Nabil Mohie Abdel Hamid, Maiada Hasan Nazmy, Bakheet Elkot Moustafa, Sahar Mohamed Saad El-din

Hayvan ve İnsanlarda Hepatosellüler Karsinomun Erken Teşhisinde Alfa-L Fukosidaz'ın Alfa-fetoproteine olan Üstünlüğü

AMAÇ: Erken tanı hepatoselüler karsinom (HCC) tedavisindeki en kritik adımdır. Çalışmada erken tanıda alfa-L- fukosidazın (AFU) klasik belirteç olan alfa-fetoproteine (AFP) kıyasla güvenilirliği incelenmiştir.YÖNTEMLER: Teorimizi kanıtlamak için çalışma hem insan hem de hayvan örneklemler kullanılacak şekilde planlanmıştır. Çalışmanın hayvan deneyi ayağında 60 Wistar faresi kontrol grubu ve 8, 16, 24 hafta dietilnitrozamine (DENA) verilen gruplar olmak üzere 4 gruba ayrılmıştır. İnsan çalışma grubu kontrol ve hafif, ileri ve metastatik olarak 4 gruba bölünen toplam 120 hastadan oluşmaktadır. Histolojik ve biyokimyasal analizler (AFP, AFU, karaciğer fonksiyon testleri, total antioksidan serum seviyeleri) ve ROC eğrileri ile korelasyon analizleri insan ve hayvan gruplarında yapılmıştır.BULGULAR: DENA-tedavi grubu zamana bağlı olarak belirgin histopatolojik değişiklikler göstermiştir. Kontrol grubu ile kıyaslandığında 6 hafta sonra bilirubin ve total antioksidanlar dışındaki tüm biyokimyasal parametrelerde, 8 hafta sonra bilirubin, albumin, AFP ve total antioksidanlar dışındaki parametrelerde ve 24 hafta sonra ise tüm biyokimyasal parametrelerde (AFP, AFU, karaciğer fonksiyon testleri ve total antioksidan serum düzeylerinde) anlamlı değişiklikler saptanmıştır. Histolojik olarak sınıflandırılmış tüm HCC gruplarının tün incelenen parametrelerinde istatistiksel olarak anlamlı sonuçlar saptanmıştır. Sınır olarak 5 μmol/l/min kabul edildiğinde ROC analizi ile yapılan incelemede AFU %90 sensitivite, %92 spesifite göstermiştir ve %91 tanısal doğruluk göstermiştir. Sınır değer 60 ng/ml olarak alındığında ise sensisivite, spesifite ve tanısal doğruluk sıraıyla %60, %76 ve %68 olarak saptanmıştır. AFU ile ALT, AST ve AFP ilişki katsayıları istatistiksel olarak anlamlıdır.SONUÇ: HCC erken tanısında erken tanıda AFU, AFP'den daha iyi bir belirteçtir. AFU sensitivite, spesivitesi daha yüksek olup diğer indekslerle AFP'ye kıyasla daha iyi korele olmuştur. İnsandan elde edilen sonuçlar teorimizi doğrulamıştır.

Anahtar Kelimeler:

Hepatoselüler karsinom, Dietilnitrozamine; Alpha-L-fucosidase; Alpha-fetoprotein; Antioksidan seviyesi; Erken tanı

Priority of Alpha-L- Fucosidase Over Alpha fetoprotein in Early Detection of Hepatocellular Carcinoma in Animals and Human

OBJECTIVE: Early detection of hepatocellular carcinoma (HCC) is the most critical step in the management process. We try to provide new insights about the possible role of alpha-L- fucosidase (AFU) to achieve more reliable detection of HCC over a classical marker alpha fetoprotein (AFP).METHODS: The study included both animal and human subjects, to legislate our theory. In animal study, 60 Male Wistar rats were classified to control, other 3 groups received di ethyl nitrosamine (DENA) for 8, 16, 24 weeks respectively. In human study: one hundred and twenty patients were assigned as: control group, 3 groups with histologically graded HCC, into mild, advanced and metastatic HCC. Histological and biochemical analysis (AFP, AFU, liver function tests, total antioxidant serum levels) in both animals and patients, as well as, receiver operating characteristic (ROC) curves and correlation analysis, were executed. RESULTS: DENA-treated groups showed significant histopathological changes in a time dependant pattern. After 24 weeks, a significant variation in biochemical parameters (AFP,AFU, liver function tests and total anti-oxidant serum levels), after 6 weeks, a significant variations in all parameters except bilirubin and total antioxidants, after 8 weeks, a significant variations in all parameters except bilirubin, albumin, AFP and total antioxidants, compared to control group. All tested biochemical parameters showed non-significant correlation, compared to AFU.All histologically-graded human HCC groups showed a highly statistically significant variations in all tested biochemical parameters. ROC analysis showed that at a cut-off value of 5 μmol/l/min, AFU yielded a sensitivity and specificity of 90% and 92%, respectively producing diagnostic accuracy of 91%. While At a cut-off value of 60 ng/ml, AFP yielded a sensitivity and specificity of 60% and 76%, respectively producing diagnostic accuracy of 68%. Correlation coefficients between AFU versus ALT, AST and AFP were statistically significantCONCLUSION: AFU is a more accurate marker than AFP for early diagnosis of HCC. AFU showed higher sensitivity, specificity and correlated more to other indices than AFP. Human data confirmed our theory.

Keywords:

Hepatocellular carcinoma (HCC), Diethylnitrosoamine (DENA), Alpha-L-Fucosidase, Alpha-fetoprotein, Liver indices antioxidant status, Early detection,

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