Fibroblast growth factor 21 is an early predictor of acute-on-chronic liver failure in critically ill patients with cirrhosis

Acute-on-chronic liver failure (ACLF) develops in acute decompensation (AD) of cirrhosis and shows high mortality. In critically ill patients, early diagnosis of ACLF could be important for therapeutic decisions (eg, renal replacement, artificial liver support, liver transplantation). This study evaluated fibroblast growth factor 21 (FGF21) as a marker of mitochondrial dysfunction in the context of ACLF. The study included 154 individuals (112 critically patients and 42 healthy controls) divided into a training and a validation cohort. In the training cohort of 42 healthy controls and 34 critically ill patients (of whom 24 were patients with cirrhosis), levels of FGF21, interleukin (IL) 6, and IL8 were measured. In the validation cohort of 78 patients with cirrhosis, 17 patients were admitted with or developed ACLF during follow-up and underwent daily clinical and nutritional assessment. Levels of FGF21 were higher in critically ill patients, especially in patients with cirrhosis admitted to the intensive care unit (ICU). Moreover, FGF21 as well as IL6 and IL8 levels were higher in patients with ACLF, but they did not increase with the severity of ACLF. Interestingly, in the validation cohort, FGF21 was also elevated in the patients who developed ACLF in the next 7 days. In these patients, FGF21 levels were an independent predictor of ACLF presence and development in multivariate analysis together with Child-Pugh score. FGF21 levels had no impact on the survival of critically ill patients with cirrhosis. In conclusion, this study demonstrates that FGF21 levels are of specific diagnostic value regarding the presence and development of ACLF in patients admitted to ICU for AD of liver cirrhosis. Further studies are warranted to address pathophysiological and possible therapeutic implications. Liver Transplantation 24 595-605 2018 AASLD.