RT Journal Article
SR Electronic
T1 Immunotherapy-related hepatitis: real-world experience from a tertiary centre
JF Frontline Gastroenterology
JO Frontline Gastroenterol
FD BMJ Publishing Group Ltd
SP 364
OP 371
DO 10.1136/flgastro-2018-101146
VO 10
IS 4
A1 Vincent Cheung
A1 Tarun Gupta
A1 Miranda Payne
A1 Mark R Middleton
A1 Jane D Collier
A1 Alison Simmons
A1 Paul Klenerman
A1 Oliver Brain
A1 Jeremy F Cobbold
YR 2019
UL http://fg.bmj.com/content/10/4/364.abstract
AB Objective Immune checkpoint inhibitors like anti-programmed cell death protein 1 (PD-1) drugs Nivolumab and Pembrolizumab and anti-cytotoxic T-lymphocyte associated (CTLA-4) drug Ipilimumab have become standard of care in many metastatic cancers. Immunotherapy-related hepatitis and cholangitis present a diagnostic and management challenge, being rare and incompletely characterised. We aim to report the incidence, features and treatments used for this in a real-world setting and to identify useful biomarkers, which can be used to predict effective use of steroids.Design Retrospective review of 453 patients started on immunotherapy over 7 years.Setting Tertiary hepatology and oncology centre.Patients 21 patients identified with immunotherapy-related hepatotoxicity.Results Hepatitis was most common in those receiving dual therapy (incidence 20%), with 75% of Grade 4 hepatitis cases occurring with ipilimumab-containing regimens. Corticosteroid monotherapy is first line treatment, but doses above 60 mg OD prednisolone do not demonstrate any additional benefit in time to hepatitis resolution. The alanine transaminase (ALT) reduction in steroid-responsive hepatitis is typically rapid (with a halving of ALT within 11 days). The commencement of additional immunosuppression (typically mycophenolate) appears safe and prompts a more rapid fall in ALT than corticosteroid use alone. Infliximab was safely used twice as hepatitis treatment. We also describe one patient with rare immunotherapy-induced biliary disease.Conclusions Vigilance is required for detection of immunotherapy-associated liver disease as, other than dual immunotherapy, we can identify no predictive factors for its development. Our data suggest that corticosteroid response is not dependent on the higher dosing regimens. Early escalation of immunosuppression may be of benefit in the absence of a rapid response to corticosteroids.