University of Texas MD Anderson Cancer Center Houston, TX, United States
Hao Chi Zhang, MD1, Melissa Taggart, MD1, Ethan Miller, MD2, Frank Fossella, MD3, Lan Wang, MD3 1University of Texas MD Anderson Cancer Center, Houston, TX; 2UT MD Anderson Cancer Center, Houston, TX; 3MD Anderson Cancer Center, Houston, TX
Introduction: Immune checkpoint inhibitor-mediated cholangiohepatitis (IMCH) is a distinct phenotype of immune-mediated hepatobiliary toxicity. Both intra- and extrahepatic biliary disease have been described. Cholangiopathy presents treatment challenges due to the risk of steroid-resistance and biliary stricturing. Society guidelines lack effective IMCH treatment strategies. We present a case of recurrent IMCH with a protracted clinical course and with complications of extrahepatic biliary disease.
Case Description/Methods: A 65-year-old woman with squamous cell carcinoma of the right lung with small focal metastases to the liver was treated with 26 cycles of pembrolizumab and developed CTCAE grade 3 IMCH with biopsy-proven cholangiohepatitis. Four weeks of prednisone (40 mg/d, with taper) yielded biochemical improvement with near-remission. IMCH recurred after pembrolizumab resumption, and re-treatment with prednisone (60 mg/d with taper) led to biochemical remission. Surveillance MRCP and subsequent ERCP revealed development of a new common hepatic duct (CHD) stricture. Less than 1 month later, she developed septic shock from bacterial cholangitis, requiring ERCP with stenting of the CHD. After only partial response to prolonged steroids was observed, intravenous tocilizumab 8 mg/kg was administered once to allow for tapering off of steroids. After 47 more days, ALT and AST were completely normalized, with prior completion of prednisone. Total steroid duration was 187 days. Her clinical course was complicated by morbidity including adrenal insufficiency, fungal hepatic abscess, fungemia, cholangitis, and biliary obstruction requiring 2 additional ERCPs with stent exchange. After a prolonged hospitalization with respiratory failure, she was transitioned to hospice and died.
Discussion: This case highlights morbidity and mortality associated with progressive cholangiopathy related to the exposure to an anti-PD-1 inhibitor, with complex sequelae that mandated balancing the need for immunosuppression with the risk for further complications associated with an extrahepatic biliary stricture. Steroid-sparing strategies such as the use of tocilizumab should be further studied for treating immune-mediated hepatobiliary toxicity. Early identification of recurrent/relapsing IMCH and early treatment escalation should be considered in cases suspected of biliary involvement in order to curtail the formation of biliary strictures, which could be permanent, as well as to reduce the risk of steroid-related adverse events.
Figure: (A) Liver biopsy (H&E, 200x): On this first diagnostic parenchymal liver biopsy, after two courses of steroid therapy, the bile duct remains injured with disorganized epithelium and scattered apoptotic bodies and intraepithelial neutrophils. There is no significant portal inflammation. (B) Fluoroscopy showing < 1 cm low-grade stenosis of the common hepatic duct, discovered after initial biochemical remission. (C) Chronological details of the patient’s clinical course with liver biochemistry lab trends and important events. (Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ERCP, endoscopic retrograde cholangiopancreatography; ICI, immune checkpoint inhibitor; MRCP, magnetic resonance cholangiopancreatography)
Disclosures: Hao Chi Zhang indicated no relevant financial relationships. Melissa Taggart indicated no relevant financial relationships. Ethan Miller indicated no relevant financial relationships. Frank Fossella indicated no relevant financial relationships. Lan Wang indicated no relevant financial relationships.
Hao Chi Zhang, MD1, Melissa Taggart, MD1, Ethan Miller, MD2, Frank Fossella, MD3, Lan Wang, MD3. P1868 - Extrahepatic Biliary Sequelae in Immune Checkpoint Inhibitor-Mediated Cholangiohepatitis: Urgent Unmet Need for Early Effective Treatment, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.