Liver Injury From Medications Used for Treating Inflammatory Bowel Disease: The Drug-Induced Liver Injury Network Experience.

BACKGROUND

We aimed to investigate and characterise DILI due to approved therapies for inflammatory bowel disease (IBD).

METHODS

Using the Drug-Induced Liver Injury Network (DILIN) prospective study, we evaluated definite, highly likely, or probable DILI attributed to IBD therapies, including use for non-IBD indications (but excluding corticosteroids). HLA allele associations were investigated.

RESULTS

Among 1806 participants, 81 (4.5%) had IBD-agent DILI: 31 biologics (27 infliximab), 35 immunomodulators (31 azathioprine/mercaptopurine), 14 aminosalicylates (11 sulfasalazine) and 1 small molecule (tofacitinib). Median age was 45 years with 75% female and 78% White. Patients with biologic-DILI were younger, had longer latency (median 124 days), predominantly hepatocellular injury (78%) and mostly mild severity (74%) with no deaths and one chronic case. Immunomodulator-DILI was mainly cholestatic or mixed, with jaundice in 57%; two were fatal, one required transplant and five became chronic. Aminosalicylate-DILI had the shortest latency (median 40 days), was hepatocellular (57%) or cholestatic (36%), often with rash (50%) or pruritus (36%), mostly mild (64%), with two chronic cases. DILI phenotype was similar with IBD and non-IBD indications. Multiple HLA alleles were associated with infliximab (HLA-DPB1*01:01, HLA-B*08:01 and HLA-DQB1*02:01) azathioprine (HLA-DR3, HLA-DRB1*03:01 and HLA-A*33:01), mercaptopurine (HLA-A*11:01 and HLA-B*37:01) and sulfasalazine (HLA-B*53:01) DILI, compared to population controls and other DILI cases.

CONCLUSIONS

Clinical features such as latency, injury pattern, jaundice and dermatologic findings help distinguish implicated agents and guide prognosis in suspected DILI from IBD therapies. HLA alleles may help identify individuals at higher DILI risk and support causality.