ABSTRACT
Elevated serum ferritin and iron accumulation in the liver are common in patients with chronic hepatitis C virus infection and have been associated with more aggressive disease and decreased response to interferon therapy, but the mechanism is unknown. Recently identified hepcidin, which is a small cysteine-rich cationic peptide produced by hepatocytes, secreted into plasma and excreted in urine, acts as regulator of intestinal iron absorption and iron recycling by the macrophage. This study was conducted to evaluate hepatic hepcidin mRNA expression in patients with chronic HCV infection and correlate its expression level with serum iron, serum ferritin and the grading and staging of liver disease. Fifty patients [40 males and 10 females] with chronic HCV infection were classified into two groups, chronic hepatitis [CH, n = 35, 28 males and 7 females] and liver cirrhosis [LC, n = 15, 12 males and 3 females]. In addition, 18 apparently healthy subjects [donors for partial liver transplantation] served as the control group. All patients were both anti-HCV and HCV RNA positive. Serum iron and serum ferritin were measured for all studied groups. Hepatic hepcidin mRNA expression level was determined by SYBR-green real-time PCR. Serum iron and ferritin were significantly higher in the patient groups compared to control group [p <0.001]. Hepatic hepcidin mRNA expression was significantly decreased in the patient groups than in the control group [p <0.001]. Also its expression was decreased in patients with liver cirrhosis than in patients with chronic hepatitis. There was a negative correlation between hepatic hepcidin mRNA and serum iron and ferritin in the patient groups. On the other hand no correlation was detected between it and histological grading of activity [r = -0.001, p >0.05]. Meanwhile there was a strong negative correlation between hepatic hepcidin mRNA and the histological stage of fibrosis [r = -0.51, p <0.001]. In conclusion failure of homeostatic regulation of hepatic hepcidin expression may be induced by HCV infection and this may cause elevation of serum iron and ferritin levels in patients with HCV infection. Therefore, understanding the role of the liver in hepcidin regulation and iron homeostasis may be helpful in the management of HCV hepatitis
Subject(s)
Humans , Male , Female , Liver Cirrhosis , Iron , RNA , Ferritins , Polymerase Chain Reaction , Chronic Disease , Antimicrobial Cationic PeptidesABSTRACT
Hepatocellular carcinoma [HCC] is one of the most frequent malignant tumors. It possesses the characteristics of high malignancy, rapid progress and poor prognosis. In recent years, studies have suggested that Epstein-Barr virus [EBV] is associated with HCC although opposite results have been subsequently reported. The present study was to determine the prevalence of EBV in HCC Egyptian patients, and whether EBV acts synergistically with hepatitis viruses in HCC carcinogenesis. The study included 61 patients, 20 HCV positive patients without HCC [16 males and 4 females] and 41 patients with proved HCC. They were subclassified into 3 groups [21 HCV positive [18 males and 3 female], 10 HBV positive [8 males and 2 females] and 10 HCC patients negative for both HCV and HBV [7 males and 3 females]]. Thorough clinical examination, abdominal ultrasonography and liver spiral CT were done. Liver function tests and serum alpha-fetoprotein [AFP], viral hepatitis markers for B and C, anti-EBV early antigen [EA-IgM], virus capsular antigen [VCA-IgMl and HCV RNA by reverse transcription PCR [RT-PCR] were measured. EBV-BamHI W DNA, and EBV-LMP1 DNA were performed by conventional PCR in the tumorus liver tissue of 41 HCC patients and the 20 noncarcinoma patients [HCV without HCC]. The positive ratios were compared between HCC subgroups and non tumorus HCV group. Our results revealed that, EBV-BamHI W DNA and/or EBV-LMP1 DNA were positive in 25 [40.9%] among overall 61 studied cases. In HCC patients, EBV-BamHI W DNA and/or EBV-LMP1 DNA were positive in 13 [61.9%] out of 21 HCV positive, 2 [20%] out of 10 HBV positive cases, 3 [30%] out of 10 cases negative for both HCV and HBV. However, it was positive in 7 [3 5%] out of 20 HCV cases without HCC [non tumotus cases]. The rate of EBV infection in HCC with HCV positive cases was significantly higher [Fisher exact=4.6 1; p<0.05] than HCC with HBV positive ones, HCC cases negative for both B and C virus [Fisher exact-4.28; p<0.05] and chronic HCV [non tumours] cases [Fisher exact=4. 19; p<0.05]. In addition, HCC in EBV DNA positive cases was associated with high HCV viral load, AST, ALT, low serum albumin, while there was no relation to AFP serum levels. In conclusion: the existence of EBV infection in HCC tissues suggests that EBV may be involved in the hepatocellular carcinogenesis in Egypt