Cholestasis in Non-Alcoholic Fatty Liver Disease And its Relationship to Disease Progression

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent cause of chronic liver disease worldwide. Most NAFLD patients have elevated alanine aminotransferase, while cholestatic enzymes are elevated less commonly. Raised cholestatic enzymes among NAFLD patients may predict a histologically more advanced disease. However, the prevalence and clinical significance of cholestasis in NAFLD is still unknown. This review intends to examine the evidence regarding the presence of cholestasis in patients with NAFLD and its relationship to disease progression. Methods: A detailed literature search was conducted using relevant terms in PubMed to identify published articles. Results: Studies have reported a link between cholestasis and liver damage in NAFLD. A study by Pennisi et al in 582 patients with biopsy-proven NAFLD or clinically diagnosed NAFLD-related compensated cirrhosis classified them as with hepatocellular(H), cholestatic (C), and mixed(M) patterns. It showed that 27% of patients with NAFLD had a cholestatic pattern. Major liver-related outcomes defined as the development of liver disease (LD) (occurrence of ascites and/or bleeding varices and/or encephalopathy and/or jaundice) or hepatocellular carcinoma (HCC) occurred in 38 patients with cholestatic pattern during a median follow-up of 66.3 months. In a study of Shipovskaya et al, 163 patients with NAFLD, cholestatic syndrome was detected in 30.1% and they had more rapid development of fibrosis. Shirin et al in biopsy-proven NAFLD patients found that 43.4% of patients had a cholestatic pattern with 31.3% patients of with cholestasis having advanced fibrosis. Sorrentino et al found patients with a cholestatic variant of NAFLD had histological evidence of cholangitis, swelling, variable bile duct loss, and bile stasis and had more severe liver disease with advanced bridging fibrosis or cirrhosis. Conclusion: Intrahepatic cholestasis occurs in a subgroup of NAFLD patients and is associated with more advanced histological impairment. Cholestasis provides a worse prognosis for advanced disease and predicts a higher risk of developing complications.