Giant Cell Hepatitis Due To Drug-Induced Autoimmune Hepatitis From Dupilumab

INTRODUCTION: Giant cell hepatitis (GCH) is a pathologic diagnosis characterized by liver inflammation and large multinucleated hepatocytes. GCH is a common pathologic entity in infants but is exceedingly rare in adults. It is typically in response to drugs, autoimmune hepatitis (AIH), viruses and malignancy. We present a case of drug-induced autoimmune hepatitis causing giant cell transformation. CASE DESCRIPTION/METHODS: A 24-year-old male with eosinophilic asthma, chronic eosinophilia, primary sclerosing cholangitis (PSC) and Crohn’s disease presented with right upper quadrant pain, jaundice, anorexia, lymphadenopathy and weight loss. Labs on admission were AST 973 (u/L), ALT 801 (u/L), AP 225 (u/L), total bilirubin 16.6 (mg/dL), direct bilirubin 11.2 (mg/dL), INR 2.4, absolute eosinophil count 20.4 (k/uL). Extensive serologic work up of acute liver injury was unrevealing with the exception of a total IgG of 5291 (mg/dL). An MRI abdomen demonstrated hepatomegaly, non-specific hepatitis and findings consistent with his known PSC. Workup for infectious, autoimmune and malignant causes of hypereosinophilia was negative. Three months prior to admission, he was started on dupilumab for his eosinophilic asthma. A liver biopsy was pursued. H&E Staining (Figure 1) noted prominent giant cell hepatocellular transformation and hepatocyte ballooning degeneration. There were plasma cell, lymphocyte and eosinophil portal infiltrates present. Trichrome staining (Figure 2) showed fibrosis in a periportal and patchy sinusoidal pattern. The pathologic analysis was most consistent with giant cell hepatitis. His clinical and pathologic diagnosis was consistent with GCH due to drug-induced AIH from dupilumab. Management included discontinuation of dupilumab and IV methylprednisolone which was transitioned to a prolonged prednisone taper at discharge. After 6 months, his liver function tests have nearly normalized. DISCUSSION: GCH is a common pathologic entity in infants but is rare in adults. Fewer than 100 reported adult cases are present in the literature. AIH followed by drug-induced and viral hepatitis are most frequently causative of GCH. Our patient’s negative serologic workup, biopsy findings, and timing of dupilumab initiation to acute hepatitis makes drug-induced autoimmune hepatitis the most likely etiology. There have been no previous reports that dupilumab has been implicated in drug-induced liver injury, drug-induced AIH or has been responsible for the pathologic diagnosis of Giant Cell Hepatitis.Figure 1.: Liver biopsy (H&E stained slide, 200x): This portal tract demonstrates a mixed inflammatory infiltrate composed of lymphocytes, plasma cells, and eosinophils without vasculitis or ductulitis. The portal tract is surrounded by the prominent multinucleated, syncytial giant hepatocytes and ballooning degeneration.Figure 2.: Liver biopsy (Massons's Trichrome stain, 200x): The trichrome staining demonstrates increased periportal fibrosis and patchy perisinusoidal fibrosis.