Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

Maaike Biewenga; Xavier P.D.M.J. Verhelst; Martine A.M.C. Baven-Pronk; Hein Putter; Aad P. van den Berg; Karin C.M.J. van Nieuwkerk; Henk R. van Buuren; Gerd Bouma; Ynte S. de Boer; Cedric Simoen; Isabelle Colle; Jeoffrey Schouten; Filip Sermon; Christophe van Steenkiste; Hans van Vlierberghe; Adriaan J. van der Meer; Frederik Nevens; Bart van Hoek; J. P.H. Drenth; N. M. van Gerven; U. Beuers; K. J. van Erpecum; J. W. den Ouden; A. Bhalla; J. T. Brouwer; J. M. Vrolijk; G. H. Koek; M. M.J. Guichelaar; E. J. van der Wouden; J. J.M. van Meyel; L. C. Baak; R. C. Verdonk; M. Klemt-Kropp; M. A.M.T. Verhagen; J. Kuijvenhoven; H. M. de Jonge; Dutch Autoimmune Hepatitis Study Group

doi:10.1002/ueg2.12112

Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

Maaike Biewenga
, Xavier P.D.M.J. Verhelst
, Martine A.M.C. Baven-Pronk
, Hein Putter
, Aad P. van den Berg
, Karin C.M.J. van Nieuwkerk
, Henk R. van Buuren
, Gerd Bouma
, Ynte S. de Boer
, Cedric Simoen
, Isabelle Colle
, Jeoffrey Schouten
, Filip Sermon
, Christophe van Steenkiste
, Hans van Vlierberghe
, Adriaan J. van der Meer
, Frederik Nevens
, Bart van Hoek^*
, J. P.H. Drenth
, N. M. van Gerven

U. Beuers, K. J. van Erpecum, J. W. den Ouden, A. Bhalla, J. T. Brouwer, J. M. Vrolijk, G. H. Koek, M. M.J. Guichelaar, E. J. van der Wouden, J. J.M. van Meyel, L. C. Baak, R. C. Verdonk, M. Klemt-Kropp, M. A.M.T. Verhagen, J. Kuijvenhoven, H. M. de Jonge, Dutch Autoimmune Hepatitis Study Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective: The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods: The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results: In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60–202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790–0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25–142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%–24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%–9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%–11.4%); C-statistic 0.744 [95% CI 0.644–0.844]). Conclusions: A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated.

Original language	English
Pages (from-to)	662-671
Number of pages	10
Journal	United European Gastroenterology Journal
Volume	9
Issue number	6
DOIs	https://doi.org/10.1002/ueg2.12112
Publication status	Published - 1 Jul 2021

Keywords

AIH
autoimmune hepatitis
autoimmune liver disease
liver transplantation
long-term survival
mortality
prognostic score
risk stratification
transplant-free survival
validation

Access to Document

10.1002/ueg2.12112Licence: CC BY-NC-ND

Cite this

Biewenga, M., Verhelst, X. P. D. M. J., Baven-Pronk, M. A. M. C., Putter, H., van den Berg, A. P., van Nieuwkerk, K. C. M. J., van Buuren, H. R., Bouma, G., de Boer, Y. S., Simoen, C., Colle, I., Schouten, J., Sermon, F., van Steenkiste, C., van Vlierberghe, H., van der Meer, A. J., Nevens, F., van Hoek, B., Drenth, J. P. H., ... Dutch Autoimmune Hepatitis Study Group (2021). Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1. United European Gastroenterology Journal, 9(6), 662-671. https://doi.org/10.1002/ueg2.12112

