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.
Highlights
The achievement of sustained virological response (SVR) among hepatitis C virus (HCV)-infected individuals is associated with a reduction in the incidence of liver complications, including hepatocellular carcinoma (HCC), as well as in all-cause mortality [1,2,3,4]
We have reported possible genetic factors involved in the Liver stiffness (LS) changes from the moment of starting anti-HCV therapy to SVR
With respect to the top SNPs identified in our genome-wide association study (GWAS), the strongest signals were linked to the NDUF2 gene
Summary
The achievement of sustained virological response (SVR) among hepatitis C virus (HCV)-infected individuals is associated with a reduction in the incidence of liver complications, including hepatocellular carcinoma (HCC), as well as in all-cause mortality [1,2,3,4]. The risk of developing liver events does not disappear after SVR, especially among pre-treatment cirrhotic patients [3,5,6]. Patients with cirrhosis must undergo life-long surveillance for liver complications [7], and some authors extend this recommendation to individuals with pre-treatment advanced fibrosis [8]. SVR achievement leads to a reduction of LS in this subset This improvement is more pronounced in patients with higher pre-treatment LS values [12,13]. It has been reported that the LS value at SVR is a strong predictor of liver disease outcome in HCV-infected patients with pre-treatment advanced fibrosis, irrespective of HIV-coinfection [14,15]
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