Volume 66, Issue 3, Pages 657-659 (March 2017) Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids  Mirjana Ziemer, Eleni Koukoulioti, Susanne Beyer, Jan C. Simon, Thomas Berg  Journal of Hepatology  Volume 66, Issue 3, Pages 657-659 (March 2017) DOI: 10.1016/j.jhep.2016.11.015 Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

Fig. 1 The course of two patients with metastatic malignant melanoma who developed grade 3 ALT increase after two and three cycles of nivolumab and pembrolizumab, respectively. (A) The course of liver enzymes and therapeutic interventions is depicted in a 73-year-old patient with acrolentiginous BRAF-/c-Kit-/NRAS-wildtype-melanoma with pulmonary, mediastinal and hilar lymph node, and bone metastasis who was treated with 3mg/kg body weight nivolumab. After two treatment cycles nivolumab had to be stopped after a grade 3 increase in transaminases and gamma-glutamyl transferase (GGT). Bilirubin was normal as well as alkaline phosphatase. Nivolumab could be safely re-started by the concomitant treatment with budesonide and UDCA. Please note, that only the course until day 203 (February 2016) is depicted, but nivolumab therapy is still ongoing and the patient has received a further 26 cycles to date (November 2016). (B) The course of liver enzymes and therapeutic interventions in an 85-year-old female with a BRAF-negative melanoma with cutaneous, spleen and pulmonary as well as cerebral metastases. After three cycles of pembrolizumab, started in December 2015, transaminases and GGT increased significantly, and bilirubin (42.77mg/dl) was elevated. The maximum alkaline phosphatase levels were 463.2 U/L and this value was reached exactly at the same time as GGT peaked to its maximum. Prothrombin time was normal. Treatment with pembrolizumab was re-started after 15weeks under treatment with budesonide and UDCA. Please note, that only the course until day 207 (July 2016) is given, but pembrolizumab therapy is still ongoing and the patient has received a further 6 uneventful cycles to date (November 2016). Journal of Hepatology 2017 66, 657-659DOI: (10.1016/j.jhep.2016.11.015) Copyright © 2016 European Association for the Study of the Liver Terms and Conditions