P1867 - Budesonide as an Alternative Steroid Agent, in Combination With Adjunctive Agents, for the Treatment of Immune Checkpoint Inhibitor-Mediated Cholangiohepatitis: A Case Study

Hao Chi Zhang, MD¹, Lan Wang, MD², Yinghong Wang, MD, PhD, MS¹, Ethan Miller, MD^3
1University of Texas MD Anderson Cancer Center, Houston, TX; ²MD Anderson Cancer Center, Houston, TX; ³UT MD Anderson Cancer Center, Houston, TX

Introduction: Immune-mediated cholangiohepatitis (IMCH) is a subtype of immune-mediated hepatotoxicity (IMH) secondary to immune checkpoint inhibitor (ICI) that may present with histologic or even extrahepatic bile duct injury. Current society guidelines treat IMH uniformly. However, clinical reports have highlighted potential challenging sequelae in IMCH. Paucity of data exist for treatment strategies other than systemic steroids, with two published cases using budesonide. We present a case of IMCH responsive to budesonide with adjuncts.

Case Description/Methods: A 55-year-old woman with recurrent ovarian cancer, with metastases to bone and lymph nodes, was evaluated for new abnormal liver enzymes. Cancer treatment included prior tremelimumab (anti-CTLA-4), which was discontinued a year prior, and durvalumab (anti-PD-L1), which was initiated about 14 months prior. Prior ICI-mediated colitis was treated with vedolizumab since prednisone caused intolerable insomnia. Baseline liver biochemistries were normal. Twenty seven days after the twelfth durvalumab infusion, liver enzymes showed CTCAE grade 3 toxicity: peak ALT 399 U/L, AST 165 U/L, and alkaline phosphatase (ALP) 456 U/L. Total bilirubin was normal. Abdominal MRI/MRCP showed no biliary abnormalities or liver lesions. Liver biopsy revealed mild lobular and portal inflammation (lymphocytes, histiocytes, plasma cells, and eosinophils) with bile duct injury. IMCH was diagnosed at the exclusion of other primary liver diseases. Despite initial and partial natural improvement, the liver enzymes increased again with peak ALT of 394 U/L and ALP of 625 U/L. To avoid prednisone due to prior intolerance, budesonide 9 mg/d, azathioprine 100 mg/d, and ursodiol were prescribed, leading to complete normalization of ALT and AST after only 12 days. Budesonide was tapered to 6 mg/d, with sustained biochemical remission at 36 days.

Discussion: IMCH is a subtype of IMH with cholestasis and bile duct injury, which can be confirmed with liver biopsy. Treating IMCH can be challenging because variable response to corticosteroids, and systemic steroids can cause substantial adverse events. In this case, budesonide, as the initial induction agent, combined with upfront adjunctive agents, yielded early response with sustained normalization of ALT, AST, and ALP at the time of writing. The use of oral budesonide as an alternative steroid option (as monotherapy or combined with an immunomodulator) should be studied further in cases where systemic corticosteroids are not favored.


Figure: (A) and (B): Liver biopsy (H&E) histology showing mild lobular and portal inflammation with bile duct injury; scattered areas in which portal tracts with expansion and inflammation comprised of lymphocytes, plasma cells, histiocytes and eosinophils; mildly injured interlobular bile ducts with nuclear disarray and lymphocytic as well as histiocytic inflammation in these portal tracts; bile ductular reaction present in some areas; no significant interface hepatitis is appreciated; lobules with mild inflammation with rare foci of hepatocellular injury; no steatosis or cholestasis. (C) Chronological timeline of the clinical course with trends in liver biochemistries in relation to treatment. (Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase)


Disclosures:
Hao Chi Zhang indicated no relevant financial relationships.
Lan Wang indicated no relevant financial relationships.
Yinghong Wang: AzurRx Pharma – Consultant. Tillotts Pharma – Consultant.
Ethan Miller indicated no relevant financial relationships.


Hao Chi Zhang, MD¹, Lan Wang, MD², Yinghong Wang, MD, PhD, MS¹, Ethan Miller, MD³. P1867 - Budesonide as an Alternative Steroid Agent, in Combination With Adjunctive Agents, for the Treatment of Immune Checkpoint Inhibitor-Mediated Cholangiohepatitis: A Case Study, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.