Quality of Life in Patients With Variant Syndromes of Autoimmune Liver Diseases—A Cross‐Sectional Multicentre Study

Natalie Uhlenbusch; Romée J. A. L. M. Snijders; Meike Mund; Maciej K. Janik; Piotr Milkiewicz; Bernd Löwe; Claudia Kroll; Joanna Raszeja‐Wyszomirska; Alessio Gerussi; Francesca Bolis; Laura Cristoferi; Pietro Invernizzi; Patricia Kovats; Mária Papp; Lisbet Grønbæk; Henning Grønbæk; Eric T. T. L. Tjwa; Luise Aamann; Henriette Ytting; Vincenzo Ronca; Kathryn Olsen; Ye H. Oo; Adriaan J. van der Meer; João Madaleno; Bernardo Canhão; Bastian Engel; Alejandro Campos‐Murguia; Richard Taubert; Özgür M. Koc; Matthijs Kramer; José A. Willemse; Ansgar W. Lohse; Joost P. H. Drenth; Tom J. G. Gevers; Christoph Schramm

doi:10.1111/liv.70526

Quality of Life in Patients With Variant Syndromes of Autoimmune Liver Diseases—A Cross‐Sectional Multicentre Study

Natalie Uhlenbusch^*
, Romée J. A. L. M. Snijders
, Meike Mund
, Maciej K. Janik
, Piotr Milkiewicz
, Bernd Löwe
, Claudia Kroll
, Joanna Raszeja‐Wyszomirska
, Alessio Gerussi
, Francesca Bolis
, Laura Cristoferi
, Pietro Invernizzi
, Patricia Kovats
, Mária Papp
, Lisbet Grønbæk
, Henning Grønbæk
, Eric T. T. L. Tjwa
, Luise Aamann
, Henriette Ytting
, Vincenzo Ronca

Kathryn Olsen, Ye H. Oo, Adriaan J. van der Meer, João Madaleno, Bernardo Canhão, Bastian Engel, Alejandro Campos‐Murguia, Richard Taubert, Özgür M. Koc, Matthijs Kramer, José A. Willemse, Ansgar W. Lohse, Joost P. H. Drenth, Tom J. G. Gevers, Christoph Schramm^*

^*Corresponding author for this work

Immunology and Immunotherapy

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

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Abstract

Background & Aims: Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) go along with reduced health‐related quality of life (HRQOL). Variant syndromes, that is, conditions with features of both PBC/PSC and AIH, are associated with higher clinical complexity and worse prognosis. Studies on HRQOL in patients with variant syndromes are lacking. We aimed to provide large‐scale evidence addressing this gap.

Methods: We included adult patients with clinical diagnoses of autoimmune liver diseases across nine countries in a cross‐sectional study. We descriptively compared demographical, clinical and patient‐reported outcomes between the conditions and investigated whether additional AIH contributes to reduced HRQOL compared to the cholestatic liver disease alone. Further, we explored the role of fatigue, cirrhosis and depression severity regarding HRQOL.

Results: N = 1275 patients were included (PBC: n = 342, PBC‐AIH: n = 160, PSC: n = 305, PSC‐AIH: n = 121, AIH: n = 347). Patients with variant syndromes showed high rates of cirrhosis and increased depressive or anxiety symptoms. Additional AIH was associated with further reduction in physical and mental HRQOL in people with PSC (physical: ΔR² = 0.012, p = 0.041; mental: ΔR² = 0.016, p = 0.020), but not with PBC (physical: ΔR² = 0.008, p = 0.081; mental: ΔR² = 0.001, p = 0.609). Physical HRQOL was associated with higher age and fatigue, while mental HRQOL was associated with lower age, fatigue, and depression severity.

Conclusions: Patients with variant syndromes of autoimmune liver diseases show high physical and mental burden, with fatigue as the main contributor. Particularly PSC‐AIH goes along with more severely reduced HRQOL compared to the cholestatic liver disease alone, which is attributable to a higher symptom burden.

