Non-Alcoholic Steatohepatitis and Autoimmune Hepatitis Cirrhosis May Have a Higher Risk of Progression to Hepatocellular Carcinoma

Abstract

Background: The evaluation of different cell proliferation and apoptosis indicators in cirrhotic tissues caused by different injuries may help recognize the etiology of cirrhosis and the risk of progression to hepatocellular carcinoma. Objectives: This study aimed to measure p53 gene expression and AMPK and pAMPK protein expressions, as well as AgNOR features in cirrhotic tissues associated with five different etiologies in comparison with simple hepatic steatosis and controls. Methods: In this case-control study, AMPK and PAMPK protein expressions, p53 gene expression, and AgNOR features were investigated in 68 cirrhotic liver tissues obtained from patients with NASH (n = 15), HBV/HCV (n = 14), AIH (n = 15), PSC (n = 15), and alcohol toxicity (n = 9) and compared with tissues from individuals with simple steatosis (n = 15) and control subjects (n = 15). Protein and gene expressions were determined using western blotting and quantitative real-time polymerase chain reaction, respectively. Silver nitrate staining was used to assess AgNOR features. Results: Significantly higher levels of AMPK and pAMPK were detected in all cirrhotic tissues compared to controls (P < 0.05). Also, a significantly and simultaneously higher p53 gene expression (P < 0.01) and AgNOR features, including total AgNOR length (TAL) (P < 0.001), total AgNOR number (TAN) (P < 0.01), and total AgNOR area (TAA) (P < 0.01), was detected in the hepatic cirrhotic tissues obtained from patients with PSC, NASH, and AIH. There was a significant positive correlation between p53 gene expression and AgNOR features in cirrhotic tissues (P < 0.01). Conclusions: Increased AMPK and pAMPK protein levels may be a general response to cirrhosis. Cirrhotic patients diagnosed with AIH, PSC, and NASH have a higher risk of progressing to hepatocellular carcinoma than those diagnosed with viral and alcoholic cirrhosis.