Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation

Abstract

Background Orthotropic liver transplantation (OLT) offers a therapeutic choice for hepatocellular carcinoma (HCC) patients. The poor outcome of liver transplantation is HCV recurrence. Several genome-wide associated studies (GWAS) have reported many genetic variants to be associated with HCV recurrence. Seven gene polymorphisms formed a cirrhosis risk score (CRS) signature that could be used to distinguish chronic HCV patients at high risk from those at low risk for cirrhosis in non-transplant patients. This study aims to examine the association of CRS score and other clinical parameters with the probability for HCC emergence and/or the rate of HCV recurrence following liver transplantation. Results Seven gene polymorphisms, forming the CRS, were genotyped by real-time PCR using allelic discrimination protocol in 199 end-stage liver disease patients (79 child A, 43 child B, and 77child C), comprising 106 patients who encountered liver transplantation. Recipient CRS scores were correlated with HCV recurrence (HCV-Rec) at the end of the third year after OLT. Around 81% (39) recipients with low steatosis (LS; < 3.5%) donor percentage revealed no HCV recurrence (non-Rec) (p<0.001). CRS score could distinguish between child A, child B, and child C only at the low-risk group. Among the HCV Rec group 27% (8/30), 40% (12/30), and 33% (10/30) fell into the high, moderate, and low CRS risk groups, respectively. Stepwise logistic regression evinced two features more likely to be seen in HCV-Rec patients: abnormal ALT [OR, 1.1; 95% CI, 1.02–1.2] and donor steatosis >3.5% [OR, 46.07; 95% CI, 1.5–1407.8]. Conclusions Accordingly, the CRS score seems to be less useful to predict HCV recurrence after OLT. ALT and donor steatosis (exceed 3.5%) can significantly promote the HCV recurrence post-OLT. Moreover, the combination of MMF and CNI positively heightens HCV recurrence.

Seven gene signature explores the impact of DAAs on the appearance of hepatocellular carcinoma in HCV infected patients

“…CRS values in J o u r n a l P r e -p r o o f the studied patients' groups were not statistically different from each other and around 60% of DAA-exposed HCC patients and 48% of DAA-unexposed HCC patients had high CRS score without reaching significant difference. Additonally, in the end stage liver disease patients who are eligible for liver transplantation, the majority had high CRS score [32]. This is illustrated by the fact that HCC originated on top of liver cirrhosis, all patients who developed HCC have elevated CRS values.…”