A205 pembrolizumab associated sclerosing cholangitis responds to combination of steroids and mycophenolic acid: a case report

Abstract Background Pembrolizumab is a check point inhibitor that targets programmed cell death receptor ligand 1 (PD-L1). However, check-point inhibitors are associated with its characteristic adverse event know as immune related adverse events that can affect a myriad of organ systems. In the hepatobiliary system, the most commonly described iRAE is hepatitis/hepatotoxicity and latest oncology guidelines offer recommendations on treatment and followup of immunotherapy related hepatitis (1). However, a more rare presentation of iRAE, that have only been described as case reports or case series, is secondary cholangitis. We report one of such a case. Aims Case report Methods Case report Results The patient is a 55 year-old Caucasian female know for lung adenocarcinoma presented to the emergency room on May 5th, 2020, having received her 8th cycle of pembrolizumab. Her blood works mildly elevated transaminitis; ALT 78 U/L, AST 11 U/L, alkaline phosphate of 130 U/L, and total bilirubin of 3.5 umol/L. MRI of the abdomen showed a normal appearing liver without focal parenchymal lesion, no biliary stones or obstructing masses, dilated common bile duct at 11 mm with small pericholecystic free fluid, and normal gall badder thickness of 2 mm. There was also notion of minimally prominent intrahepatic biliary radicles seen within the CBD. Etiology workup of cholestatic transaminitis was negative. A diagnosis of immunotherapy related sclerosing cholangitis was posed and the patient was treated with MMF and prednisone with good response. Conclusions Discussion This patient seems to have developed immunotherapy mediated cholangitis. Liver biopsy when performed in liver injury tend to show lobular hepatitis, with liver parenchyma infiltrated with lymphocytes and focal necrosis with acidophilic bodies. However, there seems to be another, less frequent pattern of injury described with pembrolizumab and associated with cholangiopathy, resembling primary biliary cholangitis. It is characterized with portal tracts enlarged with fibrosis and inflammatory cells infiltration; infiltrating cells are lymphocytes (2). Biliary epithelium with fibrosis with CD8+ T cells infiltration seem to be recurrently reported in case reports. (3, 4). Other cases have been describe in the literature. In many cases, steroid therapy was attempted, but response rates seem to be inconsistent. Nivolumab related cholangitis have been also been described and characterized by extra hepatic bile duct dilatation along with negative immunological markers such as ANA and IgG4 in patients with non-small cell lung cancer, and seems to respond only moderately to steroid therapy (6). Retrospective data of nivolumab related cholangiopathy seems to suggest that there is favourable response to the combination of MMF and steroid therapy (7). Funding Agencies None