Herpes Hepatitis Causing Fulminant Liver Failure in a Crohnʼs Disease Patient

Abstract

A 24-year old non pregnant white woman with history of Crohn's disease, started on azathioprine and mesalamine, one month prior to admission, presented with a five day history of fever, chills, diarrhea and abdominal pain. Her physical examination revealed temperature of 102.4 F, abdominal distension and epigastric tenderness. Initial labs showed normal CBC, Klebsiella pneumoniae positive urine culture, ALT 104 units/L (U/L), AST 120 U/L, and normal amylase and lipase levels. She was started on levofloxacin for UTI, and methyl prednisone and metronidazole for possible Crohn's flare. On day 2 of hospitalization, she developed vesiculopapular rash on her chest and abdomen which later spread to her extremities. Her ALT and AST increased to 1401 U/L and 2386 U/L respectively. Hepatitis A IgM, hepatitis B surface antigen, hepatitis core IgM antibody, hepatitis C antibody, ANA, chlamydia/gonococcal PCR test, ASMA, AMA and EBV serology were negative. Imaging studies including RUQ ultrasound, CT scan of abdomen/pelvis, and HIDA scan were normal. Her condition declined with fulminant hepatitis, coagulopathy, and pancytopenia. She admitted to having unprotected sex and contracting herpes simplex virus (HSV) in the past. She was empirically started on intravenous acyclovir and subsequently found positive for HSV type 2 IgM antibodies with titer >1:160. Acyclovir was continued for 14 days with near complete normalization of liver enzymes, coagulation studies, and blood counts. HSV viral load decreased from 500 million to 158,000 in 3 weeks. She was discharged on lifelong maintenance dose of acyclovir. HSV is a rare cause of fulminant hepatitis and at risk individuals include neonates, pregnant women, patients like those on steroids, immunosuppressant medications and HIV and cancer patients. Clinical features include fever, nausea, vomiting, abdominal pain, leukopenia, and coagulopathy with or without mucocutaneous lesions. Serum HSV PCR is the diagnostic modality of choice, although liver biopsy remains the gold standard. When HSV hepatitis is suspected or diagnosed, acyclovir should be empirically started, since delay in initiation of antiviral therapy leads to rapid development of sequelae and poor outcomes. To our knowledge, this is the second reported case of HSV hepatitis in a Crohn's disease patient. Hence, HSV hepatitis should be considered in the differential diagnosis of fulminant hepatitis in immunocompromised patients.