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1. ECFS standards of care on CFTR-related disorders: Identification and care of the disorders

Author

Simmonds, N.J., Southern, K.W., De Wachter, E., De Boeck, K., Bodewes, F., Mainz, J.G., Middleton, P.G., Schwarz, C., Vloeberghs, V., Wilschanski, M., Bourrat, E., Chalmers, J.D., Ooi, C.Y., Debray, D., Downey, D.G., Eschenhagen, P., Girodon, E., Hickman, G., Koitschev, A., Nazareth, D., Nick, J.A., Peckham, D., VanDevanter, D., Raynal, C., Scheers, I., Waller, M.D., Sermet-Gaudelus, I., and Castellani, C.

Published
2024
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2. Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Author

van Gerven, N., van Erpecum, K., Ouden, J den, Brouwer, J., Vrolijk, J., Gevers, T.J., Drenth, J., Guichelaar, M., Bouma, G., Schreuder, T.C.M.A., van der Wouden, E.J., Baak, L.C., Stadhouders, P., Klemt-Kropp, M., Verhagen, M., Bhalla, A., Kuijvenhoven, J., Almasio, P., Alvarez, F., Andrade, R., Arikan, C., Assis, D., Bardou-Jacquet, E., Biewenga, M., Cancado, E., Cazzagon, N., Chazouillères, O., Colloredo, G., Cuarterolo, M., Dalekos, G., Debray, D., Robles-Díaz, M., Dyson, J., Efe, C., Engel, B., Ferri, S., Fontana, R., Gatselis, N., Gerussi, A., Halilbasic, E., Halliday, N., Heneghan, M., Hirschfield, G., van Hoek, B., Hørby Jørgensen, M., Indolfini, G., Iorio, R., Invernizzi, P., Jeong, S., Jones, D., Kelly, D., Kerkar, N., Lacaille, F., Lammert, C., Leggett, B., Lenzi, M., Levy, C., Liberal, R., Lleo, A., Lohse, A., Lopez, S. Ines, de Martin, E., McLin, V., Mieli-Vergani, G., Milkiewicz, P., Mohan, N., Muratori, L., Nebbia, G., van Nieuwkerk, C., Oo, Y., Ortega, A., Páres, A., Pop, T., Pratt, D., Purnak, T., Ranucci, G., Rushbrook, S., Schramm, C., Stättermayer, A., Swain, M., Tanaka, A., Taubert, R., Terrabuio, D., Terziroli, B., Trauner, M., Valentino, P., van den Brand, F., Vergani, D., Villamil, A., Wahlin, S., Ytting, H., Zachou, K., Zeniya, M., Colapietro, Francesca, Maisonneuve, Patrick, Lytvyak, Ellina, Beuers, Ulrich, Verdonk, Robert C., van der Meer, Adriaan J., van Hoek, Bart, Kuiken, Sjoerd D., Brouwer, Johannes T., Muratori, Paolo, Aghemo, Alessio, Carella, Francesco, van den Berg, Ad P., Zachou, Kalliopi, Dalekos, George N., Di Zeo-Sánchez, Daniel E., Robles, Mercedes, Andrade, Raul J., Montano-Loza, Aldo J., van den Brand, Floris F., Slooter, Charlotte D., Macedo, Guilherme, Liberal, Rodrigo, de Boer, Ynto S., and Lleo, Ana

Published
2024
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3. Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA

Author

Hansen, B, Vandriel, S, Vig, P, Garner, W, Mogul, D, Loomes, K, Piccoli, D, Rand, E, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, E, Jacquemin, E, Bouligand, J, D'Antiga, L, Nicastro, E, Arnell, H, Fischler, B, Sokal, E, Demaret, T, Siew, S, Stormon, M, Karpen, S, Romero, R, Ebel, N, Feinstein, J, Roberts, A, Evans, H, Sundaram, S, Chaidez, A, Hardikar, W, Shankar, S, Fischer, R, Lacaille, F, Debray, D, Lin, H, Jensen, M, Jaramillo, C, Karthikeyan, P, Indolfi, G, Verkade, H, Larson-Nath, C, Quiros-Tejeira, R, Valentino, P, Rogalidou, M, Dezsofi, A, Squires, J, Schwarz, K, Calvo, P, Bernabeu, J, Zizzo, A, Nebbia, G, Bulut, P, Santos-Silva, E, Fawaz, R, Nastasio, S, Karnsakul, W, Tamara, M, Busoms, C, Kelly, D, Sandahl, T, Jimenez-Rivera, C, Banales, J, Mujawar, Q, Li, L, She, H, Wang, J, Kim, K, Oh, S, Sanchez, M, Cavalieri, M, Lee, W, Hajinicolaou, C, Lertudomphonwanit, C, Waisbourd-Zinman, O, Arikan, C, Alam, S, Carvalho, E, Melere, M, Eshun, J, Onal, Z, Desai, D, Wiecek, S, Pinto, R, Wolters, V, Garcia, J, Beretta, M, Kerkar, N, Brecelj, J, Rock, N, Lurz, E, Blondet, N, Shah, U, Thompson, R, Kamath, B, Hansen B. E., Vandriel S. M., Vig P., Garner W., Mogul D. B., Loomes K. M., Piccoli D. A., Rand E. B., Jankowska I., Czubkowski P., Gliwicz-Miedzinska D., Gonzales E. M., Jacquemin E., Bouligand J., D'Antiga L., Nicastro E., Arnell H., Fischler B., Sokal E., Demaret T., Siew S., Stormon M., Karpen S. J., Romero R., Ebel N. H., Feinstein J. A., Roberts A. J., Evans H. M., Sundaram S. S., Chaidez A., Hardikar W., Shankar S., Fischer R. T., Lacaille F., Debray D., Lin H. C., Jensen M. K., Jaramillo C., Karthikeyan P., Indolfi G., Verkade H. J., Larson-Nath C., Quiros-Tejeira R. E., Valentino P. L., Rogalidou M., Dezsofi A., Squires J. E., Schwarz K., Calvo P. L., Bernabeu J. Q., Zizzo A. N., Nebbia G., Bulut P., Santos-Silva E., Fawaz R., Nastasio S., Karnsakul W., Tamara M. L., Busoms C. M., Kelly D. A., Sandahl T. D., Jimenez-Rivera C., Banales J. M., Mujawar Q., Li L. -T., She H., Wang J. -S., Kim K. M., Oh S. H., Sanchez M. C., Cavalieri M. L., Lee W. S., Hajinicolaou C., Lertudomphonwanit C., Waisbourd-Zinman O., Arikan C., Alam S., Carvalho E., Melere M., Eshun J., Onal Z., Desai D. M., Wiecek S., Pinto R. B., Wolters V. M., Garcia J., Beretta M., Kerkar N., Brecelj J., Rock N., Lurz E., Blondet N., Shah U., Thompson R. J., Kamath B. M., Hansen, B, Vandriel, S, Vig, P, Garner, W, Mogul, D, Loomes, K, Piccoli, D, Rand, E, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, E, Jacquemin, E, Bouligand, J, D'Antiga, L, Nicastro, E, Arnell, H, Fischler, B, Sokal, E, Demaret, T, Siew, S, Stormon, M, Karpen, S, Romero, R, Ebel, N, Feinstein, J, Roberts, A, Evans, H, Sundaram, S, Chaidez, A, Hardikar, W, Shankar, S, Fischer, R, Lacaille, F, Debray, D, Lin, H, Jensen, M, Jaramillo, C, Karthikeyan, P, Indolfi, G, Verkade, H, Larson-Nath, C, Quiros-Tejeira, R, Valentino, P, Rogalidou, M, Dezsofi, A, Squires, J, Schwarz, K, Calvo, P, Bernabeu, J, Zizzo, A, Nebbia, G, Bulut, P, Santos-Silva, E, Fawaz, R, Nastasio, S, Karnsakul, W, Tamara, M, Busoms, C, Kelly, D, Sandahl, T, Jimenez-Rivera, C, Banales, J, Mujawar, Q, Li, L, She, H, Wang, J, Kim, K, Oh, S, Sanchez, M, Cavalieri, M, Lee, W, Hajinicolaou, C, Lertudomphonwanit, C, Waisbourd-Zinman, O, Arikan, C, Alam, S, Carvalho, E, Melere, M, Eshun, J, Onal, Z, Desai, D, Wiecek, S, Pinto, R, Wolters, V, Garcia, J, Beretta, M, Kerkar, N, Brecelj, J, Rock, N, Lurz, E, Blondet, N, Shah, U, Thompson, R, Kamath, B, Hansen B. E., Vandriel S. M., Vig P., Garner W., Mogul D. B., Loomes K. M., Piccoli D. A., Rand E. B., Jankowska I., Czubkowski P., Gliwicz-Miedzinska D., Gonzales E. M., Jacquemin E., Bouligand J., D'Antiga L., Nicastro E., Arnell H., Fischler B., Sokal E., Demaret T., Siew S., Stormon M., Karpen S. J., Romero R., Ebel N. H., Feinstein J. A., Roberts A. J., Evans H. M., Sundaram S. S., Chaidez A., Hardikar W., Shankar S., Fischer R. T., Lacaille F., Debray D., Lin H. C., Jensen M. K., Jaramillo C., Karthikeyan P., Indolfi G., Verkade H. J., Larson-Nath C., Quiros-Tejeira R. E., Valentino P. L., Rogalidou M., Dezsofi A., Squires J. E., Schwarz K., Calvo P. L., Bernabeu J. Q., Zizzo A. N., Nebbia G., Bulut P., Santos-Silva E., Fawaz R., Nastasio S., Karnsakul W., Tamara M. L., Busoms C. M., Kelly D. A., Sandahl T. D., Jimenez-Rivera C., Banales J. M., Mujawar Q., Li L. -T., She H., Wang J. -S., Kim K. M., Oh S. H., Sanchez M. C., Cavalieri M. L., Lee W. S., Hajinicolaou C., Lertudomphonwanit C., Waisbourd-Zinman O., Arikan C., Alam S., Carvalho E., Melere M., Eshun J., Onal Z., Desai D. M., Wiecek S., Pinto R. B., Wolters V. M., Garcia J., Beretta M., Kerkar N., Brecelj J., Rock N., Lurz E., Blondet N., Shah U., Thompson R. J., and Kamath B. M.

