Iron overload in cirrhosis is associated to liver insufficiency and circulatory dysfunction but not portal hypertension

Iron overload in liver disease not associated to hemochromatosis is increasingly recognized in cirrhosis. The aim was to evaluate the relationship between iron overload and the main underlying pathophysiological mechanisms of cirrhosis: liver insuffiency and portal hypertension.

Methods: All consecutive patients with cirrhosis who underwent hepatic hemodynamic, right heart catheterization and ferritin measurement (within 30 days) were included. Patients were excluded according to the following criteria: active neoplasia (except HCC within Milan), severe COPD, acute event in the previous 2 weeks, immunosuppression, previous TIPS or portal vein thrombosis and end-stage renal disease. Variables are described with proportions and medians (IQR). U-mann Whitney, ANOVA test and Spearman correlations were used.

Results: 51 patients were included (male 61%, age 57 (47 – 66)yrs. Child-Pugh class A11/B25/C15, MELD score 12 (10 – 16), HVPG 18 (13 – 22) mmHg. Only 12% of patients were on betablockers at the time of the study. Most patients had alcohol liver disease (53%) although only 22% had active consumption. No association was observed between ferritin according to alcohol consumption, disease etiology or BMI. No association was observed with blood cell populations, although a correlation with mean corpuscular volume (r = 0.461, p = 0.001) was observed. A positive correlation was observed between ferritin and markers of systemic inflammation (CRP, r = 0.273,p = 0.06) and hepatic inflammation (ASAT, r = 0.302, p = 0.035). No correlation between ferritin and HVPG nor the presence of clinically significant portal hypertension was seen. The results were similar when limited to the patients without betablockers. Negative correlations were observed between ferritin and markers of circulatory dysfunction such as MAP (r = –0.360, p = 0.014) and serum sodium (r =-0.419, p = 0.002). On the other hand, significant correlations were observed between ferritin and markers of liver failure such as INR (r = 0.333, p = 0.005), bilirubin (r = 0.378, p = 0.007), albumin (r = –0.265, p = 0.082) and MELD (r = 0.293 p = 0.041) and Child-Pugh score (r = 0.392, p = 0.009).

Conclusions: In cirrhosis, serum ferritin is associated to markers of liver insufficiency, inflammation and circulatory dysfunction but not portal hypertension.