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2. Increased Mortality Among Patients With vs Without Cirrhosis and Autoimmune Hepatitis

Author

Schreuder, T.C.M.A., van der Wouden, E.J., van Meyel, J.J.M., Baak, L.C., Stadhouders, P.H.G.M., Klemt-Kropp, M., Verhagen, M.A.M.T., Bhalla, A., Kuijvenhoven, J.Ph., van den Brand, Floris F., van der Veen, Koen S., de Boer, Ynto S., van Gerven, Nicole M., Lissenberg-Witte, Birgit I., Beuers, Ulrich, van Erpecum, Karel J., van Buuren, Henk R., den Ouden, Jannie W., Brouwer, Johannus T., Vrolijk, Jan M., Verdonk, Robert C., van Hoek, Bart, Koek, Ger H., Drenth, Joost P.H., Guichelaar, Marleen M.J., Mulder, Chris J.J., Bloemena, Elisabeth, van Nieuwkerk, Carin M.J., and Bouma, Gerd

Published
2019
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3. Farnesoid X receptor (FXR) activation and FXR genetic variation in inflammatory bowel disease.

Author

Nijmeijer, Rian M, Gadaleta, Raffaella M, van Mil, Saskia WC, van Bodegraven, Adriaan A, Crusius, J Bart A, Dijkstra, Gerard, Hommes, Daan W, de Jong, Dirk J, Stokkers, Pieter CF, Verspaget, Hein W, Weersma, Rinse K, van der Woude, C Janneke, Stapelbroek, Janneke M, Schipper, Marguerite EI, Wijmenga, Cisca, van Erpecum, Karel J, Oldenburg, Bas, and Dutch Initiative on Crohn, Colitis (ICC)

Subjects
Dutch Initiative on Crohn, Colitis, Colon, Ileum, Humans, Colitis, Ulcerative, Inflammatory Bowel Diseases, Receptors, Cytoplasmic and Nuclear, RNA, Messenger, Case-Control Studies, Gene Expression, Polymorphism, Single Nucleotide, Female, Male, Genetic Variation, General Science & Technology
Abstract

BackgroundWe previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD.MethodsmRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls.ResultsmRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD.ConclusionsFXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients.

Published
2011

5. Disease burden in primary sclerosing cholangitis in the Netherlands:A long-term follow-up study

Author

van Munster, Kim N., Mol, Bregje, Goet, Jorn C., van Munster, Sanne N., Weersma, Rinse K., de Vries, Annemarie C., van der Meer, Adriaan J., Inderson, Akin, Drenth, Joost P., van Erpecum, Karel J., Boonstra, Kirsten, Beuers, Ulrich, Dijkgraaf, Marcel G.W., Ponsioen, Cyriel Y., van Munster, Kim N., Mol, Bregje, Goet, Jorn C., van Munster, Sanne N., Weersma, Rinse K., de Vries, Annemarie C., van der Meer, Adriaan J., Inderson, Akin, Drenth, Joost P., van Erpecum, Karel J., Boonstra, Kirsten, Beuers, Ulrich, Dijkgraaf, Marcel G.W., and Ponsioen, Cyriel Y.

Abstract

Background & Aims: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill-described. The aim of this study was to assess long-term disease burden in a large population-based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss. Methods: All PSC patients living in a geographically defined area covering ~50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time. Results: A total of 1208 patients were included with a median follow-up of 11.2 year. Median liver transplant-free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were €12 169 and mean work productivity loss was 25%. Conclusions: Our data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time.

Published
2023

6. Systematic review with meta-analysis: branched-chain amino acid supplementation in liver disease

Author

Afdeling Dietetiek, Cancer, Epi Kanker Team C, MS Hoofd-Hals Chirurgische Oncologie, VS-DIGD, MS MDL 1, Infection & Immunity, van Dijk, Anne M, Bruins Slot, Alexandra S, Portincasa, Piero, Siegerink, Sebastiaan N, Chargi, Najiba, Verstraete, Carina J R, Bruijne, Joep de, Vleggaar, Frank P, van Erpecum, Karel J, Afdeling Dietetiek, Cancer, Epi Kanker Team C, MS Hoofd-Hals Chirurgische Oncologie, VS-DIGD, MS MDL 1, Infection & Immunity, van Dijk, Anne M, Bruins Slot, Alexandra S, Portincasa, Piero, Siegerink, Sebastiaan N, Chargi, Najiba, Verstraete, Carina J R, Bruijne, Joep de, Vleggaar, Frank P, and van Erpecum, Karel J

Published
2023

7. Liver-related complications before and after successful treatment of chronic hepatitis C virus infection in people with inherited bleeding disorders

Author

Poli Van Creveldkliniek Medisch, MS MDL 1, Infection & Immunity, Cancer, Child Health, Circulatory Health, MS Interne Geneeskunde, Isfordink, Cas J., van Erpecum, Karel J., Fischer, Kathelijn, van der Valk, Paul R., van Vulpen, Lize F.D., Schutgens, Roger E.G., Arends, Joop E., Mauser-Bunschoten, Evelien P., Poli Van Creveldkliniek Medisch, MS MDL 1, Infection & Immunity, Cancer, Child Health, Circulatory Health, MS Interne Geneeskunde, Isfordink, Cas J., van Erpecum, Karel J., Fischer, Kathelijn, van der Valk, Paul R., van Vulpen, Lize F.D., Schutgens, Roger E.G., Arends, Joop E., and Mauser-Bunschoten, Evelien P.