Abstract

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study. APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings. CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, p

Published
2024

6. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study

Author

Vandriel, S, Li, L, She, H, Wang, J, Gilbert, M, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, E, Jacquemin, E, Bouligand, J, Spinner, N, Loomes, K, Piccoli, D, D'Antiga, L, Nicastro, E, Sokal, A, Demaret, T, Ebel, N, Feinstein, J, Fawaz, R, Nastasio, S, Lacaille, F, Debray, D, Arnell, H, Fischler, B, Siew, S, Stormon, M, Karpen, S, Romero, R, Kim, K, Baek, W, Hardikar, W, Shankar, S, Roberts, A, Evans, H, Jensen, M, Kavan, M, Sundaram, S, Chaidez, A, Karthikeyan, P, Sanchez, M, Cavalieri, M, Verkade, H, Lee, W, Squires, J, Hajinicolaou, C, Lertudomphonwanit, C, Fischer, R, Larson-Nath, C, Mozer-Glassberg, Y, Arikan, C, Lin, H, Bernabeu, J, Alam, S, Kelly, D, Carvalho, E, Ferreira, C, Indolfi, G, Quiros-Tejeira, R, Bulut, P, Calvo, P, Anal, Z, Valentino, P, Desai, D, Eshun, J, Rogalidou, M, Dezsofi, A, Wiecek, S, Nebbia, G, Pinto, R, Wolters, V, Tamara, M, Zizzo, A, Garcia, J, Schwarz, K, Beretta, M, Sandahl, T, Jimenez-Rivera, C, Kerkar, N, Brecelj, J, Mujawar, Q, Rock, N, Busoms, C, Karnsakul, W, Lurz, E, Santos-Silva, E, Blondet, N, Bujanda, L, Shah, U, Thompson, R, Hansen, B, Kamath, B, Vandriel S. M., Li L. -T., She H., Wang J. -S., Gilbert M. A., Jankowska I., Czubkowski P., Gliwicz-Miedzinska D., Gonzales E. M., Jacquemin E., Bouligand J., Spinner N. B., Loomes K. M., Piccoli D. A., D'Antiga L., Nicastro E., Sokal A., Demaret T., Ebel N. H., Feinstein J. A., Fawaz R., Nastasio S., Lacaille F., Debray D., Arnell H., Fischler B., Siew S., Stormon M., Karpen S. J., Romero R., Kim K. M., Baek W. Y., Hardikar W., Shankar S., Roberts A. J., Evans H. M., Jensen M. K., Kavan M., Sundaram S. S., Chaidez A., Karthikeyan P., Sanchez M. C., Cavalieri M. L., Verkade H. J., Lee W. S., Squires J. E., Hajinicolaou C., Lertudomphonwanit C., Fischer R. T., Larson-Nath C., Mozer-Glassberg Y., Arikan C., Lin H. C., Bernabeu J. Q., Alam S., Kelly D. A., Carvalho E., Ferreira C. T., Indolfi G., Quiros-Tejeira R. E., Bulut P., Calvo P. L., Anal Z., Valentino P. L., Desai D. M., Eshun J., Rogalidou M., Dezsofi A., Wiecek S., Nebbia G., Pinto R. B., Wolters V. M., Tamara M. L., Zizzo A. N., Garcia J., Schwarz K., Beretta M., Sandahl T. D., Jimenez-Rivera C., Kerkar N., Brecelj J., Mujawar Q., Rock N., Busoms C. M., Karnsakul W., Lurz E., Santos-Silva E., Blondet N., Bujanda L., Shah U., Thompson R. J., Hansen B. E., Kamath B. M., Vandriel, S, Li, L, She, H, Wang, J, Gilbert, M, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, E, Jacquemin, E, Bouligand, J, Spinner, N, Loomes, K, Piccoli, D, D'Antiga, L, Nicastro, E, Sokal, A, Demaret, T, Ebel, N, Feinstein, J, Fawaz, R, Nastasio, S, Lacaille, F, Debray, D, Arnell, H, Fischler, B, Siew, S, Stormon, M, Karpen, S, Romero, R, Kim, K, Baek, W, Hardikar, W, Shankar, S, Roberts, A, Evans, H, Jensen, M, Kavan, M, Sundaram, S, Chaidez, A, Karthikeyan, P, Sanchez, M, Cavalieri, M, Verkade, H, Lee, W, Squires, J, Hajinicolaou, C, Lertudomphonwanit, C, Fischer, R, Larson-Nath, C, Mozer-Glassberg, Y, Arikan, C, Lin, H, Bernabeu, J, Alam, S, Kelly, D, Carvalho, E, Ferreira, C, Indolfi, G, Quiros-Tejeira, R, Bulut, P, Calvo, P, Anal, Z, Valentino, P, Desai, D, Eshun, J, Rogalidou, M, Dezsofi, A, Wiecek, S, Nebbia, G, Pinto, R, Wolters, V, Tamara, M, Zizzo, A, Garcia, J, Schwarz, K, Beretta, M, Sandahl, T, Jimenez-Rivera, C, Kerkar, N, Brecelj, J, Mujawar, Q, Rock, N, Busoms, C, Karnsakul, W, Lurz, E, Santos-Silva, E, Blondet, N, Bujanda, L, Shah, U, Thompson, R, Hansen, B, Kamath, B, Vandriel S. M., Li L. -T., She H., Wang J. -S., Gilbert M. A., Jankowska I., Czubkowski P., Gliwicz-Miedzinska D., Gonzales E. M., Jacquemin E., Bouligand J., Spinner N. B., Loomes K. M., Piccoli D. A., D'Antiga L., Nicastro E., Sokal A., Demaret T., Ebel N. H., Feinstein J. A., Fawaz R., Nastasio S., Lacaille F., Debray D., Arnell H., Fischler B., Siew S., Stormon M., Karpen S. J., Romero R., Kim K. M., Baek W. Y., Hardikar W., Shankar S., Roberts A. J., Evans H. M., Jensen M. K., Kavan M., Sundaram S. S., Chaidez A., Karthikeyan P., Sanchez M. C., Cavalieri M. L., Verkade H. J., Lee W. S., Squires J. E., Hajinicolaou C., Lertudomphonwanit C., Fischer R. T., Larson-Nath C., Mozer-Glassberg Y., Arikan C., Lin H. C., Bernabeu J. Q., Alam S., Kelly D. A., Carvalho E., Ferreira C. T., Indolfi G., Quiros-Tejeira R. E., Bulut P., Calvo P. L., Anal Z., Valentino P. L., Desai D. M., Eshun J., Rogalidou M., Dezsofi A., Wiecek S., Nebbia G., Pinto R. B., Wolters V. M., Tamara M. L., Zizzo A. N., Garcia J., Schwarz K., Beretta M., Sandahl T. D., Jimenez-Rivera C., Kerkar N., Brecelj J., Mujawar Q., Rock N., Busoms C. M., Karnsakul W., Lurz E., Santos-Silva E., Blondet N., Bujanda L., Shah U., Thompson R. J., Hansen B. E., and Kamath B. M.

Abstract

Background and Aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and Results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies.

Published
2023

7. Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)—A European Society of Organ Transplantation (ESOT) Consensus Statement

Author

Carbone, M, Della Penna, A, Mazzarelli, C, De Martin, E, Villard, C, Bergquist, A, Line, P, Neuberger, J, Al-Shakhshir, S, Trivedi, P, Baumann, U, Cristoferi, L, Hov, J, Fischler, B, Hadzic, N, Debray, D, D'Antiga, L, Selzner, N, Belli, L, Nadalin, S, Carbone M., Della Penna A., Mazzarelli C., De Martin E., Villard C., Bergquist A., Line P. D., Neuberger J. M., Al-Shakhshir S., Trivedi P. J., Baumann U., Cristoferi L., Hov J., Fischler B., Hadzic N. H., Debray D., D'Antiga L., Selzner N., Belli L. S., Nadalin S., Carbone, M, Della Penna, A, Mazzarelli, C, De Martin, E, Villard, C, Bergquist, A, Line, P, Neuberger, J, Al-Shakhshir, S, Trivedi, P, Baumann, U, Cristoferi, L, Hov, J, Fischler, B, Hadzic, N, Debray, D, D'Antiga, L, Selzner, N, Belli, L, Nadalin, S, Carbone M., Della Penna A., Mazzarelli C., De Martin E., Villard C., Bergquist A., Line P. D., Neuberger J. M., Al-Shakhshir S., Trivedi P. J., Baumann U., Cristoferi L., Hov J., Fischler B., Hadzic N. H., Debray D., D'Antiga L., Selzner N., Belli L. S., and Nadalin S.

Abstract

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines’ Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.

Published
2023

8. Long-term Outcome of Asymptomatic Patients with Graft Fibrosis in Protocol Biopsies after Pediatric Liver Transplantation

Author

Hartleif, S, Hodson, J, Lloyd, C, Cousin, V, Czubkowski, P, D'Antiga, L, Debray, D, Demetris, A, Di Giorgio, A, Evans, H, Fischler, B, Gonzales, E, Gouw, A, Hubscher, S, Jacquemin, E, Lacaille, F, Malenicka, S, Mclin, V, Markiewicz-Kijewska, M, Mazariegos, G, Rajanayagam, J, Scheenstra, R, Singer, S, Smets, F, Sokal, E, Squires, J, Sturm, E, Verkade, H, Kelly, D, Hartleif S., Hodson J., Lloyd C., Cousin V. L., Czubkowski P., D'Antiga L., Debray D., Demetris A., Di Giorgio A., Evans H. M., Fischler B., Gonzales E., Gouw A. S. H., Hubscher S. G., Jacquemin E., Lacaille F., Malenicka S., McLin V. A., Markiewicz-Kijewska M., Mazariegos G. V., Rajanayagam J. K., Scheenstra R., Singer S., Smets F., Sokal E., Squires J. E., Sturm E., Verkade H., Kelly D. A., Hartleif, S, Hodson, J, Lloyd, C, Cousin, V, Czubkowski, P, D'Antiga, L, Debray, D, Demetris, A, Di Giorgio, A, Evans, H, Fischler, B, Gonzales, E, Gouw, A, Hubscher, S, Jacquemin, E, Lacaille, F, Malenicka, S, Mclin, V, Markiewicz-Kijewska, M, Mazariegos, G, Rajanayagam, J, Scheenstra, R, Singer, S, Smets, F, Sokal, E, Squires, J, Sturm, E, Verkade, H, Kelly, D, Hartleif S., Hodson J., Lloyd C., Cousin V. L., Czubkowski P., D'Antiga L., Debray D., Demetris A., Di Giorgio A., Evans H. M., Fischler B., Gonzales E., Gouw A. S. H., Hubscher S. G., Jacquemin E., Lacaille F., Malenicka S., McLin V. A., Markiewicz-Kijewska M., Mazariegos G. V., Rajanayagam J. K., Scheenstra R., Singer S., Smets F., Sokal E., Squires J. E., Sturm E., Verkade H., and Kelly D. A.

Abstract

Background. The histological prevalence of allograft fibrosis in asymptomatic children after liver transplantation (LT) is well documented. However, long-term graft and patient survival remain unclear. This retrospective multicenter study aims to determine the prevalence of allograft fibrosis and analyze the long-term outcome for patients transplanted in childhood. Methods. We reviewed clinical data of children who had undergone 10-y protocol liver biopsies. We excluded patients with autoimmune hepatitis, primary sclerosing cholangitis, hepatitis B or C, and retransplantation. In total, 494 patients transplanted in childhood across 12 international transplant centers were included. We evaluated the development of fibrosis by comparing the results with biopsies obtained 5 and 15 y post-LT. Histological findings were correlated with graft and patient survival up to 20 y post-LT. Results. In the 10-y biopsies, periportal or pericentral fibrosis was observed in 253 patients (51%), 87 (18%) had bridging fibrosis, 30 (6%) had cirrhosis, and 124 (25%) had no fibrosis. The prevalence and stage of graft fibrosis significantly progressed from 5 to 10 y. At 10 y, the severity of fibrosis correlated significantly with inflammation. Patients with graft cirrhosis in the 10-y biopsy were more likely to die or require retransplantation subsequently (P = 0.027). Conclusions. At 10 y post-LT, most patients transplanted in childhood developed fibrosis, based on the protocol liver biopsies. Although mild-to-moderate graft fibrosis did not largely affect patient or graft survival up to 20 y post-LT, this progressive fibrosis finding has substantial implications for developing cirrhosis and portal hypertension in adult care.

