Serum ferritin concentration and transferrin saturation before liver transplantation predict decreased long-term recipient survival

Abstract

Serum ferritin (SF) concentration is a widely available parameter used to assess iron homeostasis. It has been described as a marker to identify high‐risk patients awaiting liver transplantation (LT) but is also elevated in systemic immune‐mediated diseases, metabolic syndrome, and in hemodialysis where it is associated with an inferior prognosis. This study analyzed whether SF is not only a predictor of liver‐related mortality prior to LT but also an independent marker of survival following LT. In a dual‐center, retrospective study, a cohort of 328 consecutive first‐LT patients from Hannover Medical School, Germany (2003‐2008, follow‐up 1260 days), and 82 consecutive LT patients from Regensburg University Hospital, Germany (2003‐2007, follow‐up 1355 days) as validation cohort were analyzed. In patients exhibiting SF ≥365 μg/L versus <365 μg/L prior to LT, 1‐, 3‐, and 5‐year post‐LT survival was 73.3% versus 81.1%, 64.4% versus 77.3%, and 61.1% versus 74.4%, respectively (overall survival P = 0.0097), which was confirmed in the validation cohort (overall survival of 55% versus 83.3%, P = 0.005). Multivariate analyses identified SF ≥365 μg/L combined with transferrin saturation (TFS) <55%, hepatocellular carcinoma, and the survival after LT (SALT) score as independent risk factors for death. In patients with SF concentrations ≥365 μg/L and TFS <55%, overall survival was 54% versus 74.8% in the remaining group (P = 0.003). In the validation cohort, it was 28.6% versus 72% (P = 0.017), respectively. Conclusion: SF concentration ≥365 μg/L in combination with TFS <55% before LT is an independent risk factor for mortality following LT. Lower TFS combined with elevated SF concentrations indicate that acute phase mechanisms beyond iron overload may play a prognostic role. SF concentration therefore not only predicts pre‐LT mortality but also death following LT. (HEPATOLOGY 2011;)

Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute‐on‐chronic liver failure

“…Many studies have suggested the correlation of lower levels of iron modulation proteins and CLD, but this has not been adequately studied in liver failure patients. 31 In the present study, %SAT predicted early mortality and also correlated with incidence of organ failure in ACLF patients, which suggests its potential as a prognostic marker in these patients. Various studies in the past have shown an inverse correlation of serum hepcidin with tissue iron in patients with CLD, 32,33 but none pertaining to ACLF.…”

Impact of the serum ferritin concentration in liver transplantation

“…The usefulness of SF as a predictor of a poor outcome has previously been reported in patients before and after LT. 29,30 For example, Weism € uller et al 30 reported that the SF concentration not only predicts pre-LT mortality, but also death following LT. In addition, they reported that patients with high pre-LT SF values required a significantly longer time in the ICU, indicating a higher degree of morbidity.…”

“…They suggested that iron overload was responsible for the relationship between the SF level and outcome. 30 High SF levels accompany a great many diseases, and the corollary of this is that iron-induced hydroxyl radical formation leading to oxidative damage is likely to be a contributory factor in all of them. Similar to the past report, the high-SF group in the present study showed a poorer prognosis than the low-SF group in the present study (94.0% versus 97.9%; P 5 0.322).…”

Serum iron parameters in liver cirrhosis

“…These lines of evidence suggest that iron is an important culprit in thepathogenesis of liver cirrhosis. [5,6] In some previous studies, it has been shown that increased ferritin has significant prognostic value in chronic liver disease. Serum ferritin level has recently been reported to associate with early mortality in patientswith liver cirrhosis.…”