Original language	English
Article number	e70526
Number of pages	11
Journal	Liver International
Volume	46
Issue number	3
Early online date	2 Feb 2026
DOIs	https://doi.org/10.1111/liv.70526
Publication status	Published - Mar 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

autoimmune liver diseases
variant syndrome
cholestatic liver diseases
autoimmune hepatitis
overlap syndrome
quality of life

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Stop the Clock of Chronic Inflammation
Anderson, G. (Co-Investigator) & Oo, Y. (Principal Investigator)
The Wellcome Trust
1/03/26 → 28/02/34
Project: Research
Regulatory T-Cells immunotherapy for treatment of primary biliary cholangitis.
Lee, S. (Co-Investigator), Oo, Y. (Principal Investigator), Newsome, P. (Co-Investigator), Wraith, D. (Co-Investigator), Rowe, A. (Co-Investigator) & Rowe, A. (Co-Investigator)
SIR JULES THORN CHARITABLE TRUST
1/04/19 → 31/12/27
Project: Research

Cite this

Uhlenbusch, N., Snijders, R. J. A. L. M., Mund, M., Janik, M. K., Milkiewicz, P., Löwe, B., Kroll, C., Raszeja‐Wyszomirska, J., Gerussi, A., Bolis, F., Cristoferi, L., Invernizzi, P., Kovats, P., Papp, M., Grønbæk, L., Grønbæk, H., Tjwa, E. T. T. L., Aamann, L., Ytting, H., ... Schramm, C. (2026). Quality of Life in Patients With Variant Syndromes of Autoimmune Liver Diseases—A Cross‐Sectional Multicentre Study. Liver International, 46(3), Article e70526. https://doi.org/10.1111/liv.70526

@article{3714f1d2aee44aaea28a1dc615b8923f,

title = "Quality of Life in Patients With Variant Syndromes of Autoimmune Liver Diseases—A Cross‐Sectional Multicentre Study",

abstract = "Background \& Aims: Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) go along with reduced health‐related quality of life (HRQOL). Variant syndromes, that is, conditions with features of both PBC/PSC and AIH, are associated with higher clinical complexity and worse prognosis. Studies on HRQOL in patients with variant syndromes are lacking. We aimed to provide large‐scale evidence addressing this gap. Methods: We included adult patients with clinical diagnoses of autoimmune liver diseases across nine countries in a cross‐sectional study. We descriptively compared demographical, clinical and patient‐reported outcomes between the conditions and investigated whether additional AIH contributes to reduced HRQOL compared to the cholestatic liver disease alone. Further, we explored the role of fatigue, cirrhosis and depression severity regarding HRQOL. Results: N = 1275 patients were included (PBC: n = 342, PBC‐AIH: n = 160, PSC: n = 305, PSC‐AIH: n = 121, AIH: n = 347). Patients with variant syndromes showed high rates of cirrhosis and increased depressive or anxiety symptoms. Additional AIH was associated with further reduction in physical and mental HRQOL in people with PSC (physical: ΔR2 = 0.012, p = 0.041; mental: ΔR2 = 0.016, p = 0.020), but not with PBC (physical: ΔR2 = 0.008, p = 0.081; mental: ΔR2 = 0.001, p = 0.609). Physical HRQOL was associated with higher age and fatigue, while mental HRQOL was associated with lower age, fatigue, and depression severity. Conclusions: Patients with variant syndromes of autoimmune liver diseases show high physical and mental burden, with fatigue as the main contributor. Particularly PSC‐AIH goes along with more severely reduced HRQOL compared to the cholestatic liver disease alone, which is attributable to a higher symptom burden.",

keywords = "autoimmune liver diseases, variant syndrome, cholestatic liver diseases, autoimmune hepatitis, overlap syndrome, quality of life",

