Inflammation, mitochondrial metabolism and nutrition: the multi-faceted progression of non-alcoholic fatty liver disease to hepatocellular carcinoma

When ectopic accumulation of fat in the liver is accompanied by cell death, inflammation and mitochondrial dysfunction, liver cells may switch from normal growth to an out-of-control state. One third of the population is now suffering NAFLD but estimates increase considerably in patients with consequences from comfortable lifestyles (1). This is because excessive food intake is currently responsible for the alarming increase in NAFLD prevalence and partially explains how sensitive is this condition to surgical procedures restricting the intake of nutrients. NAFLD is the common name for a wide range of phenotypes and it is a potentially serious condition that may progress from steatosis (NAFL) to steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma (HCC). This progression correlates with the severity of fibrosis but NAFLD can progress to HCC in the absence of cirrhosis, especially in an inflammatory context (2). Despite the clinical importance, the study of NAFLD progression is difficult not only because the issue is inherently complex, with multiple factors interacting simultaneously, but also because potential studies rely in invasive liver biopsy and the ensuing ethics. It is also hampered by the lack of validated non-invasive biomarkers or surrogates, effective medications and established preclinical models (3). Knowledge on basic mechanisms is also insufficient. Current efforts are directed towards understanding the heterogeneous outcomes of NAFLD and the assessment of dietary recommendations (4) but the rapid reversal of hepatic lesions after bariatric surgery may challenge some assumptions