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1. Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Author

Efe, C, Lammert, C, Tascilar, K, Dhanasekaran, R, Ebik, B, Higuera-de la Tijera, F, Caliskan, A, Peralta, M, Gerussi, A, Massoumi, H, Catana, A, Purnak, T, Rigamonti, C, Aldana, A, Khakoo, N, Nazal, L, Frager, S, Demir, N, Irak, K, Melekoglu-Ellik, Z, Kacmaz, H, Balaban, Y, Atay, K, Eren, F, Alvares-da-Silva, M, Cristoferi, L, Urzua, A, Eskazan, T, Magro, B, Snijders, R, Barutcu, S, Lytvyak, E, Zazueta, G, Demirezer-Bolat, A, Aydin, M, Heurgue-Berlot, A, De Martin, E, Ekin, N, Yildirim, S, Yavuz, A, Biyik, M, Narro, G, Kiyici, M, Akyildiz, M, Kahramanoglu-Aksoy, E, Vincent, M, Carr, R, Gunsar, F, Reyes, E, Harputluoglu, M, Aloman, C, Gatselis, N, Ustundag, Y, Brahm, J, Vargas, N, Guzelbulut, F, Garcia, S, Aguirre, J, Anders, M, Ratusnu, N, Hatemi, I, Mendizabal, M, Floreani, A, Fagiuoli, S, Silva, M, Idilman, R, Satapathy, S, Silveira, M, Drenth, J, Dalekos, G, Assis, D, Bjornsson, E, Boyer, J, Yoshida, E, Invernizzi, P, Levy, C, Montano-Loza, A, Schiano, T, Ridruejo, E, Wahlin, S, Caliskan, AR, Catana, AM, Aldana, AJG, Alvares-da-Silva, MR, Zazueta, GM, Narro, GC, Carr, RM, Reyes, EC, Gatselis, NK, Vargas, NCE, Garcia, SR, Satapathy, SK, Drenth, JPH, Dalekos, GN, Assis, DN, Boyer, JL, Yoshida, EM, Montano-Loza, AJ, Schiano, TD, Efe, C, Lammert, C, Tascilar, K, Dhanasekaran, R, Ebik, B, Higuera-de la Tijera, F, Caliskan, A, Peralta, M, Gerussi, A, Massoumi, H, Catana, A, Purnak, T, Rigamonti, C, Aldana, A, Khakoo, N, Nazal, L, Frager, S, Demir, N, Irak, K, Melekoglu-Ellik, Z, Kacmaz, H, Balaban, Y, Atay, K, Eren, F, Alvares-da-Silva, M, Cristoferi, L, Urzua, A, Eskazan, T, Magro, B, Snijders, R, Barutcu, S, Lytvyak, E, Zazueta, G, Demirezer-Bolat, A, Aydin, M, Heurgue-Berlot, A, De Martin, E, Ekin, N, Yildirim, S, Yavuz, A, Biyik, M, Narro, G, Kiyici, M, Akyildiz, M, Kahramanoglu-Aksoy, E, Vincent, M, Carr, R, Gunsar, F, Reyes, E, Harputluoglu, M, Aloman, C, Gatselis, N, Ustundag, Y, Brahm, J, Vargas, N, Guzelbulut, F, Garcia, S, Aguirre, J, Anders, M, Ratusnu, N, Hatemi, I, Mendizabal, M, Floreani, A, Fagiuoli, S, Silva, M, Idilman, R, Satapathy, S, Silveira, M, Drenth, J, Dalekos, G, Assis, D, Bjornsson, E, Boyer, J, Yoshida, E, Invernizzi, P, Levy, C, Montano-Loza, A, Schiano, T, Ridruejo, E, Wahlin, S, Caliskan, AR, Catana, AM, Aldana, AJG, Alvares-da-Silva, MR, Zazueta, GM, Narro, GC, Carr, RM, Reyes, EC, Gatselis, NK, Vargas, NCE, Garcia, SR, Satapathy, SK, Drenth, JPH, Dalekos, GN, Assis, DN, Boyer, JL, Yoshida, EM, Montano-Loza, AJ, and Schiano, TD

