The association of pretransplant ferritin level with waiting list and post-transplant survival. Does ferritin actually predict outcome?

Recent data suggest an association of serum ferritin (SF) with waiting list (WL) and postliver transplant (LT) outcomes. To assess the predictive capacity of SF on pre- and post-LT outcomes, and to identify whether recipient or donor liver siderosis is associated with post-LT survival; a retrospective analysis of 1079 patients assessed for first LT, 2000-2007 was performed. Iron deposition in the liver tissue was assessed using a semi-quantitative grading system. Median age was 54 (18-82) years and 67% were male. Seventeen per cent had hepatocellular carcinoma (HCC). Median Model for End-stage Liver Disease MELD score was 14 (6-40), ferritin was 174 µg/l (4-4597) with 36.5% had a SF ≥ µg/l. Age (OR = 1.028) and MELD score (OR = 1.158) were independently associated with WL mortality (P < 0.001), whilst SF was not (P = NS). Age (OR = 1.018), HCC (OR = 1.542) and cold ischemia time (CIT) ≥ 10 h (OR = 1.418) were independently associated with post-LT survival (P < 0.05). Explant siderosis grade <2 was seen in 376 (71.7%) patients. Patients with explant siderosis grade ≥ 2 had inferior 12-month post-LT survival (P = 0.030). Presence of graft siderosis (15.8% of patients) was not associated with survival. In conclusion, we found a limited role for SF as a prognostic indicator for pre- or post-transplant survival.

Management of hepatitis C in patients with chronic kidney disease.

Chronic kidney disease represents a global health problem. Chronic hepatitis C virus (HCV) infection is prevalent in patients with end stage renal disease (ESRD) on hemodialysis (HD) and in renal transplant recipients with significant impact on morbidity and mortality. Furthermore, HCV can cause various forms of glomerulopathy with the predominant type being cryglobulinemia associated membranoproliferative glomerulonephritis. Liver enzymes are traditionally used as markers of liver injury; however, there is wide variation in aminotransferase levels in patients with ESRD. Therefore, diagnosis of chronic hepatitis C (CHC) in patients with ESRD is based on HCV antibody testing and further confirmation with polymerase chain reaction testing. Current standard therapy for CHC is composed of pegylated interferon and ribavirin. However, this combination is challenging in patients with ESRD due to its tolerability. We describe in this review relevant issues in epidemiology, diagnosis and management of CHC in ESRD, HD and renal transplant recipients.

Increased model for end-stage liver disease score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs.

Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting list mortality in the United States. However, reports suggest an increase in resource utilization as a consequence of this. The aim of this study is to assess the correlation of MELD at transplant with post-liver transplant (LT) intensive care unit (ICU) costs. We assessed clinical and demographic variables of 402 adult patients who underwent LT at King's College Hospital, London, UK, between January 2000 and December 2003. ICU cost calculations were based on the therapeutic intervention scoring system (TISS). Graft quality was assessed using the donor risk index (DRI). Patients with a MELD score > 24 had significantly longer post-LT ICU stay (P < 0.0001) and total post-LT hospital stay (P = 0.008). In addition, they had significantly increased TISS scores, ICU cost, and need for renal replacement therapy (RRT) (P < 0.001). MELD score (by point) and MELD > 24 was associated with prolonged ICU stay (P = 0.004 and P = 0.005, respectively). On univariate analysis, etiology of alcohol-related liver disease (ALD), repeat LT, Budd-Chiari syndrome, and refractory ascites were associated with prolonged ICU stay. Using multivariate analysis, MELD > 24, refractory ascites, ALD and Budd-Chiari syndrome were associated with prolonged ICU stay. There was no association between using grafts with higher DRI and longer ICU stay, need for RRT, increased cost, or hospital survival on univariate analyses (P = not significant). Use of MELD as a method of organ allocation results in significant increase in ICU cost after LT. Using TISS as surrogate marker for ICU costs reveals that the cost implications are related to the need for RRT and prolonged ICU stay.

