The influence of functional warm ischemia time on DCD Liver Transplant Recipients' Outcomes

Duration of functional warm ischemia (f-WIT) is thought to have a causal effect on outcomes in controlled donation after circulatory death (DCD) liver transplantation (LT).status: publishe

Liver transplantation for hepatocellular carcinoma after successful treatment of macrovascular invasion

Macrovascular invasion is considered a contraindication to liver transplantation for hepatocellular carcinoma (HCC) due to a high risk of recurrence. The aim of the present multicenter study was to explore the outcome of HCC patients transplanted after a complete radiological regression of the vascular invasion by loco-regional therapies, and define sub-groups with better outcomes. Medical records of 45 patients were retrospectively reviewed and imaging was centrally assessed by an expert liver radiologist. In the 30 patients with validated diagnosis of macrovascular invasion, overall survival was 60% at 5 years. Pre-transplant alpha fetoprotein (AFP) value was significantly different between patients with and without recurrence (p=0.019) and the optimal AFP cut-off was 10ng/ml (area under curve= 0.78). Recurrence rate was 11% in patients with pre-transplant AFP <10ng/ml. The number of viable nodules (p=0.008), the presence of residual HCC (p=0.036) and satellite nodules (p=0.001) on the explant were also significantly different between patients with and without recurrence. Selected HCC patients with radiological signs of vascular invasion could be considered for transplantation, provided that they previously underwent successful treatment of the macrovascular invasion resulting in a pre-transplant AFP <10ng/ml. Their expected risk of post-transplant HCC recurrence is 11%, and further prospective validation is needed

Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.

BACKGROUND AIMS Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. The Liver Graft Assessment Following Transplantation (L-GrAFT) risk-score estimates 3-month graft-failure-free survival (area under the receiver operator characteristic [AUROC] curve=0.83), and was superior to the binary EAD (AUROC=0.68) definition and Model for Early Allograft Function (MEAF, AUROC=0.70) in the single-center derivation cohort (DC, n=2008). We sought to externally validate L-GrAFT, and compare its prognostic performance to EAD and MEAF. METHODS Accuracies of L-GrAFT, EAD, and MEAF were compared in a 3-center US validation cohort (VC, n=3201), and Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion trial cohort (n=222), with comparison of characteristics to assess generalizability. RESULTS Compared to the DC, VC and COPE patients had lower recipient median MELD scores (18 and 14 vs 31); were less likely to require pretransplant hospitalization (23.3% and 0% vs 46.1%), renal replacement therapy (8.8% and 1.8% vs 31.7%), mechanical ventilation (3.7% and 0% vs 19.8%); and had superior 1-year overall (90% and 95% vs 84%) and graft-failure-free (88% and 93% vs 81%) survival, with a lower incidence of 3-month graft failure (7.4% and 4.0% vs. 11.1%; P<0.001 for all comparisons). Despite significant differences in cohort characteristics, L-GrAFT maintained an excellent validation AUROC of 0.78, significantly superior to the EAD (AUROC=0.68, P=0.001) and MEAF scores (AUROC=0.72, P<0.001). In post-hoc analysis of COPE NMP trial, highest tertile of L-GrAFT was significantly associated with time to liver allograft (HR 2.17, P=0.016) and Clavien ≥IIIB (HR 2.60, P=0.034) and ≥IVa (HR 4.99, P=0.011) complications, and post-LT length of hospitalization (P=0.002) and renal replacement therapy (OR 3.62, P=0.016). CONCLUSIONS We have validated the L-GrAFT risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to the existing EAD and MEAF scores. L-GrAFT may standardize grading of early hepatic allograft function, and serve as a clinical end-point in translational studies aiming to mitigate ischemia-reperfusion injury. LAY SUMMARY Early allograft dysfunction negatively affects outcomes following liver transplantation (LT). In independent multicenter US and European cohorts totaling 3423 patients undergoing LT, the Liver Graft Assessment Following Transplantation (L-GrAFT) risk score is validated as a superior measure of early allograft function that accurately discriminates 3-month graft failure free survival and post-LT complications

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multi-center collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. STUDY DESIGN: Liver transplant and resection outcomes for HCC (n=2998) and cHCC-CCA (n=208) were compared in a 12-center retrospective review (2009-2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. RESULTS: Liver transplant for cHCC-CCA (n=67) and HCC (n=1814) within Milan had no significant difference in overall survival (5-yr cHCC-CCA 70.1%, HCC 73.4%, p=0.806) despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5-years, p CONCLUSIONS: Regardless of tumor burden, outcomes following liver transplant are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC results in similar overall survival justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population