Abstract

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Published
2022

3. Association between black race and presentation and liver-related outcomes of patients with autoimmune hepatitis

Author

de Boer, Y, Gerussi, A, van den Brand, F, Wong, G, Halliday, N, Liberal, R, Drenth, J, Thorburn, D, Bouma, G, Heneghan, M, van Gerven, N, Beuers, U, van Erpecum, K, van Buuren, H, den Ouden, J, Brouwer, J, Vrolijk, J, Verdonk, R, van Hoek, B, Koek, G, Guichelaar, M, Bloemena, E, van Nieuwkerk, C, Schreuder, T, van der Wouden, E, van Meyel, J, Baak, L, Stadhouders, P, Klemt-Kropp, M, Verhagen, M, Bhalla, A, Kuijvenhoven, J, de Boer, YS, van den Brand, FF, Wong, GW, Drenth, JPH, Heneghan, MA, van Gerven, NM, van Erpecum, KJ, van Buuren, HR, den Ouden, JW, Brouwer, JT, Vrolijk, JM, Verdonk, RC, Koek, GH, Guichelaar, MMJ, van Nieuwkerk, CMJ, Schreuder, TCMA, van der Wouden, EJ, van Meyel, JJM, Baak, LC, Stadhouders, PHGM, Verhagen, MAMT, Kuijvenhoven, JP, de Boer, Y, Gerussi, A, van den Brand, F, Wong, G, Halliday, N, Liberal, R, Drenth, J, Thorburn, D, Bouma, G, Heneghan, M, van Gerven, N, Beuers, U, van Erpecum, K, van Buuren, H, den Ouden, J, Brouwer, J, Vrolijk, J, Verdonk, R, van Hoek, B, Koek, G, Guichelaar, M, Bloemena, E, van Nieuwkerk, C, Schreuder, T, van der Wouden, E, van Meyel, J, Baak, L, Stadhouders, P, Klemt-Kropp, M, Verhagen, M, Bhalla, A, Kuijvenhoven, J, de Boer, YS, van den Brand, FF, Wong, GW, Drenth, JPH, Heneghan, MA, van Gerven, NM, van Erpecum, KJ, van Buuren, HR, den Ouden, JW, Brouwer, JT, Vrolijk, JM, Verdonk, RC, Koek, GH, Guichelaar, MMJ, van Nieuwkerk, CMJ, Schreuder, TCMA, van der Wouden, EJ, van Meyel, JJM, Baak, LC, Stadhouders, PHGM, Verhagen, MAMT, and Kuijvenhoven, JP