Published
2023

8. Disease burden in primary sclerosing cholangitis in the Netherlands: A long-term follow-up study

Author

van Munster, Kim N., Mol, Bregje, Goet, Jorn C., van Munster, Sanne N., Weersma, Rinse K., de Vries, Annemarie C., van der Meer, Adriaan J., Inderson, Akin, Drenth, Joost P., van Erpecum, Karel J., Boonstra, Kirsten, Beuers, Ulrich, Dijkgraaf, Marcel G.W., Ponsioen, Cyriel Y., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Gastroenterology & Hepatology

Subjects
disease burden, QALY, SDG 3 - Good Health and Well-being, PSC, work productivity loss, survival, medical costs
Abstract

Background & Aims: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill-described. The aim of this study was to assess long-term disease burden in a large population-based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss. Methods: All PSC patients living in a geographically defined area covering ~50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time. Results: A total of 1208 patients were included with a median follow-up of 11.2 year. Median liver transplant-free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were €12 169 and mean work productivity loss was 25%. Conclusions: Our data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time.

Published
2023

9. Health-related quality of life in patients with primary sclerosing cholangitis

Author

Mol, Bregje, van Munster, Kim N., Bogaards, Johannes A., Weersma, Rinse K., Inderson, Akin, de Groof, E. Joline, Rossen, Noortje G.M., Ponsioen, Willemijn, Turkenburg, Maud, van Erpecum, Karel J., Poen, Alexander C., Spanier, B. W.Marcel, Beuers, Ulrich H.W., Ponsioen, Cyriel Y., Epidemiology and Data Science, AII - Infectious diseases, APH - Methodology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Gastroenterology and Hepatology, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Surgery, Tytgat Institute for Liver and Intestinal Research, CCA - Cancer Treatment and Quality of Life, and CCA - Cancer biology and immunology

Subjects
health-related quality of life, Hepatology, inflammatory bowel disease, post-transplant, primary sclerosing cholangitis, population-based cohort, repeated measurements
Abstract

Background & Aims: Data regarding health-related quality of life (HRQoL) in primary sclerosing cholangitis (PSC) are sparse and have only been studied cross-sectionally in a disease which runs a fluctuating and unpredictable course. We aim to describe HRQoL longitudinally by using repeated measurements in a population-based cohort. Methods: Every 3 months from May 2017 up to August 2020, patients received digital questionnaires at home. These included the EQ-5D, 5-D Itch, patient-based SCCAI and patient-based HBI. The SF-36, measuring HRQoL over eight dimensions as well as a physical component summary (PCS) and mental component summary (MCS) score, was sent annually. Data were compared with Dutch reference data and a matched IBD disease control from the population-based POBASIC cohort. Mixed-effects modelling was performed to identify factors associated with HRQoL. Results: Three hundred twenty-eight patients completed 2576 questionnaires. A significant reduction of small clinical relevance in several mean HRQoL scores was found compared with the Dutch reference population: 46.4 versus 48.0, p =.018 for PCS and 47.5 versus 50.5, p =.004 for MCS scores. HRQoL outcomes were significantly negatively associated with coexisting active IBD (PCS −12.2, p

Published
2023

10. Safety and Efficacy of166Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study

Author

Reinders, Margot T.M., primary, van Erpecum, Karel J., additional, Smits, Maarten L.J., additional, Braat, Arthur J.A.T., additional, Bruijne, Joep de, additional, Bruijnen, Rutger, additional, Sprengers, Dave, additional, Man, Robert A. de, additional, Vegt, Erik, additional, IJzermans, Jan N.M., additional, Moelker, Adriaan, additional, and Lam, Marnix G.E.H., additional

Published
2022
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11. Real-life data on the impact of successful downstaging in patients with hepatocellular carcinoma:A Dutch Multicenter Study

Author

Broekhoven, Annelotte G.C., Fiocco, Marta, Sprengers, Dave, Takkenberg, R. Bart, van Meer, Suzanne, van Erpecum, Karel J., Ramsoekh, Dewkoemar, Verspaget, Hein W., Burgmans, Mark C., Osanto, Susanne, Baranski, Andrzej G., van Hoek, Bart, Coenraad, Minneke J., Broekhoven, Annelotte G.C., Fiocco, Marta, Sprengers, Dave, Takkenberg, R. Bart, van Meer, Suzanne, van Erpecum, Karel J., Ramsoekh, Dewkoemar, Verspaget, Hein W., Burgmans, Mark C., Osanto, Susanne, Baranski, Andrzej G., van Hoek, Bart, and Coenraad, Minneke J.