author = "Natalie Uhlenbusch and Snijders, \{Rom{\'e}e J. A. L. M.\} and Meike Mund and Janik, \{Maciej K.\} and Piotr Milkiewicz and Bernd L{\"o}we and Claudia Kroll and Joanna Raszeja‐Wyszomirska and Alessio Gerussi and Francesca Bolis and Laura Cristoferi and Pietro Invernizzi and Patricia Kovats and M{\'a}ria Papp and Lisbet Gr{\o}nb{\ae}k and Henning Gr{\o}nb{\ae}k and Tjwa, \{Eric T. T. L.\} and Luise Aamann and Henriette Ytting and Vincenzo Ronca and Kathryn Olsen and Oo, \{Ye H.\} and \{van der Meer\}, \{Adriaan J.\} and Jo{\~a}o Madaleno and Bernardo Canh{\~a}o and Bastian Engel and Alejandro Campos‐Murguia and Richard Taubert and Koc, \{{\"O}zg{\"u}r M.\} and Matthijs Kramer and Willemse, \{Jos{\'e} A.\} and Lohse, \{Ansgar W.\} and Drenth, \{Joost P. H.\} and Gevers, \{Tom J. G.\} and Christoph Schramm",

year = "2026",

month = mar,

doi = "10.1111/liv.70526",

language = "English",

volume = "46",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley",

number = "3",

}

Uhlenbusch, N, Snijders, RJALM, Mund, M, Janik, MK, Milkiewicz, P, Löwe, B, Kroll, C, Raszeja‐Wyszomirska, J, Gerussi, A, Bolis, F, Cristoferi, L, Invernizzi, P, Kovats, P, Papp, M, Grønbæk, L, Grønbæk, H, Tjwa, ETTL, Aamann, L, Ytting, H, Ronca, V, Olsen, K, Oo, YH, van der Meer, AJ, Madaleno, J, Canhão, B, Engel, B, Campos‐Murguia, A, Taubert, R, Koc, ÖM, Kramer, M, Willemse, JA, Lohse, AW, Drenth, JPH, Gevers, TJG & Schramm, C 2026, 'Quality of Life in Patients With Variant Syndromes of Autoimmune Liver Diseases—A Cross‐Sectional Multicentre Study', Liver International, vol. 46, no. 3, e70526. https://doi.org/10.1111/liv.70526

TY - JOUR

T1 - Quality of Life in Patients With Variant Syndromes of Autoimmune Liver Diseases—A Cross‐Sectional Multicentre Study

AU - Uhlenbusch, Natalie

AU - Snijders, Romée J. A. L. M.

AU - Mund, Meike

AU - Janik, Maciej K.

AU - Milkiewicz, Piotr

AU - Löwe, Bernd

AU - Kroll, Claudia

AU - Raszeja‐Wyszomirska, Joanna

AU - Gerussi, Alessio

AU - Bolis, Francesca

AU - Cristoferi, Laura

AU - Invernizzi, Pietro

AU - Kovats, Patricia

AU - Papp, Mária

AU - Grønbæk, Lisbet

AU - Grønbæk, Henning

AU - Tjwa, Eric T. T. L.

AU - Aamann, Luise

AU - Ytting, Henriette

AU - Ronca, Vincenzo

AU - Olsen, Kathryn

AU - Oo, Ye H.

AU - van der Meer, Adriaan J.

AU - Madaleno, João

AU - Canhão, Bernardo

AU - Engel, Bastian

AU - Campos‐Murguia, Alejandro

AU - Taubert, Richard

AU - Koc, Özgür M.

AU - Kramer, Matthijs

AU - Willemse, José A.

AU - Lohse, Ansgar W.

AU - Drenth, Joost P. H.

AU - Gevers, Tom J. G.