Published
2023

9. Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Author

Colapietro, Francesca, primary, Maisonneuve, Patrick, additional, Lytvyak, Ellina, additional, Beuers, Ulrich, additional, Verdonk, Robert C., additional, van der Meer, Adriaan J., additional, van Hoek, Bart, additional, Kuiken, Sjoerd D., additional, Brouwer, Johannes T., additional, Muratori, Paolo, additional, Aghemo, Alessio, additional, Carella, Francesco, additional, van den Berg, Ad P., additional, Zachou, Kalliopi, additional, Dalekos, George N., additional, Di Zeo-Sánchez, Daniel E., additional, Robles, Mercedes, additional, Andrade, Raul J., additional, Montano-Loza, Aldo J., additional, van den Brand, Floris F., additional, Slooter, Charlotte D., additional, Macedo, Guilherme, additional, Liberal, Rodrigo, additional, de Boer, Ynto S., additional, Lleo, Ana, additional, van Gerven, N., additional, van Erpecum, K., additional, Ouden, J den, additional, Brouwer, J., additional, Vrolijk, J., additional, Gevers, T.J., additional, Drenth, J., additional, Guichelaar, M., additional, Bouma, G., additional, Schreuder, T.C.M.A., additional, van der Wouden, E.J., additional, Baak, L.C., additional, Stadhouders, P., additional, Klemt-Kropp, M., additional, Verhagen, M., additional, Bhalla, A., additional, Kuijvenhoven, J., additional, Almasio, P., additional, Alvarez, F., additional, Andrade, R., additional, Arikan, C., additional, Assis, D., additional, Bardou-Jacquet, E., additional, Biewenga, M., additional, Cancado, E., additional, Cazzagon, N., additional, Chazouillères, O., additional, Colloredo, G., additional, Cuarterolo, M., additional, Dalekos, G., additional, Debray, D., additional, Robles-Díaz, M., additional, Dyson, J., additional, Efe, C., additional, Engel, B., additional, Ferri, S., additional, Fontana, R., additional, Gatselis, N., additional, Gerussi, A., additional, Halilbasic, E., additional, Halliday, N., additional, Heneghan, M., additional, Hirschfield, G., additional, van Hoek, B., additional, Hørby Jørgensen, M., additional, Indolfini, G., additional, Iorio, R., additional, Invernizzi, P., additional, Jeong, S., additional, Jones, D., additional, Kelly, D., additional, Kerkar, N., additional, Lacaille, F., additional, Lammert, C., additional, Leggett, B., additional, Lenzi, M., additional, Levy, C., additional, Liberal, R., additional, Lleo, A., additional, Lohse, A., additional, Lopez, S. Ines, additional, de Martin, E., additional, McLin, V., additional, Mieli-Vergani, G., additional, Milkiewicz, P., additional, Mohan, N., additional, Muratori, L., additional, Nebbia, G., additional, van Nieuwkerk, C., additional, Oo, Y., additional, Ortega, A., additional, Páres, A., additional, Pop, T., additional, Pratt, D., additional, Purnak, T., additional, Ranucci, G., additional, Rushbrook, S., additional, Schramm, C., additional, Stättermayer, A., additional, Swain, M., additional, Tanaka, A., additional, Taubert, R., additional, Terrabuio, D., additional, Terziroli, B., additional, Trauner, M., additional, Valentino, P., additional, van den Brand, F., additional, Vergani, D., additional, Villamil, A., additional, Wahlin, S., additional, Ytting, H., additional, Zachou, K., additional, and Zeniya, M., additional

Published
2023
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10. Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)—A European Society of Organ Transplantation (ESOT) Consensus Statement

Author

Carbone, M., primary, Della Penna, A., additional, Mazzarelli, C., additional, De Martin, E., additional, Villard, C., additional, Bergquist, A., additional, Line, P. D., additional, Neuberger, J. M., additional, Al-Shakhshir, S., additional, Trivedi, P. J., additional, Baumann, U., additional, Cristoferi, L., additional, Hov, J., additional, Fischler, B., additional, Hadzic, N. H., additional, Debray, D., additional, D’Antiga, L., additional, Selzner, N., additional, Belli, L. S., additional, and Nadalin, S., additional

Published
2023
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11. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

Author

Pape, S, Snijders, R, Gevers, T, Chazouilleres, O, Dalekos, G, Hirschfield, G, Lenzi, M, Trauner, M, Manns, M, Vierling, J, Montano-Loza, A, Lohse, A, Schramm, C, Drenth, J, Heneghan, M, Almasio, P, Alvarez, F, Andrade, R, Arikan, C, Assis, D, Bardou-Jacquet, E, Biewenga, M, Cancado, E, Cazzagon, N, Colloredo, G, Cuarterolo, M, Debray, D, Robles-Diaz, M, Dyson, J, Efe, C, Engel, B, Ferri, S, Fontana, R, Gatselis, N, Gerussi, A, Halilbasic, E, Halliday, N, van Hoek, B, Horby Jorgensen, M, Indolfini, G, Iorio, R, Jeong, S, Jones, D, Kelly, D, Kerkar, N, Lacaille, F, Lammert, C, Leggett, B, Levy, C, Liberal, R, Lleo, A, Ines Lopez, S, de Martin, E, Mclin, V, Mieli-Vergani, G, Milkiewicz, P, Mohan, N, Muratori, L, Nebbia, G, van Nieuwkerk, C, Oo, Y, Ortega, A, Pares, A, Pop, T, Pratt, D, Purnak, T, Ranucci, G, Rushbrook, S, Stattermayer, A, Swain, M, Tanaka, A, Taubert, R, Terrabuio, D, Terziroli, B, Valentino, P, van den Brand, F, Villamil, A, Wahlin, S, Ytting, H, Zachou, K, Zeniya, M, Pape S., Snijders R. J. A. L. M., Gevers T. J. G., Chazouilleres O., Dalekos G. N., Hirschfield G. M., Lenzi M., Trauner M., Manns M. P., Vierling J. M., Montano-Loza A. J., Lohse A. W., Schramm C., Drenth J. P. H., Heneghan M. A., Almasio P., Alvarez F., Andrade R., Arikan C., Assis D., Bardou-Jacquet E., Biewenga M., Cancado E., Cazzagon N., Colloredo G., Cuarterolo M., Dalekos G., Debray D., Robles-Diaz M., Drenth J., Dyson J., Efe C., Engel B., Ferri S., Fontana R., Gatselis N., Gerussi A., Halilbasic E., Halliday N., Heneghan M., Hirschfield G., van Hoek B., Horby Jorgensen M., Indolfini G., Iorio R., Jeong S., Jones D., Kelly D., Kerkar N., Lacaille F., Lammert C., Leggett B., Levy C., Liberal R., Lleo A., Lohse A., Ines Lopez S., de Martin E., McLin V., Mieli-Vergani G., Milkiewicz P., Mohan N., Muratori L., Nebbia G., van Nieuwkerk C., Oo Y., Ortega A., Pares A., Pop T., Pratt D., Purnak T., Ranucci G., Rushbrook S., Stattermayer A., Swain M., Tanaka A., Taubert R., Terrabuio D., Terziroli B., Valentino P., van den Brand F., Villamil A., Wahlin S., Ytting H., Zachou K., Zeniya M., Pape, S, Snijders, R, Gevers, T, Chazouilleres, O, Dalekos, G, Hirschfield, G, Lenzi, M, Trauner, M, Manns, M, Vierling, J, Montano-Loza, A, Lohse, A, Schramm, C, Drenth, J, Heneghan, M, Almasio, P, Alvarez, F, Andrade, R, Arikan, C, Assis, D, Bardou-Jacquet, E, Biewenga, M, Cancado, E, Cazzagon, N, Colloredo, G, Cuarterolo, M, Debray, D, Robles-Diaz, M, Dyson, J, Efe, C, Engel, B, Ferri, S, Fontana, R, Gatselis, N, Gerussi, A, Halilbasic, E, Halliday, N, van Hoek, B, Horby Jorgensen, M, Indolfini, G, Iorio, R, Jeong, S, Jones, D, Kelly, D, Kerkar, N, Lacaille, F, Lammert, C, Leggett, B, Levy, C, Liberal, R, Lleo, A, Ines Lopez, S, de Martin, E, Mclin, V, Mieli-Vergani, G, Milkiewicz, P, Mohan, N, Muratori, L, Nebbia, G, van Nieuwkerk, C, Oo, Y, Ortega, A, Pares, A, Pop, T, Pratt, D, Purnak, T, Ranucci, G, Rushbrook, S, Stattermayer, A, Swain, M, Tanaka, A, Taubert, R, Terrabuio, D, Terziroli, B, Valentino, P, van den Brand, F, Villamil, A, Wahlin, S, Ytting, H, Zachou, K, Zeniya, M, Pape S., Snijders R. J. A. L. M., Gevers T. J. G., Chazouilleres O., Dalekos G. N., Hirschfield G. M., Lenzi M., Trauner M., Manns M. P., Vierling J. M., Montano-Loza A. J., Lohse A. W., Schramm C., Drenth J. P. H., Heneghan M. A., Almasio P., Alvarez F., Andrade R., Arikan C., Assis D., Bardou-Jacquet E., Biewenga M., Cancado E., Cazzagon N., Colloredo G., Cuarterolo M., Dalekos G., Debray D., Robles-Diaz M., Drenth J., Dyson J., Efe C., Engel B., Ferri S., Fontana R., Gatselis N., Gerussi A., Halilbasic E., Halliday N., Heneghan M., Hirschfield G., van Hoek B., Horby Jorgensen M., Indolfini G., Iorio R., Jeong S., Jones D., Kelly D., Kerkar N., Lacaille F., Lammert C., Leggett B., Levy C., Liberal R., Lleo A., Lohse A., Ines Lopez S., de Martin E., McLin V., Mieli-Vergani G., Milkiewicz P., Mohan N., Muratori L., Nebbia G., van Nieuwkerk C., Oo Y., Ortega A., Pares A., Pop T., Pratt D., Purnak T., Ranucci G., Rushbrook S., Stattermayer A., Swain M., Tanaka A., Taubert R., Terrabuio D., Terziroli B., Valentino P., van den Brand F., Villamil A., Wahlin S., Ytting H., Zachou K., and Zeniya M.

Abstract

Background & Aims: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. Methods: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis. Results: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term ‘complete biochemical response’ defined as ‘normalization of serum transaminases and IgG below the upper limit of normal’ be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as ‘<50% decrease of serum transaminases within 4 weeks after initiation of treatment’. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for ‘any adverse event possibly related to treatment leading to potential drug discontinuation’. Conclusions: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints. Lay summary: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents

Published
2022

12. Prognosis of Children Undergoing Liver Transplantation: A 30-Year European Study

Author

Baumann, U, Karam, V, Adam, R, Fondevila, C, Dhawan, A, Sokal, E, Jacquemin, E, Kelly, D, Grabhorn, E, Pawlowska, J, D'Antiga, L, Vega, P, Debray, D, Polak, W, de Ville de Goyet, J, Verkade, H, Baumann U., Karam V., Adam R., Fondevila C., Dhawan A., Sokal E., Jacquemin E., Kelly D. A., Grabhorn E., Pawlowska J., D'Antiga L., Vega P. J., Debray D., Polak W. G., de Ville de Goyet J., Verkade H. J., Baumann, U, Karam, V, Adam, R, Fondevila, C, Dhawan, A, Sokal, E, Jacquemin, E, Kelly, D, Grabhorn, E, Pawlowska, J, D'Antiga, L, Vega, P, Debray, D, Polak, W, de Ville de Goyet, J, Verkade, H, Baumann U., Karam V., Adam R., Fondevila C., Dhawan A., Sokal E., Jacquemin E., Kelly D. A., Grabhorn E., Pawlowska J., D'Antiga L., Vega P. J., Debray D., Polak W. G., de Ville de Goyet J., and Verkade H. J.

Abstract

OBJECTIVES: The European Liver Transplant Registry has been collecting data on virtually all pediatric liver transplant (PLT) procedures in Europe since 1968. We analyzed patient outcome over time and identified parameters associated with long-term patient outcome. METHODS: Participating centers and European organ-sharing organizations provided retrospective data to the European Liver Transplant Registry. To identify trends, data were grouped into consecutive time spans: era A: before 2000, era B: 2000 to 2009, and the current era, era C: since 2010. RESULTS: From June 1968 until December 2017, 16 641 PLT were performed on 14 515 children by 133 centers. The children <7 years of age represented 58% in era A, and 66% in the current era (P <.01). The main indications for PLT were congenital biliary diseases (44%) and metabolic diseases (18%). Patient survival at 5 years is currently 86% overall and 97% in children who survive the first year after PLT. The survival rate has improved from 74% in era A to 83% in era B and 85% in era C (P <.0001). Low-volume centers (<5 PLT/year) represented 75% of centers but performed only 19% of PLT and were associated with a decreased survival rate. In the current era, however, survival rates has become irrespective of volume. Infection is the leading cause of death (4.1%), followed by primary nonfunction of the graft (1.4%). CONCLUSIONS: PLT has become a highly successful medical treatment that should be considered for all children with end-stage liver disease. The main challenge for further improving the prognosis remains the early postoperative period.

