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.