AU - Schramm, Christoph

PY - 2026/3

Y1 - 2026/3

N2 - Background & Aims: Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) go along with reduced health‐related quality of life (HRQOL). Variant syndromes, that is, conditions with features of both PBC/PSC and AIH, are associated with higher clinical complexity and worse prognosis. Studies on HRQOL in patients with variant syndromes are lacking. We aimed to provide large‐scale evidence addressing this gap. Methods: We included adult patients with clinical diagnoses of autoimmune liver diseases across nine countries in a cross‐sectional study. We descriptively compared demographical, clinical and patient‐reported outcomes between the conditions and investigated whether additional AIH contributes to reduced HRQOL compared to the cholestatic liver disease alone. Further, we explored the role of fatigue, cirrhosis and depression severity regarding HRQOL. Results: N = 1275 patients were included (PBC: n = 342, PBC‐AIH: n = 160, PSC: n = 305, PSC‐AIH: n = 121, AIH: n = 347). Patients with variant syndromes showed high rates of cirrhosis and increased depressive or anxiety symptoms. Additional AIH was associated with further reduction in physical and mental HRQOL in people with PSC (physical: ΔR2 = 0.012, p = 0.041; mental: ΔR2 = 0.016, p = 0.020), but not with PBC (physical: ΔR2 = 0.008, p = 0.081; mental: ΔR2 = 0.001, p = 0.609). Physical HRQOL was associated with higher age and fatigue, while mental HRQOL was associated with lower age, fatigue, and depression severity. Conclusions: Patients with variant syndromes of autoimmune liver diseases show high physical and mental burden, with fatigue as the main contributor. Particularly PSC‐AIH goes along with more severely reduced HRQOL compared to the cholestatic liver disease alone, which is attributable to a higher symptom burden.

AB - Background & Aims: Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) go along with reduced health‐related quality of life (HRQOL). Variant syndromes, that is, conditions with features of both PBC/PSC and AIH, are associated with higher clinical complexity and worse prognosis. Studies on HRQOL in patients with variant syndromes are lacking. We aimed to provide large‐scale evidence addressing this gap. Methods: We included adult patients with clinical diagnoses of autoimmune liver diseases across nine countries in a cross‐sectional study. We descriptively compared demographical, clinical and patient‐reported outcomes between the conditions and investigated whether additional AIH contributes to reduced HRQOL compared to the cholestatic liver disease alone. Further, we explored the role of fatigue, cirrhosis and depression severity regarding HRQOL. Results: N = 1275 patients were included (PBC: n = 342, PBC‐AIH: n = 160, PSC: n = 305, PSC‐AIH: n = 121, AIH: n = 347). Patients with variant syndromes showed high rates of cirrhosis and increased depressive or anxiety symptoms. Additional AIH was associated with further reduction in physical and mental HRQOL in people with PSC (physical: ΔR2 = 0.012, p = 0.041; mental: ΔR2 = 0.016, p = 0.020), but not with PBC (physical: ΔR2 = 0.008, p = 0.081; mental: ΔR2 = 0.001, p = 0.609). Physical HRQOL was associated with higher age and fatigue, while mental HRQOL was associated with lower age, fatigue, and depression severity. Conclusions: Patients with variant syndromes of autoimmune liver diseases show high physical and mental burden, with fatigue as the main contributor. Particularly PSC‐AIH goes along with more severely reduced HRQOL compared to the cholestatic liver disease alone, which is attributable to a higher symptom burden.

KW - autoimmune liver diseases

KW - variant syndrome

KW - cholestatic liver diseases

KW - autoimmune hepatitis

KW - overlap syndrome

KW - quality of life

U2 - 10.1111/liv.70526

DO - 10.1111/liv.70526

M3 - Article

SN - 1478-3223

VL - 46

JO - Liver International

JF - Liver International

IS - 3

M1 - e70526

ER -

Quality of Life in Patients With Variant Syndromes of Autoimmune Liver Diseases—A Cross‐Sectional Multicentre Study

Abstract

UN SDGs

Keywords

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Projects

Stop the Clock of Chronic Inflammation

Regulatory T-Cells immunotherapy for treatment of primary biliary cholangitis.

Cite this