Published
2022

13. International registry of congenital porto-systemic shunts: a multi-centre, retrospective and prospective registry of neonates, children and adults with congenital porto-systemic shunts

Author

Korff, S, Mostaguir, K, Beghetti, M, D'Antiga, L, Debray, D, Franchi-Abella, S, Gonzales, E, Guerin, F, Hachulla, A, Lambert, V, Makrythanasis, P, Roduit, N, Savale, L, Senat, M, Spaltenstein, J, van Steenbeek, F, Wildhaber, B, Zwahlen, M, Mclin, V, Korff S., Mostaguir K., Beghetti M., D'Antiga L., Debray D., Franchi-Abella S., Gonzales E., Guerin F., Hachulla A. -L., Lambert V., Makrythanasis P., Roduit N., Savale L., Senat M. -V., Spaltenstein J., van Steenbeek F., Wildhaber B. E., Zwahlen M., McLin V. A., Korff, S, Mostaguir, K, Beghetti, M, D'Antiga, L, Debray, D, Franchi-Abella, S, Gonzales, E, Guerin, F, Hachulla, A, Lambert, V, Makrythanasis, P, Roduit, N, Savale, L, Senat, M, Spaltenstein, J, van Steenbeek, F, Wildhaber, B, Zwahlen, M, Mclin, V, Korff S., Mostaguir K., Beghetti M., D'Antiga L., Debray D., Franchi-Abella S., Gonzales E., Guerin F., Hachulla A. -L., Lambert V., Makrythanasis P., Roduit N., Savale L., Senat M. -V., Spaltenstein J., van Steenbeek F., Wildhaber B. E., Zwahlen M., and McLin V. A.

Abstract

Background: Congenital portosystemic shunts (CPSS) are rare vascular malformations associated with the risk of life-threatening systemic conditions, which remain underdiagnosed and often are identified after considerable diagnostic delay. CPSS are characterized by multiple signs and symptoms, often masquerading as other conditions, progressing over time if the shunt remains patent. Which patients will benefit from shunt closure remains to be clarified, as does the timing and method of closure. In addition, the etiology and pathophysiology of CPSS are both unknowns. This rare disorder needs the strength of numbers to answer these questions, which is the purpose of the international registry of CPSS (IRCPSS). Method: A retrospective and prospective registry was designed using secuTrial® by the ISO certified Clinical Research Unit. Given that a significant number of cases entered in the registry are retrospective, participants have the opportunity to use a semi-structured minimal or complete data set to facilitate data entry. In addition, the design allows subjects to be entered into the IRCPSS according to clinically relevant events. Emphasis is on longitudinal follow-up of signs and symptoms, which is paramount to garner clinically relevant information to eventually orient patient management. The IRCPSS includes also three specific forms to capture essential radiological, surgical, and cardiopulmonary data as many times as relevant, which are completed by the specialists themselves. Finally, connecting the clinical data registry with a safe image repository, using state-of-the-art pseudonymization software, was another major focus of development. Data quality and stewardship is ensured by a steering committee. All centers participating in the IRCPSS have signed a memorandum of understanding and obtained their own ethical approval. Conclusion: Through state-of-the-art management of data and imaging, we have developed a practical, user-friendly, international registry

Published
2022

14. Severe acute hepatitis and acute liver failure of unknown origin in children: a questionnaire-based study within 34 paediatric liver centres in 22 European countries and Israel, April 2022

Author

de Kleine, R, Lexmond, W, Buescher, G, Sturm, E, Kelly, D, Lohse, A, Lenz, D, Jorgensen, M, Protopapa, P, Shteyer, E, Iorio, R, Pukite, I, Kucinskiene, R, Grima, A, Koot, B, Pop, T, De Bruyne, R, Stephenne, Vukovic, J, Mitrova, K, Kvistgaard, H, Merras-Salmio, L, Hery, G, Debray, D, Ruiz, M, Schulz-Jurgensen, S, Lurz, E, Hives, V, Cananzi, M, D'Antiga, L, di Giorgio, A, Pinon, M, Kaminska, D, Costa, I, Brecelj, J, Bartolo, G, Quintero, J, Fischler, B, Mclin, V, de Kleine R. H., Lexmond W. S., Buescher G., Sturm E., Kelly D., Lohse A. W., Lenz D., Jorgensen M. H., Protopapa P., Shteyer E., Iorio R., Pukite I., Kucinskiene R., Grima A. -M., Koot B., Pop T. L., De Bruyne R., Vukovic J., Mitrova K., Kvistgaard H., Merras-Salmio L., Hery G., Debray D., Ruiz M., Schulz-Jurgensen S., Lurz E., Hives V., Cananzi M., D'Antiga L., di Giorgio A., Pinon M., Kaminska D., Costa I. G., Brecelj J., Bartolo G. M., Quintero J., Fischler B., McLin V., de Kleine, R, Lexmond, W, Buescher, G, Sturm, E, Kelly, D, Lohse, A, Lenz, D, Jorgensen, M, Protopapa, P, Shteyer, E, Iorio, R, Pukite, I, Kucinskiene, R, Grima, A, Koot, B, Pop, T, De Bruyne, R, Stephenne, Vukovic, J, Mitrova, K, Kvistgaard, H, Merras-Salmio, L, Hery, G, Debray, D, Ruiz, M, Schulz-Jurgensen, S, Lurz, E, Hives, V, Cananzi, M, D'Antiga, L, di Giorgio, A, Pinon, M, Kaminska, D, Costa, I, Brecelj, J, Bartolo, G, Quintero, J, Fischler, B, Mclin, V, de Kleine R. H., Lexmond W. S., Buescher G., Sturm E., Kelly D., Lohse A. W., Lenz D., Jorgensen M. H., Protopapa P., Shteyer E., Iorio R., Pukite I., Kucinskiene R., Grima A. -M., Koot B., Pop T. L., De Bruyne R., Vukovic J., Mitrova K., Kvistgaard H., Merras-Salmio L., Hery G., Debray D., Ruiz M., Schulz-Jurgensen S., Lurz E., Hives V., Cananzi M., D'Antiga L., di Giorgio A., Pinon M., Kaminska D., Costa I. G., Brecelj J., Bartolo G. M., Quintero J., Fischler B., and McLin V.

Abstract

To detect potential concern about severe acute hepatitis in children, we conducted a survey among 50 ERN RARE-LIVER centres. By 26 April 2022, 34 centres, including 25 transplant centres, reported an estimated median of 3-5, 0-2 and 3-5 cases in 2021, 2020 and 2019 and a mean of 2 (range: 0-8) cases between January and April 2022 (mean in 10 large liver transplant centres: 3). Twelve centres reported suspicion of an increase, but no rise. Following a report by the United Kingdom (UK) on 5 April 2022 on the occurrence of cases of severe acute hepatitis in children aged 16 years or under, the World Health Organization (WHO) raised concerns about the possibility of an epidemic [1,2]. By 21 April, 169 possible or confirmed cases were reported fulfilling the WHO case definition [3]. The cause of the hepatitis is unknown but a link to a virus infection has been suggested due to the epidemiological pattern of cases [4,5]. The hepatitis can progress to paediatric acute liver failure (pALF) necessitating urgent liver transplantation to avoid multi-organ failure [6]. We intended to assess whether a rise in incidence of severe acute hepatitis or pALF could be observed between 1 January and 26 April 2022 in comparison to previous years, within the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) [7].

Published
2022

16. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study

Author

Vandriel, SM, Li, L-T, She, H, Wang, J-S, Gilbert, MA, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, EM, Jacquemin, E, Bouligand, J, Spinner, NB, Loomes, KM, Piccoli, DA, D'Antiga, L, Nicastro, E, Sokal, E, Demaret, T, Ebel, NH, Feinstein, JA, Fawaz, R, Nastasio, S, Lacaille, F, Debray, D, Arnell, H, Fischler, B, Siew, S, Stormon, M, Karpen, SJ, Romero, R, Kim, KM, Baek, WY, Hardikar, W, Shankar, S, Roberts, AJ, Evans, HM, Jensen, MK, Kavan, M, Sundaram, SS, Chaidez, A, Karthikeyan, P, Sanchez, MC, Cavalieri, ML, Verkade, HJ, Lee, WS, Squires, JE, Hajinicolaou, C, Lertudomphonwanit, C, Fischer, RT, Larson-Nath, C, Mozer-Glassberg, Y, Arikan, C, Lin, HC, Bernabeu, JQ, Alam, S, Kelly, DA, Carvalho, E, Ferreira, CT, Indolfi, G, Quiros-Tejeira, RE, Bulut, P, Calvo, PL, Onal, Z, Valentino, PL, Desai, DM, Eshun, J, Rogalidou, M, Dezsofi, A, Wiecek, S, Nebbia, G, Pinto, RB, Wolters, VM, Tamara, ML, Zizzo, AN, Garcia, J, Schwarz, K, Beretta, M, Sandahl, TD, Jimenez-Rivera, C, Kerkar, N, Brecelj, J, Mujawar, Q, Rock, N, Busoms, CM, Karnsakul, W, Lurz, E, Santos-Silva, E, Blondet, N, Bujanda, L, Shah, U, Thompson, RJ, Hansen, BE, Kamath, BM, Vandriel, SM, Li, L-T, She, H, Wang, J-S, Gilbert, MA, Jankowska, I, Czubkowski, P, Gliwicz-Miedzinska, D, Gonzales, EM, Jacquemin, E, Bouligand, J, Spinner, NB, Loomes, KM, Piccoli, DA, D'Antiga, L, Nicastro, E, Sokal, E, Demaret, T, Ebel, NH, Feinstein, JA, Fawaz, R, Nastasio, S, Lacaille, F, Debray, D, Arnell, H, Fischler, B, Siew, S, Stormon, M, Karpen, SJ, Romero, R, Kim, KM, Baek, WY, Hardikar, W, Shankar, S, Roberts, AJ, Evans, HM, Jensen, MK, Kavan, M, Sundaram, SS, Chaidez, A, Karthikeyan, P, Sanchez, MC, Cavalieri, ML, Verkade, HJ, Lee, WS, Squires, JE, Hajinicolaou, C, Lertudomphonwanit, C, Fischer, RT, Larson-Nath, C, Mozer-Glassberg, Y, Arikan, C, Lin, HC, Bernabeu, JQ, Alam, S, Kelly, DA, Carvalho, E, Ferreira, CT, Indolfi, G, Quiros-Tejeira, RE, Bulut, P, Calvo, PL, Onal, Z, Valentino, PL, Desai, DM, Eshun, J, Rogalidou, M, Dezsofi, A, Wiecek, S, Nebbia, G, Pinto, RB, Wolters, VM, Tamara, ML, Zizzo, AN, Garcia, J, Schwarz, K, Beretta, M, Sandahl, TD, Jimenez-Rivera, C, Kerkar, N, Brecelj, J, Mujawar, Q, Rock, N, Busoms, CM, Karnsakul, W, Lurz, E, Santos-Silva, E, Blondet, N, Bujanda, L, Shah, U, Thompson, RJ, Hansen, BE, and Kamath, BM

Abstract

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. APPROACH AND RESULTS: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p < 0.001). CONCLUSIONS: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies.

Published
2023

19. Under-vaccination in pediatric liver transplant candidates with acute and chronic liver disease-a retrospective observational study of the European reference network transplantchild

Author

Laue, T, Demir, Z, Debray, D, Cananzi, M, Gaio, P, Casotti, V, D'Antiga, L, Urbonas, V, Baumann, U, Laue T., Demir Z., Debray D., Cananzi M., Gaio P., Casotti V., D'Antiga L., Urbonas V., Baumann U., Laue, T, Demir, Z, Debray, D, Cananzi, M, Gaio, P, Casotti, V, D'Antiga, L, Urbonas, V, Baumann, U, Laue T., Demir Z., Debray D., Cananzi M., Gaio P., Casotti V., D'Antiga L., Urbonas V., and Baumann U.

