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Article ; Online: Vulnerabilities in kidney transplant recipients with COVID-19: a single center experience.

Meziyerh, Soufian / van der Helm, Danny / de Vries, Aiko P J

Transplant international : official journal of the European Society for Organ Transplantation

2020 Volume 33, Issue 11, Page(s) 1557–1561

MeSH term(s)	Adult ; Aged ; COVID-19/etiology ; COVID-19/mortality ; COVID-19/therapy ; Case-Control Studies ; Female ; Humans ; Kidney Failure, Chronic/mortality ; Kidney Failure, Chronic/surgery ; Kidney Transplantation ; Male ; Middle Aged ; Postoperative Complications/mortality ; Postoperative Complications/therapy ; Risk Factors ; Survival Analysis ; United States/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-08-26
Publishing country	Switzerland
Document type	Letter
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.1111/tri.13714
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Article ; Online: Tacrolimus and Mycophenolic Acid Exposure Are Associated with Biopsy-Proven Acute Rejection: A Study to Provide Evidence for Longer-Term Target Ranges.

Meziyerh, Soufian / van Gelder, Teun / Kers, Jesper / van der Helm, Danny / van der Boog, Paul J M / de Fijter, Johan W / Moes, Dirk Jan A R / de Vries, Aiko P J

Clinical pharmacology and therapeutics

2023 Volume 114, Issue 1, Page(s) 192–200

Abstract: Evidence to define target ranges for tacrolimus (Tac) and mycophenolic acid (MPA) exposure after the first year of kidney transplantation is limited. We investigated the association of measurements at 1 year and repeated measurements of real-world Tac- ... ...

Abstract	Evidence to define target ranges for tacrolimus (Tac) and mycophenolic acid (MPA) exposure after the first year of kidney transplantation is limited. We investigated the association of measurements at 1 year and repeated measurements of real-world Tac-trough levels (C
MeSH term(s)	Humans ; Tacrolimus/adverse effects ; Mycophenolic Acid/adverse effects ; Immunosuppressive Agents/adverse effects ; Kidney Transplantation/adverse effects ; Graft Rejection/prevention & control
Chemical Substances	Tacrolimus (WM0HAQ4WNM) ; Mycophenolic Acid (HU9DX48N0T) ; Immunosuppressive Agents
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2915
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Article ; Online: Primary sclerosing cholangitis and other risk factors for post-transplant lymphoproliferative disease after liver transplantation in adults.

Ruijter, Bastian N / Tushuizen, Maarten E / van der Helm, Danny / Hew, Mitchel / Reeven, Marjolein / Vossen, Ann C T M / Metselaar, Herold J / Alwayn, Ian P J / Dubbeld, Jeroen / Polak, Wojciech G / van Hoek, Bart

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

2023

Abstract: Post-transplant lymphoproliferative disease (PTLD) is a rare but serious complication of liver transplantation (LT) with morbidity and mortality. The risk factors for PTLD in adults are ill-defined. This study aimed to assess the risk factors for PTLD ... ...

Abstract	Post-transplant lymphoproliferative disease (PTLD) is a rare but serious complication of liver transplantation (LT) with morbidity and mortality. The risk factors for PTLD in adults are ill-defined. This study aimed to assess the risk factors for PTLD after LT in adults. All adult LT recipients between 1986 and 2016 from 2 centers in the Netherlands were included, with follow-up until 2020. PTLD was diagnosed according to the World Health Organization (WHO) classification. Potential risk factors for PTLD were assessed using multivariate Cox regression analysis. A total of 1281 patients were included, of whom 29 (2.3%) developed PTLD. Results show that independent risk factors for PTLD after LT in adults were no Epstein-Barr virus load monitoring strategy, primary sclerosing cholangitis as an indication for LT, era (historic era linked to more intense long-term immunosuppression), and Epstein-Barr virus-seronegative recipient. No other independent risk factors were identified in this study. Of the 207 patients with primary sclerosing cholangitis as an indication for LT, 13 (6.3%) developed PTLD versus 16 out of 1074 (1.5%) patients with other underlying liver diseases (log-rank p <0.001). The yearly PTLD incidence was higher in the first year than in the later years after LT (2.4%/y vs. 0.6%/y) for primary sclerosing cholangitis, but not for other indications (0.16%/y). In Epstein-Barr virus-seronegative recipients PTLD occurred earlier after LT, while in 97% of seropositive recipients it could occur very late after LT.
Language	English
Publishing date	2023-09-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2006866-9
ISSN	1527-6473 ; 1527-6465
ISSN (online)	1527-6473
ISSN	1527-6465
DOI	10.1097/LVT.0000000000000256
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Zs.A 4702: Show issues

