Incidence and risk factors of hepatocellular carcinoma in patients with autoimmune hepatitis in Asia

Abstract

Background & aims: A recent European multicenter study reported a low incidence of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH), even after cirrhosis development. In this study, we evaluated the incidence and predictors of HCC in Asian patients with AIH.

Methods: We conducted a multicenter, retrospective study on adult patients diagnosed with AIH between January 2000 and October 2023 registered in the rare intractable disease registry of the Korean National Health Insurance Database. The primary outcome was HCC incidence by competing risk analysis, with death and liver transplantation (LT) considered as competing risk factors. The secondary outcome was LT-free survival. Therapeutic efficacy was also evaluated based on the International Autoimmune Hepatitis Group response criteria.

Results: We analyzed 838 patients with biopsy-proven AIH. The median age of patients was 57.7 years, and 709 (84.6%) patients were women. Cirrhosis was present upon diagnosis in 365 (43.6%) patients. During the median follow-up period of 4.6 years, 21 (2.5%) patients developed HCC, with an annual incidence of 4.29/1,000 person-years (PY). The annual incidence of LT-free mortality was 16.44/1,000 PYs. The risk factors for HCC included cirrhosis (subdistribution hazard ratio [HR] 6.55) and hepatic decompensation (subdistribution HR 2.89). Treatment status, diabetes, cirrhosis, hepatic decompensation, and variant syndrome (adjusted HR: 5.12, 2.00, 5.50, 3.05, and 2.01, respectively; all p <0.05) were significantly associated with poor LT-free survival. Insufficient responders had a higher incidence of HCC (4.45/1,000 PYs) and poorer LT-free survival (20.3/1,000 PYs) than complete biochemical responders.

Conclusions: The incidence of HCC in Asian patients with AIH was higher than that reported in a recent European study. The risk factors included cirrhosis and hepatic decompensation at diagnosis.

Impact and implications: Autoimmune hepatitis (AIH) is rare, and the annual incidence of hepatocellular carcinoma (HCC) in patients with AIH is lower than that of other liver diseases, varying according to age, sex, and ethnicity, leading to an ongoing debate regarding the necessity for regular HCC surveillance in patients with AIH. However, most studies have focused on Western patients, and few have investigated HCC incidence in Asian populations, where the incidence of HCC is higher. Our multicenter study revealed that HCC incidence was higher in Asian populations than in Western populations. Regardless, this incidence did not meet the threshold for cost-effective surveillance. Our findings underscore the need for a nuanced approach to screening, balancing the low incidence of HCC with the presence of significant risk factors in Asian patients with AIH.