Abstract

Infection is a serious concern in the short and long term after pediatric liver transplantation. Vaccination represents an easy and cheap opportunity to reduce morbidity and mortality due to vaccine-preventable infection. This retrospective, observational, multi-center study examines the immunization status in pediatric liver transplant candidates at the time of transplantation and compares it to a control group of children with acute liver disease. Findings show only 80% were vaccinated age-appropriately, defined as having received the recommended number of vaccination doses for their age prior to transplantation; for DTP-PV-Hib, less than 75% for Hepatitis B and two-thirds for pneumococcal conjugate vaccine in children with chronic liver disease. Vaccination coverage for live vaccines is better compared to the acute control group with 81% versus 62% for measles, mumps and rubella (p = 0.003) and 65% versus 55% for varicella (p = 0.171). Nevertheless, a country-specific comparison with national reference data suggests a lower vaccination coverage in children with chronic liver disease. Our study reveals an under-vaccination in this high-risk group prior to transplantation and underlines the need to improve vaccination.

Published
2021

20. Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

Author

Montano-Loza, A.J., Ronca, V., Ebadi, M., Hansen, B.E., Hirschfield, G., Elwir, S., Alsaed, M., Milkiewicz, P., Janik, M.K., Marschall, H.U., Burza, M.A., Efe, C., Caliskan, A.R., Harputluoglu, M., Kabacam, G., Terrabuio, D., Onofrio, F.D., Selzner, N., Bonder, A., Pares, A., Llovet, L., Akyildiz, M., Arikan, C., Manns, M.P., Taubert, R., Weber, A.L., Schiano, T.D., Haydel, B., Czubkowski, P., Socha, P., Oldak, N., Akamatsu, N., Tanaka, A., Levy, C., Martin, E.F., Goel, A., Sedki, M., Jankowska, I., Ikegami, T., Rodriguez, M., Sterneck, M., Weiler-Normann, C., Schramm, C., Donato, M.F., Lohse, A., Andrade, R.J., Patwardhan, V.R., Hoek, B. van, Biewenga, M., Kremer, A.E., Ueda, Y., Deneau, M., Pedersen, M., Mayo, M.J., Floreani, A., Burra, P., Secchi, M.F., Beretta-Piccoli, B.T., Sciveres, M., Maggiore, G., Jafri, S.M., Debray, D., Girard, M., Lacaille, F., Lytvyak, E., Mason, A.L., Heneghan, M., Oo, Y.H., and Int Autoimmune Hepatitis Grp IAIHG

Subjects
Adult, Male, Hepatology, liver transplantation, recurrent disease, autoimmune liver disease, graft survival, Mycophenolic Acid, survival, Hepatitis, Autoimmune, Recurrence, Risk Factors, Immunoglobulin G, Humans, Female, Immunosuppressive Agents
Abstract

Background & Aims: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.Methods: We included 736 patients (77% female, mean age 42 +/- 1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.Results: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT

Published
2022

21. Natural history of liver disease in a large international cohort of children with Alagille syndrome: results from The GALA Study

Author

Arıkan, Çiğdem (ORCID 0000-0002-0794-2741 & YÖK ID 240198), Vandriel, S.M.; Li, L.T.; She, H.; Wang, J.S.; Gilbert, M.A.; Jankowska, I.; Czubkowski, P.; Gliwicz-Miedzi?ska, D.; Gonzales, E.M.; Jacquemin, E.; Bouligand, J.; Spinner, N.B.; Loomes, K.M.; Piccoli, D.A.; D'Antiga, L.; Nicastro, E.; Sokal, É.; Demaret, T.; Ebel, N.H.; Feinstein, J.A.; Fawaz, R.; Nastasio, S.; Lacaille, F.; Debray, D.; Arnell, H.; Fischler, B.; Siew, S.; Stormon, M.; Karpen, S.J.; Romero, R.; Kim, K.M.; Baek, W.Y.; Hardikar, W.; Shankar, S.; Roberts, A.J.; Evans, H.M.; Jensen, M.K.; Kavan, M.; Sundaram, S.S.; Chaidez, A.; Karthikeyan, P.; Sanchez, M.C.; Cavalieri, M.L.; Verkade, H.J.; Lee, W.S.; Squires, J.E.; Hajinicolaou, C.; Lertudomphonwanit, C.; Fischer, R.T.; Larson-Nath, C.; Mozer-Glassberg, Y.; Lin, H.C.; Quintero, Bernabeu J.; Alam, S.; Kelly, D.; Carvalho, E.; Ferreira, C.T.; Indolfi, G.; Quiros-Tejeira, R.E.; Bulut, P.; Calvo, P.L.; Önal, Z.; Valentino, P.L.; Desai, D.M.; Eshun, J.; Rogalidou, M.; Dezs?fi, A.; Wiecek, S.; Nebbia, G.; Borges Pinto, R.; Wolters, V.M.; Tamara, M.L.; Zizzo, A.N.; Garcia, J.; Schwarz, K.; Beretta, M.; Sandahl, T.D.; Jimenez-Rivera, C.; Kerkar, N.; Brecelj, J.; Mujawar, Q.; Rock, N.; Busoms, C.M.; Karnsakul, W.; Lurz, E.; Santos-Silva, E.; Blondet, N.; Bujanda, L.; Shah, U.; Thompson, R.J.; Hansen, B.E.; Kamath, B.M.; Global ALagille Alliance (GALA) Study Group, Koç University Hospital, School of Medicine, Arıkan, Çiğdem (ORCID 0000-0002-0794-2741 & YÖK ID 240198), Vandriel, S.M.; Li, L.T.; She, H.; Wang, J.S.; Gilbert, M.A.; Jankowska, I.; Czubkowski, P.; Gliwicz-Miedzi?ska, D.; Gonzales, E.M.; Jacquemin, E.; Bouligand, J.; Spinner, N.B.; Loomes, K.M.; Piccoli, D.A.; D'Antiga, L.; Nicastro, E.; Sokal, É.; Demaret, T.; Ebel, N.H.; Feinstein, J.A.; Fawaz, R.; Nastasio, S.; Lacaille, F.; Debray, D.; Arnell, H.; Fischler, B.; Siew, S.; Stormon, M.; Karpen, S.J.; Romero, R.; Kim, K.M.; Baek, W.Y.; Hardikar, W.; Shankar, S.; Roberts, A.J.; Evans, H.M.; Jensen, M.K.; Kavan, M.; Sundaram, S.S.; Chaidez, A.; Karthikeyan, P.; Sanchez, M.C.; Cavalieri, M.L.; Verkade, H.J.; Lee, W.S.; Squires, J.E.; Hajinicolaou, C.; Lertudomphonwanit, C.; Fischer, R.T.; Larson-Nath, C.; Mozer-Glassberg, Y.; Lin, H.C.; Quintero, Bernabeu J.; Alam, S.; Kelly, D.; Carvalho, E.; Ferreira, C.T.; Indolfi, G.; Quiros-Tejeira, R.E.; Bulut, P.; Calvo, P.L.; Önal, Z.; Valentino, P.L.; Desai, D.M.; Eshun, J.; Rogalidou, M.; Dezs?fi, A.; Wiecek, S.; Nebbia, G.; Borges Pinto, R.; Wolters, V.M.; Tamara, M.L.; Zizzo, A.N.; Garcia, J.; Schwarz, K.; Beretta, M.; Sandahl, T.D.; Jimenez-Rivera, C.; Kerkar, N.; Brecelj, J.; Mujawar, Q.; Rock, N.; Busoms, C.M.; Karnsakul, W.; Lurz, E.; Santos-Silva, E.; Blondet, N.; Bujanda, L.; Shah, U.; Thompson, R.J.; Hansen, B.E.; Kamath, B.M.; Global ALagille Alliance (GALA) Study Group, Koç University Hospital, and School of Medicine

Abstract

Background and aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced >= 1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and <= 12 months) with median total bilirubin (TB) levels between >= 5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those >= 10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those 10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to >= 5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: in this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies., This study received funding support from the following agencies: The Alagille Syndrome Alliance, Mirum Pharmaceuticals Inc. and Albireo Pharma, Inc. who provided unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation). The study sponsors were not involved in the conduct of the research study or preparation of the manuscript.

Published
2022

26. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

Author

Pape, Simon, primary, Snijders, Romée J.A.L.M., additional, Gevers, Tom J.G., additional, Chazouilleres, Oliver, additional, Dalekos, George N., additional, Hirschfield, Gideon M., additional, Lenzi, Marco, additional, Trauner, Michael, additional, Manns, Michael P., additional, Vierling, John M., additional, Montano-Loza, Aldo J., additional, Lohse, Ansgar W., additional, Schramm, Christoph, additional, Drenth, Joost P.H., additional, Heneghan, Michael A., additional, Almasio, P., additional, Alvarez, F., additional, Andrade, R., additional, Arikan, C., additional, Assis, D., additional, Bardou-Jacquet, E., additional, Biewenga, M., additional, Cancado, E., additional, Cazzagon, N., additional, Chazouillères, O., additional, Colloredo, G., additional, Cuarterolo, M., additional, Dalekos, G., additional, Debray, D., additional, Robles-Díaz, M., additional, Drenth, J., additional, Dyson, J., additional, Efe, C., additional, Engel, B., additional, Ferri, S., additional, Fontana, R., additional, Gatselis, N., additional, Gerussi, A., additional, Halilbasic, E., additional, Halliday, N., additional, Heneghan, M., additional, Hirschfield, G., additional, van Hoek, B., additional, Hørby Jørgensen, M., additional, Indolfini, G., additional, Iorio, R., additional, Jeong, S., additional, Jones, D., additional, Kelly, D., additional, Kerkar, N., additional, Lacaille, F., additional, Lammert, C., additional, Leggett, B., additional, Lenzi, M., additional, Levy, C., additional, Liberal, R., additional, Lleo, A., additional, Lohse, A., additional, Ines Lopez, S., additional, de Martin, E., additional, McLin, V., additional, Mieli-Vergani, G., additional, Milkiewicz, P., additional, Mohan, N., additional, Muratori, L., additional, Nebbia, G., additional, van Nieuwkerk, C., additional, Oo, Y., additional, Ortega, A., additional, Páres, A., additional, Pop, T., additional, Pratt, D., additional, Purnak, T., additional, Ranucci, G., additional, Rushbrook, S., additional, Schramm, C., additional, Stättermayer, A., additional, Swain, M., additional, Tanaka, A., additional, Taubert, R., additional, Terrabuio, D., additional, Terziroli, B., additional, Trauner, M., additional, Valentino, P., additional, van den Brand, F., additional, Villamil, A., additional, Wahlin, S., additional, Ytting, H., additional, Zachou, K., additional, and Zeniya, M., additional

Published
2022
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27. Proceedings of ESPGHAN Monothematic Conference 2020: 'acute Liver Failure in Children': Diagnosis and Initial Management

Author

Zellos, A. Debray, D. Indolfi, G. Czubkowski, P. Samyn, M. Hadzic, N. Gupte, G. Fischler, B. Smets, F. De Cléty, S.C. Grenda, R. Mozer, Y. Mancell, S. Jahnel, J. Auzinger, G. Worth, A. Lisman, T. Staufner, C. Baumann, U. Dhawan, A. Alonso, E. Squires, R.H. Verkade, H.J.

Abstract

Objectives:The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children.Methods:The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups.Results:In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points.Conclusions:The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future. © 2022 Lippincott Williams and Wilkins. All rights reserved.

