Patients with autoimmune hepatitis who received an early azathioprine prescription did not show a statistically significant increase in extrahepatic malignancy compared with patients who did not, according to a retrospective nationwide cohort study using South Korean health insurance claims data published in BMC Gastroenterology. The analysis, based on Health Insurance Review and Assessment Service records from 2008 to 2020, found similar rates of new cancers outside the liver in both groups, but the authors caution that the study design and follow-up length prevent any firm conclusion about long-term oncologic safety.
The researchers identified 8,280 patients with autoimmune hepatitis, of whom 3,059 received at least one azathioprine prescription within 180 days of diagnosis and 5,221 did not. Group assignment was fixed at day 180 after diagnosis, and follow-up began at that point.
Over follow-up that averaged roughly four years, extrahepatic malignancy developed in 136 patients in the early azathioprine group, an incidence of 1.36 per 100 person-years, and in 219 patients in the comparison group, an incidence of 1.23 per 100 person-years. The incidence rate ratio was 1.11 with a 95 percent confidence interval of 0.89 to 1.37 and a P value of 0.356. In Cox regression models adjusted for age, sex, diabetes mellitus, cirrhosis, and corticosteroid use, the hazard of extrahepatic malignancy in the early azathioprine group was 1.09 times that of the no-early-azathioprine group, with a 95 percent confidence interval of 0.79 to 1.51 and a P value of 0.600, meaning the difference was not statistically significant.
The researchers also examined malignancies at specific sites and found no statistically significant differences for any individual location. For lymphoma and multiple myeloma combined, there were 8 events in the early azathioprine group versus 12 in the comparison group, yielding an adjusted hazard ratio of 1.78 with a wide confidence interval of 0.49 to 6.51. For non-melanoma skin cancer, there were 10 events versus 16, with an adjusted hazard ratio of 1.18 and a confidence interval of 0.38 to 3.71. The authors note that these wide intervals reflect the limited number of events and leave open the possibility of moderate differences in either direction that the study was not powered to exclude.
Several design features limit interpretation. The exposure definition captured only early prescriptions, so patients who started azathioprine later remained classified in the no-early-azathioprine group, which would tend to dilute any true difference between the groups. The mean follow-up of about four years may be too short to detect malignancies with long latency periods, particularly lymphomas associated with prolonged immunosuppression. The authors explicitly state that, given the exposure definition, the possibility of later azathioprine use in the comparison group, the follow-up duration, and the wide confidence intervals, no conclusion on long-term oncologic safety can be drawn from this analysis. The study therefore reports an absence of a detected association over a defined observation window rather than evidence of safety or harm over longer time horizons, and it does not establish a causal relationship between azathioprine and cancer risk in either direction.
Subject of Research: The association between early azathioprine treatment and extrahepatic malignancy risk in patients with autoimmune hepatitis
Article Title: Azathioprine treatment and the risk of extrahepatic malignancy in patients with autoimmune hepatitis: a nationwide cohort study using Korean claims data
Article References: Yoo, S. H., Lee, J. I., & Lee, H. W. (2026). Azathioprine treatment and the risk of extrahepatic malignancy in patients with autoimmune hepatitis: a nationwide cohort study using Korean claims data. BMC Gastroenterology. https://doi.org/10.1186/s12876-026-05486-x
Image Credits: AI Generated
DOI: 10.1186/s12876-026-05486-x
Keywords: autoimmune hepatitis, azathioprine, extrahepatic malignancy, nationwide cohort study, Korean claims data, immunosuppression, lymphoma, non-melanoma skin cancer, HIRA database, hazard ratio, drug safety, hepatology
News Source: Nathaniel Bowman. (October 29, 2026). Early azathioprine in autoimmune hepatitis shows no clear extrahepatic cancer risk in Korean cohort. Scienmag.
