Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.9038
Revised: March 3, 2014
Accepted: April 21, 2014
Published online: July 21, 2014
Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has become one, if not the most common, cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.
Core tip: The molecular mechanism associated with the accumulation of fatty acids in the liver cells and the resulting molecular cascade leading to hepatic damage is far from being understood. Due to the development of reliable in vitro and in vivo models, we are starting to open the “black box”. This will lead to a better understanding of the active clinical condition and hopefully to a more effective treatment. This article critically reviews what is known and what has still to be discovered about the link between the accumulation of fat within the liver and the resulting damage.