Published
2019

4. Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis

Author

Rosendahl, J, Kirsten, H, Hegyi, E, Kovacs, P, Weiss, FU, Laumen, H, Lichtner, P, Ruffert, C, Chen, JM, Masson, E, Beer, S, Zimmer, C, Seltsam, K, Alguel, H, Buehler, F, Bruno, Marco, Bugert, P, Burkhardt, R, Cavestro, GM, Cichoz-Lach, H, Farre, A, Frank, J, Gambaro, G, Gimpfl, S, Grallert, H, Griesmann, H, Gruetzmann, R, Hellerbrand, C, Hegyi, P, Hollenbach, M, Iordache, S, Jurkowska, G, Keim, V, Kiefer, F, Krug, S, Landt, O, De Leo, M, Lerch, MM, Levy, P, Loeffler, M, Loehr, M, Ludwig, M, Macek, M, Malats, N, Malecka-Panas, E, Malerba, G, Mann, K, Mayerle, J, Mohr, S, te Morsche, RHM, Motyka, M, Mueller, S, Mueller, T, Noethen, MM, Pedrazzoli, S, Pereira, SP, Peters, A, Pfuetzer, R, Real, FX, Rebours, V, Ridinger, M, Rietschel, M, Roesmann, E, Saftoiu, A, Schneider, A, Schulz, HU, Soranzo, N, Soyka, M, Simon, P, Skipworth, J, Stickel, F, Strauch, K, Stumvoll, M, Testoni, PA, Toenjes, A, Werner, L, Werner, J, Wodarz, N, Ziegler, M, Masamune, A, Moessner, J, Ferec, C, Michl, P, Drenth, JPH, Witt, H, Scholz, M, Sahin-Toth, M, Rosendahl, J, Kirsten, H, Hegyi, E, Kovacs, P, Weiss, FU, Laumen, H, Lichtner, P, Ruffert, C, Chen, JM, Masson, E, Beer, S, Zimmer, C, Seltsam, K, Alguel, H, Buehler, F, Bruno, Marco, Bugert, P, Burkhardt, R, Cavestro, GM, Cichoz-Lach, H, Farre, A, Frank, J, Gambaro, G, Gimpfl, S, Grallert, H, Griesmann, H, Gruetzmann, R, Hellerbrand, C, Hegyi, P, Hollenbach, M, Iordache, S, Jurkowska, G, Keim, V, Kiefer, F, Krug, S, Landt, O, De Leo, M, Lerch, MM, Levy, P, Loeffler, M, Loehr, M, Ludwig, M, Macek, M, Malats, N, Malecka-Panas, E, Malerba, G, Mann, K, Mayerle, J, Mohr, S, te Morsche, RHM, Motyka, M, Mueller, S, Mueller, T, Noethen, MM, Pedrazzoli, S, Pereira, SP, Peters, A, Pfuetzer, R, Real, FX, Rebours, V, Ridinger, M, Rietschel, M, Roesmann, E, Saftoiu, A, Schneider, A, Schulz, HU, Soranzo, N, Soyka, M, Simon, P, Skipworth, J, Stickel, F, Strauch, K, Stumvoll, M, Testoni, PA, Toenjes, A, Werner, L, Werner, J, Wodarz, N, Ziegler, M, Masamune, A, Moessner, J, Ferec, C, Michl, P, Drenth, JPH, Witt, H, Scholz, M, and Sahin-Toth, M

Published
2018

5. Safe use of proton pump inhibitors in patients with cirrhosis

Author

Weersink, RA, Bouma, M, Burger, D, Drenth, JPH, Harkes-Idzinga, SF, Hunfeld, Nicole, Metselaar, Herold, Monster-Simons, MH, van Putten, SAW, Taxis, K, Borgsteede, Sander, Weersink, RA, Bouma, M, Burger, D, Drenth, JPH, Harkes-Idzinga, SF, Hunfeld, Nicole, Metselaar, Herold, Monster-Simons, MH, van Putten, SAW, Taxis, K, and Borgsteede, Sander

Published
2018

7. Fluid hydration to prevent post-ERCP pancreatitis in average-to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial): study protocol for a randomized controlled trial

Author

Smeets, X, da Costa, DW, Fockens, P, Mulder, CJJ, Timmer, R, Kievit, W, Zegers, M, Bruno, Marco, Besselink, MGH, Vleggaar, FP, van der Hulst, RWM, Poen, AC (Alexander), Heine, GDN, Venneman, NG, Kolkman, JJ, Baak, LC, Romkens, TEH, Dijk, SM, Hallensleben, Noortje, van de Vrie, W, Seerden, TCJ, Tan, A, Voorburg, A, Poley, Jan-werner, Witteman, BJ, Bhalla, A, Hadithi, M, Thijs, WJ, Schwartz, MP, Vrolijk, JM (Jan), Verdonk, RC, van Delft, F, Keulemans, Y, van Goor, H, Drenth, JPH, van Geenen, EJM, Smeets, X, da Costa, DW, Fockens, P, Mulder, CJJ, Timmer, R, Kievit, W, Zegers, M, Bruno, Marco, Besselink, MGH, Vleggaar, FP, van der Hulst, RWM, Poen, AC (Alexander), Heine, GDN, Venneman, NG, Kolkman, JJ, Baak, LC, Romkens, TEH, Dijk, SM, Hallensleben, Noortje, van de Vrie, W, Seerden, TCJ, Tan, A, Voorburg, A, Poley, Jan-werner, Witteman, BJ, Bhalla, A, Hadithi, M, Thijs, WJ, Schwartz, MP, Vrolijk, JM (Jan), Verdonk, RC, van Delft, F, Keulemans, Y, van Goor, H, Drenth, JPH, and van Geenen, EJM