@article{3bcd32f7b3144964bfe301fd0a52affd,

title = "Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1",

abstract = "Background: No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective: The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods: The prognostic score was developed using uni- \& multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results: In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60–202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95\% CI 0.790–0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25–142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5\% vs. 15.7\% (95\% CI: 6.3\%–24.2\%); moderate risk group 5.8\% versus 4.3\% (95\% CI: 0.0\%–9.1\%); low risk group 1.9\% versus 5.4\% (95\% CI: 0.0\%–11.4\%); C-statistic 0.744 [95\% CI 0.644–0.844]). Conclusions: A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated.",

keywords = "AIH, autoimmune hepatitis, autoimmune liver disease, liver transplantation, long-term survival, mortality, prognostic score, risk stratification, transplant-free survival, validation",

author = "Maaike Biewenga and Verhelst, \{Xavier P.D.M.J.\} and Baven-Pronk, \{Martine A.M.C.\} and Hein Putter and \{van den Berg\}, \{Aad P.\} and \{van Nieuwkerk\}, \{Karin C.M.J.\} and \{van Buuren\}, \{Henk R.\} and Gerd Bouma and \{de Boer\}, \{Ynte S.\} and Cedric Simoen and Isabelle Colle and Jeoffrey Schouten and Filip Sermon and \{van Steenkiste\}, Christophe and \{van Vlierberghe\}, Hans and \{van der Meer\}, \{Adriaan J.\} and Frederik Nevens and \{van Hoek\}, Bart and Drenth, \{J. P.H.\} and \{van Gerven\}, \{N. M.\} and U. Beuers and \{van Erpecum\}, \{K. J.\} and \{den Ouden\}, \{J. W.\} and A. Bhalla and Brouwer, \{J. T.\} and Vrolijk, \{J. M.\} and Koek, \{G. H.\} and Guichelaar, \{M. M.J.\} and \{van der Wouden\}, \{E. J.\} and \{van Meyel\}, \{J. J.M.\} and Baak, \{L. C.\} and Verdonk, \{R. C.\} and M. Klemt-Kropp and Verhagen, \{M. A.M.T.\} and J. Kuijvenhoven and \{de Jonge\}, \{H. M.\} and \{Dutch Autoimmune Hepatitis Study Group\}",

note = "Funding Information: We thank the other members of the Dutch Auto-Immune Hepatitis Study Group for fruitful discussions regarding the manuscript: J.P.H. Drenth (Radboud UMC Nijmegen); N.M. van Gerven (Rode Kruis ziekenhuis; Beverwijk); U. Beuers (AMC Amsterdam); K.J. van Erpecum (UMCU Utrecht); J.W. den Ouden and A. Bhalla (Hagaziekenhuis den Haag); J.T. Brouwer (Reinier de Graaf Gasthuis Delft); J.M. Vrolijk (Rijnstate hospital Arnhem); G.H. Koek (MUMC, Maastricht); M.M.J. Guichelaar (Medisch Spectrum Twente, Enschede); E.J. van der Wouden (Isala hospital Zwolle); J.J.M van Meyel and L.C. Baak (OLVG, Amsterdam); R.C. Verdonk (St. Antonius Hospital Nieuwegein); M. Klemt-Kropp (Noordwest Ziekenhuisgroep Alkmaar); M.A.M.T. Verhagen (Diakonessenhuis, Utrecht); J. Ph. Kuijvenhoven (Spaarne Gasthuis Haarlem); H.M. de Jonge (Jeroen Bosch ziekenhuis den Bosch); MB was supported by unrestricted grants from Zambon Pharma. No other financial support received for this study. Publisher Copyright: {\textcopyright} 2021 The Authors. UEG Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.",

year = "2021",

month = jul,

day = "1",

doi = "10.1002/ueg2.12112",

language = "English",

volume = "9",

pages = "662--671",

journal = "United European Gastroenterology Journal",

issn = "2050-6406",

publisher = "John Wiley \& Sons Inc.",

number = "6",

}

Biewenga, M, Verhelst, XPDMJ, Baven-Pronk, MAMC, Putter, H, van den Berg, AP, van Nieuwkerk, KCMJ, van Buuren, HR, Bouma, G, de Boer, YS, Simoen, C, Colle, I, Schouten, J, Sermon, F, van Steenkiste, C, van Vlierberghe, H, van der Meer, AJ, Nevens, F, van Hoek, B, Drenth, JPH, van Gerven, NM, Beuers, U, van Erpecum, KJ, den Ouden, JW, Bhalla, A, Brouwer, JT, Vrolijk, JM, Koek, GH, Guichelaar, MMJ, van der Wouden, EJ, van Meyel, JJM, Baak, LC, Verdonk, RC, Klemt-Kropp, M, Verhagen, MAMT, Kuijvenhoven, J, de Jonge, HM & Dutch Autoimmune Hepatitis Study Group 2021, 'Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1', United European Gastroenterology Journal, vol. 9, no. 6, pp. 662-671. https://doi.org/10.1002/ueg2.12112

TY - JOUR

T1 - Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

AU - Biewenga, Maaike

AU - Verhelst, Xavier P.D.M.J.

