepatic steatosis, fibrosis and progression to cirrhosis in some, but not all, studies [6,7,8,9,10]

Summary

Introduction

It is estimated that about 170 million people are infected with hepatitis C virus (HCV) world-wide, and that more than 350.000 people die annually from chronic hepatitis C (CHC) related end-stage liver disease [1]. The influence of HCV genotypes in development of liver fibrosis is not well established. Numerous subtypes (e.g., subtypes 1a and 1b within genotype 1 and subtypes 3a and 3b within genotype 3) exist. HCV genotype 1 has been associated with higher mortality, AIDS in HIV/HCV coinfected, and hepatocellular carcinoma [3,4,5], whereas HCV genotype 3 has been associated with development of hepatic steatosis, fibrosis and progression to cirrhosis in some, but not all, studies [6,7,8,9,10]

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