The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma

authors:

avatar Olfat Hammam 1 , avatar Ola Mahmoud 2 , * , avatar Manal Zahran 2 , avatar Sohair Aly 3 , avatar Karim Hosny 4 , avatar Amira Helmy 5 , avatar Amgad Anas 6

Departments of Pathology, Theodor Bilharz Research Institute, Egypt
Departments of Hematology, Theodor Bilharz Research Institute, mahmoudola5@yahoo.com, Egypt
Malaysia and Medicinal Chemistry Department, Advanced Dental and Medical institute, IPPT, USM, NRC, Egypt
Surgical Department, Kasr El Aini Hospital, Egypt
Departments of Electron Microscopy, Theodor Bilharz Research Institute, Egypt
Departments of Gastroenterology, Theodor Bilharz Research Institute, Egypt
Hepatitis Monthly: Vol.12, issue 11; 6132
published online: November 30, 2012
article type: Research Article
received: May 23, 2012
accepted: August 15, 2012
DOI: https://doi.org/10.5812/hepatmon.6132

how to cite: Hammam O, Mahmoud O, Zahran M, Aly S, Hosny K, et al. The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma. Hepat Mon. 2012;12(11):6132. https://doi.org/10.5812/hepatmon.6132.

Abstract

Background:

The Fas receptor/ligand system including soluble forms is the most important apoptotic initiator in the liver. Dysregulation of this pathway may contribute to abnormal cell proliferation and cell death and is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells.

Objectives:

To analyze the role of Fas system Fas/ Fas ligand (Fas/ FasL) in the multi-step process of hepatic fibrosis/carcinogenesis, and to use of the serum markers as possible candidate biomarkers for early detection of hepatocellular carcinoma (HCC).

Patients and Methods:

Ninety patients were enrolled: 30 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis, and 30 cases of HCC and hepatitis V virus (HCV) infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, were served as normal controls. Serum soluble Fas (sFas) levels were measured using ELISA technique; Fas and FasL proteins were detected in hepatic tissue by indirect Immuno-histochemical technique (IHC); electron microscopic (EM) and immune electron microscopic examinations were performed for detection of Fas expression on lymphocytes.

Results:

Hepatic expression of both Fas and FasL as well as expression of Fas on separated lymphocytes were significantly increased in the diseased groups (P < 0. 01) compared to the control specimens. The highest expression was noticed in CHC specimens, particularly with the necro-inflammatory activity and advancement of the fibrosis. The sFas in cirrhotic patients and HCC were significantly higher than that in normal controls and CHC without cirrhosis group (P < 0.01).

Conclusions:

Apoptosis and the Fas system were significantly involved in the process of converting liver cirrhosis into hepatocellular carcinoma. Down-regulation of Fas expression, up regulation of FasL expression in hepatocytes, and elevation of serum sFas levels were important in tumor evasion from immune surveillance, and in hepatic carcinogenesis.

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