Nonalcoholic fatty liver disease (NAFLD), now the leading cause of liver damage worldwide, is epidemiologically
associated with obesity, insulin resistance and type 2 diabetes, and is a potentially progressive condition
to advanced liver fibrosis and hepatocellular carcinoma. However, there is huge interindividual variability in
liver disease susceptibility. Inherited factors also play an important role in determining disease predisposition. During
the last years, common variants in PNPLA3, TM6SF2, MBOAT7 and GCKR have been demonstrated to predispose
to the full spectrum of NAFLD pathology by facilitating hepatic fat accumulation in the presence of environmental
triggers. Other variants regulating inflammation and fibrogenesis then modulate liver disease progression in
those at higher risk. Evidence is also accumulating that rare variants are involved in disease predisposition. In the
future, evaluation of genetic risk factors may be exploited to stratify the risk of liver-related complications of the
disease, and to guide hepatocellular carcinoma surveillance and choose pharmacological therapy.
Protocols for Mitochondria as the Target of Pharmacological Therapy in the Context of Nonalcoholic Fatty Liver Disease (NAFLD)
