Objective: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). Background: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). Methods: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). Results: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59–78) years, recipient age: 62 (IQR: 55–65) years, labMELD: 15 (IQR: 9–25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221–828) vs 796 (IQR: 477–1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12–56) vs 52 (IQR: 35–98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4–8) vs 8 (IQR: 5–18) days, P = 0.045; 20 (IQR: 16–27) vs 36 (IQR: 23–62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). Conclusion: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and its mortality is third among all solid tumors, behind carcinomas of the lung and the colon. Despite continuous advancements in the management of this disease, the prognosis for HCC remains inferior compared to other tumor entities. While orthotopic liver transplantation (OLT) and surgical resection are the only two curative treatment options, OLT remains the best treatment strategy as it not only removes the tumor but cures the underlying liver disease. As the applicability of OLT is nowadays limited by organ shortage, major liver resections – even in patients with underlying chronic liver disease – are adopted increasingly into clinical practice. Against the background of the oftentimes present chronical liver disease, locoregional therapies have also gained increasing significance. These strategies range from radiofrequency ablation and trans-arterial chemoembolization to selective internal radiation therapy and are employed in both curative and palliative intent, individually, as a bridging to transplant or in combination with liver resection. The choice of the appropriate treatment, or combination of treatments, should consider the tumor stage, the function of the remaining liver parenchyma, the future liver remnant volume and the patient’s general condition. This review aims to address the topic of multimodal treatment strategies in HCC, highlighting a multidisciplinary treatment approach to further improve outcome in these patients.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Abbreviations: AASLD American Association for the Study of Liver Diseases AUC area under the curve AUROC area under the receiver operating characteristics curve BAR balance of risk BC body composition BMI body mass index CCI comprehensive complication index CDC lavien-Dindo classification CT computed tomography EAD early allograft dysfunction EASL European Association for the Study of the Liver ECD extended criteria donor FFP unitsfresh frozen plasma units HU Hounsfield unit ICH International Conference on Harmonisation ICU Intensive Care Unit KPS Karnofsky Performance Score MELD Model of End-stage Liver Disease OLT orthotopic liver transplantation RBC units red blood cell units ROC receiver operating characteristics SM-RA skeletal muscle radiation attenuation SMI skeletal muscle index SMM skeletal muscle mass SOFT survival outcomes following liver transplantation TEur Thousand Euros UH-RWTH University Hospital of the RWTH University VFA visceral fat area1 Muscle wasting and alterations of body composition are linked to clinical outcomes in numerous medical conditions. The role of myosteatosis in posttransplant outcomes remains to be determined. Here we investigated skeletal muscle mass and myosteatosis as prognostic factors in patients undergoing orthotopic liver transplantation (OLT). The data of 225 consecutive OLT recipients from a prospective database were retrospectively analyzed (May 2010-December 2017). Computed tomography-based skeletal-muscleindex (muscle mass), visceral-fat-area (visceral adiposity), and mean skeletal-muscle-radiation-attenuation (myosteatosis) were calculated using a segmentation tool. Cut-off values of myosteatosis resulted in a good stratification of patients into low-and high-risk groups in terms of morbidity (Clavien-Dindo ≥3b). Patients with myosteatosis had significantly higher complication rates (90-day Comprehensive Complication Index 68 ± 32vs 44 ± 30, P < .001) and also displayed significantly longer intensive care (18 ± 25 vs 11 ± 21 days, P < .001) and hospital stay (56 ± 55 vs 33 ± 24 days, P < .001). Estimated costs were 44% higher compared to patients without myosteatosis. Multivariable analysis identified myosteatosis as an independent prognostic factor for major morbidity (odds ratio: 2.772, confidence interval: 1.516-5.066, P = .001). Adding myosteatosis to the well-established Balance-of-Risk-(BAR) score resulted in an increased prognostic value compared to the original BAR score. Myosteatosis may be a useful parameter to predict perioperative outcome in patients undergoing OLT, supporting the role of muscle quality (myosteatosis) over quantity (muscle mass) in this setting. K E Y W O R D Sbody composition, clinical decision-making, clinical research/practice, complication, liver transpla...

IntroductionOrthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT.Methods and analysisHOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1–2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia–reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT.Ethics and disseminationThe study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018.Trial registration numberNCT03124641.

In the face of a critical organ shortage in the Western world, various strategies are employed to expand the donor pool for orthotopic liver transplantation (OLT). Among them is the transplantation of organs from extended criteria donors, a valuable source of liver allografts, however, characterized by potential risks for post-OLT complications and inferior outcomes. In recent years, machine perfusion (MP) of the explanted donor liver as well as regional perfusion techniques has witnessed significant advancements. Here, we aim to discuss different modes of dynamic organ preservation in OLT. These include hypothermic and normothermic MP, hypothermic oxygenated machine perfusion (HOPE), controlled oxygenated rewarming as well as regional perfusion protocols. Over recent years, multiple feasibility trials have demonstrated the clinical prospects of MP. In the context of OLT using organs from extended criteria donors, MP has numerous advantages compared to conventional cold storage, some of which include the preservation and reconditioning of borderline transplantable organs and the viability assessment of high-risk donor allografts. This review aims to address the topic of liver allograft MP, highlighting particularly the current trends in clinical applications and future perspectives. Furthermore, different approaches of liver storage and reconditioning are reviewed in the context of ongoing research.