Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Francesca Colapietro, Patrick Maisonneuve, Ellina Lytvyak, Ulrich Beuers, Robert C. Verdonk, Adriaan J. van der Meer, Bart van Hoek, Sjoerd D. Kuiken, Johannes T. Brouwer, Paolo Muratori, Alessio Aghemo, Francesco Carella, Ad P. van den Berg, Kalliopi Zachou, G. Dalekos, Daniel E. Di Zeo-Sánchez, Mercedes Robles, R. Andrade, Aldo J. Montano-Loza, Floris F. van den BrandCharlotte D. Slooter, Guilherme Macedo, Rodrigo Liberal, Ynto S. de Boer, Ana Lleo*, Dutch AIH Study Group, the International Autoimmune Hepatitis Group, N. van Gerven, J. den Ouden, J. Brouwer, J. Vrolijk, M. Guichelaar, G. Bouma, M. Verhagen, A. Bhalla, M. Biewenga, S. Ferri

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


Background and Aims: 

Autoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors.


We performed a retrospective, observational, multicentric study of patients included in the International Autoimmune Hepatitis Group Retrospective Registry. The assessed clinical outcomes were HCC development, liver transplantation, and death. Fine and Gray regression analysis stratified by centre was applied to determine the effects of individual covariates; the cumulative incidence of HCC was estimated using the competing risk method with death as a competing risk. 


A total of 1,428 patients diagnosed with AIH from 1980 to 2020 from 22 eligible centres across Europe and Canada were included, with a median follow-up of 11.1 years (interquartile range 5.2-15.9). Two hundred and ninety-three (20.5%) patients had cirrhosis at diagnosis. During follow-up, 24 patients developed HCC (1.7%), an incidence rate of 1.44 cases/1,000 patient-years; the cumulative incidence of HCC increased over time (0.6% at 5 years, 0.9% at 10 years, 2.7% at 20 years, and 6.6% at 30 years of follow-up). Patients who developed cirrhosis during follow-up had a significantly higher incidence of HCC. The cumulative incidence of HCC was 2.6%, 4.6%, 5.6% and 6.6% at 5, 10, 15, and 20 years after the development of cirrhosis, respectively. Obesity (hazard ratio [HR] 2.94, p = 0.04), cirrhosis (HR 3.17, p = 0.01), and AIH/PSC variant syndrome (HR 5.18, p = 0.007) at baseline were independent risk factors for HCC development. 


HCC incidence in AIH is low even after cirrhosis development and is associated with risk factors including obesity, cirrhosis, and AIH/PSC variant syndrome.

Impact and implications: 

The risk of developing hepatocellular carcinoma (HCC) in individuals with autoimmune hepatitis (AIH) seems to be lower than for other aetiologies of chronic liver disease. Yet, solid data for this specific patient group remain elusive, given that most of the existing evidence comes from small, single-centre studies. In our study, we found that HCC incidence in patients with AIH is low even after the onset of cirrhosis. Additionally, factors such as advanced age, obesity, cirrhosis, alcohol consumption, and the presence of the AIH/PSC variant syndrome at the time of AIH diagnosis are linked to a higher risk of HCC. Based on these findings, there seems to be merit in adopting a specialized HCC monitoring programme for patients with AIH based on their individual risk factors.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalJournal of Hepatology
Issue number1
Early online date4 Oct 2023
Publication statusPublished - Jan 2024

Bibliographical note

Publisher Copyright:
© 2023 European Association for the Study of the Liver


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