Low serum ceruloplasmin concentration is common in patients with cirrhosis and a MELD independent predictor of liver transplantation or death

Background and Aims:

Reduced concentrations of the ferroxidase ceruloplasmin (CP) are indicative of Wilson disease, but also commonly found in patients with NAFLD. The aim of the present study was to determine the prognostic relevance of CP in an unselected cohort of cirrhotic patients.

Method:

Patients referred for PNPLA3 genotyping to the Hepatology Laboratory at the Medical University of Innsbruck were retrospectively assessed and included if the diagnosis cirrhosis was made. Demographic, clinical and biochemical parameters were extracted from patient records.

Results:

Reduced CP concentration of ≤0.2 g/L was present in 11.7% (72/613) of patients. The prevalence of low CP was 75% in Wilson disease, 23% in hemochromatosis, followed by 16% in alcoholic cirrhosis and 13% in with NAFLD. Median NaMELD score was significantly higher in the patient group with CP < 0.2 g/L (p < 0.001) and a significant negative correlation between CP and INR but not with albumin was found. Correlation analysis further showed a significant association between CP and markers of iron metabolism/inflammation (transferrin, transferrin saturation, C-reactive protein). Median time to transplantation/death as combined endpoint was also significantly reduced in the group with low CP concentration (p = 0.012). CP but not PNPLA3 genotype was an independent predictor of the time to transplantation or death in a Cox proportional hazards model also including age and NaMELD.

Conclusion:

Hypoceruloplasminemia is common in an unselected cohort of patients with liver cirrhosis. The negative association of CP with C-reactive protein and INR confirm its role as a marker of hepatic function and inflammation. CP is a NaMELD-independent predictor of survival indicating that ferroxidase-activity is implicated in the progression of cirrhosis.