Non-alcoholic steatohepatitis patients exhibit reduced CD47, and increased sphingosine, cholesterol and MCP1 levels in the erythrocyte membranes

Non-alcoholic steatohepatitis (NASH) constitutes a significant cause of deaths, liver transplantations and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NASH, present phosphatidylserine exposure which is then recognized by Kupffer cells. This event leads to erythrophagocytosis, and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NASH patients release the chemokine MCP1, leading to increased TNF-α release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. In addition, increased MCP1 release could be either signal-induced, or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 by ELISA, and cholesterol and sphingosine with thin-layer chromatography. 18 patients (8 men, 10 women aged 56.7+/-11.5 years) and 14 healthy controls (7 men, 7 women aged 39.3+/-15.5 years) participated in our study. The erythrocyte CD47 levels were decreased in the erythrocyte membranes of NASH patients (844+/-409 pg/ml) compared to healthy controls (2969+/-1936 pg/ml) with P(Healthy>NAFLD)=99.1%, while the levels of MCP1 were increased in NASH patients (389+/-255 pg/ml), compared to healthy controls (230+/-117 pg/ml) with P(Healthy<NAFLD)=88.9%. Moreover, in erythrocyte membranes there was a statistically significant accumulation of sphingosine and cholesterol in NASH patients, compared to healthy controls. Our results imply that erythrocytes release chemotactic (find me signals) MCP1, while containing reduced (do not eat me signals) CD47. These molecules can lead to erythrophagocytosis. Next, increased (goodbye signals) sphingosine and cholesterol could augment inflammation by metabolic reprogramming.

A Novel Strategy for Preventing Posttransplant Large-For-Size Syndrome in Adult Liver Transplant Recipients: A Pilot Study

There are two causes of graft compression in the large-for-size syndrome (LFSS). One is a shortage of intra-abdominal space for the liver graft, and the other is the size discrepancy between the anteroposterior dimensions of the liver graft and the lower right hemithorax of the recipient. The former could be treated using delayed fascial closure or mesh closure, but the latter may only be treated by reduction of the right liver graft to increase space. Given that split liver transplantation has strict requirements regarding donor and recipient selections, reduced-size liver transplantation, in most cases, may be the only solution. However, surgical strategies for the reduction of the right liver graft for adult liver transplantations are relatively unfamiliar. Herein, we introduce a novel strategy of HuaXi-ex vivo right posterior sectionectomy while preserving the right hepatic vein in the graft to prevent LFSS and propose its initial indications.

Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation

In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.

An Overview of Paediatric Liver Transplant in Hospital Selayang: 2002 to 2015

Introduction: Hospital Selayang started the liver transplant program in 2002. We report a total of 81 liver transplant cases until year 2015. Among these, paediatric cases constitute almost half. This report aims to review the demography and outcome of paediatric liver transplant cases. Methodology: Case notes of all paediatric patients underwent liver transplant from year 2002 to 2015 were retrospectively reviewed. Results: A total of 38 paediatric cases received liver transplantations from year 2002 to 2015. Age at transplantation ranged from 11 months to 16 years old (mean age 6 years) and weight ranged from 6.47 to 63 kilogram (mean 18kg). There were 20 males and 18 females, 20 of them were Malay, whereas Chinese and Indian were 13 and 4 respectively. Eighteen cases were living-related and 20 cases were cadaveric liver transplants. For recipient blood group, O+ is the commonest. Biliary atresia was the most common indication for liver transplant (22 cases; 58%), followed by intrahepatic cholestasis disorders (5 cases; 13%) and metabolic disease (4 cases; 10%). Post transplantation, there were 6 (16%) biliary complications, 12 (32%) vascular complications, 26 (68%) developed early onset infection, 13% had acute rejection and 2 graft failure. Out of the 38 transplants, 79% of them survive after 1 year, and 69.7% survive after 5 years. The common causes of mortality were sepsis and vascular complications. Conclusion: Despite limited resources, a successful paediatric liver transplant programme has been established in Hospital Selayang with good survival rate.

New possibilities for testing direct arterial liver perfusion after liver transplantation

The aim of the study was to show new promising possibilities of direct perfusion test for the transplanted liver.Materials and methods. We have performed 246 liver transplantations (1998–2020). Since 2015 arterial complications were detected in 24 (23%) patients after 105 transplantations complicated by liver hypoperfusion: splenic artery steal syndrome (n = 8), hepatic artery thrombosis (n = 7), combination of hepatic artery stenosis and steal syndrome (n = 6), hepatic artery stenosis (n = 3). Endovascular interventions were performed in these cases for revascularization. Direct perfusion test was performed in 8 patients.Results. The liver perfusion index increased from 0.27 (0.13–0.45) to 0.62 (0.33–0.89) after endovascular procedures. Sufficient perfusion was ≥0.65.Conclusion. Direct liver perfusion test makes possible to identify and objectify graft blood supply, timely and adequate correction, and reduces the risk of developing biliary ischemic complications.

ABO Incompatible Liver Transplantation in Children: A 20 Year Experience from Centres in the TransplantChild European Reference Network

An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of AB0i pediatric liver transplantations performed in European reference centers now belonging to the TransplantChild, European Reference Network (ERN). Data from medical records were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, selected post-transplant complications, and patient and graft survival. A total of 142 patients (pts) with transplants between 1986 and 2018 in 8 European transplant centers were included in the study. The indications for liver transplantation were: cholestatic diseases in 62 pts, acute liver failure in 42 pts, and other conditions in the remaining 38 pts. Sixty-six patients received grafts from living donors, and seventy-six received grafts from deceased donors. Both patient and graft survival were significantly affected by deceased donor type, urgent transplantation, and the development of vascular complications. In the multivariate analysis, vascular complications had a negative impact on patient and graft survival, while a longer time from the first AB0i LT in the study showed better results, suggesting an international learning experience. In conclusion, we believe that AB0i LT in children is now a safe procedure that may be adopted more readily in children.