Lektin-reaktives Alpha-Fetoprotein bei Patienten mit Tyrosinämie Typ I

Zusammenfassung

Hintergrund: Trotz Einführung der medikamentösen Therapie mit NTBC besteht bei der Tyrosinämie Typ I weiterhin das Risiko der Entwicklung eines hepatozellulären Karzinoms (HCC). Wesentlich für die Risikoabschätzung eines Patienten ist bisher das Gesamt-α-Fetoprotein. Die mögliche klinische Bedeutung der L3-Subfraktion nach Lektin-Elektrophorese sollte untersucht werden. Patienten: Insgesamt 41 Patienten mit TTI wurden untersucht, davon 5 bei Erstmanifestation der Erkrankung. Die übrigen 36 Patienten befanden sich in Dauertherapie. Von diesen Patienten hatten 10 ein erhöhtes AFP, ohne dass bisher ein Tumor nachgewiesen worden war. Methoden: In einem Lektin-haltigen Agarosegel können Lektin-reaktive und nicht-Lektin-reaktive AFP-Fraktionen elektrophoretisch getrennt werden. Lektin-reaktives, L3-AFP wird vermehrt bei malignen Lebertumoren nachgewiesen. Ergebnisse: Von den 10 Patienten mit erhöhtem AFP, die als Risikopatienten für die Entwicklung eines Karzinoms einzuschätzen sind, fanden sich drei Patienten mit histologisch nachgewiesenem Karzinom, zwei von diesen Patienten wiesen ein erhöhtes L3-AFP auf. Schlussfolgerung: Möglicherweise könnte das Lektin-reaktive AFP als zusätzlicher Tumormarker verwandt werden. Die prospektive Evaluation des Lektin-reaktiven AFPs bei TTI an einem größeren Patientenkollektiv erscheint sinnvoll.

Abstract

Despite the introduction of NTBC into the treatment of tyrosinaemia type I (TT1) and a considerable improvement in the outcome of these patients, the principal risk of developing hepatocellular carcinoma (HCC) in this metabolic disorder remains mainly in those children with late introduction of NBTC after the second year of life. Serial total α-Fetoprotein (AFP) levels are used to evaluate the individual risk to develop malignant changes. A failure of AFP to decrease on adaequate treatment or a secondary increase after a period of falling levels have been an indication for liver transplantation. Lectin-reactive α-Fetoprotein is a recently described marker to distinguish hepatocellular carcinoma from benign liver disease in adult cirrhotic patients. Aims: To investigate if the analysis for Lectin-reactive α-Fetoprotein would lead to earlier detection of HCC compared to a judgement based on the evolution of standard total AFP alone. Patients: We report the analysis of 12 patients with TTI and histologically proven HCC. There of 5 were diagnosed under one year of age, but NTBC treatment was started between 2 years 3 month and 7 years of age except in one case in which NTBC was introduced when the diagnosis of TTI was made. The remainder of the patients cover up to the age of 15 years. All patients had been treated with NTBC. Methods: Lectin containing agarose gel for AFP electrophoresis leads to AFP separation according to different affinities of the varying carbohydrate chains of AFP to lectins. Results: AFP subfractions could be identified in all 12 patients. In 6 patients the L3-AFP rose before the total AFP. In 3 patients the rise in L3-AFP was consistent with the rise of the total AFP and in 3 patients the L3-AFP was raised after the total AFP or did not increase at all. Discussion: We were able to identify 6 out of 12 patients who had an early increase of L3-AFP before they developed a change in total AFP levels. The clinical significance of these early changes need to be determined. Lectin-affinity electrophoresis may have a potential role as an additional tool that may help to discriminate benign liver disease from HCC in TTI. Conclusions: We suggest the further evaluation of lectin-reactive AFP in TTI.

Schlüsselwörter

Tyrosinämie Typ I - α-Fetoprotein - Lektin-Elektrophorese - Hepatozelluläres Karzinom

Key words

tyrosinaemia type I - α-fetoprotein - lectin electrophoresis - hepatocellular carcinoma

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1 With kind permission of the following co-workers of the study group:J. E. Heubi, Cincinnati, C. Dionisi-Vici, Rom; J. A. Dias, Porto; O. Bernard, Paris; M. Stern, Tübingen; M. A. Vilaseca, Barcelona; B. Abu-Libdeh, Jerusalem; P. Jara, Madrid; D. Gould, New York; E. Pronicka, Warschau; R. de Kremer, Buenos Aires