A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure

Abstract

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes.

Genetic Susceptibility to Hepatocellular Carcinoma in Patients with Chronic Hepatitis Virus Infection

“…In the era of direct antiviral agents (DAAs), there is still an estimated 5% of HCV patients not achieving SVR, and the impact of DAAs on HCC occurrence or recurrence remains conflicting [ 94 ]. Several studies have been conducted on HCV-infected patients receiving DAAs, which have employed either a genome-wide association study (GWAS) or a candidate gene approach to identify genetic variants associated with risk factors for the development of HCC, such as non-SVR rate, elevation in serum ALT levels, or changes in liver stiffness [ 95 , 96 , 97 ].…”

Omics in Clinical Practice: How Far Are We?

“…Corma-Gómez et al [ 3 ] performed a genome-wide association analysis for unrevealing genes that could be involved in the aetiopathogenesis of liver stiffness after antiviral therapy for hepatitis C infection. Subsequent system biology approaches revealed conformational changes in DNA as a key element of the process, allowing the early diagnosis of subjects at risk of developing this unwanted side effect of hepatitis therapy.…”