S2405 Post-Infantile Giant Cell Hepatitis

Abstract

INTRODUCTION: Post-infantile giant cell hepatitis (PIGCH) is a rare disorder among adults. Diagnosis is dependent on liver biopsy and its histologic hallmark is the presence of hepatocyte-derived multinucleated giant cells. This is thought to be due to increased hepatocyte regenerative activity that occurs as a response to noxious stimuli including viral infections, autoimmune disorders, leukemia and drug reactions. We report two cases of PIGCH including its management and outcome. CASE DESCRIPTION/METHODS: Case 1 is a 62-year-old African American male who presented with jaundice, dark urine and generalized malaise. Past medical history notable for alcohol use disorder in remission and chronic hepatitis C treated with antiviral therapy. Physical examination revealed jaundice. Bloodwork included ALT 2,300 U/L, AST 1,900 U/L, ALP 186 U/L, GGT 177 U/L, serum total bilirubin 29 mg/dL, direct bilirubin 20 mg/dL, AFP level 25 μg/L and INR 1.5. Infectious work up was negative and abdominal ultrasound was normal. Autoimmune markers ANA, SMA and AMA were positive. Liver biopsy showed severe syncytial giant cell hepatitis with 75% loss of hepatocytes. Patient was started on steroids with complete normalization of his transaminases on four month follow up. Case 2 is a 69-year-old Caucasian male with history of dyslipidemia, hypertension and chronic lymphocytic leukemia (CLL) on Ibrutinib, who presented with generalized malaise. He denied any alcohol, tobacco, or substance use. Physical examination revealed jaundice. Bloodwork included AST 2,385 U/L, ALT 5,609 U/L, ALP 286 U/L, total bilirubin 31.3 mg/dL, direct bilirubin 23.6 mg/dL and INR was 1.1. Infectious and autoimmune work up was negative. Abdominal ultrasound was normal. Liver biopsy showed syncytial giant cell hepatitis with CLL infiltrates on most portal tracks. Patient was started on steroids with temporary normalization of transaminases. Unfortunately, one week later, the patient died due to cancer-related complications. DISCUSSION: PIGCH has been commonly associated with autoimmune hepatitis but only a few case reports of CLL-associated PIGCH exist. Given its heterogeneous etiologies, PIGCH is difficult to prognosticate and manage. However, it should be considered in all patients with acute liver injury or chronic liver disease of unknown disease. Despite having a good response to immunosuppressive therapy, patients may still develop severe progressive disease requiring liver transplantation. Hence, prompt recognition and treatment is crucial.Figure 1.: The multinucleated giant cell hepatocytes (see arrows) are seen in H&E stained sections of biopsy. These are reactively altered hepatocytes (rather than multinucleated giant cell histiocytes). Immunoperoxidase stains show (see inset images) that within multinucleated hepatocytes, nuclei are strongly positive for Cyclin-D1 and cytoplasm is strongly positive for cytokeratin CK8/CK18 (Cam5.2).Figure 2.: In Case 2, the same stains were used as in Case 1 however the portal tract contains an infiltrate of neoplastic lymphoid cells (CLL).