Recognition of 7 genes signature (Cirrhosis Risk Score) in the diagnosed non-responders to DAAs therapy by intra-PBMCs nested HCV RNA PCR.

Abstract

Background and aims: Predictors of chronic HCV response to oral antiviral therapy (OAT) are related to host genetic variations. Single nucleotide polymorphisms (SNP) and alleles variations of host genes in association with hepatic fibro-cirrhotic changes have a distinct role in OAT outcomes. The current research evaluated the association of Cirrhosis-Risk-Scores (CRS) values, based on the correlation of seven genes signature-SNPs, with sonographic liver parenchymal changes in determining OAT outcomes.

Methods: All study subjects (n = 54) were recruited three months after completing OAT and classified into three groups. Group I (n = 21) had negative HCV PCR, group II (n = 17) showed positive solitary intra-PBMCs HCV infection, and group III(n = 16) was serum HCV RNA PCR-positive. All study-population were subjected to examination by hepatic-ultrasound (US), FIB-4-scoring, and screening for 7 gene-signature that addressed CRS values as low, intermediate, and high depending on gene SNPs identification.

Results: Group I showed a significant association with low CRS values compared to other groups (P < 0.001). Solitary intra- PBMCs HCV infection in group II was significantly combined with intermediate CRS values in comparison to groups I and III (P < 0.001). The high CRS values were significantly found in group III when compared to groups I and II (P < 0.01). On US imaging, low CRS values were common in normally appeared hepatic parenchyma (P < 0.001) and high CRS values were frequent in coarse-liver (P < 0.001), while bright-liver-tissues appearance was mainly detected in the intermediate CRS category (P = 0.09). On FIB-4 scoring, high CRS value were associated with hepatic fibro-cirrhosis compared to intermediate (P < 0.001) and low (P = 0.08) CRS-categories.

Conclusion: The current study concluded the association of (a) high CRS values with coarse liver in viral-RNA serologic relapse, (b) low CRS values with normal liver tissues in sustained virologic response (SVR), (c) intermediate CRS values with bright liver in solitary PBMCs relapse.