Abstract

Patients with Barcelona Clinic Liver Cancer intermediate stage hepatocellular carcinoma (HCC) theoretically are an excellent group to consider downstaging using locoregional therapy (LRT) since they do not have extrahepatic spread or vascular invasion. Once successful, this can change the treatment strategy from palliative to curative intention. Although downstaging therapy is suggested in guidelines, it is still not widely accepted. Moreover, studies on downstaging are mainly performed in high-incidence HCC countries. Therefore, our aim was to gain insight in therapeutic strategies in patients with intermediate stage HCC and their impact on intention-to-treat survival in a real-life setting in a low-incidence HCC country. We retrospectively analyzed data from the national Dutch HCC registry. From this database, consisting of 1409 patients with a diagnosis of HCC between 2005-2013 in 5 Dutch tertiary referral centers, we identified 165 patients with intermediate stage HCC. Out of these patients, 63 (38%) were not offered LRT, whereas 102 (62%) did receive LRT. Subsequently, 50 (49%) of the 102 patients who received LRT were successfully downstaged. Eleven patients (22% of successfully downstaged patients) eventually underwent liver transplantation. Cox regression analysis showed that a lower MELD score, an AFP value <100 ng/ml, successful downstaging and liver transplantation (all ≤p = 0.01) were positively associated to overall survival. In conclusion, our results demonstrate that LRT is not routinely offered to intermediate stage HCC patients in the Netherlands. Nevertheless, we showed that patients with intermediate stage HCC who are successfully downstaged have a survival benefit compared to those who were not.

Published
2022

12. Safety and Efficacy of 166Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study

Author

Cancer, Researchgr. Nucleaire Geneeskunde, MS MDL 1, Infection & Immunity, MS Radiologie, Other research (not in main researchprogram), Reinders, Margot T.M., van Erpecum, Karel J., Smits, Maarten L.J., Braat, Arthur J.A.T., Bruijne, Joep de, Bruijnen, Rutger, Sprengers, Dave, Man, Robert A.de, Vegt, Erik, IJzermans, Jan N.M., Moelker, Adriaan, Lam, Marnix G.E.H., Cancer, Researchgr. Nucleaire Geneeskunde, MS MDL 1, Infection & Immunity, MS Radiologie, Other research (not in main researchprogram), Reinders, Margot T.M., van Erpecum, Karel J., Smits, Maarten L.J., Braat, Arthur J.A.T., Bruijne, Joep de, Bruijnen, Rutger, Sprengers, Dave, Man, Robert A.de, Vegt, Erik, IJzermans, Jan N.M., Moelker, Adriaan, and Lam, Marnix G.E.H.

Published
2022

13. Nutritional status in patients with hepatocellular carcinoma: Potential relevance for clinical outcome

Author

Afdeling Dietetiek, MS Hoofd-Hals Chirurgische Oncologie, VS-DIGD, MS MDL 1, Cancer, Infection & Immunity, van Dijk, Anne M, Coppens, Bart J P, van Beers, Maartje A, Bruins Slot, Alexandra S, Verstraete, Carina J R, de Bruijne, Joep, Vleggaar, Frank P, van Erpecum, Karel J, Afdeling Dietetiek, MS Hoofd-Hals Chirurgische Oncologie, VS-DIGD, MS MDL 1, Cancer, Infection & Immunity, van Dijk, Anne M, Coppens, Bart J P, van Beers, Maartje A, Bruins Slot, Alexandra S, Verstraete, Carina J R, de Bruijne, Joep, Vleggaar, Frank P, and van Erpecum, Karel J

Published
2022

15. Non-alcoholic fatty liver disease: identical etiologic factors in patients with type 1 and type 2 diabetes

Author

Endocrinologie, Unit Opleiding Aios, MS MDL 1, Infection & Immunity, Cancer, MS Interne Geneeskunde, Circulatory Health, Unit Opleiding MDL, de Vries, Marieke, El-Morabit, Fatima, van Erpecum, Karel J., Westerink, Jan, Bac, Simon T., Kaasjager, H. A.H.(Karin), de Valk, Harold W., Endocrinologie, Unit Opleiding Aios, MS MDL 1, Infection & Immunity, Cancer, MS Interne Geneeskunde, Circulatory Health, Unit Opleiding MDL, de Vries, Marieke, El-Morabit, Fatima, van Erpecum, Karel J., Westerink, Jan, Bac, Simon T., Kaasjager, H. A.H.(Karin), and de Valk, Harold W.

Published
2022

22. Should we continue surveillance for hepatocellular carcinoma and gastroesophageal varices in patients with cirrhosis and cured HCV infection?

Author

Isfordink, Cas J., Maan, Raoel, de Man, Robert A., van Erpecum, Karel J., van der Meer, Adriaan J., Isfordink, Cas J., Maan, Raoel, de Man, Robert A., van Erpecum, Karel J., and van der Meer, Adriaan J.

