This study was performed to examine the possible association of iron overload with infectious complications and survival among liver transplant recipients.

We conducted a systematic review and meta-analysis of studies published in the PubMed, Embase, Web of Science, and Cochrane Library databases up to September 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted to estimate the association of iron overload with infectious outcomes and overall survival after liver transplantation.

Eight studies involving 2817 recipients met the inclusion criteria. Iron overload was strongly associated with an increased risk of infection after liver transplantation (HR, 1.66; 95% CI, 1.03-2.68). An increase in the serum ferritin level was associated with an increased risk of infection after liver transplantation (HR, 1.44; 95% CI, 1.09-1.91). Iron overload was a significant predictor of worse overall survival (HR, 1.35; 95% CI, 1.11-1.64). In addition, a high serum ferritin level was significantly associated with an increased risk of death (HR, 1.34; 95% CI, 1.10-1.64).

Iron overload may be associated with a higher risk of infectious complications and a worse prognosis among liver transplant recipients.

The prognostic value of serum ferritin remains elusive in the literature. We aimed to examine the association between serum ferritin and mortality risk in cirrhosis.

A total of 257 cirrhotic patients were recruited. The cut-off of serum ferritin was determined by X-tile. The Cox regression and Kaplan-Meier method were used. A 1:1 propensity score matching (PSM) was performed to diminish the impacts of selection bias and possible confounders.

The difference regarding mortality was mostly significant for serum ferritin >158 ng/mL. Before PSM, serum ferritin >158 ng/mL was an independent predictor of mortality. However, the clinical relevance of high ferritin level for prognostication was blunted after PSM (survival rate: 86.8% vs 96.3%, P = .078). Cox regression indicated that model for end-stage liver disease remains only independent risk factor of 180-day mortality after PSM.

Serum ferritin may not serve as an independent prognostic indicator of mortality risk in decompensated cirrhotic patients.

Ethanol increases iron absorption. Therefore, increased amount of iron reaches the liver, and exerts pro-oxidant effects and stimulates ferritin synthesis and hepatic stellate cell activation, promoting fibrosis and inflammation. These mechanisms would theoretically support a role of ferritin as a marker of the transition to liver cirrhosis, and, consequently, as a prognostic factor, but there is controversy regarding its behavior in alcoholics. We analyzed among 238 severe alcoholics the prognostic value of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC), and the relationships of these variables with liver function, proinflammatory markers (C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor α), and the presence of cirrhosis. Patients showed higher serum ferritin (Z = 2.50, p = 0.031) but lower transferrin (t(264) = 4.81, p < 0.001), TIBC (t(262) = 4.44, p < 0.001), and iron (Z = 3.19, p = 0.001) values compared with 32 age- and sex-matched controls. Ferritin was related to inflammatory cytokines such as IL-8 (ρ = 0.18, p = 0.012) and to IL-6 (ρ = 0.16, p = 0.016), but not to liver function. On the contrary, cirrhotics showed lower transferrin (t(234) = 4.77, p < 0.001) and TIBC (t(232) = 4.67, p < 0.001), but higher TSI (Z = 3.35, p < 0.001) than non-cirrhotics. Transferrin, TSI, and TIBC were related to liver function impairment (marked differences among the Child's groups regarding transferrin (KW (2) = 22.83, p < 0.001), TSI (KW (2) = 15.81, p < 0.001), and TIBC (KW (2) = 21.38, p < 0.001) but only weakly to inflammation (inverse relationships between IL-6 and total iron (ρ = - 0.16, p = 0.017), TIBC (ρ = - 0.20, p = 0.002), and transferrin (ρ = - 0.20, p = 0.003). In accordance, albumin, IL-6, alcohol quitting, and TSI, in this order, were independently related to mortality, but not ferritin or iron.

Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.

To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival.

From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death.

At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)].

Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.

Patients with end-stage liver disease are known to suffer from a significantly high risk of mortality, but accurate prediction of the course of disease is challenging.

The study aim was to evaluate the independent prognostic and clinical importance of serum levels of ferritin and transferrin for 90-day survival of patients with liver disease.

Patients with end-stage liver disease treated during a 2-year period were enrolled retrospectively in a single-centre study. Unmatched and propensity score matching (PSM) analyses were applied.

