HFE mutations, serum iron indices, and hepatic iron: impact on fibrosis severity and steatosis in patients with chronic hepatitis C genotype 4

Iron overload may cause or contribute to hepatic injuiy and fibrosis. Mutations in tbr HFE gene may influence development or progression of chronic liver disease by increasing iron stores or modulating immune responses. The aim of this work was to assess the influence of HFE mutations and serum and hepatic measures of iron status on fibrosis severity and steatosis in patients with chronic hepatitis C genotype 4. We studied 47 patients [33 males, 14 females, mean age 43.46 +/- 13.54 years] with chronic HCV infection. Serum iron indices were determined in all participants. Hepatitis C virus RMA was detected in patients' sera by reverse transcriptase-polymerase chain reaction [RT-PCR]. Liver biopsies were taken to evaluate steatosis, fibrosis, and hepatic iron depositions. We used the method of polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] to analyze the HFE mutations. Twenty-three patients 23/47 [48.936%] had increased serum iron stores and only eleven patients 11/47 [23.40%] had positive hepatic iron stain. There was a significant difference between hepatic steatosis subgroups as regards inflammatory grading and fibrosis staging [p <0.001]. Ferritin level was significantly correlated with fibrosis severity and steatosis grading. Hepatic iron deposition was significantly correlated only with steatosis grading but not with fibrosis severity. Heterozyosity for H63D allele was noted to be five patients 5/47 [10.638%] in CHC patients. Our data demonstrated no significant difference in the prevalence of HFE mutations between the HCV patients with increased serum iron store and others without Also, the same results were noticed in patients with and without hepatic iron deposition. Ferritin level should be better considered as a surrogate marker of severe fibrosis in chronic hepatitis C. The prevalence of HFE mutations associated with hereditary hemochromatosis is not increased in the patients with CHC. The HFE mutations may not contribute to iron accumulation in the CHC patients even when serum iron overload is observed in these patients

Genetic polymorphism of glutathione-S- transferase [GST-M1 and GST-T1] in schistosomiasis -associated bladder cancer in Egyptian patients

This work was carried out on three groups, 30 Egyptian patients with Schistosoma haematobium [S. haematobium] with bladder cancer [15], and without bladder cancer [15], as well as 15 normal individuals as a control. All the individuals were subjected to measurement of serum level of GST by using ELISA technique and genotyping for GST-M1 and GST-T1 using PCR technique. The results proved that GST serum level was significantly deceased in S. haematobium patients with bladder cancer as compared to the other groups. The PCR results for the GST-M1 and GST-T1 genotyping showed 4 categories, [M1+ve/T1+ve, M1+ve/T1-ve, M1-ve/T1+ve, M1-ve/T1/-ve]. There was a significant decrease in enzyme levels in patients with GST-M1-ve/T1-ve as compared to the other categories. Besides, there was a significant increased risk for bladder cancer development in patients with combined gene deletion [OR = 40] which represented mainly in S. haematobium patients with bladder cancer [53.3% = M1-ve/T1-ve]

