Purpose: Spontaneous Hepatitis Be antigen seroconversion (development of hepatitis Be antibody) can be associated with acute exacerbation of chronic hepatitis B virus (HBV)infection. The clinical spectrum of this exacerbation can vary from completely asymptomatic to typical symptoms of acute hepatitis to hepatic decompensation. We present a patient who developed fulminant hepatic failure (FHF)at the time of HBeAg seroconversion successfully treated with orthotopic liver transplantation (OLT). A 52 year old Caucasian female with PMH of HTN, ruptured cerebral aneurysm with right-sided hemiparesis and rheumatoid arthritis, but no known history of liver disease, presented with a 3-week history of abdominal pain, nausea, vomiting, and jaundice. Physical exam was remarkable for only jaundice, scleral icterus, diffuse abdominal tenderness, and lower extremities edema. Her labs showed ALT 304 U/L, AST 462 U/L, Alkaline phosphatase 209 U/L, bilirubin 6.1 mg/dl, (conjugated 3.6 mg/dl), and INR 2.4. The work up for the etiology of her liver disease was negative, except for hepatitis B. The HBV serology showed positive HBsAg, HBcIgM, HBeAb and negative HBeAg and HBsAb. Abdominal CT scan showed 15.2 cm liver without arterially enhancing lesions or biliary dilatation, patent hepatic vasculature and no ascites. Transjugular liver biopsy revealed extensive hepatic parenchymal extinction, severe activity (grade 4)and periportal fibrosis (stage 2). The stains for HBsAg and HBcAb were positive. The patient was started on Entecavir but developed hepatic encephalopathy in 2 days. At that point her total bilirubin was 10.1 mg/dl, INR 4.5, creatinine 0.6 mg/dl and MELD score 32. The patient was rapidly evaluated and listed as status 1 for OLT. She was transplanted 2 days later. After the OLT she was started on Tacrolimus, Mycophenolate mofetil, Hepatitis B immunoglobulin and continued on Entecavir. She had uncomplicated postoperative course and was discharged in 1 week. Her most recent HBV serology (4 months post OLT) showed HBsAb 682IU/L and HBV DNA less than 20 IU/ml. Most patients with chronic HBV infection eventually transition (either spontaneously or as a result of treatment)from immune-active phase to an inactive carrier state as they clear HBeAg and develop HBeAb (seroconversion). About 2/3 of the spontaneous seroconversions are preceded by hepatitis flare due to more robust immune clearance of the hepatocytes containing replicating HBV. In extreme cases this vigorous immune response can result in FHF. Even though HBV is the most common viral cause of FHF, it is not clear how often FHF is due to seroconversion and also what percentage of OLTs are done because of HBV seroconversion.