The study cohort comprised 286 patients with end-stage liver disease, of which 22.9% died during the observational period. High serum ferritin levels and low serum transferrin levels were associated significantly with increased 90-day mortality in the unmatched (p < 0.001) and PSM study population (p = 0.017). Serum levels of ferritin and transferrin had high prognostic capability to predict 90-day survival similar to the Model for End-stage Liver Disease. Patients with serum ferritin values >1030.5 µg/l had a 50% risk of dying within 11 days after measurement, which translated up to a 90-day mortality of 83%.

Serum levels of ferritin and transferrin have independent and excellent capabilities to determine prognosis in patients with end-stage liver disease. Ferritin measurements can reliably identify those with high mortality in daily practice.

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.

Serum ferritin and transferrin have been identified as prognostic markers in patients with chronic diseases. In this study, we investigated if these parameters can predict outcome in patients with acute liver failure.

A total of 102 consecutive patients with acute liver failure were retrospectively analysed. The patients were grouped by outcome: spontaneous recovery vs liver transplantation and/or death or survival vs death. Routine laboratory parameters, transferrin and ferritin concentrations in serum, and anthropomorphic data collected on admission were analysed.

Non-spontaneously recovering patients had higher ferritin (12 252±25 791 vs 4434.4±9027.2 μg/L; P<.05) and lower transferrin levels (140.4±66.7 vs 206.9±65.8 mg/dL; P<.05) than spontaneously recovering patients. Similarly non-survivors exhibited higher serum ferritin and lower transferrin than non-transplanted survivors. Patients with severe hepatic inflammation (A3) had higher ferritin levels compared to patients with mild-moderate inflammation (A1-2) (5280±5094 vs 2361±2737 μg/L; P=.025). ROC analysis of single parameters was performed in non-transplanted patients, resulting in an area under the curve, sensitivity and specificity of 0.812%, 83.3%, and 77.1% for age, 0.871%, 84.1% and 75% for transferrin and 0.802%, 91.7% and 62.9% for ferritin. A model incorporating age, MELD and transferrin had the best predictive value with an area under the curve of 0.947, a sensitivity of 100% and corresponding specificity of 77.8%.

High ferritin and low transferrin levels are associated with worse outcome in patients with acute liver failure. A model incorporating age, MELD score and transferrin outperformed MELD score for 90-day overall survival of non-transplanted patients.

Hepatic iron accumulation is considered to be a cofactor that influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation (RFA).

We measured SF levels in 103 HCC patients (median age 70, M/F = 82.5%/17.5%) who underwent RFA between 2005 and 2010. Correlation between SF and other prognostic factors at baseline was analyzed. SF levels were entered into a Cox model and their influence on OS and TTR was evaluated in univariate and multivariate analyses.

SF did not correlate with α-fetoprotein (rho: -0.12, P = 0.22), neutrophil/lymphocyte ratio (rho: -0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18, P = 0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage (P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal prognostic cut-off point for SF. Median OS was 62 months (54-78) and survival rate was 97%, 65%, and 52% at 1, 4, and 5 years, respectively. Performance status and SF were the only predictors of OS at multivariate analysis. Median TTR was 38 months (34-49) with a recurrence-free survival rate of 82.5%, 26.2%, and 23.3% at 1, 4, and 5 years, respectively, while SF and age were the only predictors of TTR.

SF level, possibly reflecting the degree of hepatic inflammation and fibrosis, is a negative risk factor for survival and recurrence after percutaneous RFA in HCC patients.

LiMAx has been recently proposed as a new quantitative liver function test. Thus, we aimed to evaluate the diagnostic ability of LiMAx to assess short-term survival in liver transplant candidates and compare its performance to the model for end-stage liver disease (MELD) and indocyanine green plasma disappearance rate (ICG-PDR). Liver function of 167 chronic liver failure patients without hepatocellular carcinoma was prospectively investigated when they were evaluated for liver transplantation. Primary study endpoints were liver-related death within 6 months of follow-up. Within 6 months of follow-up, 18 patients died and 36 underwent liver transplantation. Median LiMAx results on evaluation day were significantly lower in patients who died (99 μg/kg/h vs. 55 μg/kg/h; P = 0.024), while median ICG-PDR results did not differ within both groups (4.4%/min vs. 3.5%/min; P = 0.159). LiMAx showed a higher negative predictive value (NPV: 0.93) as compared with ICG-PDR (NPV: 0.90) and the MELD (NPV: 0.91) in predicting risk of death within 6 months. In conclusion, LiMAx provides good prognostic information of liver transplant candidates. In particular, patients who are not at risk of death can be identified reliably by measuring actual enzymatic liver function capacity.