Abstract

Hepatocellular carcinoma (HCC) and variceal bleeding are among the most common causes of liver-related mortality in patients with hepatitis C virus (HCV)-induced cirrhosis. Current guidelines recommend HCC and gastroesophageal varices (GEV) surveillance in patients with HCV infection and cirrhosis. However, since the recent introduction of direct-acting antivirals, most patients with cirrhosis are now cured of their chronic HCV infection. As virological cure is considered to substantially reduce the risk of cirrhosis-related complications, this review discusses the current literature concerning the surveillance of HCC and GEV in patients with HCV-induced cirrhosis with a focus on the setting following sustained virological response.

Published
2021

24. Viral hepatitis in haemophilia: historical perspective and current management

Author

Poli Van Creveldkliniek Medisch, MS MDL 1, Infection & Immunity, Cancer, Isfordink, Cas J., van Erpecum, Karel J., van der Valk, Marc, Mauser-Bunschoten, Evelien P., Makris, Michael, Poli Van Creveldkliniek Medisch, MS MDL 1, Infection & Immunity, Cancer, Isfordink, Cas J., van Erpecum, Karel J., van der Valk, Marc, Mauser-Bunschoten, Evelien P., and Makris, Michael

Published
2021

28. Liver decompensation in HIV/Hepatitis B coinfection in the combination antiretroviral therapy era does not seem increased compared to hepatitis B mono-infection

Author

Lieveld, Faydra I., Smit, Colette, Richter, Clemens, van Erpecum, Karel J., Spanier, Bernhard W.M., Gisolf, Elisabeth H., Vrolijk, Jan M., Siersema, Peter D., Hoepelman, Andy I.M., Reiss, Peter, Arends, Joop E., Lieveld, Faydra I., Smit, Colette, Richter, Clemens, van Erpecum, Karel J., Spanier, Bernhard W.M., Gisolf, Elisabeth H., Vrolijk, Jan M., Siersema, Peter D., Hoepelman, Andy I.M., Reiss, Peter, and Arends, Joop E.

Published
2019

29. REtrieval And cure of Chronic Hepatitis C (REACH) : Results of micro-elimination in the Utrecht province

Author

Kracht, Patricia A.M., Arends, Joop E., van Erpecum, Karel J., Thijsen, Steven F.T., Vlaminckx, Bart J.M., Weersink, Annemarie J.L., Wensing, Anne M.J., Deege, Marjolein P.H., Dimmendaal, Marieke, Stadhouders, Paul H.G.M., Friederich, Philip W., Verhagen, Marc A.M.T., Boland, Greet J., Hoepelman, Andy I.M., Kracht, Patricia A.M., Arends, Joop E., van Erpecum, Karel J., Thijsen, Steven F.T., Vlaminckx, Bart J.M., Weersink, Annemarie J.L., Wensing, Anne M.J., Deege, Marjolein P.H., Dimmendaal, Marieke, Stadhouders, Paul H.G.M., Friederich, Philip W., Verhagen, Marc A.M.T., Boland, Greet J., and Hoepelman, Andy I.M.

Published
2019

31. Liver decompensation in HIV/Hepatitis B coinfection in the combination antiretroviral therapy era does not seem increased compared to hepatitis B mono-infection

Author

MS MDL 1, Cancer, MS Infectieziekten, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Lieveld, Faydra I., Smit, Colette, Richter, Clemens, van Erpecum, Karel J., Spanier, Bernhard W.M., Gisolf, Elisabeth H., Vrolijk, Jan M., Siersema, Peter D., Hoepelman, Andy I.M., Reiss, Peter, Arends, Joop E., MS MDL 1, Cancer, MS Infectieziekten, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Lieveld, Faydra I., Smit, Colette, Richter, Clemens, van Erpecum, Karel J., Spanier, Bernhard W.M., Gisolf, Elisabeth H., Vrolijk, Jan M., Siersema, Peter D., Hoepelman, Andy I.M., Reiss, Peter, and Arends, Joop E.

Published
2019

32. Adherence to ursodeoxycholic acid therapy in patients with cholestatic and autoimmune liver disease

Author

MS MDL 1, Onderzoek, MS Interne Geneeskunde, Infection & Immunity, Cancer, Leoni, Maria Cristina, Amelung, Linde, Lieveld, Faydra I., van den Brink, Janneke, de Bruijne, Joep, Arends, Joop E., van Erpecum, Carel Peter, van Erpecum, Karel J., MS MDL 1, Onderzoek, MS Interne Geneeskunde, Infection & Immunity, Cancer, Leoni, Maria Cristina, Amelung, Linde, Lieveld, Faydra I., van den Brink, Janneke, de Bruijne, Joep, Arends, Joop E., van Erpecum, Carel Peter, and van Erpecum, Karel J.

