S2557 A Case of Immune-Mediated Liver Injury Secondary to Olaparib

Abstract

INTRODUCTION: Immune mediated drug-induced liver injury (IM-DILI) presents with a hepatocellular or mixed pattern of liver injury that, for some patients, persists after drug withdrawal. Olaparib is an oral inhibitor of poly-ADP-ribose polymerase and is approved for treatment of relapsed metastatic ovarian cancer with BRCA 1/2 mutations. Mild alterations in liver tests have been reported in < 5% of treated patients. CASE DESCRIPTION/METHODS: A 56-year-old female with BRCA1 mutation and relapsed metastatic ovarian cancer was admitted to the hospital in August 2019 due to a severe acute hepatocellular liver injury with jaundice, elevated INR, and concern for impending fulminant liver failure (Table 1). Her liver tests had previously been normal prior to and until three months after she had started olaparib in May 2019. She had no alcohol history or use of herbal supplements. Physical examination was notable for jaundice, mild right upper quadrant tenderness, and no hepatic encephalopathy. Computed tomography showed mild hepatomegaly with periportal edema. Laboratory work-up for infectious, metabolic, and autoimmune etiologies of liver injury was negative. Liver biopsy revealed areas of submassive necrosis with lobular collapse, moderate to severe portal and lobular inflammation with predominantly lymphocytes, cholestasis with focal hepatocyte rosette formation, acute cholangitis with bile duct injury and ductular proliferation, and ceroid-laden histiocytes, consistent with IM-DILI. No portal fibrosis was seen. Olaparib was promptly withdrawn and prednisone (60 mg/day) was initiated. Liver tests had significantly improved within 4 weeks (Table 1 and Figure 1) and prednisone was tapered while liver enzymes normalized. DISCUSSION: We report the first case of IM-DILI secondary to olaparib use in the United States. Olaparib is largely metabolized by the liver through cytochrome P450 and it is hypothesized that reactive metabolites can bind cellular proteins, leading to the creation of neo-antigens and subsequent liver injury. This case report highlights the need for close monitoring of liver tests while on olaparib and that the diagnosis of IM-DILI and prompt initiation of corticosteroids should be considered if an acute liver injury develops.Table 1.: Liver tests and INR values after olaparib withdrawalFigure 1.: A graphical illustration of livers tests and INR after olaparib was withdrawn and prednisone was started.Figure 2.: liver biopsy shows areas of submassive necrosis with lobular collapse. Note that no viable hepatocytes are identified in this microscopic area.