HCV RNA detection in hepatic and extrahepatic tissues after DAA-induced sustained virologic response

Abstract

The complete eradication of hepatitis C virus (HCV) from both hepatic and extrahepatic compartments following successful direct-acting antiviral (DAA) therapy remains an area of ongoing investigation. This study aimed to detect HCV RNA signals in serum and tissue samples from 40 patients who had achieved a sustained virologic response (SVR). Paired serum samples (pre-treatment and post-SVR) were analyzed concurrently with liver, gallbladder, bile, pancreatic, and splenic tissues. These tissue samples were obtained during clinically indicated surgical procedures performed 4-12 weeks after SVR. HCV RNA was quantified using a real-time PCR assay, adapted exploratorily for tissue matrices. Statistical analysis encompassed paired comparisons for serum samples and descriptive analysis for tissue findings. All patients exhibited complete clearance of serum HCV RNA post-treatment (p < 0.001). Nevertheless, HCV RNA signals were detected in 11 of 40 liver tissue samples (27.5%) and in 6 of 40 gallbladder and bile samples (15%). Furthermore, detection was observed in the sole pancreatic sample (1/1) and in two of three splenic samples (2/3). Due to the constrained sample sizes, the extrahepatic findings are presented descriptively. Viral load measurements varied across tissues and are reported as median values with interquartile ranges. In conclusion, HCV RNA signals were detected in hepatic and selected extrahepatic tissues despite undetectable serum PCR following DAA therapy. It is crucial to note that these findings represent molecular detection exclusively and do not confirm active viral replication or persistence. These results should be considered exploratory and necessitate validation through strand-specific assays and larger patient cohorts.