Risk of extrahepatic malignancies in patients with autoimmune hepatitis: a nationwide cohort study

Introduction: Nationwide, population-based data on the risk of extrahepatic malignancy in patients with autoimmune hepatitis (AIH) in Asian countries are scarce. This study aimed to examine the risk of developing extrahepatic malignancies in a nationwide cohort of patients with AIH. Methods: Using claims data from the Korean National Health Insurance Service database, patients diagnosed with AIH between 2007 and 2019 (n=7,382) were matched in a 1:8 ratio with an age- and sex-matched control population (n=58,320). We compared the incidence rates (IRs) and hazard ratios (HRs) of overall and specific extrahepatic malignancies between the two groups, while also examining the impact of immunosuppressant use. Results: During a median follow-up period of 5.2 years, a total of 3,713 extrahepatic malignancies developed. The IR of extrahepatic malignancy in AIH patients (990.8 cases per 100,000 person-years) was comparable to that in the matched controls (937.6 cases per 100,000 person-years), with an HR of 0.93 (95% CI, 0.81–1.07; P = 0.30). However, a significantly higher risk of hematologic malignancies, particularly lymphoma or myeloma (HR, 2.66; 95% CI, 1.70–4.17; P <0.001), was observed. The use of glucocorticoids (HR, 0.74; 95% CI, 0.31–1.75; P =0.50) or azathioprine (HR, 2.12; 95% CI, 0.90–5.02; P =0.09) had no impact on the risk of lymphoma or myeloma in patients with AIH. Discussion: In this nationwide, population-based cohort, AIH was not associated with an increased risk of overall extrahepatic malignancy compared with age- and sex-matched controls. However, AIH itself increased the risk of lymphoma or myeloma, independent of immunosuppressant use.