4. Discussion
NAFLD, extrahepatic cancers, NASH, breast, colorectal, esophageal, and pancreatic,, weight loss
HEPATOCELLULAR CARCINOMA, LIVER FIBROSIS
This post hoc analysis of the NASHFit trial found serum FGF21 to be markedly decreased following 20 weeks of moderate-intensity aerobic exercise training and without clinically significant body weight loss compared with standard clinical care. This finding supports a novel mechanism to explain the observed reduction in MRI-measured liver fat and improvement in serum biomarkers of liver fibrosis in patients with NASH who do undertake aerobic exercise. This is the first study to show that improvement in serum FGF21 is sustained with a long-term exercise training in patients exclusively with NASH, extending the findings of previous study by Taniguchi et al. of 27 elderly Japanese men without established NAFLD which found a short-term five-week aerobic exercise program to decrease serum FGF21 [FGF21 regulates energy metabolism and is largely expressed in the liver, although it can be found in other tissues, including adipose tissue [The results of a recent study [The relationship between FGF21 and cardiorespiratory fitness is also of great interest given that VOFGF21 is also implicated in the development of extrahepatic cancers found more commonly in patients with NAFLD, including breast, colorectal, esophageal, and pancreatic, as well as hepatocellular carcinoma [This study has multiple strengths in that it uses paired samples from a highly rigorous clinical trial conducted in a population of patients with NASH who were well phenotyped and studied systematically. Possible limitations include the sample size (although this study is powered similar to previously published exercise trials in patients with NAFLD), the lack of liver histology, the inability of the study design to evaluate long-term clinical outcomes, and the fact that serum FGF21 was not possible to measure for each patient who completed the NASHFit trial.