Key Points
• Conclusion/Relevance: “Chronic positive energy balance overwhelms safe fat storage depots in subcutaneous WAT [white adipose tissue], leading to ectopic fat storage in unsafe sites such as VAT [visceral adipose tissue] and liver. This causes insulin resistance, metabolic syndromes, and, as is increasingly clear, EHC [extrahepatic cancer]. Clinicians and their patients should be made aware that fatty liver is just the tip of an iceberg; NAFLD [non-alcoholic fatty liver disease] is an indicator of an underlying plethora of metabolic disturbances. Aggressive measures must be instituted early to reverse it. Obesity and NAFLD will continue to rise and will overwhelm the health care system in a not-too-distant future. Current advice on the control of obesity such as lifestyle changes is a clear failure. It would be prudent to investigate the causative link(s) between NAFLD and EHCs with the ultimate aim of discovering methods to uncouple them.”
• The authors of the review cited a meta-analysis of 26 studies that correlated NAFLD with the following EHCs: prostate, esophagus, colon, breast, stomach, pancreas, and cholangiocarcinoma.
• The authors suggested that NAFLD patients specifically be screened for EHCs including colon, prostate, and breast, which are all already commonly screened for in many countries. “Prospective studies are required in this setting—especially to study the cost-effectiveness of screening and whether this leads to reduction of mortality—the only meaningful endpoint of screening studies.”
• The mechanisms tying NAFLD and EHCs need to elucidated—especially in terms of remote effects—but, at a molecular level, could involve hormones; insulin and insulin-like growth factor-1 (IGF-1) have been hypothesized to play a role based on some data. Moreover, the liver secretes many hepatocytes with proliferative potentials, including FGF21 and fetuin-A. Various cytokines including irisin, leptin and adiponectin can also impact tumor growth.