AU - Baven-Pronk, Martine A.M.C.

AU - Putter, Hein

AU - van den Berg, Aad P.

AU - van Nieuwkerk, Karin C.M.J.

AU - van Buuren, Henk R.

AU - Bouma, Gerd

AU - de Boer, Ynte S.

AU - Simoen, Cedric

AU - Colle, Isabelle

AU - Schouten, Jeoffrey

AU - Sermon, Filip

AU - van Steenkiste, Christophe

AU - van Vlierberghe, Hans

AU - van der Meer, Adriaan J.

AU - Nevens, Frederik

AU - van Hoek, Bart

AU - Drenth, J. P.H.

AU - van Gerven, N. M.

AU - Beuers, U.

AU - van Erpecum, K. J.

AU - den Ouden, J. W.

AU - Bhalla, A.

AU - Brouwer, J. T.

AU - Vrolijk, J. M.

AU - Koek, G. H.

AU - Guichelaar, M. M.J.

AU - van der Wouden, E. J.

AU - van Meyel, J. J.M.

AU - Baak, L. C.

AU - Verdonk, R. C.

AU - Klemt-Kropp, M.

AU - Verhagen, M. A.M.T.

AU - Kuijvenhoven, J.

AU - de Jonge, H. M.

AU - Dutch Autoimmune Hepatitis Study Group

N1 - Funding Information: We thank the other members of the Dutch Auto-Immune Hepatitis Study Group for fruitful discussions regarding the manuscript: J.P.H. Drenth (Radboud UMC Nijmegen); N.M. van Gerven (Rode Kruis ziekenhuis; Beverwijk); U. Beuers (AMC Amsterdam); K.J. van Erpecum (UMCU Utrecht); J.W. den Ouden and A. Bhalla (Hagaziekenhuis den Haag); J.T. Brouwer (Reinier de Graaf Gasthuis Delft); J.M. Vrolijk (Rijnstate hospital Arnhem); G.H. Koek (MUMC, Maastricht); M.M.J. Guichelaar (Medisch Spectrum Twente, Enschede); E.J. van der Wouden (Isala hospital Zwolle); J.J.M van Meyel and L.C. Baak (OLVG, Amsterdam); R.C. Verdonk (St. Antonius Hospital Nieuwegein); M. Klemt-Kropp (Noordwest Ziekenhuisgroep Alkmaar); M.A.M.T. Verhagen (Diakonessenhuis, Utrecht); J. Ph. Kuijvenhoven (Spaarne Gasthuis Haarlem); H.M. de Jonge (Jeroen Bosch ziekenhuis den Bosch); MB was supported by unrestricted grants from Zambon Pharma. No other financial support received for this study. Publisher Copyright: © 2021 The Authors. UEG Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - Background: No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective: The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods: The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results: In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60–202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790–0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25–142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%–24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%–9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%–11.4%); C-statistic 0.744 [95% CI 0.644–0.844]). Conclusions: A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated.

AB - Background: No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective: The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods: The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results: In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60–202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790–0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25–142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%–24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%–9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%–11.4%); C-statistic 0.744 [95% CI 0.644–0.844]). Conclusions: A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated.

KW - AIH

KW - autoimmune hepatitis

KW - autoimmune liver disease

KW - liver transplantation

KW - long-term survival

KW - mortality

KW - prognostic score

KW - risk stratification

KW - transplant-free survival

KW - validation

U2 - 10.1002/ueg2.12112

DO - 10.1002/ueg2.12112

M3 - Article

SN - 2050-6406

VL - 9

SP - 662

EP - 671

JO - United European Gastroenterology Journal

JF - United European Gastroenterology Journal

IS - 6

ER -

Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

Abstract

Keywords

Access to Document

Fingerprint

Cite this