Incidence of osteonecrosis after renal transplantation

The incidence of osteonecrosis was 24% in 248 patients who had received 262 kidney transplants 1971-1982. However, based only on patients at risk, i.e. alive with functioning transplants, the incidence at 1, 3 and 6 years was found to be 13, 27 and 36%; after six years no new cases were found. the relative increase in body-weight at 180 days was predictive as regards risk for osteonecrosis, while the cumulative dose of steroids was not. This suggests that individual sensitivity to steroids rather than the absolute cumulative dose is involved in the development of osteonecrosis

Fibrinolysis during liver transplantation is enhanced by using solvent/detergent virus-inactivated plasma (ESDEP)

After the introduction of solvent/detergent-treated plasma (ESDEP) in our hospital, an increased incidence of hyperfibrinolysis was observed (75% vs 29%; P = 0.005) compared with the use of fresh frozen plasma for liver transplantation. To clarify this increased incidence, intraoperative plasma samples of patients treated with fresh frozen plasma or ESDEP were analyzed in a retrospective observational study. During the anhepatic phase, plasma levels of D-dimer (6.58 vs 1.53 microg/mL; P = 0.02) and fibrinogen degradation products (60 vs 23 mg/L; P = 0.018) were significantly higher in patients treated with ESDEP. After reperfusion, differences increased to 23.5 vs 4.7 microg/mL (D-dimer, P = 0.002) and 161 vs 57 mg/L (fibrinogen degradation products, P = 0.001). The amount of plasma received per packed red blood cell concentrate, clotting tests, and levels of individual clotting factors did not show significant differences between the groups. alpha(2)-Antiplasmin levels, however, were significantly lower in patients receiving ESDEP during the anhepatic phase (0.37 vs 0.65 IU/mL; P < 0.001) and after reperfusion (0.27 vs 0.58 IU/mL; P = 0.001). Analysis of alpha(2)-antiplasmin levels in ESDEP alone showed a reduction to 0.28 IU/mL (normal >0.95 IU/mL) because of the solvent/detergent process. Therapeutic consequences for the use of ESDEP in orthotopic liver transplantation are discussed in view of an increased incidence of hyperfibrinolysis caused by reduced levels of alpha(2)-antiplasmin in the solvent/detergent-treated plasma. IMPLICATIONS: The use of solvent/detergent virus-inactivated plasma is of increasing importance in the prevention of human immunodeficiency virus and hepatitis C virus transmission. Since the use of this plasma during orthotopic liver transplantation has increased, the incidence of hyperfibrinolysis was observed. Clotting analysis of the patients revealed small alpha(2)-antiplasmin concentrations because of the solvent/detergent process

Quality of life in Dutch patients with primary biliary cholangitis:Discrepancies between patients’ perspectives and objective disease parameters

Aim: This study aims to assess the health-related quality of life (HRQoL) in a Dutch population of patients with primary biliary cholangitis (PBC) in relation to the prognosis and need for second line-therapy, based on both objective disease parameters and patients’ perspectives. Methods: In this cross-sectional multicenter study, HRQoL was assessed by using the Dutch PBC-40 according to objective clinical parameters and patients’ perspectives on treatment and prognosis. Results: In total, 178/269 (66%) patients responded; mean age 61.2 (SD 9.9) years and 165 (92.7%) women. The PBC-40 domain scores did not differ according to the GLOBE score response (p &gt; 0.05 for all) or according to the POISE criteria (p &gt; 0.05), except for the domain itch (p = 0.031). Patients who considered their survival to be impaired scored higher on all domains as compared to those expecting a normal prognosis (p &lt; 0.05). Similarly, PBC-40 domain scores were higher among patients who considered that they were in need of additional therapy compared to those who did not (p &lt; 0.05 for all, except for domain itch [p = 0.056]). However, 45/62 (72.6%) patients with a self-expected impaired prognosis had a GLOBE score indicative of a normal prognosis. Twenty-five of the 40 (62.5%) patients who believed they needed additional therapy were below POISE criteria. Conclusion: The HRQoL of patients with PBC was impaired in terms of nonfavorable disease status according to the expectations of patients, but not according to objective disease parameters. Substantial discrepancies between patients’ perspectives and objective parameters were observed, which highlights the need for better patient guidance among patient with PBC.</p

