2331 Post-Infantile Giant Cell Hepatitis Leading to Severe Acute Liver Injury in Chronic Lymphocytic Leukemia (CLL): Progression of CLL vs. Drug Induced Liver Injury (DILI)

Abstract

INTRODUCTION: Post-infantile giant cell hepatitis (PIGCH) is a form of hepatocyte degeneration, triggered by noxious injury. Underlying etiologies are autoimmune, drug-induced, virus mediated and miscellaneous e.g. sickle cell, CLL, post-transplant. While only occurring in 5 per 100,000 adults, when present, rapid progression to liver failure can result in a 50% mortality rate. CASE DESCRIPTION/METHODS: A 76 yo lady with a history of anemia, remote breast cancer in remission, and CLL (not on treatment), presented with a 3-week history of fatigue, nausea and jaundice following a 5-day course of azithromycin and prednisone (20 mg OD), and one dose of ceftriaxone, for acute bronchitis. Exam revealed jaundice and abdominal distension. Admission labs: AST 4233U/L, ALT 3175U/L, ALP 187IU/L, total bilirubin 9.4 (7.1 direct) mg/dl, sodium 131mEq/L, BUN 27, Cr 0.7 mg/dl. INR 1.4. WBC 68.3/µL, hemoglobin 8.2 g/dl, platelets 233/µL. CT Abd/Pelvis without contrast: mild periportal edema, with enlarged liver, otherwise normal. Workup for viral hepatitis, other viruses and autoimmune serologies was negative, other than ANA titer of 1:640. Tox screen and mass spectrometry were negative. Given worsening liver injury, liver biopsy was obtained, which had active hepatitis with giant cell transformation, patchy necrosis, and CLL in portal areas (Figure 1). The patient was recommended high-dose prednisone, but she deferred therapy. Labs were followed closely, with remarkable improvement within a few days. She was discharged on ursodiol. On follow-up 2 months later, a mild transaminitis was persistent, so prednisone therapy was started with subsequent resolution of her hepatitis. However, subsequent imaging revealed development of cirrhosis. DISCUSSION: Treatment of PIGCH is dependent on underlying etiology, with autoimmune pathology having the best prognosis described in the literature versus variable courses for drug induced PIGCH, once the offending agent is stopped. In our patient, the trigger for giant cell transformation was suspected to be drug induced liver injury, from treatment with azithromycin/ceftriaxone. Interestingly, CLL itself can spontaneously transform to PIGCH as well, with treatment of CLL improving prognosis. Our patient did not want immunosuppressive therapy initially. Although her acute liver injury spontaneously improved, she did develop cirrhosis as a long-term complication. PIGCH must be aggressively treated/monitored to prevent life-threatening fulminant hepatic failure, or subsequent cirrhosis.