Published
2022

28. Treatment and monitoring of children with chronic hepatitis C in the Pre-DAA era: A European survey of 38 paediatric specialists

Author

Indolfi, G, Bailey, H, Serranti, D, Giaquinto, C, Thorne, C, Sokal, E, Debray, D, Girard, M, Feiterna-Sperling, C, Wirth, S, Guidi, R, Verucchi, G, D'Antiga, L, Nicastro, E, Maggiore, G, Trapani, S, Ricci, S, Resti, M, Giacomet, V, Benincaso, A, Nebbia, G, Iorio, R, Cananzi, M, Riva, S, Bossi, G, Dodi, I, Nobili, V, Comparcola, D, Garazzino, S, Calvo, P, Pokorska-Spiewak, M, Pawlowska, M, Goncalves, C, Goncalves, I, Bals, M, Tudor, A, Noguera-Julian, A, Ramos, J, Fischler, B, Mclin, V, Brown, M, Kelly, D, Davison, S, Turkova, A, Bamford, A, Indolfi G., Bailey H., Serranti D., Giaquinto C., Thorne C., Sokal E., Debray D., Girard M., Feiterna-Sperling C., Wirth S., Guidi R., Verucchi G., D'Antiga L., Nicastro E., Maggiore G., Trapani S., Ricci S., Resti M., Giacomet V., Benincaso A. R., Nebbia G., Iorio R., Cananzi M., Riva S., Bossi G., Dodi I., Nobili V., Comparcola D., Garazzino S., Calvo P. L., Pokorska-Spiewak M., Pawlowska M., Goncalves C., Goncalves I., Bals M., Tudor A. M., Noguera-Julian A., Ramos J. T., Fischler B., McLin V., Brown M., Kelly D., Davison S., Turkova A., Bamford A., Indolfi, G, Bailey, H, Serranti, D, Giaquinto, C, Thorne, C, Sokal, E, Debray, D, Girard, M, Feiterna-Sperling, C, Wirth, S, Guidi, R, Verucchi, G, D'Antiga, L, Nicastro, E, Maggiore, G, Trapani, S, Ricci, S, Resti, M, Giacomet, V, Benincaso, A, Nebbia, G, Iorio, R, Cananzi, M, Riva, S, Bossi, G, Dodi, I, Nobili, V, Comparcola, D, Garazzino, S, Calvo, P, Pokorska-Spiewak, M, Pawlowska, M, Goncalves, C, Goncalves, I, Bals, M, Tudor, A, Noguera-Julian, A, Ramos, J, Fischler, B, Mclin, V, Brown, M, Kelly, D, Davison, S, Turkova, A, Bamford, A, Indolfi G., Bailey H., Serranti D., Giaquinto C., Thorne C., Sokal E., Debray D., Girard M., Feiterna-Sperling C., Wirth S., Guidi R., Verucchi G., D'Antiga L., Nicastro E., Maggiore G., Trapani S., Ricci S., Resti M., Giacomet V., Benincaso A. R., Nebbia G., Iorio R., Cananzi M., Riva S., Bossi G., Dodi I., Nobili V., Comparcola D., Garazzino S., Calvo P. L., Pokorska-Spiewak M., Pawlowska M., Goncalves C., Goncalves I., Bals M., Tudor A. M., Noguera-Julian A., Ramos J. T., Fischler B., McLin V., Brown M., Kelly D., Davison S., Turkova A., and Bamford A.

Abstract

The burden of paediatric Hepatitis C virus (HCV) infection across Europe is unknown, as are current policies regarding monitoring and treatment. This collaborative study aimed to collect aggregate data to characterise the population of ≤18-year-olds with HCV infection in specialist follow up in a 12-month period (2016) across the PENTAHep European consortium, and investigate current policies around monitoring and treatment. A cross-sectional, web-based survey was distributed in April 2017 to 50 paediatricians in 19 European countries, covering patients' profile, and monitoring and treatment practices. Responses were received from 38/50 clinicians collectively caring for 663 children with chronic HCV infection of whom three-quarters were aged ≥6 years and 90% vertically infected. HCV genotype 1 was the most common (n 380; 57.3%), followed by genotype 3, 4 and 2. Seventeen children (3%) with chronic HCV infection were diagnosed with cirrhosis, and six were reported to have received liver transplantation for HCV-related liver disease. The majority (n 425; 64.1%) of the European children with HCV infection remained treatment-naive in 2016. Age affected clinicians' attitudes towards treatment; 94% reported being willing to use direct-acting antivirals, if available, in adolescents (aged ≥11 years), 78% in children aged 6-10 and 42% in those 3-5 years of age (Pearson correlation coefficient −0.98; P 0.0001). This survey provides the largest characterisation of the population of children in clinical follow-up for chronic HCV infection in Europe, alongside important contextual information on their management and treatment. Discussion is needed around strategies and criteria for use of direct-acting antivirals in these children.

Published
2019

29. Similarities and differences in allocation policies for pediatric liver transplantation across the world

Author

Fischler, B, Baumann, U, D'Agostino, D, D'Antiga, L, Dezsofi, A, Debray, D, Durmaz, O, Evans, H, Frauca, E, Hadzic, N, Jahnel, J, Loveland, J, Mclin, V, Ng, V, Nobili, V, Pawłowska, J, Sharif, K, Smets, F, Verkade, H, Hsu, E, Horslen, S, Bucuvalas, J, Fischler B., Baumann U., D'Agostino D., D'Antiga L., Dezsofi A., Debray D., Durmaz O., Evans H., Frauca E., Hadzic N., Jahnel J., Loveland J., McLin V., Ng V. L., Nobili V., Pawłowska J., Sharif K., Smets F., Verkade H. J., Hsu E., Horslen S., Bucuvalas J., Fischler, B, Baumann, U, D'Agostino, D, D'Antiga, L, Dezsofi, A, Debray, D, Durmaz, O, Evans, H, Frauca, E, Hadzic, N, Jahnel, J, Loveland, J, Mclin, V, Ng, V, Nobili, V, Pawłowska, J, Sharif, K, Smets, F, Verkade, H, Hsu, E, Horslen, S, Bucuvalas, J, Fischler B., Baumann U., D'Agostino D., D'Antiga L., Dezsofi A., Debray D., Durmaz O., Evans H., Frauca E., Hadzic N., Jahnel J., Loveland J., McLin V., Ng V. L., Nobili V., Pawłowska J., Sharif K., Smets F., Verkade H. J., Hsu E., Horslen S., and Bucuvalas J.

Abstract

Objectives:We aimed to investigate national allocation policies for pediatric liver transplantation (LT).Method:A survey was prepared by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Hepatology Committee in collaboration with the North American Studies of Pediatric Liver Transplantation consortium. The survey was sent to pediatric hepatologists and transplant surgeons worldwide. National data were obtained from centrally based registries.Results:Replies were obtained from 15 countries from 5 of the world continents. Overall donation rate varied between 9 and 35 per million inhabitants. The number of pediatric LTs was 4 to 9 per million inhabitants younger than 18 years for 13 of the 15 respondents. In children younger than 2 years mortality on the waiting list (WL) varied between 0 and 20%. In the same age group, there were large differences in the ratio of living donor LT to deceased donor LT and in the ratio of split liver segments to whole liver. These differences were associated with possible discrepancies in WL mortality.Conclusions:Similarities but also differences between countries were detected. The described data may be of importance when trying to reduce WL mortality in the youngest children.

Published
2019

30. Efficacy and safety of prolonged-release tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus – a Phase 2, open-label, single-arm, one-way crossover study

Author

Rubik, J, Debray, D, Kelly, D, Iserin, F, Webb, N, Czubkowski, P, Vondrak, K, Sellier-Leclerc, A, Rivet, C, Riva, S, Tonshoff, B, D'Antiga, L, Marks, S, Reding, R, Kazeem, G, Undre, N, Rubik J., Debray D., Kelly D., Iserin F., Webb N. J. A., Czubkowski P., Vondrak K., Sellier-Leclerc A. -L., Rivet C., Riva S., Tonshoff B., D'Antiga L., Marks S. D., Reding R., Kazeem G., Undre N., Rubik, J, Debray, D, Kelly, D, Iserin, F, Webb, N, Czubkowski, P, Vondrak, K, Sellier-Leclerc, A, Rivet, C, Riva, S, Tonshoff, B, D'Antiga, L, Marks, S, Reding, R, Kazeem, G, Undre, N, Rubik J., Debray D., Kelly D., Iserin F., Webb N. J. A., Czubkowski P., Vondrak K., Sellier-Leclerc A. -L., Rivet C., Riva S., Tonshoff B., D'Antiga L., Marks S. D., Reding R., Kazeem G., and Undre N.

Abstract

There are limited clinical data regarding prolonged-release tacrolimus (PR-T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR-T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate-release tacrolimus (IR-T), on a 1:1 mg total-daily-dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy-confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole-blood trough levels (target 3.5–15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6–17.7% of patients across follow-up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug-related treatment-emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR-T to PR-T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.

Published
2019

31. Comparative pharmacokinetics of tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus to prolonged-release tacrolimus formulation

Author

Rubik, J, Debray, D, Iserin, F, Vondrak, K, Sellier-Leclerc, A, Kelly, D, Czubkowski, P, Webb, N, Riva, S, D'Antiga, L, Marks, S, Rivet, C, Tonshoff, B, Kazeem, G, Undre, N, Rubik J., Debray D., Iserin F., Vondrak K., Sellier-Leclerc A. -L., Kelly D., Czubkowski P., Webb N. J. A., Riva S., D'Antiga L., Marks S. D., Rivet C., Tonshoff B., Kazeem G., Undre N., Rubik, J, Debray, D, Iserin, F, Vondrak, K, Sellier-Leclerc, A, Kelly, D, Czubkowski, P, Webb, N, Riva, S, D'Antiga, L, Marks, S, Rivet, C, Tonshoff, B, Kazeem, G, Undre, N, Rubik J., Debray D., Iserin F., Vondrak K., Sellier-Leclerc A. -L., Kelly D., Czubkowski P., Webb N. J. A., Riva S., D'Antiga L., Marks S. D., Rivet C., Tonshoff B., Kazeem G., and Undre N.

Abstract

This study was a Phase II, open-label, multicenter, single-arm, cross-over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T). In Days −30 to −1 of screening period, patients received their IR-T-based regimen; during Days 1-7, patients received study IR-T (same dose as screening). On Day 7, the first 24-hours PK profile was taken; patients were then converted to PR-T (1 mg:1 mg), with a second 24-hours PK profile taken on Day 14. The primary end-point was tacrolimus area under the blood concentration–time curve over 24 hours (AUC24); secondary end-points were maximum concentration Cmaxand concentration at 24 hours C24. The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%-125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1). PR-T:IR-T LSM ratio (90% CI) was similar overall for AUC24, max, and C24, and for kidney and liver recipients for AUC24 (LSM ratio, kidney 91.8%; liver 104.1%) and C24 (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC24 and C24, and between PR-T and IR-T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR-T to PR-T at the same total daily dose, using the same therapeutic drug monitoring method.

Published
2019

32. Health-related quality of life in pre-adolescent liver transplant recipients with biliary atresia: A cross-sectional study

Author

Miserachs, M, Parmar, A, Bakula, A, Hierro, L, D'Antiga, L, Goldschmidt, I, Debray, D, A McLin, V, Casotti, V, Pawlowska, J, Camarena, C, R Otley, A, Baumann, U, L Ng, V, Miserachs M., Parmar A., Bakula A., Hierro L., D'Antiga L., Goldschmidt I., Debray D., A McLin V., Casotti V., Pawlowska J., Camarena C., R Otley A., Baumann U., L Ng V., Miserachs, M, Parmar, A, Bakula, A, Hierro, L, D'Antiga, L, Goldschmidt, I, Debray, D, A McLin, V, Casotti, V, Pawlowska, J, Camarena, C, R Otley, A, Baumann, U, L Ng, V, Miserachs M., Parmar A., Bakula A., Hierro L., D'Antiga L., Goldschmidt I., Debray D., A McLin V., Casotti V., Pawlowska J., Camarena C., R Otley A., Baumann U., and L Ng V.

