B K Straub1, D A Ridder2, A Schad2, C Loquai3, J M Schattenberg4. 1. Institut für Pathologie, Universitätsmedizin Mainz, Johannes Gutenberg-Universität Mainz, Langenbeckstr. 1, 55131, Mainz, Deutschland. beate.straub@unimedizin-mainz.de. 2. Institut für Pathologie, Universitätsmedizin Mainz, Johannes Gutenberg-Universität Mainz, Langenbeckstr. 1, 55131, Mainz, Deutschland. 3. Hautklinik und Poliklinik, Universitätsmedizin Mainz, Johannes-Gutenberg-Universität Mainz, Mainz, Deutschland. 4. 1. Medizinische Klinik, Universitätsmedizin Mainz, Johannes Gutenberg-Universität Mainz, Mainz, Deutschland.
Abstract
BACKGROUND: Drug-induced liver injury is increasing, especially in elderly patients with polymedication and multimorbidity. OBJECTIVES: Clinicopathologic correlation of immune-mediated liver injury, specifically liver injury following therapy with immune checkpoint inhibitors against PD-1, PDL-1, and CTLA4. METHODS: Histologic assessment of liver biopsies of nine patients after therapy with immune checkpoint inhibitors and correlation with clinical parameters. RESULTS: In all nine patients, liver injury was apparent after variable administration of immune checkpoint inhibitors. Transaminase levels were increased up to a maximum of 3818 U/l. Liver histology showed liver injury resembling autoimmune hepatitis respective cholangitis. In two patients, veno-occlusive disease was seen. Corticosteroid therapy was initiated in eight patients, subsequently four patients showed decreasing transaminases and five patients died of tumor progress. In three patients, it remains unclear whether liver injury by immune checkpoint inhibitors may have ultimately contributed to the fatal course, especially in one patient with liver cirrhosis and hepatocellular carcinoma. CONCLUSIONS: Therapy with immune checkpoint inhibitors may lead to potentially fatal immune phenomena in susceptible patients, which may affect liver and/or other organs independently. Other causes of hepatopathy need to be ruled out clinically and/or histologically.
BACKGROUND: Drug-induced liver injury is increasing, especially in elderly patients with polymedication and multimorbidity. OBJECTIVES: Clinicopathologic correlation of immune-mediated liver injury, specifically liver injury following therapy with immune checkpoint inhibitors against PD-1, PDL-1, and CTLA4. METHODS: Histologic assessment of liver biopsies of nine patients after therapy with immune checkpoint inhibitors and correlation with clinical parameters. RESULTS: In all nine patients, liver injury was apparent after variable administration of immune checkpoint inhibitors. Transaminase levels were increased up to a maximum of 3818 U/l. Liver histology showed liver injury resembling autoimmune hepatitis respective cholangitis. In two patients, veno-occlusive disease was seen. Corticosteroid therapy was initiated in eight patients, subsequently four patients showed decreasing transaminases and five patients died of tumor progress. In three patients, it remains unclear whether liver injury by immune checkpoint inhibitors may have ultimately contributed to the fatal course, especially in one patient with liver cirrhosis and hepatocellular carcinoma. CONCLUSIONS: Therapy with immune checkpoint inhibitors may lead to potentially fatal immune phenomena in susceptible patients, which may affect liver and/or other organs independently. Other causes of hepatopathy need to be ruled out clinically and/or histologically.
Entities:
Keywords:
Acute liver failure; Drug induced or toxic liver injury; Drug-related side effects and adverse reactions; Polymedication; Transaminases
Authors: V H Koelzer; K Glatz; L Bubendorf; A Weber; A Gaspert; G Cathomas; A Lugli; A Zippelius; W Kempf; K D Mertz Journal: Pathologe Date: 2017-05 Impact factor: 1.011
Authors: Gary Joseph Doherty; Adam M Duckworth; Susan E Davies; George F Mells; Rebecca Brais; Susan V Harden; Christine A Parkinson; Pippa G Corrie Journal: ESMO Open Date: 2017-10-10