Z Gastroenterol 2019; 57(01): e32
DOI: 10.1055/s-0038-1677126
2. Clinical Hepatology, Surgery, LTX
Georg Thieme Verlag KG Stuttgart · New York

In severe alcoholic hepatitis, serum transferrin predicts mortality independently of disease severity

K Hamesch
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
,
SR Atkinson
2   Department of Hepatology, Imperial College London, London, United Kingdom;
,
I Spivak
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
,
N Guldiken
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
,
I Theurl
3   Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology, Pneumology), Innsbruck Medical University, Innsbruck, Austria
,
H Zoller
4   Department of Medicine, Medical University and University Hospital of Innsbruck, Innsbruck, Austria
,
C Trautwein
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
,
MR Thursz
2   Department of Hepatology, Imperial College London, London, United Kingdom;
,
P Strnad
1   Medical Clinic III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

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Background:

Severe alcoholic hepatitis (AH) confers substantial mortality but the underlying pathogenesis remains incompletely understood. Deranged iron parameters are common in liver disease patients and constitute attractive outcome predictors. Alcoholic liver disease was particularly well studied and alcohol was shown to suppress the production of the iron-regulatory hormone hepcidin. Therefore, we analysed the role of iron parameters in patients with severe AH.

Methods:

Ferritin, transferrin, iron, transferrin saturation (TSAT), non-transferrin bound iron (NTBI), soluble transferrin receptor (sTfR), and hepcidin were measured in sera from 828 patients with severe AH recruited prospectively via the STOPAH trial. Potential regulators of the established negative acute-phase protein (APP) transferrin were assessed in primary mouse hepatocytes.

Results:

AH patients had diminished serum transferrin (median 93 mg/dl), but increased ferritin (median 625 ng/dl) and TSAT (median 70%). Among iron parameters, baseline transferrin was the best predictor of 28-day (AUROC 0.72, 95% CI 0.67 – 0.78) and 90-day survival (AUROC 0.65, 95% CI 0.61 – 0.70). Transferrin's predictive ability was comparable to the established scores MELD, GAHS, or DF and was independently associated in multivariable analysis. In contrast, NTBI and sTfR as the markers of excess unbound iron and functional iron deficiency, respectively, did not have an obvious prognostic importance. In primary hepatocytes, treatment with TGFβ1 or the HNF4α inhibitor BI6015 suppressed the production of the negative APP transferrin, while exposure to TNFα, IL1β, and IL6 had no effect.

Conclusion:

Serum parameters of iron metabolism, particularly transferrin as a negative acute phase reactant, are strongly associated with outcome in severe AH. Accordingly, serum transferrin predicts 28- and 90-day mortality with a performance comparable to commonly used scoring systems. Transferrin's decrease may reflect an impaired HNF4α axis.