Title : Immune checkpoint inhibitor-related cholangitis: A single-centre retrospective case series and management outcomes
Abstract:
Background: Since immune checkpoint inhibitors (ICIs) have been introduced for over a decade, a massive improvement in cancer survival rate (median 7.8 to 19.0 months) has occurred but can precipitate immune-related adverse events across organ systems. Immune checkpoint inhibitor (ICI)-related cholangitis is a rare but significant side effect which clinically and radiologically can overlap with sclerosing cholangitis that can be severe enough to stop immunotherapy.
Aim: To evaluate the clinical features, radiological findings, and management outcomes of ICI- related cholangitis
Methods: We conducted a 4-year retrospective review of ICI hepatotoxicities at our centre. Out of 70 patients from our hepatotoxicity logs with ICI-induced toxicity, 5 cases of ICI-cholangitis (~7% incidence). Cholangitis diagnosis was made after identification of ICI-Hepatitis (raised Alkph and bilirubin) along with biliary imaging (ultrasound, computed tomography-CT and/or Magnetic Resonance Cholangiopancreatography-MRCP) showing ductal dilatation and inflammatory changes (e.g., ductal wall thickening, and multifocal strictures) all consistent with ICI- induced cholangiopathy. No infectious or obstructed causes were found; liver biopsy was not performed. We also collected demographics, cancer type, cancer treatment, diagnostic workup, management, and outcomes data.
Results: Median age was 74 years (range 62–83), with a 3:2 male-to-female ratio. All patients had advanced lung cancer (mainly small cell and squamous carcinoma) treated with chemo-immunotherapy, Immune agents used were anti-PD-1- Pembrolizumab - (n=4) or anti-PD-L1 -Atezolizumab -(n=1). Cholangitis onset occurred after a median of 11 (range 5- 16) ICI cycles. Notably, all patients had finished 4 cycles of chemo-immunotherapy and were receiving single agent maintenance immunotherapy at the time cholangitis developed; in one case, MRCP described progressive dilatation of both the intrahepatic and extrahepatic biliary ducts; the CBD measured 11mm from 8 mm. Generalised bile duct mural thickening, peri- biliary intrahepatic signal change and delayed mural enhancement are suggestive of inflammatory changes. without an obstructing mass or stone.
Management included immunotherapy discontinuation, steroids, and ursodeoxycholic acid (UDCA). UDCA was given to all 5 patients only after the scans, while corticosteroids were given only to 2 patients. Although, all patients improved biochemically, complete resolution was not fully achieved with one case persisting despite high-dose steroids plus UDCA, while only one case had complete resolution with using UDCA alone. Two cases underwent ICI rechallenge with one experienced recurrence of ICI-cholangitis. At 3-6 months’ follow up, three were alive (two with ongoing cancer therapy) and two had died from cancer progression.
Conclusion: In this series, ICI-related cholangitis was rare but clinically significant and can overlap with sclerosing cholangitis. It typically emerges during maintenance immunotherapy. UDCA with ICI cessation may be sufficient for biochemical improvement, whereas rechallenge carries risk of relapse. Early recognition and multidisciplinary collaboration are essential. The oncologist, and gastroenterologist/hepatologist should coordinate, and the radiologist should be alerted to the possibility of ICI- related cholangitis when interpreting scans. Since 2022, European Society for Medical Oncology (ESMO) endorse UDCA with corticosteroids as the primary treatment for ICI-cholangitis. Given that UDCA is well tolerated and first line in other cholestatic liver diseases, we advocate starting UDCA early before imaging.