Published
2019

33. REtrieval And cure of Chronic Hepatitis C (REACH): Results of micro-elimination in the Utrecht province

Author

MS Infectieziekten, MS Interne Geneeskunde, Infection & Immunity, MS MDL 1, Cancer, MMB opleiding Arts microbioloog, MMB Medische Staf, MMB Staf diagnostiek, Circulatory Health, Kracht, Patricia A.M., Arends, Joop E., van Erpecum, Karel J., Thijsen, Steven F.T., Vlaminckx, Bart J.M., Weersink, Annemarie J.L., Wensing, Anne M.J., Deege, Marjolein P.H., Dimmendaal, Marieke, Stadhouders, Paul H.G.M., Friederich, Philip W., Verhagen, Marc A.M.T., Boland, Greet J., Hoepelman, Andy I.M., MS Infectieziekten, MS Interne Geneeskunde, Infection & Immunity, MS MDL 1, Cancer, MMB opleiding Arts microbioloog, MMB Medische Staf, MMB Staf diagnostiek, Circulatory Health, Kracht, Patricia A.M., Arends, Joop E., van Erpecum, Karel J., Thijsen, Steven F.T., Vlaminckx, Bart J.M., Weersink, Annemarie J.L., Wensing, Anne M.J., Deege, Marjolein P.H., Dimmendaal, Marieke, Stadhouders, Paul H.G.M., Friederich, Philip W., Verhagen, Marc A.M.T., Boland, Greet J., and Hoepelman, Andy I.M.

Published
2019

34. Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection

Author

Lieveld, Faydra I., Swaans, Niels, Newsum, Astrid M., Ho, Cynthia K. Y., Schinkel, Janke, Molenkamp, Richard, van der Meer, Jan T. M., Arends, Joop E., Hoepelman, Andy I. M., Wensing, Anne M. J., Siersema, Peter D., van Erpecum, Karel J., Boland, Greet J., Other departments, Medical Microbiology and Infection Prevention, and Infectious diseases

Subjects
Genotype 1a, RC581-951, Hepatitis C virus, Drug resistance, virus diseases, HIV, Specialties of internal medicine, Q80K
Abstract

Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection. Material and methods: HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. Results: 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p

Published
2016

36. Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial

Author

Seinstra Beatrijs A, Defreyne Luc, Lambert Bieke, Lam MarnixGEHH, Verkooijen Helena M, van Erpecum Karel J, van Hoek Bart, van Erkel Arian R, Coenraad Minneke J, Al Younis Imad, van Vlierberghe Hans, and van den Bosch MauriceAAJ

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (90Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. Methods/design In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease. Patients assigned to TACE will receive a maximum of three consecutive transarterial treatment sessions. Patients will undergo structural follow-up for a timeframe of two years post treatment. Post procedural magnetic resonance imaging (MRI) will be performed at one and three months post trial entry and at three-monthly intervals thereafter for two years to assess tumor response. Primary outcome will be time to progression. Secondary outcomes will be overall survival, tumor response according to the modified RECIST criteria, toxicities/adverse events, treatment related effect on total liver function, quality of life, treatment-related costs and cost-effectiveness. Trial registration NCT01381211

Published
2012
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37. Increased Mortality Among Patients With vs Without Cirrhosis and Autoimmune Hepatitis

Author

van den Brand, Floris F., primary, van der Veen, Koen S., additional, de Boer, Ynto S., additional, van Gerven, Nicole M., additional, Lissenberg-Witte, Birgit I., additional, Beuers, Ulrich, additional, van Erpecum, Karel J., additional, van Buuren, Henk R., additional, den Ouden, Jannie W., additional, Brouwer, Johannus T., additional, Vrolijk, Jan M., additional, Verdonk, Robert C., additional, van Hoek, Bart, additional, Koek, Ger H., additional, Drenth, Joost P.H., additional, Guichelaar, Marleen M.J., additional, Mulder, Chris J.J., additional, Bloemena, Elisabeth, additional, van Nieuwkerk, Carin M.J., additional, Bouma, Gerd, additional, Schreuder, T.C.M.A., additional, van der Wouden, E.J., additional, van Meyel, J.J.M., additional, Baak, L.C., additional, Stadhouders, P.H.G.M., additional, Klemt-Kropp, M., additional, Verhagen, M.A.M.T., additional, Bhalla, A., additional, and Kuijvenhoven, J.Ph., additional

Published
2019
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39. The Impact of Hepatitis C Virus Direct-Acting Antivirals on Patient-Reported Outcomes : A Dutch Prospective Cohort Study

Author

Kracht, Patricia A.M., Lieveld, Faydra I., Amelung, Linde M., Verstraete, Carina J.R., Mauser-Bunschoten, Eveline P., de Bruijne, Joep, Siersema, Peter D., Hoepelman, Andy I.M., Arends, Joop E., van Erpecum, Karel J., Kracht, Patricia A.M., Lieveld, Faydra I., Amelung, Linde M., Verstraete, Carina J.R., Mauser-Bunschoten, Eveline P., de Bruijne, Joep, Siersema, Peter D., Hoepelman, Andy I.M., Arends, Joop E., and van Erpecum, Karel J.

