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, Lleo Ana
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.
Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy.
J Hepatol. 2024 Jan;80(1):53-61. doi: 10.1016/j.jhep.2023.09.010. Epub 2023 Oct 5.
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.
自身免疫性肝炎（AIH）是一种病因不明的罕见慢性肝病；肝细胞癌（HCC）的风险尚不清楚，且危险因素未明确界定。我们旨在调查多中心AIH队列中HCC的风险，并确定预测因素。
我们对国际自身免疫性肝炎小组回顾性登记处纳入的患者进行了一项回顾性、观察性、多中心研究。评估的临床结局为HCC发生、肝移植和死亡。采用按中心分层的Fine和Gray回归分析来确定个体协变量的影响；使用以死亡作为竞争风险的竞争风险法估计HCC的累积发病率。
纳入了1980年至2020年期间来自欧洲和加拿大22个符合条件中心的1428例诊断为AIH的患者，中位随访时间为11.1年（四分位间距5.2 - 15.9年）。293例（20.5%）患者在诊断时患有肝硬化。随访期间，24例患者发生HCC（1.7%），发病率为1.44例/1000患者年；HCC的累积发病率随时间增加（随访5年时为0.6%，10年时为0.9%，20年时为2.7%，30年时为6.6%）。随访期间发生肝硬化的患者HCC发病率显著更高。肝硬化发生后5年、10年、15年和20年时HCC的累积发病率分别为2.6%、4.6%、5.6%和6.6%。基线时肥胖（风险比[HR] 2.94，p = 0.04）、肝硬化（HR 3.17，p = 0.01）和AIH/PSC变异综合征（HR 5.18，p = 0.007）是HCC发生的独立危险因素。
即使在发生肝硬化后，AIH患者的HCC发病率也较低，且与肥胖、肝硬化和AIH/PSC变异综合征等危险因素相关。
自身免疫性肝炎（AIH）患者发生肝细胞癌（HCC）的风险似乎低于其他慢性肝病病因的患者。然而，鉴于现有证据大多来自小型单中心研究，该特定患者群体的确切数据仍然难以获得。在我们的研究中，我们发现即使在肝硬化发病后，AIH患者的HCC发病率也较低。此外，高龄、肥胖、肝硬化、饮酒以及AIH诊断时存在AIH/PSC变异综合征等因素与HCC的较高风险相关。基于这些发现，似乎有必要根据AIH患者的个体危险因素为其采用专门的HCC监测方案。