Abstract

Objective: Pediatric recipients of liver transplantation (LT) often report lower Health-Related Quality of Life (HRQOL) than healthy controls when assessed on generic HRQOL measurement tools. The recent addition of the Pediatric Liver Transplant Quality of Life (PeLTQL), a novel disease-specific HRQOL instrument for pediatric LT recipients, into the clinical armamentarium of tools now routinely available to clinical care teams, provides the unique opportunity to identify disease-related challenges in children who have undergone this life-saving intervention. This study assesses HRQOL in pre-adolescent aged patients with a primary diagnosis of biliary atresia (BA) who underwent LT as an infant, using both generic and disease-specific HRQOL instruments validated for children. We also examined modifiable factors associated with HRQOL after pediatric LT. Methods: HRQOL was the primary outcome of this study assessed using the disease-specific PeLTQL and the generic Pediatric Quality of Life Inventory 4.0 (PedsQL). Exposure variables of interest included medication status (e.g., monotherapy, dual therapy) and participation in sports. Results: A total of 70 (56% female, mean age 9.89 ± 1.25 years) pediatric LT recipients (mean interval since LT was 9.0 ± 1.26 years) comprised the study cohort. LT recipients reported significantly lower PedsQL Scores relative to the general population. Immunosuppression monotherapy was associated with higher patient-reported PeLTQL Scores, and sports participation was associated with higher parent-reported PedsQL Scores. Conclusions: Pre-adolescents who underwent LT as an infant with BA, self-report low HRQOL on both disease-specific and generic HRQOL tools. Further research targeting sports participation and simplifying immunosuppression may further optimize quality of life years restored by life-saving LT.

Published
2019

33. Immune status in children before liver transplantation — A cross-sectional analysis within the ChilsSFree multicentre cohort study

Author

Mohring, T, Karch, A, Falk, C, Laue, T, D'Antiga, L, Debray, D, Hierro, L, Kelly, D, Mclin, V, Mckiernan, P, Pawlowska, J, Czubkowski, P, Mikolajczyk, R, Baumann, U, Goldschmidt, I, Mohring T., Karch A., Falk C. S., Laue T., D'Antiga L., Debray D., Hierro L., Kelly D., McLin V., McKiernan P., Pawlowska J., Czubkowski P., Mikolajczyk R. T., Baumann U., Goldschmidt I., Mohring, T, Karch, A, Falk, C, Laue, T, D'Antiga, L, Debray, D, Hierro, L, Kelly, D, Mclin, V, Mckiernan, P, Pawlowska, J, Czubkowski, P, Mikolajczyk, R, Baumann, U, Goldschmidt, I, Mohring T., Karch A., Falk C. S., Laue T., D'Antiga L., Debray D., Hierro L., Kelly D., McLin V., McKiernan P., Pawlowska J., Czubkowski P., Mikolajczyk R. T., Baumann U., and Goldschmidt I.

Abstract

Background: Both, markers of cellular immunity and serum cytokines have been proposed as potential biomarkers for graft rejection after liver transplantation. However, no good prognostic model is available for the prediction of acute cellular rejection. The impact of underlying disease and demographic factors on immune status before pediatric liver transplantation (pLTx) is still poorly understood. We investigated expression of immune markers before pLTx, in order to better understand the pre-transplant immune status. Improved knowledge of the impact of pre-transplant variables may enhance our understanding of immunological changes post pLTx in the future. Methods: This is a cross-sectional analysis of data from the ChilSFree study, a European multicentre cohort study investigating the longitudinal patterns of immune response before and after pLTx. Immune cell counts and soluble immune markers were measured in 155 children 1–30 days before pLTx by TruCount analysis and BioPlex assays. Results were logarithmised due to skewed distributions and then compared according to age, sex, and diagnosis using t-tests, ANOVAs, and Tukey post-hoc tests. The association between immune markers at time of pLTx and patients' age was assessed using a fractional polynomial approach. Multivariable regression models were used to assess the relative contribution of each factor. Results: Sex had no effect on immune status. We found strong evidence for age-specific differences in the immune status. The majority of immune markers decreased in a log-linear way with increasing age. T and B cells showed a sharp increase within the first months of life followed by a log-linear decline in older age groups. Several immune markers were strongly associated with underlying diagnoses. The effects of age and underlying disease remained virtually unchanged when adjusting for each other in multivariable models. Discussion: We show for the first time that age and diagnosis are major independent determina

Published
2019

34. INTRAHEPATIC AND EXTRAHEPATIC CONGENITAL PORTOSYSTEMIC SHUNTS DIFFER IN IN CLINICAL PRESENTATION AND OUTCOMES IN CHILDREN

Author

Mclin, V, Franchi-Abella, S, Debray, D, Korff, S, Casotti, V, Colledan, M, D'Antiga, L, De Goyet, J, Lurz, E, Stephenne, X, Rock, N, Hierro, L, Kanavaki, I, Lipsich, J, Lopez-Santamaria, M, Magnusson, M, Mozer-Glassberg, Y, Ponce, M, Prieto, C, Durmaz, O, Varma, S, Guerin, F, Pop, T, Wildhaber, B, Gonzales, E, McLin VA, Franchi-Abella S, Debray D, Korff S, Casotti V, Colledan M, D'Antiga L, De Goyet JD, Lurz E, Stephenne X, Rock N, Hierro L, Kanavaki I, Lipsich J, Lopez-Santamaria M, Magnusson M, Mozer-Glassberg Y, Ponce MD, Prieto C, Durmaz O, Varma S, Guerin F, Pop T, Wildhaber B, Gonzales EM, Mclin, V, Franchi-Abella, S, Debray, D, Korff, S, Casotti, V, Colledan, M, D'Antiga, L, De Goyet, J, Lurz, E, Stephenne, X, Rock, N, Hierro, L, Kanavaki, I, Lipsich, J, Lopez-Santamaria, M, Magnusson, M, Mozer-Glassberg, Y, Ponce, M, Prieto, C, Durmaz, O, Varma, S, Guerin, F, Pop, T, Wildhaber, B, Gonzales, E, McLin VA, Franchi-Abella S, Debray D, Korff S, Casotti V, Colledan M, D'Antiga L, De Goyet JD, Lurz E, Stephenne X, Rock N, Hierro L, Kanavaki I, Lipsich J, Lopez-Santamaria M, Magnusson M, Mozer-Glassberg Y, Ponce MD, Prieto C, Durmaz O, Varma S, Guerin F, Pop T, Wildhaber B, and Gonzales EM

Published
2019

37. Efficacy and Safety of Two Salts of Trientine in the Treatment of Wilson Disease

Author

Poujois A, Obadia Ma, Woimant F, Debray D, and Morvan E

Subjects
Text mining, business.industry, polycyclic compounds, Medicine, Disease, biochemical phenomena, metabolism, and nutrition, Bioinformatics, business
Abstract

BackgroundWilson disease (WD) is one of the few genetic disorders that can be successfully treated with pharmacological agents. Copper-chelating agents (D-penicillamine and Trientine salts) and zinc salts have been demonstrated to be effective. There are two salts of trientine. Trientine dihydrochloride salt (TETA 2HCL) is unstable at room temperature and requires storage at 2-8°C. Trientine tetrahydrochloride (TETA 4HCL) is a more stable salt of trientine that can be stored at room temperature. No comparative study between both salts of trientine has been performed to date. As the two chemical forms were available in France between 1970 and 2009, we conducted a study to evaluate their efficacy and safety profiles. MethodsThis retrospective cohort study was conducted by reviewing data from the national WD registry in France. Forty-three WD patients who received TETA 2HCL or TETA 4HCL monotherapy for at least one year until 2010 were included. Primary endpoints were hepatic and neurological outcomes. Secondary endpoints were the events leading to a discontinuation of medication. Results: Changes in medication were common, leading to the analysis of 57 treatment sequences of TETA 4HCL or TETA 2HCL. The mean duration of treatment sequence was significantly longer in the TETA 4 HCL group (12.6 years) than in the TETA 2HCL group (7.6 years) (p=0.011). No difference in efficacy was detected. Both treatments were well tolerated except for a case of recurrence of lupus erythematosus-like syndrome in the TETA 2HCL group. The major reason for interruption of TETA 4HCL was due to a discontinuation in production of this salt. The reasons for stopping TETA 2HCL were mainly due to adherence issues largely attributed to the cold storage requirement. ConclusionsThe two salts of trientine were effective in treating patients with WD. However, interruption of TETA 2HCL was frequent, linked to the cold storage requirement. As adherence to treatment is a key factor in the successful management of WD, physicians need to be even more vigilant in detecting adherence difficulties in patients receiving treatment with TETA 2HCL.

Published
2021
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38. Impact of genotype, serum bile acids, and surgical biliary diversion on native liver survival in FIC1 deficiency

Author

Arıkan, Çiğdem (ORCID 0000-0002-0794-2741 & YÖK ID 240198), van Wessel, D. B. E.; Thompson, R. J.; Gonzales, E.; Jankowska, I.; Shneider, B. L.; Sokal, E.; Grammatikopoulos, T.; Kadaristiana, A.; Jacquemin, E.; Spraul, A.; Lipiński, P.; Czubkowski, P.; Rock, N.; Shagrani, M.; Broering, D.; Algoufi, T.; Mazhar, N.; Nicastro, E.; Kelly, D.; Nebbia, G.; Arnell, H.; Fischler, B.; Hulscher, J. B. F.; Serranti, D.; Debray, D.; Lacaille, F.; Goncalves, C.; Hierro, L.; Muñoz Bartolo, G.; Mozer-Glassberg, Y.; Azaz, A.; Brecelj, J.; Dezsőfi, A.; Luigi Calvo, P.; Krebs-Schmitt, D.; Hartleif, S.; van der Woerd, W. L.; Wang, J. S.; Li, L. T.; Durmaz, Ö.; Kerkar, N.; Hørby Jørgensen, M.; Fischer, R.; Jimenez-Rivera, C.; Alam, S.; Cananzi, M.; Laverdure, N.; Ferreira, C. T.; Ordonez, F.; Wang, H.; Sency, V.; Kim, K. M.; Chen, H. L.; Carvalho, E.; Fabre, A.; Quintero Bernabeu, J.; Alonso, E. M.; Sokol, R. J.; Suchy, F. J.; Loomes, K. M.; McKiernan, P. J.; Rosenthal, P.; Turmelle, Y.; Rao, G. S.; Horslen, S.; Kamath, B. M.; Rogalidou, M.; Karnsakul, W. W.; Hansen, B.; Verkade, H. J., Arıkan, Çiğdem (ORCID 0000-0002-0794-2741 & YÖK ID 240198), and van Wessel, D. B. E.; Thompson, R. J.; Gonzales, E.; Jankowska, I.; Shneider, B. L.; Sokal, E.; Grammatikopoulos, T.; Kadaristiana, A.; Jacquemin, E.; Spraul, A.; Lipiński, P.; Czubkowski, P.; Rock, N.; Shagrani, M.; Broering, D.; Algoufi, T.; Mazhar, N.; Nicastro, E.; Kelly, D.; Nebbia, G.; Arnell, H.; Fischler, B.; Hulscher, J. B. F.; Serranti, D.; Debray, D.; Lacaille, F.; Goncalves, C.; Hierro, L.; Muñoz Bartolo, G.; Mozer-Glassberg, Y.; Azaz, A.; Brecelj, J.; Dezsőfi, A.; Luigi Calvo, P.; Krebs-Schmitt, D.; Hartleif, S.; van der Woerd, W. L.; Wang, J. S.; Li, L. T.; Durmaz, Ö.; Kerkar, N.; Hørby Jørgensen, M.; Fischer, R.; Jimenez-Rivera, C.; Alam, S.; Cananzi, M.; Laverdure, N.; Ferreira, C. T.; Ordonez, F.; Wang, H.; Sency, V.; Kim, K. M.; Chen, H. L.; Carvalho, E.; Fabre, A.; Quintero Bernabeu, J.; Alonso, E. M.; Sokol, R. J.; Suchy, F. J.; Loomes, K. M.; McKiernan, P. J.; Rosenthal, P.; Turmelle, Y.; Rao, G. S.; Horslen, S.; Kamath, B. M.; Rogalidou, M.; Karnsakul, W. W.; Hansen, B.; Verkade, H. J.