Infections after auxiliary partial liver transplantation. Experiences in the first ten patients

Summary In ten auxiliary partial liver transplant recipients selective bowel decontamination (SBD) was used to reduce infections due to gram-negative microorganisms and fungi. During SBD no gram-negative infections occurred. Candida peritonitis was observed in one patient. After discontinuation of SBD serious infections of gram-negative origin did occur and three fungal infections were seen. SBD seems to have a favourable effect in reducing infections by gram-negative microorganisms and fungi. Most striking was the number of enterococcal infections that occurred. Five out of ten patients developed enterococcal infections which in two cases contributed to a fatal outcome. These infections occurred after increase of the number of enterococci in faeces and concomitant positive cultures of bile, ascites or wound drains. This increase could be due to the use of SBD. Also, the kind of biliary anastomosis may play an important role in the relatively high incidence of enterococcal infections. In the postoperative period, recurrence of hepatitis B infection in the liver graft was observed in all patients with cirrhosis due to this virus. Problems caused by other viral infections or protozoal infections remained limited in these ten patients. Zusammenfassung Bei Patienten, bei denen eine auxiliäre, partielle Lebertransplantation durchgeführt wurde, wurde die selektive Darmdekontamination (SBD) eingesetzt, um Infektionen durch gramnegative Mikroorganismen und Pilze zu vermindern. Während SBD traten keine Infektionen durch gramnegative Bakterien auf. Bei einem Patienten wurde eine Candida-Peritonitis beobachtet. Nach Beendigung der SBD kam es zu schweren Infektionen durch gramnegative Bakterien, außerdem zu drei Pilzinfektionen. SBD hat offensichtlich einen günstigen Einfluß im Hinblick auf eine Verminderung von Infektionen durch gramnegative Erreger und Pilze. Bemerkenswert hoch war die Zahl der aufgetretenen Enterokokkeninfektionen. Bei fünf der zehn Patienten traten Enterokokkeninfektionen auf, die in zwei Fällen den letalen Ausgang mitbestimmten. Diesen Infektionen gingen ein Anstieg der Enterokokkenzahlen im Stuhl und zugleich positive Kulturen in Galle, Aszites und Wunddrainagen voraus. Es ist möglich, daß die SBD die Zunahme von Enterokokkeninfektionen begünstigte. Auch die Art der Gallengangsanastomose kann hierzu wesentlich beigetragen haben. Bei allen Patienten, bei denen die Zirrhose durch Hepatitis B Virus verursacht war, kam es postoperativ zu einem Rezidiv durch dieses Virus im Lebertransplantat. Probleme durch andere virale oder Protozoeninfektionen hielten sich bei diesen zehn Patienten in Grenzen

Randomized Trial of Ciclosporin with 2-h Monitoring vs. Tacrolimus with Trough Monitoring in Liver Transplantation:DELTA Study

Background and Aims: Previous trials comparing cyclosporine and tacrolimus after liver transplantation (LT) showed conflicting results. Most used trough monitoring for cyclosporine (C0), leading to less accurate dosing than with 2-h monitoring (C2). Only one larger trial compared C2 with tacrolimus based on trough level (T0) after LT, with similar treated biopsy-proven acute rejection (tBPAR) and graft loss, while a smaller trial had less tBPAR with C2 compared to T0. Therefore, it is still unclear which calcineurin inhibitor is preferred after LT. We aimed to demonstrate superior efficacy (tBPAR), tolerability, and safety of C2 or T0 after first LT. Methods: Patients after first LT were randomized to C2 or T0. tBPAR, patient-and graft survival, safety and tolerability were the main endpoints, with analysis by Fisher test, Kaplan–Meier survival analysis and log-rank test. Results: In intention-to treat analysis 84 patients on C2 and 85 on T0 were included. Cumulative incidence of tBPAR C2 vs. T0 was 17.7% vs. 8.4% at 3 months (p=0.104), and 21.9% vs. 9.7% at 6 and 12 months (p=0.049). One-year cumulative mortality C2 vs. T0 was 15.5% vs. 5.9% (p=0.049) and graft loss 23.8% vs. 9.4% (p=0.015). Serum triglyceride and LDL-cholesterol was lower with T0 than with C2. Incidence of diarrhea in T0 vs, C2 was 64% vs. 31% (p≤0.001), with no other differences in safety and tolerability. Conclusions: In the first year after LT immunosuppression with T0 leads to less tBPAR and better patient-/re-transplant-free survival as compared to C2.</p

