Novel Method Could Help Predict Patients at Higher Risk of Chronic Hepatitis C Progression

Genetic variants in interferon signaling pathways may serve as useful prognostic markers of chronic hepatitis C virus (CHC) progression, a recent study published in PLOS One suggests.

An estimated 71 million individuals are living with CHC worldwide. Many patients with CHC will go on to develop progressive liver inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma.

The emergence of antiviral drugs has made significant progression in eradicating HCV; however, a proportion of patients are still unable to receive these therapies due to comorbidities and socioeconomic reasons.

Heterogeneous progression of CHC is displayed depending on a broad set of factors, such as a patient’s genetic profile, according to the authors.

In the study, investigators sought to evaluate the effect of certain genetic variants—–located in the crucial interferon alpha and lambda signaling pathways––on the hepatic necroinflammatory activity (NIA) of patients with CHC.

Liver biopsies were obtained from 119 patients with CHC, and the METAVIR classification system was used to scale and classify as low or high grade.

In a candidate gene approach, the investigators selected 63 SNPs located in 30 different genes related to interferon pathways using the Illumina GoldenGate Genotyping Assay. Statistical association was determined by logistic regression, and the significantly associated SNPS were further adjusted by other covariates, according to the report.

The results of the study showed 7 SNPS—located in the IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2(rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes—were significantly related to severe NIA grade.

Clinical variables regarding the main characteristics and the 7 SNPs indicated that elevated HIA was notably associated with aspartate aminotransferase (AST) serum levels, but not with other clinical factors, such as viral genotype, ALT, GGT, or viral load.

The findings also showed that TYK2 (rs280519) and RNASEL (rs3738579) were independent factors strongly associated with elevated NIA. In the ROC_AUC analysis, AST concentration showed a moderate AUC value, similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs.

Interestingly, the model, including all the above variables, showed the best predictive values.

The authors noted that the findings highlight the importance of developing an in-depth functional study aimed at elucidating the prognostic potential of rs280519 or the linked SNPs for the progression of CHC.

“The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression,” the authors concluded. “Further validation in larger cohorts of patients is needed.”