Tolloid-like 1 genetic variants determine fibrosis regression in chronic hepatitis C patients with curative antivirals

Chung-Feng Huang,Jee-Fu Huang,Ming-Lung Yu,Wan-Long Chuang,Ching-I Huang,Jyh-Jou Chen,Ming-Lun Yeh,Zu-Yau Lin,Shinn-Cherng Chen,Chia-Yen Dai

doi:10.1038/s41598-018-33448-1

Abstract

Hepatitis C virus (HCV) eradication by antivirals promote fibrosis modification. Whether host genetics determined fibrosis regression in chronic hepatitis C (CHC) patients with sustained virological response (SVR) is to be determined. One hundred and fifty-six SVR patients with paired liver biopsy before and after antivirals were enrolled. Host genetic factors including single nucleotide polymorphism rs17047200 of tolloid-like 1(TLL-1) were analyzed for their association with fibrosis modification. The proportions of improved, unchanged and worsening fibrotic stags were 39.1% (n = 61), 39.1% (n = 61), and 21.8% (n = 34), respectively. The rate of annual fibrotic improvement was 0.16 ± 0.79. There was a significant trend of increased fibrotic improvement rate in patients from F01 to F4 (P < 0.001). However, the rate of improvement seemed more limited in cirrhotic patients among those with advanced liver disease. Patients with fibrotic improvement had a significantly higher proportion of TLL-1 rs17047200 AA genotype compared to those without (92.5% vs. 79.3%, p = 0.039). Logistic regression analysis revealed that the TLL-1 rs17047200 AA genotype was the only independent factor associated with fibrosis improvement (odds ratio/95% confidence intervals: 3.2/1.01–10.12, p = 0.047). Compared with TLL-1 rs17047200 non-AA carriers, a significantly higher proportion of fibrosis improvement in AA genotype carriers was observed among patients with F0-2 (33.3% vs. 0%, p = 0.005) but not with F34 (70% vs. 80%, p = 1). We concluded that TLL-1 genetic variants determined fibrotic improvement in CHC with curative antivirals, particularly in patients with mild liver disease.

Highlights

The chronic inflammatory state during hepatitis C virus (HCV) infection drives liver fibrogenesis, which in turns leads to end-stage liver disease
We demonstrated that the majority of patients have stable or improved liver fibrotic stages after Hepatitis C virus (HCV) eradication
We identified that TLL-1 genetic variation was the only factor associated with fibrotic improvement

Summary

Introduction

The chronic inflammatory state during hepatitis C virus (HCV) infection drives liver fibrogenesis, which in turns leads to end-stage liver disease. The determining factors largely include environmental factors (e.g., alcohol consumption and diabetics1), virological factors (e.g., HCV genotype 3, hepatitis B virus [HBV] and human immunodeficiency virus co-infection) and host factors (e.g., age at infection and sex[2,3]). Host genetic predispositions, such as genetic variants of interleukin 28B (IL-28B), patatin-like phospholipase domain-containing 3 (PNPLA3) and other immunogenetic profiles, have been recognized as potential determinants of liver fibrosis progression[1,2,4]. We aimed to elucidate the modification of fibrosis after viral eradication in well-characterized CHC patients who received paired liver biopsy before and after achieving SVR. We aimed to explore the potential contribution of host genetic factors to fibrotic modification in this Taiwanese cohort

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