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Article ; Online: Epstein-Barr Viral Load Monitoring Strategy and the Risk for Posttransplant Lymphoproliferative Disease in Adult Liver Transplantation : A Cohort Study.

Ruijter, Bastian N / Wolterbeek, Ron / Hew, Mitchell / van Reeven, Marjolein / van der Helm, Danny / Dubbeld, Jeroen / Tushuizen, Maarten E / Metselaar, Herold / Vossen, Ann C T M / van Hoek, Bart

Annals of internal medicine

2023 Volume 176, Issue 2, Page(s) 174–181

Abstract: Background: Primary infection with or reactivation of Epstein-Barr virus (EBV) can occur after liver transplant (LT) and can lead to posttransplant lymphoproliferative disease (PTLD). In pediatric LT, an EBV-DNA viral load (EBV VL) monitoring strategy, ... ...

Abstract	Background: Primary infection with or reactivation of Epstein-Barr virus (EBV) can occur after liver transplant (LT) and can lead to posttransplant lymphoproliferative disease (PTLD). In pediatric LT, an EBV-DNA viral load (EBV VL) monitoring strategy, including the reduction of immunosuppression, has led to a lower incidence of PTLD. For adult LT recipients with less primary infection and more EBV reactivation, it is unknown whether this strategy is effective. Objective: To examine the effect of an EBV VL monitoring strategy on the incidence of PTLD after LT in adults. Design: Cohort study. Setting: Two university medical centers in the Netherlands. Patients: Adult recipients of first LT in Leiden between September 2003 and January 2017 with an EBV VL monitoring strategy formed the monitoring group (M1), recipients of first LT in Rotterdam between January 2003 and January 2017 without such a strategy formed the contemporary control group (C1), and those who had transplants in Leiden between September 1992 and September 2003 or Rotterdam between 1986 and January 2003 formed the historical control groups (M0 and C0, respectively). Measurements: Influence of EBV VL monitoring on incidence of PTLD. Results: After inverse probability of treatment weighting of the 4 groups to achieve a balance among the groups for important patient characteristics, differences within hospitals between the historical and recent era in cumulative incidences-expressed as the number of events per 1000 patients measured at 5-, 10-, and 15-year follow-up-showed fewer events in the contemporary era in both centers. This difference was considerably larger in the monitoring center, whereas the 95% CI included the null value of 0 for point estimates. Limitation: Retrospective, low statistical power, and incompletely balanced groups, and non-EBV PTLD cannot be prevented. Conclusion: Monitoring EBV VL may reduce PTLD incidence after LT in adults; larger studies are warranted. Primary funding source: None.
MeSH term(s)	Humans ; Child ; Adult ; Herpesvirus 4, Human/genetics ; Epstein-Barr Virus Infections/epidemiology ; Cohort Studies ; Liver Transplantation/adverse effects ; Retrospective Studies ; Viral Load ; Lymphoproliferative Disorders/epidemiology ; Lymphoproliferative Disorders/etiology ; Lymphoproliferative Disorders/prevention & control ; DNA, Viral
Chemical Substances	DNA, Viral
Language	English
Publishing date	2023-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M22-0364
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Article ; Online: Mycophenolic Acid Exposure Determines Antibody Formation Following SARS-CoV-2 Vaccination in Kidney Transplant Recipients: A Nested Cohort Study.

Meziyerh, Soufian / Bouwmans, Pim / van Gelder, Teun / van der Helm, Danny / Messchendorp, Lianne / van der Boog, Paul J M / de Fijter, Johan W / Moes, Dirk Jan A R / de Vries, Aiko P J

Clinical pharmacology and therapeutics

2023 Volume 114, Issue 1, Page(s) 118–126

Abstract: Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID-19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been ... ...

