C0539 - Leflunomide-Induced Severe Hepatotoxicity Treated With Ursodeoxycholic Acid

Shane Quo, DO¹, Claudia Marcano, MD¹, Wisam Zakko, MD^2
1University of Miami Holy Cross Hospital, Fort Lauderdale, FL; ²MD, Fort Lauderdale, FL

Introduction: Drug induced liver injury (DILI) is common usually leading to mild elevations in liver enzymes but on rare occasions cause severe liver injury and it is regarded as the most common cause for acute liver failure in the US. Leflunomide is a disease-modifying antirheumatic agent approved for rheumatoid arthritis (RA) and psoriatic arthritis (PA). Mild elevations in the liver enzymes is a common side effect but rare severe hepatotoxicity and fatalities have been reported. We present a case of severe liver injury related to leflunomide with no preexisting liver disease, or use of other hepatotoxic drugs whose prolonged pruritus and cholestasis responded to ursodeoxycholic acid (UDCA).

Case Description/Methods: 57-year-old female who was started on Leflunomide for uncontrolled RA was referred to our clinic due to elevated liver enzymes and jaundice. The patient reported rapid improvement of joint pain with Leflunomide but on 5^th and 6^th week of treatment she started complaining of diarrhea, nausea, fatigue and pruritus. Her only other medications were Olmesartan and Ketorolac. Labs revealed AST 253, ALT 810, Alk Phos of 466 and Bilirubin of 4.0. Leflunomide was immediately discontinued. Work up showed negative hepatitis serologies and autoimmune markers. MRI with MRCP was normal. On week 8 and 9 she had persistent severe pruritus and progressive increase in bilirubin. UDCA 500 mg twice daily was started. A week later bilirubin decreased and itching resolved. Figure 1 shows this trend.

Discussion: Leflunomide is used for RA and PA and can be associated with symptomatic severe liver injury. The liver injury arises after 1 to 6 months of therapy and present with a cholestatic or hepatocellular pattern. On weeks 5-6 of treatment, our patient was symptomatic with diarrhea, nausea, and pruritus. A mixed hepatocellular and cholestatic pattern was noted on week 7, with an improvement of liver enzymes within a week of stopping treatment, however, with progressive elevation of bilirubin and troublesome persistent pruritus that responded promptly to UDCA. This case underscores the importance of monitoring liver enzymes in patients on Leflunomide, at least once monthly for the first six months, and immediate discontinuation when liver enzymes increase more than three times upper normal. In our patient, worsening jaundice and persistent pruritus responded promptly to UDCA which supports data that shows possible benefits of UDCA in the treatment of DILI.





Disclosures:


Shane Quo, DO¹, Claudia Marcano, MD¹, Wisam Zakko, MD². C0539 - Leflunomide-Induced Severe Hepatotoxicity Treated With Ursodeoxycholic Acid, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.