Published
2018

40. The Impact of Hepatitis C Virus Direct-Acting Antivirals on Patient-Reported Outcomes: A Dutch Prospective Cohort Study

Author

MS Infectieziekten, MS MDL 1, Functieafdeling, Poli Van Creveldkliniek Medisch, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Cancer, Kracht, Patricia A.M., Lieveld, Faydra I., Amelung, Linde M., Verstraete, Carina J.R., Mauser-Bunschoten, Eveline P., de Bruijne, Joep, Siersema, Peter D., Hoepelman, Andy I.M., Arends, Joop E., van Erpecum, Karel J., MS Infectieziekten, MS MDL 1, Functieafdeling, Poli Van Creveldkliniek Medisch, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Cancer, Kracht, Patricia A.M., Lieveld, Faydra I., Amelung, Linde M., Verstraete, Carina J.R., Mauser-Bunschoten, Eveline P., de Bruijne, Joep, Siersema, Peter D., Hoepelman, Andy I.M., Arends, Joop E., and van Erpecum, Karel J.

Published
2018

41. Overcoming Outpatient Loss to Follow-up as a Barrier to Efficiently Instituting Hepatitis B Liver-related Care

Author

Lieveld, Faydra I, Arends, Joop E, Amelung, Linde, Dijk, Eva, Gisolf, Elisabeth H, Vrolijk, Jan M, van Erpecum, Karel J, Siersema, Peter D, Spanier, Bernhard W M, Hoepelman, Andy I M, Richter, Clemens, Lieveld, Faydra I, Arends, Joop E, Amelung, Linde, Dijk, Eva, Gisolf, Elisabeth H, Vrolijk, Jan M, van Erpecum, Karel J, Siersema, Peter D, Spanier, Bernhard W M, Hoepelman, Andy I M, and Richter, Clemens

Published
2017

42. Overcoming Outpatient Loss to Follow-up as a Barrier to Efficiently Instituting Hepatitis B Liver-related Care

Author

MS MDL 1, Infection & Immunity, MS Interne Geneeskunde, Cancer, MS Infectieziekten, Circulatory Health, Lieveld, Faydra I, Arends, Joop E, Amelung, Linde, Dijk, Eva, Gisolf, Elisabeth H, Vrolijk, Jan M, van Erpecum, Karel J, Siersema, Peter D, Spanier, Bernhard W M, Hoepelman, Andy I M, Richter, Clemens, MS MDL 1, Infection & Immunity, MS Interne Geneeskunde, Cancer, MS Infectieziekten, Circulatory Health, Lieveld, Faydra I, Arends, Joop E, Amelung, Linde, Dijk, Eva, Gisolf, Elisabeth H, Vrolijk, Jan M, van Erpecum, Karel J, Siersema, Peter D, Spanier, Bernhard W M, Hoepelman, Andy I M, and Richter, Clemens

Published
2017

43. The hepatitis C virus nonstructural protein 3 Q80K polymorphism is frequently detected and transmitted among HIV-infected MSM in the Netherlands

Author

MS MDL 1, Infection & Immunity, MMB, MS Interne Geneeskunde, Cancer, Newsum, Astrid M., Ho, Cynthia K Y, Lieveld, Faydra, Van De Laar, Thijs J W, Koekkoek, Sylvie M., Rebers, Sjoerd P., Van Der Meer, Jan T M, Wensing, Anne M J, Boland, Greet J., Arends, Joop E., Van Erpecum, Karel J., Prins, Maria, Molenkamp, Richard, Schinkel, Janke, MS MDL 1, Infection & Immunity, MMB, MS Interne Geneeskunde, Cancer, Newsum, Astrid M., Ho, Cynthia K Y, Lieveld, Faydra, Van De Laar, Thijs J W, Koekkoek, Sylvie M., Rebers, Sjoerd P., Van Der Meer, Jan T M, Wensing, Anne M J, Boland, Greet J., Arends, Joop E., Van Erpecum, Karel J., Prins, Maria, Molenkamp, Richard, and Schinkel, Janke

Published
2017

44. No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long-term follow-up

Author

van Meer, Suzanne, de Man, Robert A., van den Berg, Aad P., Houwen, Roderick H. J., Linn, Francisca H. H., van Oijen, Martijn G. H., Siersema, PD, van Erpecum, Karel J., and Groningen Institute for Organ Transplantation (GIOT)

Subjects
MUTATIONS, cirrhosis, CLINICAL PRESENTATION, CARCINOGENESIS, COPPER, COHORT, hepatocellular carcinoma, DIAGNOSIS, digestive system diseases, Wilson disease
Abstract

