Screening for abnormal glycosylation in a cohort of adult liver disease patients

Congenital Disorders of Glycosylation (CDG) are a rapidly expanding group of rare genetic defects in glycosylation. In a novel CDG subgroup of Vacuolar-ATPase assembly defects various degrees of hepatic injury have been described, including end stage liver disease. However, the CDG diagnostic workflow can be complex as liver disease per se may be associated with abnormal glycosylation. Therefore, we collected serum samples of patients with a wide range of liver pathology to study the performance and yield of two CDG screening methods. Our aim was to identify glycosylation patterns that could help to differentiate between primary and secondary glycosylation defects in liver disease. To this end, we analyzed serum samples of 1042 adult liver disease patients. This cohort consisted of 567 liver transplant candidates and 475 chronic liver disease patients. Our workflow consisted of screening for abnormal glycosylation by transferrin isoelectric focusing (tIEF), followed by in-depth analysis of the abnormal samples with quadruple time-of-flight mass spectrometry (QTOF-MS). Screening with tIEF resulted in identification of 247 (26%) abnormal samples. QTOF-MS analysis of 110 of those did not reveal glycosylation abnormalities comparable with those seen in V-ATPase assembly factor deficiencies. However, two patients presented with isolated sialylation deficiency. Fucosylation was significantly increased in liver transplant candidates compared to healthy controls and patients with chronic liver disease. In conclusion, a significant percentage of patients with liver disease presented with abnormal CDG screening results, however, not indicative for a V-ATPase assembly factor defect. Advanced glycoanalytical techniques assist in the dissection of secondary and primary glycosylation defects. This article is protected by copyright. All rights reserved

Selected liver grafts from donation after circulatory death can be safely used for retransplantation – a multicenter retrospective study

Due to the growing number of liver transplantations (LTs), there is an increasing number of patients requiring retransplantation (reLT). Data on the use of grafts from extended criteria donors (ECD), especially donation after circulatory death (DCD), for reLT are lacking. We aimed to assess the outcome of patients undergoing reLT using a DCD graft in the Netherlands between 2001 and July 2018. Propensity score matching was used to match each DCD-reLT with three DBD-reLT cases. Primary outcomes were patient and graft survival. Secondary outcome was the incidence of biliary complications, especially nonanastomotic strictures (NAS). 21 DCD-reLT were compared with 63 matched DBD-reLTs. Donors in the DCD-reLT group had a significantly lower BMI (22.4 vs. 24.7 kg/m2, P-value = 0.02). Comparison of recipient demographics and ischemia times yielded no significant differences. Patient and graft survival rates were comparable between the two groups. However, the occurrence of nonanastomotic strictures after DCD-reLT was significantly higher (38.1% vs. 12.7%, P-value = 0.02). ReLT with DCD grafts does not result in inferior patient and graft survival compared with DBD grafts in selected patients. Therefore, DCD liver grafts should not routinely be declined for patients awaiting reLT

Donor hepatectomy time influences ischemia-reperfusion injury of the biliary tree in donation after circulatory death liver transplantation

Background: Donor hepatectomy time is associated with graft survival after liver transplantation. The aim of this study was to identify the impact of donor hepatectomy time on biliary injury during donation after circulatory death liver transplantation. Methods: First, bile duct biopsies of livers included in (pre)clinical machine perfusion research were analyzed. Secondly, of the same livers, bile samples were collected during normothermic machine perfusion. Lastly, a nationwide retrospective cohort study was performed including 273 adult patients undergoing donation after circulatory death liver transplantation between January 1, 2002 and January 1, 2017. Primary endpoint was development of non-anastomotic biliary strictures within 2 years of donation after circulatory death liver transplantation. Cox proportiona

Donor diabetes mellitus is a risk factor for diminished outcome after liver transplantation: a nationwide retrospective cohort study

With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post-transplant outcomes. From a national cohort of adult liver transplant recipients (1996–2016), all recipients transplanted with a liver from a DM donor (n = 69) were matched 1:2 with recipients of livers from non-DM donors (n = 138). The primary end-point included early post-transplant outcome, such as the incidence of primary nonfunction (PNF), hepatic artery thrombosis (HAT), and 90-day graft survival. Cox regression analy

Infusion of DDAVP does not improve primary hemostasis in patients with cirrhosis

Background & Aims: Cirrhosis frequently affects multiple components of hemostasis. Reversal of the coagulopathy of these patients is frequently required in case of bleeding episodes, or as prophylaxis before invasive procedures. Although 1-deamino-8-D-arginine vasopressin (DDAVP) is widely used as a pro-hemostatic agent in patients with cirrhosis, it is unclear whether DDAVP truly enhances hemostasis in these patients. Here we investigated the hemostatic effects of a single bolus of DDAVP in patients with cirrhosis. Methods: Ten patients with cirrhosis (child B or C) and ten patients with mild haemophilia A received an intravenous single bolus of 0.3 microgram/kg DDAVP. Plasma was collected prior to and at 1, 3, 6, and 24 h after DDAVP administration. Levels of Von Willebrand factor (VWF), VWF propeptide, factor VIII (FVIII), and ADAMTS13 were measured in all plasma samples, whereas VWF multimers and functional VWF-dependent platelet adhesion were determined in the samples pre- and 1 h after DDAVP administration. Results: Following DDAVP administration, VWF, FVIII, and VWF propeptide levels increased in patients with haemophilia, while patients with cirrhosis only showed an increase in VWF propeptide and FVIII levels. High molecular weight VWF multimers and VWF-dependent platelet adhesion increased in patients with haemophilia one hour after DDAVP administration, but did not change in the patients with cirrhosis. Levels of ADAMTS13 were unaffected in both patient groups after DDAVP. Conclusion: The lack of relevant effects of DDAVP on laboratory indices of primary hemostasis in patients with cirrhosis is in line with previous clinical study results in these patients