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

Characterization of Antigen-Presenting Cell Subsets in Human Liver-Draining Lymph Nodes

T-cell immunity in the liver is tightly regulated to prevent chronic liver inflammation in response to antigens and toxins derived from food and intestinal bacterial flora. Since the main sites of T cell activation in response to foreign components entering solid tissues are the draining lymph nodes (LN), we aimed to study whether Antigen-Presenting Cell (APC) subsets in human liver lymph-draining LN show features that may contribute to the immunologically tolerant liver environment. Healthy liver LN, iliac LN, spleen and liver perfusates were obtained from multi-organ donors, while diseased liver LN were collected from explanted patient livers. Inguinal LN were obtained from kidney transplant recipients. Mononuclear cells were isolated from fresh tissues, and immunophenotypic and functional characteristics of APC subsets were studied using flowcytometry and in ex vivo cultures. Healthy liver-draining LN contained significantly lower relative numbers of CD1c+ conventional dendritic cells (cDC2), plasmacytoid DC (PDC), and CD14+CD163+DC-SIGN+ macrophages (MF) compared to inguinal LN. Compared to spleen, both types of LN contained low relative numbers of CD141hi cDC1. Both cDC subsets in liver LN showed a more activated/mature immunophenotype than those in inguinal LN, iliacal LN, spleen and liver tissue. Despite their more mature status, cDC2 isolated from hepatic LN displayed similar cytokine production capacity (IL-10, IL-12, and IL-6) and allogeneic T cell stimulatory capacity as their counterparts from spleen. Liver LN from patients with inflammatory liver diseases showe

Characterization of Antigen-Presenting Cell Subsets in Human Liver-Draining Lymph Nodes

T-cell immunity in the liver is tightly regulated to prevent chronic liver inflammation in response to antigens and toxins derived from food and intestinal bacterial flora. Since the main sites of T cell activation in response to foreign components entering solid tissues are the draining lymph nodes (LN), we aimed to study whether Antigen-Presenting Cell (APC) subsets in human liver lymph-draining LN show features that may contribute to the immunologically tolerant liver environment. Healthy liver LN, iliac LN, spleen and liver perfusates were obtained from multi-organ donors, while diseased liver LN were collected from explanted patient livers. Inguinal LN were obtained from kidney transplant recipients. Mononuclear cells were isolated from fresh tissues, and immunophenotypic and functional characteristics of APC subsets were studied using flowcytometry and in ex vivo cultures. Healthy liver-draining LN contained significantly lower relative numbers of CD1c+ conventional dendritic cells (cDC2), plasmacytoid DC (PDC), and CD14+CD163+DC-SIGN+ macrophages (MF) compared to inguinal LN. Compared to spleen, both types of LN contained low relative numbers of CD141hi cDC1. Both cDC subsets in liver LN showed a more activated/mature immunophenotype than those in inguinal LN, iliacal LN, spleen and liver tissue. Despite their more mature status, cDC2 isolated from hepatic LN displayed similar cytokine production capacity (IL-10, IL-12, and IL-6) and allogeneic T cell stimulatory capacity as their counterparts from spleen. Liver LN from patients with inflammatory liver diseases showed a further reduction of cDC1, but had increased relative numbers of PDC and MF. In steady state conditions human liver LN contain relatively low numbers of cDC2, PDC, and macrophages, and relative numbers of cDC1 in liver LN decline during liver inflammation. The paucity of cDC in liver LN may contribute to immune tolerance in the liver environment