Published
2018

8. Black Ethnicity Affects the Clinical Presentation and Outcome in Autoimmune Hepatitis

Author

de Boer, Y, Gerussi, A, Van den Brand, F, Wong, G, Haliday, N, Liberals, R, Drenth, J, Thorburn, D, Bouma, G, Heneghan, M, de Boer, YS, Van den Brand, FF, Wong, GW, Drenth, JPH, Heneghan, MA, de Boer, Y, Gerussi, A, Van den Brand, F, Wong, G, Haliday, N, Liberals, R, Drenth, J, Thorburn, D, Bouma, G, Heneghan, M, de Boer, YS, Van den Brand, FF, Wong, GW, Drenth, JPH, and Heneghan, MA

Published
2018

9. Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

Author

Lantinga, MA, D'Agnolo, HMA, Casteleijn, NF, de Fijter, JW, Meijer, E, Messchendorp, AL, Peters, DJM, Salih, Mahdi, Spithoven, EM, Soonawala, D, Visser, FW, Wetzels, JFM, Zietse, R., Drenth, JPH, Gansevoort, RT, Lantinga, MA, D'Agnolo, HMA, Casteleijn, NF, de Fijter, JW, Meijer, E, Messchendorp, AL, Peters, DJM, Salih, Mahdi, Spithoven, EM, Soonawala, D, Visser, FW, Wetzels, JFM, Zietse, R., Drenth, JPH, and Gansevoort, RT

Published
2017

11. Drug-Drug Interactions Between Direct-Acting Antivirals and Psychoactive Medications

Author

Smolders, EJ, de Kanter, CTMM, de Knegt, Rob, van der Valk, M, Drenth, JPH, Burger, DM, Smolders, EJ, de Kanter, CTMM, de Knegt, Rob, van der Valk, M, Drenth, JPH, and Burger, DM

Abstract

Treatment options for chronic hepatitis C virus (HCV) infection have drastically changed since the development and licensing of new potent direct-acting antivirals (DAAs). The majority of DAAs are extensively metabolized by liver enzymes and have the ability to influence cytochrome P450 (CYP) enzymes. Additionally, these DAAs are both substrates and inhibitors of drug transporters, which makes the DAAs both possible victims or perpetrators of drug-drug interactions (DDIs). There is a high prevalence of mental illnesses such as depression or psychosis in HCV-infected patients; therefore, psychoactive medications are frequently co-administered with DAAs. The majority of these psychoactive medications are also metabolized by CYP enzymes but remarkably little information is available on DDIs between psychoactive medications and DAAs. Hence, the aim of this review is to provide an overview of the interaction mechanisms between DAAs and psychoactive agents. In addition, we describe evidenced-based interactions between DAAs and psychoactive drugs and identify safe options for the simultaneous treatment of mental illnesses and chronic HCV infection.

Published
2016

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

Author

Berden, FAC, de Knegt, Rob, Blokzijl, H, Kuiken, SD, van Erpecum, KJL, Willemse, SB, den Hollander, J, van Vonderen, MGA, Friederich, P, van Hoek, B, van Nieuwkerk, CMJ, Drenth, JPH, Kievit, W, Berden, FAC, de Knegt, Rob, Blokzijl, H, Kuiken, SD, van Erpecum, KJL, Willemse, SB, den Hollander, J, van Vonderen, MGA, Friederich, P, van Hoek, B, van Nieuwkerk, CMJ, Drenth, JPH, and Kievit, W

Abstract

Background Approval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials. Methods We performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclusion criteria of registration trials to our cohort to determine eligibility. We compared effectiveness and safety in eligible vs. ineligible patients, and performed sensitivity analyses with strict criteria. Further, we used log binomial regression to assess relative risks of criteria on outcomes. Results In this cohort (n = 467) 47% of patients would have been ineligible for registration trials. Main exclusion criteria were related to hepatic decompensation and co-morbidity (cardiac disease, anemia, malignancy and neutropenia), and were associated with an increased risk for serious adverse events (RR 1.45-2.31). Ineligible patients developed significantly more serious adverse events than eligible patients (27% vs. 11%, p<0.001). Effectiveness was decreased if strict criteria were used. Conclusions Nearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population.

Published
2016

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