Abstract	Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID-19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure-response relationship between mycophenolic acid 12-hour area under the curve (AUC
MeSH term(s)	Humans ; Antibodies ; Antibody Formation ; Cohort Studies ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Kidney Transplantation/adverse effects ; Mycophenolic Acid/adverse effects ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies ; COVID-19 Vaccines ; Mycophenolic Acid (HU9DX48N0T)
Language	English
Publishing date	2023-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2872
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Article: Vulnerabilities in kidney transplant recipients with COVID-19: a single center experience

Meziyerh, Soufian / van der Helm, Danny / de Vries, Aiko P J

Transplant. int

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #696274
Database	COVID19

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

Ruijter, Bastian N / Inderson, Akin / van den Berg, Aad P / Metselaar, Herold J / Dubbeld, Jeroen / Tushuizen, Maarten E / Porte, Robert J / Polak, Wojciech / van der Helm, Danny / van Reeven, Marjolein / Rodriguez-Girondo, Mar / van Hoek, Bart

Journal of clinical and translational hepatology

2023 Volume 11, Issue 4, Page(s) 839–849

Abstract: 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). ... ...

Abstract	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 ( 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.
Language	English
Publishing date	2023-03-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019822-7
ISSN	2310-8819 ; 2225-0719
ISSN (online)	2310-8819
ISSN	2225-0719
DOI	10.14218/JCTH.2022.00348
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Article ; Online: Oncofetal Protein CRIPTO Is Involved in Wound Healing and Fibrogenesis in the Regenerating Liver and Is Associated with the Initial Stages of Cardiac Fibrosis.

Karkampouna, Sofia / van der Helm, Danny / Scarpa, Mario / van Hoek, Bart / Verspaget, Hein W / Goumans, Marie-Jose / Coenraad, Minneke J / Kruithof, Boudewijn P T / Kruithof-de Julio, Marianna

Cells

2021 Volume 10, Issue 12

Abstract: Oncofetal protein, CRIPTO, is silenced during homeostatic postnatal life and often re-expressed in different neoplastic processes, such as hepatocellular carcinoma. Given the reactivation of CRIPTO in pathological conditions reported in various adult ... ...

Abstract	Oncofetal protein, CRIPTO, is silenced during homeostatic postnatal life and often re-expressed in different neoplastic processes, such as hepatocellular carcinoma. Given the reactivation of CRIPTO in pathological conditions reported in various adult tissues, the aim of this study was to explore whether CRIPTO is expressed during liver fibrogenesis and whether this is related to the disease severity and pathogenesis of fibrogenesis. Furthermore, we aimed to identify the impact of CRIPTO expression on fibrogenesis in organs with high versus low regenerative capacity, represented by murine liver fibrogenesis and adult murine heart fibrogenesis. Circulating CRIPTO levels were measured in plasma samples of patients with cirrhosis registered at the waitlist for liver transplantation (LT) and 1 year after LT. The expression of CRIPTO and fibrotic markers (αSMA, collagen type I) was determined in human liver tissues of patients with cirrhosis (on a basis of viral hepatitis or alcoholic disease), in cardiac tissue samples of patients with end-stage heart failure, and in mice with experimental liver and heart fibrosis using immuno-histochemical stainings and qPCR. Mouse models with experimental chronic liver fibrosis, induced with multiple shots of carbon tetrachloride (CCl
MeSH term(s)	Adenoviridae/metabolism ; Animals ; Cell Proliferation ; Collagen/metabolism ; Disease Models, Animal ; End Stage Liver Disease/metabolism ; Epidermal Growth Factor/metabolism ; Fibrosis ; GPI-Linked Proteins/metabolism ; Hepatocytes/metabolism ; Hepatocytes/pathology ; Intercellular Signaling Peptides and Proteins/metabolism ; Ligands ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Liver Regeneration ; Male ; Membrane Glycoproteins/metabolism ; Mice, Inbred C57BL ; Myocardium/metabolism ; Myocardium/pathology ; Neoplasm Proteins/metabolism ; Up-Regulation ; Wound Healing ; Mice
Chemical Substances	GPI-Linked Proteins ; Intercellular Signaling Peptides and Proteins ; Ligands ; Membrane Glycoproteins ; Neoplasm Proteins ; TDGF1 protein, human ; Tdgf1 protein, mouse ; Epidermal Growth Factor (62229-50-9) ; Collagen (9007-34-5)
Language	English
Publishing date	2021-11-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10123325
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Article ; Online: Selected liver grafts from donation after circulatory death can be safely used for retransplantation - a multicenter retrospective study.