Abstract

Mutations in ATP8B1 can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1 (PFIC1). The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide novel insights by using the largest genetically defined cohort of FIC1 deficiency patients to date. This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication); FIC1-A (n=67; no PPTM), FIC1-B (n=29; one PPTM) or FIC1-C (n=34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18y. NLS was comparable between FIC1-A, FIC1-B, and FIC1-C (%NLS at age 10y: 67%, 41%, and 59%, respectively; P=0.12), despite FIC1-C undergoing SBD less often (%SBD at age 10y: 65%, 57%, and 45%, respectively; P=0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10y; sBAs <194 µmol/L: 49% versus sBAs ≥194 µmol/L: 15%; P=0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P=0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P=0.06) and post-SBD sBA concentrations <65μmol/L (P=0.05) tended to be associated with improved NLS. Conclusion: Less than half of FIC1 deficiency patients reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

Published
2021

41. Immune monitoring after pediatric liver transplantation - the prospective ChilSFree cohort study

Author

Goldschmidt, I, Karch, A, Mikolajczyk, R, Mutschler, F, Junge, N, Pfister, E, Mohring, T, D'Antiga, L, Mckiernan, P, Kelly, D, Debray, D, Mclin, V, Pawlowska, J, Hierro, L, Daemen, K, Keil, J, Falk, C, Baumann, U, Goldschmidt I., Karch A., Mikolajczyk R., Mutschler F., Junge N., Pfister E. D., Mohring T., d'Antiga L., McKiernan P., Kelly D., Debray D., McLin V., Pawlowska J., Hierro L., Daemen K., Keil J., Falk C., Baumann U., Goldschmidt, I, Karch, A, Mikolajczyk, R, Mutschler, F, Junge, N, Pfister, E, Mohring, T, D'Antiga, L, Mckiernan, P, Kelly, D, Debray, D, Mclin, V, Pawlowska, J, Hierro, L, Daemen, K, Keil, J, Falk, C, Baumann, U, Goldschmidt I., Karch A., Mikolajczyk R., Mutschler F., Junge N., Pfister E. D., Mohring T., d'Antiga L., McKiernan P., Kelly D., Debray D., McLin V., Pawlowska J., Hierro L., Daemen K., Keil J., Falk C., and Baumann U.

Abstract

Background: Although trough levels of immunosuppressive drugs are largely used to monitor immunosuppressive therapy after solid organ transplantation, there is still no established tool that allows for a validated assessment of functional degree of immunosuppression or the identification of clinically relevant over- or under-immunosuppression, depending on graft homeostasis. Reliable non-invasive markers to predict biopsy proven acute rejection (BPAR) do not exist. Literature data suggest that longitudinal measurements of immune markers might be predictive of BPAR, but data in children are scarce. We therefore propose an observational prospective cohort study focusing on immune monitoring in children after liver transplantation. We aim to describe immune function in a cohort of children before and during the first year after liver transplantation and plan to investigate how the immune function profile is associated with clinical and laboratory findings. Methods: In an international multicenter prospective approach, children with end-stage liver disease who undergo liver transplantation are enrolled to the study and receive extensive immune monitoring before and at 1, 2, 3, 4 weeks and 3, 6, 12 months after transplantation, and whenever a clinically indicated liver biopsy is scheduled. Blood samples are analyzed for immune cell numbers and circulating levels of cytokines, chemokines and factors of angiogenesis reflecting immune cell activation. Statistical analysis will focus on the identification of trajectorial patterns of immune reactivity predictive for systemic non-inflammatory states, infectious complications or BPAR using joint modelling approaches. Discussion: The ChilSFree study will help to understand the immune response after pLTx in different states of infection or rejection. It may provide insight into response mechanisms eventually facilitating immune tolerance towards the graft. Our analysis may yield an applicable immune panel for non-invasive early d

Published
2018

43. Early and Late Factors Impacting Patient and Graft Outcome in Pediatric Liver Transplantation: Summary of an ESPGHAN Monothematic Conference

Author

Mclin, V, Allen, U, Boyer, O, Bucuvalas, J, Colledan, M, Cuturi, M, D'Antiga, L, Debray, D, Dezsofi, A, de Goyet, J, Dhawan, A, Durmaz, O, Falk, C, Feng, S, Fischler, B, Franchi-Abella, S, Frauca, E, Ganschow, R, Gottschalk, S, Hadzic, N, Hierro, L, Horslen, S, Hubscher, S, Karam, V, Kelly, D, Maecker-Kolhoff, B, Mazariegos, G, Mckiernan, P, Melk, A, Nobili, V, Ozgenc, F, Reding, R, Sciveres, M, Sharif, K, Socha, P, Toso, C, Vajro, P, Verma, A, Wildhaber, B, Baumann, U, Mclin VA, Allen U, Boyer O, Bucuvalas J, Colledan M, Cuturi MC, d'Antiga L, Debray D, Dezsofi A, de Goyet JD, Dhawan A, Durmaz O, Falk C, Feng S, Fischler B, Franchi-Abella S, Frauca E, Ganschow R, Gottschalk S, Hadzic N, Hierro L, Horslen S, Hubscher S, Karam V, Kelly D, Maecker-Kolhoff B, Mazariegos G, McKiernan P, Melk A, Nobili V, Ozgenc F, Reding R, Sciveres M, Sharif K, Socha P, Toso C, Vajro P, Verma A, Wildhaber BE, Baumann U, Mclin, V, Allen, U, Boyer, O, Bucuvalas, J, Colledan, M, Cuturi, M, D'Antiga, L, Debray, D, Dezsofi, A, de Goyet, J, Dhawan, A, Durmaz, O, Falk, C, Feng, S, Fischler, B, Franchi-Abella, S, Frauca, E, Ganschow, R, Gottschalk, S, Hadzic, N, Hierro, L, Horslen, S, Hubscher, S, Karam, V, Kelly, D, Maecker-Kolhoff, B, Mazariegos, G, Mckiernan, P, Melk, A, Nobili, V, Ozgenc, F, Reding, R, Sciveres, M, Sharif, K, Socha, P, Toso, C, Vajro, P, Verma, A, Wildhaber, B, Baumann, U, Mclin VA, Allen U, Boyer O, Bucuvalas J, Colledan M, Cuturi MC, d'Antiga L, Debray D, Dezsofi A, de Goyet JD, Dhawan A, Durmaz O, Falk C, Feng S, Fischler B, Franchi-Abella S, Frauca E, Ganschow R, Gottschalk S, Hadzic N, Hierro L, Horslen S, Hubscher S, Karam V, Kelly D, Maecker-Kolhoff B, Mazariegos G, McKiernan P, Melk A, Nobili V, Ozgenc F, Reding R, Sciveres M, Sharif K, Socha P, Toso C, Vajro P, Verma A, Wildhaber BE, and Baumann U

Abstract

As pediatric liver transplantation comes of age, experts gathered to discuss current paradigms and define gaps in knowledge warranting research to further improve patient and graft outcomes. Identified areas ripe for collaborative research include understanding the molecular and cellular mechanisms of tolerance and the role of donor-specific antibodies, considering ways to expand donor pool, minimizing long-term side effects of immunosuppression, and fine-tuning surgical techniques to minimize biliary and vascular complications. Copyright © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Published
2017

44. Congenital porto-systemic shunts in children: preliminary results from the IRCPSS

Author

McLin, Valérie, Franchi-Abella, S, Debray, D., Korff, S, Casotti V, Colledan, M, d'Antiga, L, de Ville de Goyet, J, Lurz, E., Stéphenne, Xavier, ROCK, Nathalie, 52nd Annual Meeting ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology and Nutrition), UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique

Abstract

Objectives and Study: Our aim was to use data from patients followed by centers participating in the first International Registry for Congenital Porto-Systemic Shunts (IRCPSS) to identify trends that might inform therapeutic strategies according to shunt anatomy. Methods: Data were collected retrospectively (descriptive patient data, mode of presentation, complications, management). Intrahepatic (IH) was defined as porto-hepatic and extrahepatic (EH) as a porto-systemic communication occurring either upstream of the portal vein or originating at the portal vein. Persistent ductus venosus were considered EH. Results: 246 children were identified with either intrahepatic (IH) or extrahepatic shunts (EH): 122 IH and 120 EH. 3 patients had both IH and EH. 24% of all CPSS were identified pre-natally. Among patients diagnosed pre-natally, a majority had IH shunts (75%). 189 (76%) patients were diagnosed post-natally at a mean age of 39.1 mo (0-200) for IH and 61.9mo (0-192) for EH. IH and EH shunts were equally frequent when diagnosed after birth. IH shunts were more often an incidental finding. Among patients diagnosed post-natally, symptoms were equally frequent among patients with IH (57%) or EH (61%) CPSS and are summarized in Table 1. In addition, patients with EH CPSS were more likely to have several symptoms than patients with IH CPSS. They were also more likely to have liver nodules on imaging (40.7% vs 26%). Closure: 184 children with CPSS were closed including 11 patients with 2 steps closure. Among these 184 patients 54 % of IH CPSS and 5% of EH CPSS closed spontaneously. 46% of IH CPSS required medical or surgical closure of which nearly 40% for a preventive indication. 94% of patients with EH CPSS were closed through a procedure, of which 41% were preventive. Conclusion: IH and EH shunts were equally frequent in this multicenter retrospective cohort of CPSS in children. CPSS are a cause of severe symptoms in children and should be sought in infants with hypoglycemia or cholestasis. In older children, they should be considered in the differential diagnosis of liver nodules, cardiopulmonary symptoms or neurocognitive deficits. Given the potential severity of complications, preventative closure was often performed, although timing and approach need further study, something which the IRCPSS aims to address.

Published
2019

46. Congenital porto-systemic shunts in children: preliminary results from the IRCPSS

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, McLin, V., Franchi-Abella, S, Debray, D., Korff, S., Casotti, V., Colledan, M., d'Antiga, L., de Ville de Goyet, J., Lurz, E., Stéphenne, Xavier, ROCK, Nathalie, Hierro, L., Kanavaki, A., Lipsich, J., Lopez-Santamaria, M., Magnusson, M., Mozer-Glassberg, Y., Ponce, M.D., Prieto, C., Ugurcan, O.D., Varma, S., Guerin, F., Pop,T., Wildhaber, B., Gonzales, E., The International Liver Congress (EASL), UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, McLin, V., Franchi-Abella, S, Debray, D., Korff, S., Casotti, V., Colledan, M., d'Antiga, L., de Ville de Goyet, J., Lurz, E., Stéphenne, Xavier, ROCK, Nathalie, Hierro, L., Kanavaki, A., Lipsich, J., Lopez-Santamaria, M., Magnusson, M., Mozer-Glassberg, Y., Ponce, M.D., Prieto, C., Ugurcan, O.D., Varma, S., Guerin, F., Pop,T., Wildhaber, B., Gonzales, E., and The International Liver Congress (EASL)

Abstract

Background: • Congenital portosystemic shunts (CPSS) are increasingly diagnosed in children and adults owing to high resolution imaging. • Their natural history is incompletely understood. • CPSS may be associated with life-threatening complications. • There are no established predictors of spontaneous closure. •Among patients in whom CPSS does not close spontaneously, is unclear which patients will develop complications, consequently which shunts require closure. Aim: To use preliminary data from 15/28 centers participating in the International Registry for Congenital Porto-Systemic Shunts (IRCPSS) to identify trends that might inform management decisions

Published
2019

48. Transplantation/Digestive tract

Author

Durand, P., Jacquemin, E., Chardot, C., Iserin, F., Dousset, B., Devictor, D., Weiss, Irwin, Erian, Cherif, Ament, Marvin, Vargas, Jorge, McDiarmid, Sue, Brill, Judith, Le Pommelet, C., Debray, D., Sasbón J., Centeno M., Entin E., Acerenza M., Ciocca M., Goñi J., Bianco G., Weller G., Imventarza O., Ruza F., Calvo C., Dorao P. G., Filgueiras D., Alvarez E., Delgado M. A., Flores, J. Casado, Mora, E., García Teresa M. A., Azagra, A. Martínez, Serrano, A., Ibiza E., Abengochea A., Modesto V., Abengochea B., Arago J., Sanchis R., Varas R., Garcia E., Booker P. D., Prosser D. P., Franks R., Phuong, Kiel Dang, and Thanh, Hai Le

Published
1996
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