Natural History of Simple Steatosis or Nonalcoholic Fatty Liver

The histological spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. Ballooning degeneration of hepatocytes with or without fibrosis is the key feature that differentiates NASH from NAFL. Liver biopsy is the only reliable method for diagnosing NAFL and differentiating it from NASH. Although the epidemiology of NAFLD is well described, the need for invasive biopsy limits our knowledge of the community prevalence of NAFL. Recent data suggest that the biochemical composition of hepatic steatosis may have a bearing on the disease. Triglycerides, the most commonly accumulated lipid, have a cytoprotective role because of their inert nature. Several paired liver biopsy studies and longitudinal follow-up studies have shown that NAFL is not completely benign as previously envisaged. NAFL can indeed progress to NASH and severe fibrosis, with progression being influenced by presence of baseline or worsening metabolic risk factors. Overall, NAFL carries a low risk of liver-related and overall mortality although the risk of cardiovascular mortality is similar to that of NASH. Current concepts suggest the presence of a dynamic bidirectional cycling between NAFL and NASH with slow progression of fibrosis in majority of the patients. The fact that ultimately it is the onset of progressive fibrosis that dictates clinical outcomes brings into question the relevance of distinguishing NAFL from NASH.