van Reeven, Marjolein / van Leeuwen, Otto B / van der Helm, Danny / Darwish Murad, Sarwa / van den Berg, Aad P / van Hoek, Bart / Alwayn, Ian P J / Polak, Wojciech G / Porte, Robert J

Transplant international : official journal of the European Society for Organ Transplantation

2020 Volume 33, Issue 6, Page(s) 667–674

Abstract: 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 ...

Abstract	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/m
MeSH term(s)	Brain Death ; Death ; Graft Survival ; Humans ; Liver ; Netherlands ; Reoperation ; Retrospective Studies ; Tissue Donors ; Tissue and Organ Procurement
Language	English
Publishing date	2020-03-09
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.1111/tri.13596
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Article ; Online: Local but not systemic administration of mesenchymal stromal cells ameliorates fibrogenesis in regenerating livers.

van der Helm, Danny / Barnhoorn, Marieke C / de Jonge-Muller, Eveline S M / Molendijk, Ilse / Hawinkels, Luuk J A C / Coenraad, Minneke J / van Hoek, Bart / Verspaget, Hein W

Journal of cellular and molecular medicine

2019 Volume 23, Issue 9, Page(s) 6238–6250

Abstract: Chronic liver injury leads to the accumulation of myofibroblasts resulting in increased collagen deposition and hepatic fibrogenesis. Treatments specifically targeting fibrogenesis are not yet available. Mesenchymal stromal cells (MSCs) are fibroblast- ... ...

Abstract	Chronic liver injury leads to the accumulation of myofibroblasts resulting in increased collagen deposition and hepatic fibrogenesis. Treatments specifically targeting fibrogenesis are not yet available. Mesenchymal stromal cells (MSCs) are fibroblast-like stromal (stem) cells, which stimulate tissue regeneration and modulate immune responses. In the present study we assessed whether liver fibrosis and cirrhosis can be reversed by treatment with MSCs or fibroblasts concomitant to partial hepatectomy (pHx)-induced liver regeneration. After carbon tetrachloride-induced fibrosis and cirrhosis, mice underwent a pHx and received either systemically or locally MSCs in one of the two remaining fibrotic/cirrhotic liver lobes. Eight days after treatment, liver fibrogenesis was evaluated by Sirius-red staining for collagen deposition. A significant reduction of collagen content in the locally treated lobes of the regenerated fibrotic and cirrhotic livers was observed in mice that received high dose MSCs. In the non-MSC-treated counterpart liver lobes no changes in collagen deposition were observed. Local fibroblast administration or intravenous administration of MSCs did not ameliorate fibrosis. To conclude, local administration of MSCs after pHx, in contrast to fibroblasts, results in a dose-dependent on-site reduction of collagen deposition in mouse models for liver fibrosis and cirrhosis.
MeSH term(s)	Animals ; Carbon Tetrachloride/toxicity ; Collagen/metabolism ; Disease Models, Animal ; Fibroblasts/transplantation ; Fibrosis/chemically induced ; Fibrosis/genetics ; Fibrosis/pathology ; Fibrosis/therapy ; Hepatic Stellate Cells/transplantation ; Humans ; Liver/growth & development ; Liver/pathology ; Liver Cirrhosis/chemically induced ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Liver Cirrhosis/therapy ; Liver Regeneration/genetics ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Mice
Chemical Substances	Collagen (9007-34-5) ; Carbon Tetrachloride (CL2T97X0V0)
Language	English
Publishing date	2019-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.14508
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