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Fibroblast growth factor 21 predicts acute-on-chronic liver failure progression

Fibroblast growth factor 21 levels predicted the presence and development of acute-on-chronic liver failure in patients admitted to intensive care unit for acute decompensated cirrhosis, according to a recently published study.

“Fibroblast grow factor 21 (FGF21) is highly expressed and secreted by the liver and has profound effects on glucose and lipid metabolism,” Astrid Ruiz-Margáin, MSc, from the Instituto Nacional de Ciencias Médicas y Nutrición, México, and colleagues wrote. “FGF21 is regarded as a marker of mitochondrial dysfunction and has been used as a biomarker in extrahepatic diseases.”

To evaluate FGF21 as a predictor of ACLF development and mortality, Ruiz-Margáin and colleagues recruited 42 healthy controls and 34 patients admitted to the ICU. Twenty-four ICU patients were critically ill with decompensated cirrhosis and 10 were critically ill without cirrhosis.

Compared with controls, FGF21 levels were higher in critically ill patients and highest in those with cirrhosis. Additionally, FGF21 levels were significantly higher in patients with ACLF compared with those without ACLF.

To confirm the observed association, the researchers recruited 78 patients from ICU for a larger cohort study. They followed patients daily for an average of 8 days during ICU stay. Nine patients presented with ACLF and eight patients developed ACLF during hospitalization.

In the validation cohort, patients with ACLF had higher FGF21 levels than those without ACLF. Patients with ACLF plus ascites and malnutrition had significantly higher FGF21 values compared with those without ACLF.

Higher FGF21 levels correlated significantly with higher MELD (r = 0.338; P = .012), MELD-sodium (r = 0.374; P = .009) and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores.

The researchers observed that an FGF21 level cutoff of 309 pg/dL had a good area under curve (0.79) with sensitivity of 73.3% and specificity of 72.5%. Multivariate analysis showed that both Child-Pugh score and FGF21 levels above 309 pg/dL independently and significantly correlated with ACLF incidence.

While neither univariate nor multivariate analysis showed an association between FGF21 and mortality, the researchers observed that CLIF-Consortium ACLF score independently predicted mortality (HR = 1.271; 95% CI, 1.023-1.580).

“FGF21 is a good predictor of ACLF and organ failure, it is quite specific for cirrhosis and seems independent of etiology and systemic inflammation,” the researchers concluded. “This study suggests that mitochondrial dysfunction plays a role in the development of organ failure and ACLF. This could help the clinicians to identify patients at higher risk of this condition at the time of the admittance, and therefore set up a different approach including a more aggressive and earlier therapy, as well as a closer follow-up.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.