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A Multifactorial Mystery of Hyperbilirubinemia in a Patient With Primary Sclerosing Cholangitis and Crohn’s Disease Treated With Infliximab
AIBD 2023
Background:
Primary sclerosing cholangitis (PSC) is an inflammatory disease often associated with inflammatory bowel disease (IBD). PSC occurs most frequently with ulcerative colitis (UC) although there is an association with Crohn’s disease (CD). Elevated serum bilirubin correlates with disease activity of PSC and suggests biliary obstruction. However, this could represent intrinsic liver injury secondary to hepatotoxic medications. Many medications can cause drug induced liver injury (DILI), including tumor necrosis factor alpha inhibitors (anti-TNF-alpha) such as infliximab. We present a case of drug-induced autoimmune hepatitis due to infliximab in a patient with CD and PSC.
Methods:
A 49-year-old-female with a past history of CD, PSC, dermatomyositis, and sarcoidosis presented to the Emergency Department with abdominal pain, jaundice, and vomiting. The patient denied bleeding or changes in bowel movements. CD was initially diagnosed 14 years prior. Infliximab was used only intermittently since diagnosis due to difficulty with follow up although with no known history of anti-drug antibodies. Most recently, intravenous (IV) infliximab 900 mg every 5 weeks was utilized continuously over the past year with clinical remission. Upon evaluation, laboratory findings included total bilirubin 7.3 mg/dL (range 0.2-1.2 mg/dL), direct bilirubin 5.7 mg/dL (range 0.0-0.5 mg/dL), aspartate aminotransferase (AST) 835 U/L (range 5-34 U/L), alanine transaminase (ALT) 830 U/L (range 5-45 U/L), and alkaline phosphatase (ALP) 191 U/L (range 35-150 U/L). Previously, these values were normal. Contrary to symptoms, these findings were consistent with hepatocellular injury. Immunoglobulin G (IgG) 2,294 (range 552-1,631 mg/dL) and F-actin (Smooth Muscle) antibody IgG 24 (range 0-19 U/L). Magnetic Resonance Cholangiopancreatography (MRCP) displayed acute hepatitis and biliary inflammation with dilation of left intrahepatic bile duct with suspicion for stricture near confluence. Endoscopic retrograde cholangiopancreatography (ERCP) showed diffuse intrahepatic stricturing without a dominant stricture and sludge. Endoscopic ultrasound-guided liver biopsy (EUS-LB) was performed at time of ERCP as biliary findings did not explain abnormal hepatic function. Histology showed portal triaditis, dense lymphoplasmacytic infiltrates, piecemeal necrosis, and patchy bile duct damage consistent with drug-induced autoimmune hepatitis associated with infliximab.
Results:
Due to serologic and histologic findings, infliximab was discontinued. The patient was transitioned to ustekinumab with standard Intravenous (IV) induction dose followed by subcutaneous (SQ) maintenance dosing 90 mg every 8 weeks and remained in clinical remission. Hepatic function normalized two months after discontinuation of infliximab.
Conclusions:
Heightened suspicion of drug-induced liver injury should be considered with IBD patients on anti-TNF-alpha therapy presenting with hepatocellular pattern of liver injury. Therefore, a thoughtful multidisciplinary approach including hepatology and advanced endoscopy should be involved in these cases with the ability to utilize endoscopic opportunity to obtain liver biopsy at time of ERCP if there is concern for hepatocellular injury. The presence of autoimmune serologies may also cause diagnostic confusion as these elevations can occur with DILI, which further reinforces the important consideration of liver biopsy. Change in therapy must be addressed with evidence of liver injury due to anti-TNF-alpha therapy.
