Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2011, vol. 20, nr 3, May-June, p. 263–273

Publication type: original article

Language: English

Expression of IGF-I and Viral Proteins (C, NS3, NS5A) in the Livers of Patients with Chronic HCV Infection

Ekspresja IGF-I oraz białek wirusowych (C, NS3, NS5A) w wątrobie pacjentów z przewlekłym zakażeniem HCV

Aldona Kasprzak1,, Agnieszka Adamek2,, Wiesława Przybyszewska1,, Witold Szaflarski1,, Karolina Sterzyńska1,, Agnieszka Seraszek3,, Iwona Mozer-Lisewska2,, Elżbieta Kaczmarek3,, Wiesława Biczysko3,

1 Department of Histology and Embryology, University of Medical Sciences, Poznań, Poland

2 Department of Infectious Diseases, University of Medical Sciences, Poznań, Poland

3 Department of Clinical Pathomorphology, University of Medical Sciences, Poznań, Poland

Abstract

Background. Hepatitis C virus (HCV) infection leads to chronic hepatitis in over 80% of infected individuals and is regarded as the most important factor in the development of hepatocellular carcinoma (HCC). The involvement of HCV genome products in the etiology of HCC has been proven. The role of Insulin-like Growth Factors I and II (IGF-I and II) as markers of HCV progression to liver cirrhosis and HCC remains relatively unrecognized.
Objectives. The aim of the study was to evaluate HCV protein (C, NS3, NS5A) and IGF-I tissue expression in liver biopsies obtained from patients with long-lasting HCV infection and to correlate them with clinical data.
Material and Methods. The study was conducted on liver biopsies obtained from chronic hepatitis C (CH-C) patients (n = 30), fragments of patients’ livers (n = 6), and a tissue microarray including samples from livers with HCC (n = 57) and control livers (n = 9). The immunocytochemical ABC and ImmunoMax techniques were used. The intensity of HCV protein expression was evaluated on a semiquantitative scale and the expression of IGF-I was demonstrated using a spatial visualization technique.
Results. In hepatocytes the cytoplasmic localization of IGF-I was demonstrated. The mean expression of IGF-I was most pronounced in the control livers, in which it was significantly higher than in patients with CH-C or patients with HCC. In patients with CH-C no correlation could be demonstrated between the cellular expression of IGF-I on the one hand and the grade of inflammation activity (grading), stage of fibrosis (staging), steatosis, serum HCV RNA and alpha-fetoprotein levels on the other. Positive correlations were detected between tissue expressions of IGF-I and two HCV proteins: C and NS3. Negative correlations were detected between the expression of IGF-I and the activity of both aminotransferases (ALT and AspAT). In patients with HCC no relationship could be established between the expression of IGF-I and the histological malignancy of the tumor.
Conclusion. Lower tissue expression of IGF-I was found in the patients with damaged livers (CH-C and HCC) in comparison with the control livers. This decrease correlated with increased aminotransferases activity in the patients with chronic hepatitis C. In the HCV-infected livers, a positive correlation was found between IGF-I expression and the expression of two HCV viral proteins: C and NS3.

Streszczenie

Wprowadzenie. Zakażenie wirusem C zapalenia wątroby (HCV) prowadzi do przewlekłego zapalenia wątroby u ponad 80% zakażonych i uznaje się je za najważniejszy czynnik ryzyka rozwoju pierwotnego raka wątroby (HCC). W etiologii HCC dowiedziono udziału produktów genomu HCV. Mało jest poznana rola insulinopodobnych czynników wzrostu (insulin-like growth factors) I i II (IGF-I i II) jako markerów progresji zakażenia HCV w kierunku marskości wątroby i HCC.
Cel pracy. Ocena tkankowej ekspresji białek HCV (C, NS3, NS5A) oraz IGF-I w biopunktatach wątroby pacjentów z długotrwałym zakażeniem HCV oraz ich korelacji z danymi klinicznymi.
Materiał i metody. Do badań zakwalifikowano biopunktaty wątroby pacjentów z przewlekłym zapaleniem wątroby typu C (CH-C) (n = 30), fragmenty wątroby pacjentów (n = 6) i tkankowy panel z rakiem wątrobowokomórkowym (HCC) (n = 57) oraz fragmenty kontrolnej wątroby (n = 9). Zastosowano metodę immunocytochemiczną ABC i ImmunoMax. Nasilenie ekspresji białek HCV oceniono w skali półilościowej, a ekspresję IGF-I z zastosowaniem techniki wizualizacji przestrzennej.
Wyniki. Wykazano cytoplazmatyczne umiejscowienie IGF-I w hepatocytach. Średnia ekspresja IGF-I była największa w kontrolnej wątrobie, istotnie większa niż u pacjentów z CH-C i pacjentów z HCC. U pacjentów z CH-C nie wykazano korelacji między komórkową ekspresją IGF-I a aktywnością zapalną, nasileniem włóknienia, stłuszczeniem, surowiczym stężeniem HCV RNA oraz alfafetoproteiny. Pozytywne korelacje dotyczyły tkankowej ekspresji IGF-I oraz dwóch białek HCV: C oraz NS3. Negatywne korelacje wykazano między ekspresją IGF-I a aktywnością obu aminotransferaz (ALT i AspAT). U pacjentów z HCC nie udało się wykazać zależności między ekspresją IGF-I i stopniem złośliwości histologicznej nowotworu.
Wnioski. Wykazano obniżoną tkankową ekspresję IGF-I u pacjentów z uszkodzoną wątrobą (CH-C i HCC) w porównaniu z wątrobą kontrolną, obniżenie to korelowało ze zwiększoną aktywnością aminotransferaz u pacjentów z przewlekłym zapaleniem wątroby typu C. W zakażonej HCV wątrobie wykazano pozytywną korelację między ekspresją IGF-I i dwóch białek wirusowych HCV: C i NS3.

Key words

chronic infection with HCV, insulin-like growth factor-I, immunocytochemistry, spatial visualization technique

Słowa kluczowe

przewlekłe zakażenie HCV, insulinopodobny czynnik wzrostu I, immunocytochemia, technika wizualizacji przestrzennej

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