Abstract
With the availability of potent antiviral therapies, complete suppression of hepatitis B virus (HBV) replication and total eradication of hepatitis C virus (HCV) can now be achieved. Despite these advances, hepatocellular carcinoma (HCC) still develops in a substantial proportion of cirrhotic patients, suggesting that host factors remain critical. Dysregulation of miRNAs is noted in many cancers, and circulating miRNAs can be readily assayed. In this study, we aimed to develop a circulating miRNA signature to assess the risk of HCC in cirrhotic patients. We first discovered that HBV- and HCV-related cirrhotic patients had distinguishable circulating miRNA profiles. A cohort of 330 cirrhotic patients was then compared against a cohort of 42 early HCC patients with complete remission. A score comprising 5 miRNAs and a binary etiology variable was established that was capable of differentiating between these two groups (AUC = 72.5%, P < 0.001). The 330 cirrhotic patients were further stratified into high- and low-risk groups, and all patients were longitudinally followed for 752 (11–891) days. Of them, 19 patients developed HCC. The high-risk group had significantly higher cumulative HCC incidence (P = 0.038). In summary, a circulating miRNA-based score was developed that is capable of assessing HCC risks in cirrhotic patients.
Highlights
Several virological predictors are associated with hepatocellular carcinoma (HCC) risk in chronic hepatitis B1, 2
Three criteria were established for determination of miRNA candidates: (1) the miRNA was reported with a similar role in HCC in at least two reports in the literature; (2) the miRNA could be clinically correlated with HCC patient survival; and (3) the miRNA was readily detectable using stem-loop RT-qPCR
Few predictive models for HCC occurrence are available for hepatitis B virus (HBV)- or hepatitis C virus (HCV)-related cirrhotic patients[3, 14, 28]
Summary
Several virological predictors are associated with HCC risk in chronic hepatitis B1, 2. A subsequent study attempting to understand the accuracy of these scoring systems in patients receiving antiviral treatment discovered that the independent predictors for HCC include only older age, liver cirrhosis and virological. A recent retrospective analysis for antiviral-treated chronic hepatitis B patients revealed that the virological factors were no longer useful for HCC prediction and that only cirrhosis and therapeutic methods were independent predictors[8]. In a study assessing HCC risk in interferon-treated, chronic hepatitis C patients, the following factors were included to formulate a scoring system: host factors, HCV genotype and sustained virological response[14]. We enrolled a cohort of HBV- and/or HCV-related liver cirrhosis patients who were regularly followed in liver clinics with sporadic HCC development during follow-up Another cohort of early HCC patients under complete remission was included for comparative analysis. The aims of this study were (i) to understand whether differential miRNA profiles could be identified between cirrhotic patients with different hepatitis viral etiologies and (ii) to build a prediction model for HCC risk in cirrhotic patients with viral hepatitis
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