Acute liver failure (ALF) is a fatal and challenging disease even for patients without underlying diseases. In this paper, we aimed to share our opinion about a treatment option for cholestatic fulminant hepatitis where transplantation is not an option. A 36- year- old male with sickle- cell anemia (SCA) and G6PD deficiency presented with jaundice and fever. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin and international normalized ratio (INR) levels were 335 mg/dl, 430 mg/dl, 30 mg/dl, 18 mg/dl and 1.2, respectively at the admission. HBsAg was positive. Hepatitis B virus (HBV) DNA was 64.000.000 IU/ml. On the third week of admission, ALT, AST, total bilirubin and direct bilirubin levels increased up to 270 mg/dl, 460 mg/dl, 71 mg/dl and 47 mg/dl, respectively. INR prolongation accompanied. Hepatic encephalopathy developed. Entecavir 1x1 mg and fresh frozen plasma was started. The condition of the patient continued to deteriorate and, MELD score was 38. After two sessions of plasmapheresis, ALT, AST, total bilirubin, direct bilirubin and INR levels decreased to 30 mg/dl, 90 mg/dl, 9 mg/dl, 4 mg/dl, 1.2, respectively. The patient was discharged eventually. Plasmapheresis can be thought as treatment for patients in whom liver transplantation is not an option or for patients pending transplantation.