Long-term follow-up after liver transplantation for erythropoietic protoporphyria.

OBJECTIVE: Erythropoietic protoporphyria (EPP) is an inherited disorder of haem synthesis, causing excess of protoporphyrin in blood, skin, liver and other organs. Protoporphyrin causes rapidly progressive liver failure in a minority of EPP patients. Long-term follow-up after liver transplantation for EPP is poorly documented. DESIGN: Two EPP patients were followed for 7 years after liver transplantation. Porphyrin levels were monitored and serial liver biopsies were taken. RESULTS: After transplantation, serum protoporphyrin levels remained elevated. In one patient, long periods with normal liver tests, low protoporphyrin levels and the absence of photosensitivity were followed by episodes of cholestasis and elevated protoporphyrin levels in blood, faeces and liver tissue. These episodes could be managed successfully with blood transfusions and changes in medication. The simultaneous rise of protoporphyrin concentration in both blood and faeces in this patient argues for increased protoporphyrin production as the cause of liver cell injury. The other patient acquired hepatitis B infection during the transplantation. From 3 months onwards she had continuously elevated liver tests, cholestasis, elevated protoporphyrin levels in blood, faeces and liver tissue, and photosensitivity. In this case, cholestasis and impaired protoporphyrin excretion may have played an important role in the persistent liver injury. Sequential liver biopsies of both patients showed various degrees of liver injury related to variations of the hepatic protoporphyrin concentrations. Eight and six months respectively after liver transplantation the livers of both patients showed fibrosis and hepatocellular protoporphyrin accumulation. CONCLUSIONS: The main cause of liver damage in EPP is overproduction of protoporphyrin in the bone marrow. Liver transplantation must be considered as symptomatic therapy with a high-risk for recurrent disease.

Type IIIb glycogen storage disease associated with end-stage cirrhosis and hepatocellular carcinoma. The Liver Transplant Group.

Type III glycogen storage disease (GSD) is a disorder of carbohydrate metabolism caused by a deficiency of debranching enzyme. Different subtypes with different clinical pictures have been recognized. During childhood and early adulthood, the symptoms generally regress, and normal adulthood appears possible in most patients without symptoms or signs of cirrhosis. We report on an adult patient with GSD who developed endstage cirrhosis and a small hepatocellular carcinoma. She had GSD subtype IIIb, i.e., there were no signs of cardiomyopathy, myopathy, or neuropathy. She underwent a successful transplantation, representing the first case treated this way for this indication to our knowledge, and she is doing well after 1 year. Debranching enzyme activity was absent both in the liver and in the leukocytes before transplantation. The debranching enzyme activity remained absent in the leukocytes after transplantation. We conclude that patients with GSD type III may develop end-stage cirrhosis and hepatocellular carcinoma and therefore need hepatological follow-up during adulthood.

Doppler ultrasound of the hepatic artery and vein performed daily in the first two weeks after orthotopic liver transplantation. Useful for the diagnosis of acute rejection?

RATIONALE AND OBJECTIVES: To analyze changes in Doppler ultrasound variables in relation to liver biopsy findings for the diagnosis of acute rejection after orthotopic liver transplantation (OLT), the authors performed in a prospective study 316 Doppler ultrasound examinations in the first 2 weeks after OLT on 23 patients. METHODS: Recordings were obtained daily from the hepatic artery (resistive index [RI]) and hepatic vein (damping index [DI]). Correlations were explored between the Doppler ultrasound findings and histologic data. The chi-square test was used to analyze differences in Doppler ultrasound variables in patients with and without acute rejection. RESULTS: Serial Doppler ultrasound examinations showed a significant increase in the RI in 11 of 22 patients (50%); the 23rd patient was excluded because of hepatic artery thrombosis. Despite an agreement in 15 of 22 patients (68%) no statistically significant correlation could be found (positive predictive value 6/11 = 55%; negative predictive value 9/11 = 82%; chi-square = 3.14; P > 0.05). A significant increase in the DI was observed in 14 of 23 patients (61%). However, no statistically significant correlation could be found as well with this parameter (positive predictive value 6/14 = 43%; negative predictive value 6/9 = 67%; chi-square = 0.00; P > 0.05). CONCLUSION: Serial Doppler ultrasound examinations were not helpful in predicting acute rejection.

Neutrophil cytoplasmic autoantibodies after liver transplantation in patients with primary sclerosing cholangitis.

The immunopathogenic importance of neutrophil cytoplasmic autoantibodies in ulcerative colitis and primary sclerosing cholangitis is unknown. These autoantibodies were investigated before and after liver transplantation in 9 patients with primary sclerosing cholangitis. Sera from 10 patients transplanted for metabolic disorders or hemangioma served as controls. Before liver transplantation neutrophil cytoplasmic autoantibodies, producing a perinuclear pattern by indirect immunofluorescence on ethanol fixed neutrophils, were present in all patients with primary sclerosing cholangitis. A decline in titer was noted in the first months after liver transplantation. During long-term follow up, the autoantibodies remained present and most often the titer did not differ from before transplantation. They were not directed against proteinase 3, myeloperoxidase, elastase or lactoferrin. All but one of the control patients were negative for the autoantibody. No relation was seen, before or after transplantation, with ulcerative colitis or proctocolectomy. There was no recurrence of primary sclerosing cholangitis in any of the patients as judged by liver histology. We conclude that neutrophil cytoplasmic autoantibodies remain present after liver transplantation for primary sclerosing cholangitis and that its synthesis is not related to the presence of the diseased organ(s). The primary disease process in primary sclerosing cholangitis and ulcerative colitis may well be a disturbance of the immune system.