P2461 - An Unusual Presentation of Immune Checkpoint Inhibitor Hepatotoxicity With Cholestatic Transaminitis

Soha Afzal, DO, MS¹, Alexandra Davies, DO¹, Madhu Vennikandam, MD², Jannel Lee-Allen, MD^1
1McLaren Greater Lansing/MSU, Lansing, MI; ²Sparrow Hospital/MSU, Lansing, MI

Introduction: Hepatotoxicity is an uncommon but known adverse effect of immune checkpoint inhibitors (ICI). Hepatotoxicity frequently will present with elevations in ALT or AST levels, rarely patients will have elevations in ALP. Nonetheless, these patients are still considered in the category of immune checkpoint inhibitor hepatotoxicity (ICIH). Here we present a case of a patient with fatal cholestatic ICIH (CICIH) and discuss updates in evaluation, management, and areas of further exploration.

Case Description/Methods: An 83-year-old male presented to an emergency room facility twice in the span of three months. He initially presented from his oncologist’s office due to elevated liver enzyme levels. He was asymptomatic but was noticeably jaundiced with scleral icterus. He had a medical history of lung cancer treated with pembrolizumab which was discontinued six months prior for concerns of possible ICIH. He was placed on two months of steroid therapy and later initiated mycophenolate mofetil. Labs revealed ALT 99 unit/L, AST 93 unit/L, ALP 1,163 unit/L, total bilirubin 15.5 mg/dL, and direct bilirubin >10 mg/dL. Workup to rule out other causes of elevated transaminase levels was unrevealing. He was discharged home with Medrol 1mg/kg/day and mycophenolate mofetil 1000 mg twice daily.

On his second presentation, he was weak and confused. His labs this visit noted ALT 96 unit/L, AST 104 unit/L, ALP 1,319 unit/L, total bilirubin 14.1 mg/dL, direct bilirubin >10 mg/dL, and an unmeasurable indirect bilirubin level. Liver biopsy pathology showed acute cholestasis with bile pools, periportal neutrophils, and ballooning change consistent with acute ascending cholangitis. The patient’s clinical picture did not support acute ascending cholangitis. Oncology recommended IV solumedrol and increasing tacrolimus to 1 mg twice daily. After continued treatment, his ALP trended down to 1,332 unit/L. The patient was discharged home and was transitioned to oral prednisone at 2 mg/kg/day, tacrolimus 1 mg twice daily, and mycophenolate mofetil at 1,000 mg twice daily. Five days after discharge home, the patient passed away in his home.

Discussion: Our patient was unique in his presentation since his ALP levels were elevated greatly compared to his AST and ALT levels. This was found to be a rare presenting feature of ICIH. Studies have reported the utilization of indoleamine 2,3-dioxygenase 1 for diagnosing CICIH. As such, alternative pathophysiology for CICIH must be considered. This may help to tailor treatment in the future.


Disclosures:


Soha Afzal, DO, MS¹, Alexandra Davies, DO¹, Madhu Vennikandam, MD², Jannel Lee-Allen, MD¹. P2461 - An Unusual Presentation of Immune Checkpoint Inhibitor Hepatotoxicity With Cholestatic Transaminitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.