Table Info

Table 2.

The clinical course of immune checkpoint inhibitor-induced cholangitis cases

Cases	Imaging		Treatment						Timepoint	Liver function tests
Cases	US	MRCP	UDCA	Cortico-steroids	MMF	TAC	IFX	NAC	Timepoint	Bil**	ALP	GGT	AST	ALT
Case 1			750 mg	4 mg/kg IVMP	1.5 g BD	3 mg BD	5 mg/kg	*	Pre-ICI	5	85	24	20	10
									Day 0	20	981	998	420	389
									MRCP	21	601	862	124	176
									Peak	141	1142	1672	272	352
									Day 482 (most recent)	30	524	1078	76	80
Case 2			-	500 mg IVMP	1 g BD	3 mg BD	-	*	Pre-ICI	12	155	192	51	N/A
									Day 0	5	301	474	44	117
									MRCP	76	808	2249	454	1197
									Peak (and most recent)	453	1165	2785	219	547
Case 3			-	4 mg/kg IVMP	1.25 g BD	3 mg BD	5 mg/kg	-	Pre-ICI	7	147	166	38	50
									Day 0	17	1088	2952	130	183
									MRCP	37	1084	3278	146	247
									Peak	65	1404	4994	262	278
									Day 482 (most recent)	33	974	2559	40	75

Green indicates performed/received, and red indicates not performed/received. The highest doses received for each treatment are specified. Day 0 refers to the day of immune checkpoint inhibitor-induced hepatotoxicity diagnosis, liver function tests are provided for the day of MRCP. Peak values were selected based on the day of the patient’s highest measured bilirubin value. ICI-H: immune checkpoint inhibitor-induced hepatotoxicity; US: ultrasound; MRCP: magnetic resonance cholangiopancreatography; UDCA: ursodeoxycholic acid; mg/kg: milligrams per kilograms of bodyweight; IVMP: intravenous methylprednisolone; MMF: mycophenolate mofetil; BD: twice-daily; TAC: tacrolimus; IFX: infliximab; NAC: N-acetylcysteine; Bil: bilirubin; ALP: alkaline phosphatase; GGT: γ-glutamyltransferase; AST: aspartate aminotransferase; ALT: alanine aminotransferase. *: see [9]; **: μmol/L. All other liver function tests in units per litre

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1002250_sup_1.pdf.

Declarations

Author contributions

SG: Data curation, Investigation, Methodology, Visualization, Writing—original draft, Writing—review & editing. NS: Investigation, Visualization, Writing—review & editing. AOB: Conceptualization, Data curation, Methodology, Supervision, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Cases were identified as part of a retrospective evaluation which had received regional approval (institution name: Clatterbridge Cancer Centre NHS Foundation Trust; registration number 2324-08).

Consent to participate

Informed consent to participate in the study was exempted by the local information governance officer, due to the completely anonymous nature of the information.

Consent to publication

Not applicable.

Availability of data and materials

Partial raw data (clinical records including documentation and imaging reports) for this manuscript are not publicly available because data contains personally identifiable information that may be restricted from public access to protect individuals’ privacy.

Funding

SG is a recipient of an NIHR Academic Clinical Fellowship. AOB is a holder of a UKRI ESRC [ES/W011484/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Robert C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun. 2020;11:3801. [DOI] [PubMed] [PMC]

Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al.; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022;386:1973–85. [DOI] [PubMed] [PMC]

Jin Y, Wei J, Weng Y, Feng J, Xu Z, Wang P, et al. Adjuvant Therapy With PD1/PDL1 Inhibitors for Human Cancers: A Systematic Review and Meta-Analysis. Front Oncol. 2022;12:732814. [DOI] [PubMed] [PMC]

Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, et al.; ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:1217–38. [DOI] [PubMed]

Common terminology criteria for adverse events (CTCAE) version 5.0 [Internet]. Maryland: National Cancer Institute; [cited 2024 Apr 4]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50

Reynolds K, Thomas M, Dougan M. Diagnosis and Management of Hepatitis in Patients on Checkpoint Blockade. Oncologist. 2018;23:991–7. [DOI] [PubMed] [PMC]

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373:23–34. Erratum in: N Engl J Med. 2018;379:2185. [DOI] [PubMed] [PMC]

Pi B, Wang J, Tong Y, Yang Q, Lv F, Yu Y. Immune-related cholangitis induced by immune checkpoint inhibitors: a systematic review of clinical features and management. Eur J Gastroenterol Hepatol. 2021;33:e858–67. [DOI] [PubMed] [PMC]

Intravenous N-acetylcysteine (NAC) for paracetamol overdose: reminder of authorised dose regimen; possible need for continued treatment with NAC [Internet]. Richmond: The National Archives Kew; [cited 2024 Apr 4]. Available from: https://www.gov.uk/drug-safety-update/intravenous-n-acetylcysteine-nac-for-paracetamol-overdose-reminder-of-authorised-dose-regimen-possible-need-for-continued-treatment-with-nac

10.

Berry P, Kotha S, Zen Y, Papa S, Menabawey TE, Webster G, et al. Immune checkpoint inhibitor-related cholangiopathy: Novel clinicopathological description of a multi-centre cohort. Liver Int. 2023;43:147–54. [DOI] [PubMed]

11.

Dougan M, Wang Y, Rubio-Tapia A, Lim JK. AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review. Gastroenterology. 2021;160:1384–93. [DOI] [PubMed]

12.

Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021;39:4073–126. Erratum in: J Clin Oncol. 2022;40:315. [DOI] [PubMed]

13.

Maurea S, Caleo O, Mollica C, Imbriaco M, Mainenti PP, Palumbo C, et al. Comparative diagnostic evaluation with MR cholangiopancreatography, ultrasonography and CT in patients with pancreatobiliary disease. Radiol Med. 2009;114:390–402. [DOI] [PubMed]

14.

Caruso M, Stanzione A, Prinster A, Pizzuti LM, Brunetti A, Maurea S, et al. Role of advanced imaging techniques in the evaluation of oncological therapies in patients with colorectal liver metastases. World J Gastroenterol. 2023;29:521–35. [DOI] [PubMed] [PMC]

15.

Caruso M, Romeo V, Stanzione A, Buonerba C, Di Lorenzo G, Maurea S. Current Imaging Evaluation of Tumor Response to Advanced Medical Treatment in Metastatic Renal-Cell Carcinoma: Clinical Implications. Appl Sci. 2021;11:6930. [DOI]