Metallothionein [MTI and MT II] gene expression in hepatocellular carcinoma

Hepatocellular carcinoma [HCC] is one of the most frequent human tumors worldwide, and commonly evolves from chronic hepatitis and liver cirrhosis. It is therefore very important to detect and evaluate the progressing state of chronic hepatic disorders. Recently, serum metal levels such as copper [Cu] and zinc [Zn] have been reported to be highly sensitive in the diagnosis of some diseases. Hypozincemia and marked hypercupremia have been reported in patients with digestive, hepatic, breast, and lung cancers. Also much attention was paid to the association between metallothioneins [MTs] and chronic liver diseases including HCC. Available informations suggested that MTs might play important roles in carcinogenic and apoptotic process of some tumors. The aim of the present study was to throw the light on the role of zinc, copper and metallothioneine in the diagnosis of chronic liver diseases and to clarify the role of metallothioneins [MTs] I and II mRNA expression in hepatocellular carcinoma. This study was carried out on 45 patients with liver diseases [15 patients with chronic hepatitis, 15 patients with liver cirrhosis and 15 patients with HCC] as well as 15 healthy individuals as a control group. All patients and controls were subjected to estimation of serum copper, zinc and metallothioneine levels also their tissue levels were estimated in all patient groups. Metallothioneins [MT I and MT II] mRNA expression by RT-PCR were done for all cases. The results of the present study documented a significant decrease in serum and tissue levels of zinc and metallothioneine with concomitant increase in copper levels in all patient groups. More changes were documented in HCC patients. Concerning the PCR results of MT genes expression, there was a significant decrease in MT I and MT II mRNA expression in HCC patients when compared to the other groups. They also decreased in patients with liver cirrhosis when compared to the control group and patients with chronic hepatitis. In contrast their expressions do not show significant decrease in chronic hepatitis when compared to the control group. On the basis of these results, it could be concluded that serum zinc, copper, and metallothioneines levels may be used as a non-invasive biochemical markers for early detection of the progression of chronic liver diseases. Moreover, the progressive decrease in MT I and MT II gene expression may play an important role in carcinogenesis of HCC

Genetic polymorphism of glutathione-s-transferase [GST-M1 and GST-T1] in Egyptian schistosomiasis -associated bladder cancer

Bladder cancer is a common neoplasm around the world. In Egypt, the majority of bladder cancer is associated with Schistosoma haematobium [S. haematobium]. Glutathione-s-transferase [GST] represents an important family of metabolizing enzymes that catalyzes the conjugation of large variety of endogenous and exogenous compounds including carcinogens and anti cancer drugs and their metabolites with reduced glutathione. Individuals with very low levels of GSTs are at increased risk for the development of carcinoma and inflammatory diseases. The potential role of GST gene polymorphism on bladder cancer susceptibility is less certain. So, the aim of this work was to study GST-M1 and GST-T1 genes polymorphism in Egyptian patients with S. haematobium to clarify its role on bladder cancer susceptibility in those patients. This was carried out on three groups, 15 Egyptian patients with S. haematobium with bladder cancer, 15 Egyptian patients with S. haematobium without bladder cancer and 10 normal individual as a control group. All individuals were subjected to measurement of serum level of GST using ELISA technique and genotyping for GST-M1 and GST-T1 using PCR technique. The results proved that GST serum level in Schistosoma patients without bladder cancer was decreased but not statistically significant if compared to control group, in contrast it was significantly deceased in Schistosoma patients with bladder cancer if compared to the other groups. PCR results for GST-M1 and GST-T1 genotyping had shown 4 categories, in control group [M1+ve/T1+ve [80%], M1+ve/T1-ve[10%], M1-ve/T1+ve[10%], M1-ve/T1/-ve[0%]], in Schistosoma without bladder cancer [M1+ve/T1+ve[66.7%], M1+ve /T1-ve[13.3%], M1-ve/T1+ve[13.3%], M1 -ve/T1-ve[6.7%]], while in Schistosoma patients with bladder cancer [M1+ve/T1+ve[13.3%], M1+ve/T1-ve[13.3%], M1-ve/T1+ve[20%] and M1-ve/T1-ve [53.3%]]. It was demonstrated a significant decrease in enzyme levels in patients with homozygous deletions of both GST-M1 and GST-T1 genes [GST-M1-ve/T1-ve] if compared to the other three categories of genotyping. Moreover, there was a significant increased risk for development of bladder cancer in patients with combined gene deletion [OR=40] which represented mainly in Schistosoma patients with bladder cancer [53.3% were M1-ve/T1-ve]. Bladder cancer is a common multifactorial disease, and genetic polymorphism especially in GST-M1 and GST-T1 could play an important role as a risk factors in development of urinary bladder cancer among Egyptian with Schistosoma haematobium. So, it could be used for early prediction of risk group in order to help them by follow up for early diagnosis or by cancer chemoprotection