Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants

• Published in: PloS one Vol. 17; no. 6; p. e0269641
• Main Authors: Chuaypen, Natthaya, Siripongsakun, Surachate, Hiranrat, Pantajaree, Tanpowpong, Natthaporn, Avihingsanon, Anchalee, Tangkijvanich, Pisit
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.06.2022; Public Library of Science (PLoS)
• Subjects: Acyltransferase; Antiviral agents; Antiviral Agents - therapeutic use; Antiviral drugs; Biology and Life Sciences; Biopsy; Body mass; Body mass index; Body size; Care and treatment; Development and progression; Diabetes; Diabetes mellitus; Eradication; Fatty liver; Fatty Liver - diagnostic imaging; Fatty Liver - drug therapy; Fatty Liver - genetics; Fibrosis; Genetic diversity; Genetic factors; Genetic variance; Genotype; Genotypes; Hepacivirus - genetics; Hepatitis C; Hepatitis C - drug therapy; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; HIV; Human immunodeficiency virus; Humans; Infections; Lipase - genetics; Lipase - therapeutic use; Liver; Liver Cirrhosis - complications; Liver Cirrhosis - diagnostic imaging; Liver Cirrhosis - genetics; Magnetic resonance; Magnetic resonance imaging; Medicine and Health Sciences; Membrane Proteins - genetics; Multivariate analysis; Patients; Physical Sciences; Polymorphism, Single Nucleotide; Proton density (concentration); Protons; Research and Analysis Methods; Steatosis; Viruses; Thailand; United States > US; Bangkok Thailand
• DOI: 10.1371/journal.pone.0269641
• ISSN: 1932-6203

Significant liver fibrosis regression occurs after hepatitis C virus (HCV) therapy. However, the impact of direct-acting antivirals (DAAs) on steatosis is less clear. This study was aimed at evaluating serial fibrosis and steatosis alterations in patients with HCV genotype 1, who achieved sustained virological response (SVR). We enrolled 55 HCV mono-infected and 28 HCV/HIV co-infected patients receiving elbasvir/grazoprevir from a clinical trial. Fibrosis and steatosis were assessed at baseline, follow-up week-24 (FUw24) and week-72 (FUw72) by magnetic resonance elastography (MRE) and proton density fat fraction (PDFF), respectively. Patatin-like phospholipase domain-containing protein 3 ( PNPLA3 ) rs738409, transmembrane six superfamily member 2 ( TM6SF2 ) rs58542926 and membrane bound O-acyltransferase domain-containing 7 ( MBOAT7 ) rs641738 polymorphisms were determined by allelic discrimination. Overall, mean MRE decreased significantly from baseline to FUw24 and FUw72. At FUw72, patients with baseline F2-F4 had higher rate of ≥30% MRE decline compared with individuals with baseline F0-F1 (30.2%vs.3.3%, P = 0.004). In multivariate analysis, significant fibrosis was associated with MRE reduction. The prevalence of steatosis (PDFF≥5.2%) at baseline was 21.7%. Compared to baseline, there were 17 (20.5%) patients with decreased PDFF values at FUw72 (<30%), while 23 (27.7%) patients had increased PDFF values (≥30%). Regarding the overall cohort, mean PDFF significantly increased from baseline to FUw72, and displayed positive correlation with body mass index (BMI) alteration. In multivariate analysis, the presence of diabetes, PNPLA3 CG+GG genotypes and increased BMI at FUw72 were significantly associated with progressive steatosis after SVR. Other genetic variants were not related to fibrosis and steatosis alteration. This study concluded that HCV eradication was associated with fibrosis improvement. However, progressive steatosis was observed in a proportion of patients, particularly among individuals with metabolic derangement and PNPLA3 variants. The combined clinical parameters and host genetic factors might allow a better individualized strategy in this sub-group of patients to alleviate progressive steatosis after HCV cure.