Abstract
Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by an inherited deficiency of mitochondrial ferrochelatase. This deficiency results in accumulation of protoporphyrin, a heme precursor, in bone marrow, skin, nervous system, and liver. In some patients, toxic levels of protoporphyrins in the liver cause chronic liver disease, cirrhosis, and hepatic failure. Liver transplantation is the only treatment available; however, the risk of allograft dysfunction is high as a result of continued, excessive protoporphyrin production due to the underlying systemic enzyme deficiency. We present the case of a 40 year-old man with EPP, diagnosed at age 6, who underwent orthotopic liver transplantation (OLT) at age 25. By age 31, biopsy-proven recurrent EPP with liver dysfunction was identified in the allograft with subsequent hepatic failure seven years later at age 38. A second liver transplant was complicated by a biliary anastomotic leak requiring further surgery and prolonged hospitalization. Six months prior to a second liver transplant, the patient was started on 4 mg/kg hemin infusions every week; following second liver transplant, the frequency was increased to twice weekly to maintain graft function. Infusions have been well tolerated and administered at home through a central venous catheter and there has been no evidence of iron overload. Three months following second transplant, blood alkaline phosphatase, ALT, AST, and bilirubin were 1009, 53, 64, and 11.5, respectively. Fourteen months after the second allograft, these levels are 234, 65, 65, and 1.2, respectively. Prior to hemin therapy, erythrocyte protoporphyrin level was 6600 mg/dl and was 5573 mg/dl immediately before second allograft. With twice weekly hemin, erythrocyte protoporphyrin level fourteen months after transplantation is 1240 mg/dl - greatly reduced but still elevated above the normal range. A liver biopsy three months after the second allograft showed cholestasis and biliary obstruction consistent with recurrent porphyria, but no subsequent biopsy has been performed yet despite improvement in alkaline phosphatase, bilirubin, and transaminase levels. This case study confirms an earlier report of clinical graft stabilization with hemin infusions after orthotopic liver transplantation for erythropoietic protoporphyria (Dellon et al., Transplantation2002; 73:911–5) and to our knowledge is the first case of long-term hemin use to maintain the integrity of a second liver allograft. Further follow-up and biopsy will be needed to determine the impact of this strategy on preserving graft function.
Large paracetamol overdose -- higher dose NAC is required - CON
