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

Autoimmune Hepatitis Hepatocellular carcinoma Immunosuppressive therapy Liver cancer

Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
05 Oct 2023
Historique:
received: 01 02 2023
revised: 28 08 2023
accepted: 01 09 2023
pubmed: 7 10 2023
medline: 7 10 2023
entrez: 6 10 2023
Statut: aheadofprint

Résumé

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. 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.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
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.
METHODS METHODS
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.
RESULTS RESULTS
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.
CONCLUSIONS CONCLUSIONS
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 UNASSIGNED
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.

Identifiants

DOI: 10.1016/j.jhep.2023.09.010 PMID: 37802188
pubmed: 37802188
pii: S0168-8278(23)05095-X
doi: 10.1016/j.jhep.2023.09.010
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

N van Gerven (N)
K van Erpecum (K)
J den Ouden (JD)
J Brouwer (J)
J Vrolijk (J)
T Gevers (T)
J Drenth (J)
M Guichelaar (M)
G Bouma (G)
T C M A Schreuder (TCMA)
E J van der Wouden (EJ)
L C Baak (LC)
P Stadhouders (P)
M Klemt-Kropp (M)
M Verhagen (M)
A Bhalla (A)
J Kuijvenhoven (J)
P Almasio (P)
F Alvarez (F)
R Andrade (R)
C Arikan (C)
D Assis (D)
E Bardou-Jacquet (E)
M Biewenga (M)
E Cancado (E)
N Cazzagon (N)
O Chazouillères (O)
G Colloredo (G)
M Cuarterolo (M)
G Dalekos (G)
D Debray (D)
M Robles-Díaz (M)
J Drenth (J)
J Dyson (J)
C Efe (C)
B Engel (B)
S Ferri (S)
R Fontana (R)
N Gatselis (N)
A Gerussi (A)
E Halilbasic (E)
N Halliday (N)
M Heneghan (M)
G Hirschfield (G)
B van Hoek (B)
M Hørby Jørgensen (M)
G Indolfini (G)
R Iorio (R)
P Invernizzi (P)
S Jeong (S)
D Jones (D)
D Kelly (D)
N Kerkar (N)
F Lacaille (F)
C Lammert (C)
B Leggett (B)
M Lenzi (M)
C Levy (C)
R Liberal (R)
A Lleo (A)
A Lohse (A)
S Ines Lopez (SI)
E de Martin (E)
V McLin (V)
G Mieli-Vergani (G)
P Milkiewicz (P)
N Mohan (N)
L Muratori (L)
G Nebbia (G)
C van Nieuwkerk (C)
Y Oo (Y)
A Ortega (A)
A Páres (A)
T Pop (T)
D Pratt (D)
T Purnak (T)
G Ranucci (G)
S Rushbrook (S)
C Schramm (C)
A Stättermayer (A)
M Swain (M)
A Tanaka (A)
R Taubert (R)
D Terrabuio (D)
B Terziroli (B)
M Trauner (M)
P Valentino (P)
F van den Brand (F)
D Vergani (D)
A Villamil (A)
S Wahlin (S)
H Ytting (H)
K Zachou (K)
M Zeniya (M)

Informations de copyright

Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Auteurs

Francesca Colapietro (F)

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Patrick Maisonneuve (P)

Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy.

Ellina Lytvyak (E)

Department of Medicine, Division of Preventive Medicine, University of Alberta, Edmonton, Alberta, Canada.

Ulrich Beuers (U)

Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands.

Robert C Verdonk (RC)

Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, The Netherlands.

Adriaan J van der Meer (AJ)

Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands.

Bart van Hoek (B)

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.

Sjoerd D Kuiken (SD)

Department of Gastroenterology and Hepatology, OLVG, Amsterdam, the Netherlands.

Johannes T Brouwer (JT)

Reinier de Graaf Medical Center, Delft, the Netherlands.

Paolo Muratori (P)

Division of Internal Medicine, Morgagni-Pierantoni Hospital, Forlì 47100, Italy; Department of Science for the Quality of Life, University of Bologna, Bologna, Italy.

Alessio Aghemo (A)

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Francesco Carella (F)

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Ad P van den Berg (AP)

University Medical Center Groningen, University of Groningen, the Netherlands.

Kalliopi Zachou (K)

Department of Medicine and Research, Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110, Larissa, Greece.

George N Dalekos (GN)

Department of Medicine and Research, Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110, Larissa, Greece.

Daniel E Di Zeo-Sánchez (DE)

Liver Unit, Vírgen de Victoria University Hospital-IBIMA, University of Málaga, CIBERehd, Malaga, Spain.

Mercedes Robles (M)

Liver Unit, Vírgen de Victoria University Hospital-IBIMA, University of Málaga, CIBERehd, Malaga, Spain.

Raul J Andrade (RJ)

Liver Unit, Vírgen de Victoria University Hospital-IBIMA, University of Málaga, CIBERehd, Malaga, Spain.

Aldo J Montano-Loza (AJ)

Department of Medicine, Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.

Floris F van den Brand (FF)

Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Charlotte D Slooter (CD)

Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Guilherme Macedo (G)

Department of Gastroenterology and Hepatology, Centro Hospitalar São João, Porto, Portugal.

Rodrigo Liberal (R)

Department of Gastroenterology and Hepatology, Centro Hospitalar São João, Porto, Portugal.

Ynto S de Boer (YS)

Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Ana Lleo (A)

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. Electronic address: ana.lleo@humanitas.it.

Classifications MeSH