Association of Sat-a and Alu methylation status with HCV-induced chronic liver disease and hepatocellular carcinoma

Background: The combination of epigenetic and genetic abnormalities contributes together to the development of liver cancer. The methylation status of the repetitive elements (REs) in DNA has been investigated in a variety of human illnesses. However, the methylation patterns of Sat-alpha and Alu REs in chronic liver disease (CLD) and hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) have never been studied before.Methodology: In this study, 3 groups of participants including 50 patients having HCV-induced CLD, 50 patients having HCV-induced HCC, and 46 healthy subjects were subjected to measurement of Sat-alpha and Alu methylation using the quantitative MethyLight assay.Results: Sat-alpha and Alu methylation percentages decreased significantly in both CLD and HCC, compared to control. Also, a significant Sat-alpha hypomethylation was detected in HCC, compared to CLD. In addition, Sat-alpha and Alu methylation showed a significant decline as lesion size grew. However, only Sat-alpha hypomethylation was significantly increased in association with portal vein thrombosis and the MELD score. Sat-alpha methylation per-centage had the highest sensitivity and specificity for diagnosing HCC (100% and 84.4%) followed by alpha-feto-protein (80% and 84.4%) and Alu methylation (66% and 61.5%). Furthermore, there was a strong positive correlation between Sat-alpha and Alu methylation.Conclusions: Measuring Sat-alpha and Alu methylation provides us with a new tool for early detecting HCV-induced CLD and hepatocarcinogenesis. Sat-alpha has the potential to be utilized as an independent predictive parameter for HCC development and progression because of its ability to distinguish between CLD and HCC with their different MELD scores.

Automated summary

This study found that methylation of Sat-alpha and Alu decreased significantly in chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Sat-alpha hypomethylation was particularly observed in HCC compared to CLD. The methylation of both Sat-alpha and Alu decreased as the lesion size grew. Sat-alpha methylation percentage showed the highest sensitivity and specificity in diagnosing HCC. There was also a strong positive correlation between Sat-alpha and Alu methylation.