Case Series: Severe cholangitis as an immune checkpoint inhibitor induced adverse event in four cases: management and treatment options including tocilizumab and ursodeoxycholic acid
- 1The Royal Marsden Hospital NHS Foundation Trust
- 2Imperial College Healthcare NHS Trust
- 3Royal Free Hospital NHS Foundation Trust
Abstract
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized treatment of multiple malignancies, nevertheless, their clinical use can be associated with adverse events (AE). ICI-induced cholangitis (ICI-C) belongs to rare AEs. Poor response to glucocorticosteroids (GCS) is observed, deaths related to ICI-C were reported.
Main findings and therapeutic interventions: We share four detailed cases (two males and two females) of severe ICI-C (severity assessed based on DILIN criteria). All patients were jaundiced (bilirubin >90 µmol/L), one had cholestatic liver injury, two had mixed liver injury and one had a rather hepatocellular liver injury based on R factor in DILI. Three were treated with programmed cell death protein (anti-PD1) or ligand 1 antibodies, one with anti-PD1 and cytotoxic T-lymphocyte-associated protein-4 antibodies. Onset of liver injury was observed during treatment (2), three weeks after last infusion (1) and four months after last treatment (1). Laboratory tests excluded infections, malignant infiltration and autoimmune profile was typically negative. Another drug induced injury was excluded. MRCP and EUS were used as imaging methods of choice. A liver biopsy was organized due to absent response to corticosteroids and second line immunosupressive medication, as cholangitis was suspected. Histology was confirmatory for ICI-C in all cases. Predominant infiltration by CD8 positive lymphocytes was shown. Treatment with tocilizumab, anti-IL-6 receptor antibody, and ursodeoxycholic acid were used in three cases.
Outcomes: Three patients with ICI-C confirmed histologically received tocilizumab and ursodeoxycholic acid with an excellent effect. Decrease in bilirubin was observed within 72 hours. Significant improvement/normalization of liver enzymes followed. No side effects of tocilizumab were reported. Patient who did not receive tocilizumab (maximum bilirubin 349 µmol/L, encephalopathy; cholestatic liver injury – R factor 0.8) died.
Conclusion: We advocate for urgent work-up including early liver biopsy the more that immune mediated liver injury from checkpoint inhibitors can cause different laboratory pictures including mixed ones as well as hepatocellular injury (if assessed by DILIN) and still ICI-C can be confirmed on histology. Treatment with tocilizumab, in combination with ursodeoxycholic acid, can be considered in severe cases of ICI-C.
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BibTeX
@article{kohoutova2026case,
title = {{Case Series: Severe cholangitis as an immune checkpoint inhibitor induced adverse event in four cases: management and treatment options including tocilizumab and ursodeoxycholic acid}},
author = {Darina Kohoutova and Joshua Shur and Monica Terlizzo and Robert Goldin and Matthew Foxton and Nicholas Powell and Douglas Macdonald and Naureen Starling and Sheela Rao and Kevin Joseph Harrington and Kate Young and Sanjay Popat and Nicos Fotiadis and Edward W. Johnston and Sameer Zar and Daniel Levine and Maroua Hafi and Pablo Jimenez-Labaig and Abu Taher and David C. Cunningham},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1929147},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929147/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Series: Severe cholangitis as an immune checkpoint inhibitor induced adverse event in four cases: management and treatment options including tocilizumab and ursodeoxycholic acid
AU - Darina Kohoutova
AU - Joshua Shur
AU - Monica Terlizzo
AU - Robert Goldin
AU - Matthew Foxton
AU - Nicholas Powell
AU - Douglas Macdonald
AU - Naureen Starling
AU - Sheela Rao
AU - Kevin Joseph Harrington
AU - Kate Young
AU - Sanjay Popat
AU - Nicos Fotiadis
AU - Edward W. Johnston
AU - Sameer Zar
AU - Daniel Levine
AU - Maroua Hafi
AU - Pablo Jimenez-Labaig
AU - Abu Taher
AU - David C. Cunningham
PY - 2026
DA - 2026/10/27
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1929147
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929147/full
AB - Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized treatment of multiple malignancies, nevertheless, their clinical use can be associated with adverse events (AE). ICI-induced cholangitis (ICI-C) belongs to rare AEs. Poor response to glucocorticosteroids (GCS) is observed, deaths related to ICI-C were reported. Main findings and therapeutic interventions: We share four detailed cases (two males and two females) of severe ICI-C (severity assessed based on DILIN criteria). All patients were jaundiced (bilirubin >90 µmol/L), one had cholestatic liver injury, two had mixed liver injury and one had a rather hepatocellular liver injury based on R factor in DILI. Three were treated with programmed cell death protein (anti-PD1) or ligand 1 antibodies, one with anti-PD1 and cytotoxic T-lymphocyte-associated protein-4 antibodies. Onset of liver injury was observed during treatment (2), three weeks after last infusion (1) and four months after last treatment (1). Laboratory tests excluded infections, malignant infiltration and autoimmune profile was typically negative. Another drug induced injury was excluded. MRCP and EUS were used as imaging methods of choice. A liver biopsy was organized due to absent response to corticosteroids and second line immunosupressive medication, as cholangitis was suspected. Histology was confirmatory for ICI-C in all cases. Predominant infiltration by CD8 positive lymphocytes was shown. Treatment with tocilizumab, anti-IL-6 receptor antibody, and ursodeoxycholic acid were used in three cases. Outcomes: Three patients with ICI-C confirmed histologically received tocilizumab and ursodeoxycholic acid with an excellent effect. Decrease in bilirubin was observed within 72 hours. Significant improvement/normalization of liver enzymes followed. No side effects of tocilizumab were reported. Patient who did not receive tocilizumab (maximum bilirubin 349 µmol/L, encephalopathy; cholestatic liver injury – R factor 0.8) died. Conclusion: We advocate for urgent work-up including early liver biopsy the more that immune mediated liver injury from checkpoint inhibitors can cause different laboratory pictures including mixed ones as well as hepatocellular injury (if assessed by DILIN) and still ICI-C can be confirmed on histology. Treatment with tocilizumab, in combination with ursodeoxycholic acid, can be considered in severe cases of ICI-C.
SN - 1664-3224
ER -