Liver transplantation in patients with a history of migration: A German single center comparative analysis

Liver transplant (LT) programs in Germany increasingly face a multiethnic patient population. To date no outcome data for LT in patients with a history of migration is available for Germany. This complicates decision-making before wait-listing such patients. We conducted a single-center cohort analysis of all primary LT between April 2007 and December 2015, stratified for the history of migration to investigate differences in the outcome. We found transplant rates resembling the proportion of persons with a history of migration in the general public in the region of our center. Differences were found concerning age at LT and prevalence of underlying diseases. Re-Transplant rates, Kaplan-Meier Estimates for overall survival, also after stratification for viral hepatitis, sex, ethnicity or presence of a language-barrier showed no statistical differences. The multivariate analysis showed no migration-related covariate associated with a negative outcome. These results stand in contrast to most of the previous evidence from North America and the UK and need to be taken into consideration during the wait-listing process of patients with a history of migration in need of a LT in centers in the Eurotransplant region

Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma

BACKGROUND Liver transplantation and liver resection are curative options for early hepatocellular carcinoma (HCC). The outcome is in part depended on the immunological response to the malignancy. In this study, we aimed to identify immunological profiles of non-HCV/non-HBV HCC patients. METHODS Thirty-nine immune cell subsets were measured with multicolor flow cytometry. This immunophenotyping was performed in peripheral blood (PB) and tumor specimens of 10 HCC resection patients and 10 healthy donors. The signatures of the highly differential leukocyte count (hDIF) were analyzed using multidimensional techniques. Functional capability was measured using intracellular IFN-γ staining (Trial Registration DRKS00013567). RESULTS The hDIF showed activation (subsets of T-, B-, NK- and dendritic cells) and suppression (subsets of myeloid-derived suppressor cells and T- and B-regulatory cells) of the antitumor response. Principal component analysis of PB and tumor infiltrating leukocytes (TIL) illustrated an antitumor activating gradient. TILs showed functional capability by secreting IFN-γ but did not kill HCC cells. CONCLUSIONS In conclusion, the measurement of the hDIF shows distinct differences in immune reactions against non-HBV/non-HCV HCC and illustrates an immunosuppressive gradient toward peripheral blood. TRIAL REGISTRATION DRKS00013567

Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Liver Transplantation Mitigates Post-Reperfusion Syndrome and Perioperative Electrolyte Shifts

(1) Background: Post-reperfusion syndrome (PRS) and electrolyte shifts (ES) represent considerable challenges during liver transplantation (LT) being associated with significant morbidity. We aimed to investigate the impact of hypothermic oxygenated machine perfusion (HOPE) on PRS and ES in LT. (2) Methods: In this retrospective study, we compared intraoperative parameters of 100 LTs, with 50 HOPE preconditioned liver grafts and 50 grafts stored in static cold storage (SCS). During reperfusion phase, prospectively registered serum parameters and vasopressor administration were analyzed. (3) Results: Twelve percent of patients developed PRS in the HOPE cohort vs. 42% in the SCS group (p = 0.0013). Total vasopressor demand in the first hour after reperfusion was lower after HOPE pretreatment, with reduced usage of norepinephrine (-26%;p = 0.122) and significant reduction of epinephrine consumption (-52%;p = 0.018). Serum potassium concentration dropped by a mean of 14.1% in transplantations after HOPE, compared to a slight decrease of 1% (p < 0.001) after SCS. The overall incidence of early allograft dysfunction (EAD) was reduced by 44% in the HOPE group (p = 0.04). (4) Conclusions: Pre-transplant graft preconditioning with HOPE results in higher hemodynamic stability during reperfusion and lower incidence of PRS and EAD. HOPE has the potential to mitigate ES by preventing hyperpotassemic complications that need to be addressed in LT with HOPE-pre-treated grafts

Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3(+) (p = 0.016) and CD8(+) (p = 0.028) independently predicted better OS and DFS, respectively. CD20(+) showed a trend towards better DFS (p = 0.076). Scoring of CD3(+), CD8(+), and CD20(+) independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3(+) cells is an independent predictor of better OS, and CD8(+) cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients

Liver Transplant Oncology: Towards Dynamic Tumor-Biology-Oriented Patient Selection

While liver transplantation was initially considered as a curative treatment modality only for hepatocellular carcinoma, the indication has been increasingly extended to other tumor entities over recent years, most recently to the treatment of non-resectable colorectal liver metastases. Although oncologic outcomes after liver transplantation (LT) are consistently good, organ shortage forces stringent selection of suitable candidates. Dynamic criteria based on tumor biology fulfill the prerequisite of an individual oncological prediction better than traditional morphometric criteria based on tumor burden. The availability of specific (neo-)adjuvant therapies and customized modern immunosuppression may further contribute to favorable post-transplantation outcomes on the one hand and simultaneously open the path to LT as a curative option for advanced stages of tumor patients. Herein, we provide an overview of the oncological LT indications, the selection process, and expected oncological outcome after LT