Clinical Case Summary
A 59-years-old caucasian female patient with Crohn’s Disease (CD) A3L3B3 (Montreal Classification), erythema nodosum episodes. Due to lithiasis, while performing a cholecystectomy, a heterogenous liver was found and a biopsy revealed primary sclerosing cholangitis (PSC).
Since the CD’s diagnosis in 1992, the patient has been on mesalamine (5-ASA). During her disease course, she needed treatment with steroids 4 times. She was started on azathioprine but interrupted it due acute pancreatitis. Last time on steroids was on 2012, and since then she had been on clinical remission on 5-ASA. In 2019, the patient presented perianal disease and terminal ileitis. This justified the decision to start Infliximab (IFX) therapy.
Although asymptomatic, routine analysis at the 4th IFX infusion revealed abnormal liver biochemical tests with a hepatocellular pattern: alanine aminotransferase 449U/L(<55); aspartate aminotransferase 284U/L(<34), other enzymes were normal. Subsequent studies revealed only positive antinuclear antibody(1/640). A liver biopsy was performed in order to guide the therapeutical management. The biopsy revealed a cholestatic pattern hepatitis compatible with hepatotoxicity as well as PSC and steatosis, without features of auto-immune hepatitis (AIH). The histologic findings supported the diagnosis of IFX associated AI-like Hepatitis. IFX was stopped with slight improvement of liver enzymes and prednisolone was started. There was complete liver enzymes normalization at 7th week, the patient was started on Ustekinumab, with no complications after 6 months.
As anti-TNF drugs’ use is rapidly increasing, associated autoimmune diseases may follow. Immune-mediated DILI related to IFX is still a rare entity but, considering that most cases are asymptomatic, monitoring liver function is mandatory for all patients. The differential diagnosis between AIH and IFX AI-like Hepatitis is challenging but essential due to therapeutic implications.
References
Rodrigues S, Lopes S, Magro F, Cardoso H, Horta e Vale AM, Marques M, Mariz E, Bernardes M, Lopes J, Carneiro F, Macedo G. Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy: A single center report of 8 cases. World J Gastroenterol. 2015 Jun 28;21(24):7584-8. doi: 10.3748/wjg.v21.i24.7584. PMID: 26140007; PMCID: PMC4481456.