Background and AimsData on risk of hepatocellular carcinoma (HCC) in patients with Wilson disease are scarce. We determine HCC risk in a well-defined cohort of Wilson patients. MethodsAll patients with a confirmed diagnosis of Wilson disease (Leipzig score4) in three Dutch university referral hospitals were included in this retrospective cohort study. End of follow-up was defined as date of diagnosis of HCC, liver transplantation, death, or last available hospital visit. Also, a meta-analysis was performed to determine incidence and mortality rate of HCC in Wilson disease based on all published cohorts. ResultsIn total, 130 patients with Wilson disease were followed during a median follow-up of 15 years (range 0.1-51.2). At baseline, cirrhosis was present in 74 patients (57% of total: 64% compensated, and 36% decompensated). At end of follow-up, liver disease severity was improved, stable or deteriorated in 20%, 46%, and 24% of all cases (10% unknown), respectively. Two patients developed HCC (one despite excellent decoppering after 50 years follow-up, the other with newly diagnosed Wilson disease). Estimated annual HCC risk for all patients was 0.09% (95% confidence interval [CI]: 0.01-0.28). Subgroup analysis in cirrhotic patients revealed an annual HCC risk of 0.14% (95% CI: 0.02-0.46). The meta-analysis showed an annual HCC risk of 0.04% (95% CI: 0.01-0.10) and HCC mortality rate of 2.6/10000 person-years (95% CI: 0.7-7.0). ConclusionsEven in case of cirrhosis, HCC risk is low in Wilson disease. Our data do not support regular HCC surveillance in Wilson disease.

Published
2015

45. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

Author

Nijmeijer, Rian M, Schaap, Frank G, Smits, Alexander J J, Kremer, Andreas E, Akkermans, Louis M A, Kroese, A.B., Rijkers, Ger T, Schipper, Marguerite E I, Verheem, André, Wijmenga, Cisca, Gooszen, Hein G, van Erpecum, Karel J, Dep IRAS, Sub IRAS Tox CMT/NTX, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA1, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Surgery, RS: NUTRIM - R2 - Gut-liver homeostasis, Other departments, Dep IRAS, Sub IRAS Tox CMT/NTX, Risk Assessment of Toxic and Immunomodulatory Agents, and IRAS RATIA1

Subjects
Male, Gene Expression, Receptors, Cytoplasmic and Nuclear, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Gene Knockout Techniques, Medizinische Fakultät, GROWTH-FACTOR 19, Medicine and Health Sciences, Electric Impedance, Intestinal Mucosa, Receptor, Mice, Knockout, Multidisciplinary, Pancreatitis, Acute Necrotizing, EXOCRINE PANCREAS, Animal Models, NUCLEAR RECEPTOR FXR, INTESTINAL BARRIER DYSFUNCTION, Acute pancreatitis, Medicine, medicine.symptom, Anatomy, ORGAN FAILURE, Research Article, EXPRESSION, medicine.medical_specialty, Science, Inflammation, Endocrine System, Mouse Models, Gastroenterology and Hepatology, Biology, BINDING PROTEIN, Research and Analysis Methods, Polymorphism, Single Nucleotide, Model Organisms, Ileum, Internal medicine, medicine, Genetics, Animals, Humans, ddc:610, Pancreas, Genetic Association Studies, FGF15, Biology and Life Sciences, FGF19, Human Genetics, medicine.disease, Fibroblast Growth Factors, Mice, Inbred C57BL, MICE, Endocrinology, GALLSTONE DISEASE, Nuclear receptor, Pancreatitis, Case-Control Studies, Genetics of Disease, BILE, Farnesoid X receptor, Gene Function
Abstract

Contains fulltext : 170664.PDF (Publisher’s version ) (Open Access) BACKGROUND: Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the pancreas, exhibits anti-inflammatory effects by inhibiting NF-kappaB activation and is implicated in maintaining intestinal barrier integrity and preventing bacterial overgrowth and translocation. Here we explore, with the aid of complementary animal and human experiments, the potential role of FXR in acute pancreatitis. METHODS: Experimental acute pancreatitis was induced using the CCK-analogue cerulein in wild-type and Fxr-/- mice. Severity of acute pancreatitis was assessed using histology and a semi-quantitative scoring system. Ileal permeability was analyzed in vitro by Ussing chambers and an in vivo permeability assay. Gene expression of Fxr and Fxr target genes was studied by quantitative RT-PCR. Serum FGF19 levels were determined by ELISA in acute pancreatitis patients and healthy volunteers. A genetic association study in 387 acute pancreatitis patients and 853 controls was performed using 9 tagging single nucleotide polymorphisms (SNPs) covering the complete FXR gene and two additional functional SNPs. RESULTS: In wild-type mice with acute pancreatitis, ileal transepithelial resistance was reduced and ileal mRNA expression of Fxr target genes Fgf15, SHP, and IBABP was decreased. Nevertheless, Fxr-/- mice did not exhibit a more severe acute pancreatitis than wild-type mice. In patients with acute pancreatitis, FGF19 levels were lower than in controls. However, there were no associations of FXR SNPs or haplotypes with susceptibility to acute pancreatitis, or its course, outcome or etiology. CONCLUSION: We found no evidence for a major role of FXR in acute human or murine pancreatitis. The observed altered Fxr activity during the course of disease may be a secondary phenomenon.

