Liver disease severity predicts carcinogenesis of dysplastic liver nodules in cirrhosis

Abstract

While dysplastic liver nodules in cirrhosis are pre-malignant, little is known about the predictors of hepatocarcinogenesis of these lesions. This was a retrospective observational study of subjects with cirrhosis who had at least one hypervascular, non-malignant intrahepatic nodule on imaging while undergoing outpatient management by a tertiary hepatology referral centre between Jan 2009 and Jan 2019. Clinical and biochemical parameters were collected. The primary endpoint was transformation to hepatocellular carcinoma (HCC) as determined by Liver Imaging Reporting and Data System. During the study period, 163 non-malignant hypervascular nodules were identified in 77 patients; 147 had at least 6 months of follow up imaging and 16 received upfront radiofrequency ablation upon detection. During a median follow up of 38.5 months (IQR 16.5–74.5), 25 (17%) of the 147 hypervascular nodules being monitored transformed to HCC. On multivariate analysis, Child–Pugh grade was found to be the only independent predictor of nodule transformation into HCC (p = 0.02). Those with Child–Pugh B and C liver disease had a 10.1 (95% CI 1.22–83.8; p = 0.03) and 32.6-fold (95% CI 2.3–467; p = 0.01) increased risk respectively for HCC transformation compared to Child–Pugh A subjects. This large, single centre study demonstrates that around 20% of dysplastic nodules in cirrhotic patients undergo hepatocarcinogenesis during follow up, and that Child Pugh grade is the only independent predictor of transformation to HCC. Additional prospective studies are warranted to better understand the risk profile of these nodules, and how best they should be managed.

Loss of liver function in chronic liver disease: An identity crisis

“…Recovery of HNF4 levels at later time-points after liver resection is required for the restoration of liver function and hepatocellular quiescence [64]. Therefore, a persistently impaired function of key liver TFs such as HNF4 will result in the shutdown of hepatocellular functions and the perpetuation of a proliferative and dedifferentiated status, a fertile ground for HCC development [20,140].…”