Successful Living-Donor Liver Transplantation for Wilson's Disease With Hemophagocytic Syndrome

Abstract

Hemophagocytic syndrome (HPS) is a rare but well recognized complication of a range of conditions including infections, immunodeficiency states, malignancies, lymphoproliferative, and autoimmune diseases. Prognosis is reported to be markedly poor (1–3), with a survival rate of 23% to 60% in patients with HPS and 50% after liver transplantation (LT) (4–11). Here, we describe a case of LT for Wilson's disease (WD) combined with HPS. To our knowledge, this is the first case report of a patient affected by these two conditions concurrently. A 10-year-old girl was admitted to our hospital for WD. Two weeks later, she developed a persistent spiking fever, with constant elevation at 39–41°C, as well as lymphadenopathy and hepatosplenomegaly with hepatic dysfunction. Primary Epstein-Barr virus (EBV) infection at presentation was confirmed by real-time polymerase chain reaction. Bone marrow aspiration (BMA) showed active phagocytosis with benign findings. The liver biopsy specimen showed evidence of cirrhosis but EBV was not detected. HPS and liver cirrhosis consistent with WD was diagnosed. The patient was treated with methylprednisolone (1 mg/kg/day). On the 60th admission day, BMA showed ongoing HPS. The methylprednisolone dose was increased to 3 mg/kg/day as a steroid bolus injection, with the addition of cyclosporine A at 1 mg/kg/day. Therapeutic plasma exchange (PE) with fresh frozen plasma was started. Although general clinical condition after PE treatment showed mild improvement, the deterioration in liver function continued, with total bilirubin increasing to 30.0 mg/dl and the persistence of massive ascites, coagulopathy, and hyperammonemia. On the 120th admission day, living-donor liver transplantation (LDLT) from her ABO-identical father was performed. The patient progressed under tacrolimus-based immunosuppression, and the clinical course continued uneventfully with the exception of hyperferritinemia. After function of the transplanted graft had stabilized, however, the hyperferritinemia gradually returned to the normal range (Fig. 1). The patient continued to improve and was discharged 2 months after LDLT. She was well in herself with normal liver function 8 months after LDLT.FIGURE 1.: Clinical course. BMA indicates bone marrow aspiration; Bx, liver biopsy; HPS, hemophagocytic syndrome; LDLT, living-donor liver transplantation; PE, plasma exchange; CyA, cyclosporine A; Tac, tacrolimus.Although some liver failure patients with HPS have been referred for urgent LT, indications for LT in this situation remain largely unknown. One LT patient died 44 days after operation due to progressive HPS (11). In our case, fever, lymphadenopathy, and hyperferritinemia indicated HPS, which was confirmed by BMA. Hyperferritinemia is reported to be a valuable marker of the acute phase reaction of HPS (11). EBV may trigger HPS with the subsequent persistence of a cytokine storm. The HPS in the present case may have been associated with WD-related end-stage liver disease, although this is an extremly rare clinical feature of WD. Despite conventional medical treatment, hyperferritinemia persisted. We consider that the patient's liver function gradually deteriorated due to end-stage liver disease for WD. If the liver failure had been induced from the cytokine storm of HPS, LT alone would have been insufficient because of the high risk of recurrence without treatment of the hypercytokinemia. In cases in which HPS is caused by hypercytokinemia due to liver failure, LT may be an ideal treatment for both liver failure and HPS. In the present case, hyperferritinemia gradually improved with stabilization of the transplanted graft. Further, we consider that if the HPS does not resolve, bone marrow transplantation may be anticipated as a safe therapeutic option in the presence of stable liver function provided by LT. Satoshi Yokoyama Mureo Kasahara Daisuke Morioka Akinari Fukuda Department of Transplant Surgery National Center for Child Health and Development Tokyo, Japan Katsuhiro Arai Department of Gastroenterology National Center for Child Health and Development Tokyo, Japan Tetsuya Mori Yoko Shioda Department of Pediatric Oncology National Center for Child Health and Development Tokyo, Japan Satoshi Nakagawa Naoki Shimizu Department of Anesthesia and Intensive Care National Center for Child Health and Development Tokyo, Japan Atsuko Nakagawa Department of Pathology National Center for Child Health and Development Tokyo, Japan