Published
2014

46. Gallstones

Author

Lammert, Frank, Gurusamy, Kurinchi, Ko, Cynthia W., Miquel, Juan Francisco, Méndez-Sánchez, Nahum, Portincasa, Piero, Van Erpecum, Karel J., Van Laarhoven, Cees J., Wang, David Q H, Lammert, Frank, Gurusamy, Kurinchi, Ko, Cynthia W., Miquel, Juan Francisco, Méndez-Sánchez, Nahum, Portincasa, Piero, Van Erpecum, Karel J., Van Laarhoven, Cees J., and Wang, David Q H

Published
2016

47. Risk factors for primary sclerosing cholangitis

Author

Boonstra, Kirsten, de Vries, Elisabeth M G, van Geloven, Nan, van Erpecum, Karel J., Spanier, Marcel, Poen, Alexander C, van Nieuwkerk, Carin M, Witteman, Ben J, Tuynman, Hans A, Naber, Anton H, Kingma, Paul J, Beuers, Ulrich, Ponsioen, Cyriel Y, Epi PSC PBC Study Group, Boonstra, Kirsten, de Vries, Elisabeth M G, van Geloven, Nan, van Erpecum, Karel J., Spanier, Marcel, Poen, Alexander C, van Nieuwkerk, Carin M, Witteman, Ben J, Tuynman, Hans A, Naber, Anton H, Kingma, Paul J, Beuers, Ulrich, Ponsioen, Cyriel Y, and Epi PSC PBC Study Group

Published
2016

48. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis

Author

Nevens, Frederik, Andreone, Pietro, Mazzella, Giuseppe, Strasser, Simone I, Bowlus, Christopher, Invernizzi, Pietro, Drenth, Joost P H, Pockros, Paul J, Regula, Jaroslaw, Beuers, Ulrich, Trauner, Michael, Jones, David E, Floreani, Annarosa, Hohenester, Simon, Luketic, Velimir, Shiffman, Mitchell, van Erpecum, Karel J, Vargas, Victor, Vincent, Catherine, Hirschfield, Gideon M, Shah, Hemant, Hansen, Bettina, Lindor, Keith D, Marschall, Hanns-Ulrich, Kowdley, Kris V, Hooshmand-Rad, Roya, Marmon, Tonya, Sheeron, Shawn, Pencek, Richard, MacConell, Leigh, Pruzanski, Mark, Shapiro, David, POISE Study Group, Nevens, Frederik, Andreone, Pietro, Mazzella, Giuseppe, Strasser, Simone I, Bowlus, Christopher, Invernizzi, Pietro, Drenth, Joost P H, Pockros, Paul J, Regula, Jaroslaw, Beuers, Ulrich, Trauner, Michael, Jones, David E, Floreani, Annarosa, Hohenester, Simon, Luketic, Velimir, Shiffman, Mitchell, van Erpecum, Karel J, Vargas, Victor, Vincent, Catherine, Hirschfield, Gideon M, Shah, Hemant, Hansen, Bettina, Lindor, Keith D, Marschall, Hanns-Ulrich, Kowdley, Kris V, Hooshmand-Rad, Roya, Marmon, Tonya, Sheeron, Shawn, Pencek, Richard, MacConell, Leigh, Pruzanski, Mark, Shapiro, David, and POISE Study Group

Published
2016

49. Limited Generalizability of Registration Trials in Hepatitis C : A Nationwide Cohort Study

Author

Berden, Floor A C, de Knegt, Robert J, Blokzijl, Hans, Kuiken, Sjoerd D, van Erpecum, Karel J L, Willemse, Sophie B, den Hollander, Jan, van Vonderen, Marit G A, Friederich, Pieter, van Hoek, Bart, van Nieuwkerk, Carin M J, Drenth, Joost P H, Kievit, Wietske, Berden, Floor A C, de Knegt, Robert J, Blokzijl, Hans, Kuiken, Sjoerd D, van Erpecum, Karel J L, Willemse, Sophie B, den Hollander, Jan, van Vonderen, Marit G A, Friederich, Pieter, van Hoek, Bart, van Nieuwkerk, Carin M J, Drenth, Joost P H, and Kievit, Wietske

Published
2016

50. Adherence to ribavirin in chronic hepatitis C patients on antiviral treatment : Results from a randomized controlled trial using real-time medication monitoring

Author

van Vlerken, Lotte G, Lieveld, Faydra I, van Meer, Suzanne, Koek, Ger H, van Nieuwkerk, Karin M J, Friederich, Pieter, Arends, Joop E, Siersema, Peter D, Burger, David M, van Erpecum, Karel J, van Vlerken, Lotte G, Lieveld, Faydra I, van Meer, Suzanne, Koek, Ger H, van Nieuwkerk, Karin M J, Friederich, Pieter, Arends, Joop E, Siersema, Peter D, Burger, David M, and van Erpecum, Karel J

Published
2016

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