Impact of comorbidity on waiting list and post-transplant outcomes in patients undergoing liver retransplantation.

AIM: To determine the impact of Charlson comorbidity index (CCI) on waiting list (WL) and post liver retransplantation (LRT) survival. METHODS: Comparative study of all adult patients assessed for primary liver transplant (PLT) (n = 1090) and patients assessed for LRT (n = 150), 2000-2007 at our centre. Demographic, clinical and laboratory variables were recorded. RESULTS: Median age for all patients was 53 years and 66% were men. Median model for end stage liver disease (MELD) score was 15. Median follow-up was 7-years. For retransplant patients, 84 (56%) had ≥ 1 comorbidity. The most common comorbidity was renal impairment in 66 (44.3%). WL mortality was higher in patients with ≥ 1 comorbidity (76% vs 53%, P = 0.044). CCI (OR = 2.688, 95%CI: 1.222-5.912, P = 0.014) was independently associated with WL mortality. Patients with MELD score ≥ 18 had inferior WL survival (Log-Rank 6.469, P = 0.011). On multivariate analysis, CCI (OR = 2.823, 95%CI: 1.563-5101, P = 0.001), MELD score ≥ 18 (OR 2.506, 95%CI: 1.044-6.018, P = 0.04), and requirement for organ support prior to LRT (P < 0.05) were associated with reduced post-LRT survival. Donor/graft parameters were not associated with survival (P = NS). Post-LRT mortality progressively increased according to the number of transplanted grafts (Log-Rank 18.455, P < 0.001). Post-LRT patient survival at 1-, 3- and 5-years were significantly inferior to those of PLT at 88% vs 73%, P < 0.001, 81% vs 71%, P = 0.018 and 69% vs 55%, P = 0.006, respectively. CONCLUSION: Comorbidity increases WL and post-LRT mortality. Patients with MELD ≥ 18 have increased WL mortality. Patients with comorbidity or MELD ≥ 18 may benefit from earlier LRT. LRT for ≥ 3 grafts may not represent appropriate use of donated grafts.

The effect of changes of model for end-stage liver disease score during waiting time on post-liver transplant mortality.

OBJECTIVE: Model for End-Stage Liver Disease (MELD) score is found to be a robust predictor of mortality while on waiting list for liver transplantation. However, studies have shown inconsistent results for transplant MELD as a predictor of posttransplant mortality. AIM: To find whether utilization of MELD at listing, at transplant, or Δ MELD while waiting can predict outcome at a national transplant center, which is not part of an organ sharing network. METHOD: Retrospective analysis of patients listed for liver transplantation at the New Zealand Liver Transplant Unit (NZLTU) with calculation of MELD score at the time of listing and at transplant with/without adjustment points for hepatocellular carcinoma (HCC). RESULTS: Between 1998 and 2005, 264 adult patients were listed for liver transplantation. Median age at transplant was 49 years (range 16-70) and 65% were male. The most common etiology was viral hepatitis (50%). A total of 48 patients (20%) had known HCC. MELD scores (adjusted and nonadjusted) at listing and at transplantation were similar across all primary liver diseases (P = 0.88, 0.93, respectively). Adjusted MELD scores were significantly higher in patients listed for HCC compared to those without HCC (P < 0.001; hazard ratio 1.33; 95% confidence interval = 1.21-1.46). MELD scores at transplant did not correlate with either 3 or 12 months mortality (P = 0.336, 0.228, respectively). This finding was consistent whether the change of MELD during waiting time was >1 point or less (P = 0.67). Waiting time does not appear to influence posttransplant survival (P = 0.75). CONCLUSION: In a country with a single transplant center and organ retrieval organization, the addition of MELD score to current minimal listing criteria does not improve prioritization of patients on the waiting list or predict posttransplant survival. Also, adjusting MELD score for HCC would unfairly disadvantage patients listed without HCC.