Transferrin as a predictor of survival in cirrhosis

Abstract

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 decompensated 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 carcinoma were excluded. Survival analysis was carried out by Cox regression by using baseline laboratory parameters, and findings 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 transplant‐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 independently 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.

Inflammation, etiologies and Model for End‐stage Liver Disease score: What makes liver disease patients susceptible to developing colorectal neoplasia?

“…Decreased transferrin is a marker of both inflammation and deteriorating liver synthesis capacities . A higher MELD score is associated with a decreased number of adenomas and decreased transferrin.…”

“…Decreased transferrin is a marker of both inflammation 25 and deteriorating liver synthesis capacities. 26 A higher MELD score is associated with a decreased number of adenomas and decreased transferrin. If transferrin was only a marker of liver disease severity, decreased transferrin would have to be associated with decreased neoplasia.…”

Characterization of Oxidative Stress and Ammonia According to the Different Grades of Hepatic Encephalopathy

“…Dysbiosis or pathogenic microorganisms can trigger a severe leukocyte infiltration that stimulates neutrophils to produce RNOS and secrete myeloperoxidase, chemokines, and proinflammatory cytokines [29,30]. In addition, the chronic imbalance in the antioxidant defense systems (enzymatic: catalase, superoxide dismutase, and glutathione peroxidase or nonenzymatic: zinc, selenium, magnesium, vitamins and proteins as albumin, globulins, bilirubin, ceruloplasmin, transferrin) [4,31,32] favors the establishment of OxS. These events perpetuate a continuous cycle of cell damage in DNA, proteins, lipids/fatty acids (lipid peroxidation), and potential cell death (apoptosis) in the exposed organ [33].…”

Reply

“…Except for hyperferritinemia and increased transferrin saturation-also commonly present in patients with cirrhosis-no additional comorbidities were found in our patient. (4) Explant liver histology revealed stainable iron in hepatocytes compatible with hemochromatosis. In search for the causes of the iron overload, full-exome sequencing was performed in this patient, and potentially disease-causing mutations were identified in at least 3 iron genes, none of which would be sufficient to cause iron overload alone.…”

“…The alpha-1-antitrypsin Z-allele and iron are both increasingly recognized as independent risk factors for liver disease progression. (4,5) Iron overload is an important cofactor in selected patients with A1ATD, but the case presented by Meister et al illustrates that coincident hemochromatosis is not the exclusive cause for rapid liver disease progression in A1ATD. These observations could be a rationale for prospective studies to assess if all patients with A1ATD or only specific subgroups should undergo enhanced surveillance or even receive MELD exception on the liver transplant waiting list.…”