The Troubling Link Between Non-alcoholic Fatty Liver Disease (NAFLD) and Extrahepatic Cancers (EHC)

Nonalcoholic fatty liver disease is specifically related to the risk of hepatocellular cancer but not extrahepatic malignancies

“…It is known that weight loss of 5% reverses NAFLD. However, the Women Health Initiative study indicates that while an intentional 5% weight loss reduced the risk of endometrial cancer, it did not reduce the risk of other obesity-related cancers (colon, breast, pancreas, kidney, thyroid, or liver) (29,30). The ultimate proof will probably come from long-term follow-up of patients specifically treated for NAFLD without other metabolic disturbances; this should clarify whether the ultimate cause lies in the liver or in the adipose tissue (29).…”

“…However, the Women Health Initiative study indicates that while an intentional 5% weight loss reduced the risk of endometrial cancer, it did not reduce the risk of other obesity-related cancers (colon, breast, pancreas, kidney, thyroid, or liver) (29,30). The ultimate proof will probably come from long-term follow-up of patients specifically treated for NAFLD without other metabolic disturbances; this should clarify whether the ultimate cause lies in the liver or in the adipose tissue (29). Despite previous studies suggesting the higher risk of extrahepatic cancers in patients with NAFLD, this did not result in significant changes in clinical practice; however, there is a unanimous agreement on the importance of finding reliable and cost-effective noninvasive diagnostic markers of NAFLD to improve clinical care and facilitate NAFLD research.…”

“…reflect insulin resistance and "metabolic" obesity that includes deposition of lipid in the visceral cavity, skeletal muscle, pancreas, and kidney-these can all occur in the absence of NAFLD (26)(27)(28). A recent study (16) suggested that NAFLD was associated with a higher risk of incident cancers, while obesity alone was not; however, ectopic fat deposition, which cannot be measured by BMI, seems to be the common underlying factor in the pathogenesis of metabolic disorders and metabolic cancers (29). Instead of considering NAFLD as a mediator of the obesity-cancer association, we suggest metabolic dysregulation to be a possible mediator of this association.…”

“…Measuring metabolic dysregulation is a significant barrier for studying the NAFLD-obesity-cancer relationship. Whether NAFLD directly causes cancer is difficult to establish, and there could be another proximate cause for both fatty liver and cancer (29). It is known that weight loss of 5% reverses NAFLD.…”

Irisin Is Related to Non-Alcoholic Fatty Liver Disease (NAFLD)

“…The presence of NAFLD is associated with the risk of health consequences. They result from both the natural progression of liver disease (non-alcoholic steatohepatitis—NASH, cirrhosis and hepatocellular carcinoma—HCC) and an increased risk of developing other pathologies, such as cardiovascular complications (cardiovascular disease—CVD, including heart failure, atrial fibrillation and chronic subclinical and clinical coronary syndrome) and non-HCC malignant neoplasms (including mainly the large intestine, breast, prostate, lung and pancreas) [ 5 , 6 ]. Recently, attention has also been paid to the relationship between NAFLD and NAFLD-related chronic kidney disease (CKD) and the impact of NAFLD on its severity, regardless of established cardiovascular risk factors [ 7 ].…”