Transferrin as a Predictor of Survival
Benedikt Schaefer ,
Thomas Reiberger ,
and Heinz Zoller
Department of Medicine, Medical University and University Hospital of Innsbruck, Innsbruck, Austria;
Department of Medical
Statistics, Informatics, and Health Economics, Medical University Innsbruck, Innsbruck, Austria; and
Department of Medicine
III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
Patients with cirrhosis frequently present with high serum ferritin and low transferrin concentrations, reﬂecting impaired
liver function and inﬂammation. Recent studies have shown that transferrin and its saturation with iron are Model for
End-Stage Liver Disease–independent predictors of mortality in patients with acute-on-chronic liver failure or decompen-
sated cirrhosis. The aim of this study was to evaluate the prognostic utility of serum iron parameters in relation to markers
of liver function and immune activation. Clinical, demographic, and biochemical data were retrospectively analyzed from a
cohort of 1255 consecutive patients with cirrhosis (age 18 years) who presented from August 1, 2004 until December
31, 2014 at the University Hospital of Innsbruck. Patients with malignancies at diagnosis including hepatocellular carci-
noma were excluded. Survival analysis was carried out by Cox regression by using baseline laboratory parameters, and ﬁnd-
ings were validated in an independent patient cohort. During a median follow-up of 2.4 years, 193 deaths occurred and
254 patients underwent liver transplantation. In patients with transferrin < 180 mg/dL, 3-month, 1-year, and 5-year trans-
plant-free survival estimates were signiﬁcantly lower (91.7%, 79.0%, and 30.5%) when compared with the group of patients
with transferrin 180 mg/dL (98.9%, 95.5%, and 68.0%, P < 0.001). Transferrin predicted transplant-free survival inde-
pendently of Model for End-Stage Liver Disease–sodium (MELD-Na) and C-reactive protein (CRP) in multivariate
regression analysis including all patients. When patients with alcoholic or nonalcoholic fatty liver disease were excluded,
transferrin was in addition an albumin-independent predictor of transplant-free survival. In conclusion, the association of
transferrin with transplant-free survival is independent of MELD-Na score and CRP. In patients without fatty liver
disease, transferrin also predicts survival independently of albumin.
Liver Transplantation 24 343–351 2018 AASLD.
Received August 9, 2017; accepted November 2, 2017.
The Model for End-Stage Liver Disease (MELD) has
evolved as a reference staging system for cirrhosis and
is used for prognosis, evaluation for liver transplantation,
and donor liver allocation.
age, or albumin into modiﬁed MELD scores im-
proves accuracy in predicting survival in patients with
In search for additional prognostic
parameters, high ferritin at the time of listing for liver
transplantation was identiﬁed as an independent predic-
tor of wait-list mortality,
but the prognostic utility of
ferritin could not be reproduced in a larger cohort.
When transferrin saturation was taken into consider-
ation, ferritin could predict mortality on the waiting list
and after orthotopic liver transplantation.
Iron overload was therefore proposed as a risk factor
for mortality in patients with liver disease. Accordingly,
transferrin and transferrin saturation have also been
identiﬁed as predictors of survival in patients with
decompensated cirrhosis and acute-on-chronic liver fail-
Transferrin is lower in patients with
cirrhosis and impaired synthetic function.
tin and low transferrin can indicate inﬂammation,
which is also a risk factor for disease progression and
mortality in cirrhosis. In addition, alcohol and metabolic
factors can directly affect iron metabolism.
Abbreviations: a1-ATD, alpha 1-antitrypsin deﬁciency; ACLF,
acute-on-chronic liver failure; ALD, alcoholic liver disease; AUC,
area under the curve; CI, conﬁdence interval; CRP, C-reactive pro-
tein; HBV, hepatitis B virus; HCV, hepatitis C virus; HH, heredi-
tary hemochromatosis; HR, hazard ratio; INR, international
normalized ratio; MELD, Model for End-Stage Liver Disease;
MELD-Na, Model for End-Stage Liver Disease–sodium; NAFLD,
nonalcoholic fatty liver disease; PBC, primary biliary cirrhosis; PSC,
primary sclerosing cholangitis; ROC, receiver operating characteristic;
UNOS, United Network for Organ Sharing.
VIVEIROS ET AL.