Non-histological assessment of liver fibrosis in HCV infection.

This study found a correlation between some serum markers [AST/ALT ratio, level of matrix metalloproteinase 9 (MMP9), level of viraemia and HCV serotype] and severity of liver fibrosis in HCV-infected patients. The study included 72 human cases referred to the Early Cancer Detection Unit, for liver biopsy assessment. The severity of liver fibrosis was staged using the METAVIR scoring system into 4 stages. The level of viraemia did not differ significantly in the different stages of liver fibrosis. Also, the type of HCV had no effect on the severity of liver fibrosis. However, the transaminases ratio differed significantly in the different fibrosis stages (P < 0.01). This serum test has a relatively high sensitivity and specificity (92.6% and 94.3%, respectively) in diagnosing severe fibrosis and cirrhosis. The level of MMP9 was, however, inversely correlated with the fibrosis stages and was found to have an 88.9% sensitivity and an 88.6% specificity when diagnosing severe fibrosis and cirrhosis. Although, the sensitivity of these serum markers did not reach 100%, yet their use can reduce the number of liver biopsies when diagnosing and treating HCV-infected patients.

Hepatitis C virus infection at Sharkia Governorate, Egypt: seroprevalence and associated risk factors.

Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population based serologic studies are needed to estimate the prevalence of infection and to develop and evaluate prevention efforts. A sample of 1422 individuals was included in the study by using multistage sampling technique. Their age ranged from 4-78 years with a mean age (34.7 +/- 18.5), 782 were males (55%) and 640 were females (45%). Exposures and demographic characteristics were obtained through a predesigned questionnaire. Antibody to HCV was assessed using micro-particle enzyme immunoassay (MEIA) enzyme assay by IMX, and the HCV RNA was tested by Real-time PCR technique using ABI Prism 7700 system. The seroprevalence of antibodies to HCV were 23.4% and 27.4% in urban and rural areas respectively, with an overall prevalence (25.8%). This reflects prior HCV infection but not necessarily a current liver disease. Prevalence was higher among males than females and increased sharply with age, from 4.8% in those < 20 years old to (41.9%) in older ages (> or = 40 years). Those who were not educated and farmers had a significantly high prevalence. The significant predictors of HCV infection were previous parenteral therapy for schistosomiasis (OR = 4.3, 95% CI = 3.6-7.9), among those over 20 years of age (3.5, 2.18-5.8), blood transfusion (4.1, 2.4-6.9), invasive procedures (surgery and endoscopy), and use of contaminated syringes and needles. Also, shaving at community barbers added significance to the model. Exposures not significantly related to HCV seropositivity were gender, active infection with Schistosoma mansoni, sutures or intravenous and urinary catheterization, water pipe "goza" smoking in group.

New concept in histopathological grading and staging of chronic hepatitis C infection at Sharkia Governorate, Egypt.

Hepatitis C virus (HCV) has been estimated by the WHO to infect 170 million patients worldwide, with a high prevalence rate (about 24.5%) among Egyptians. The disease could be presented with variable hepatic lesions ranging from mild inflammation, fibrosis, cirrhosis to even end stage liver disease and hepatocellular carcinoma. The Knodell histology activity index, published in 1981, was the first system of its type and is widely regarded as the benchmark for objective, semi-quantitative reproducible description of the various morphological lesions of chronic hepatitis. Other proposals for semi-quantitative evaluation have followed. In this study, when applying these systems on the present cases (109 liver biopsies taken from Egyptian patients infected with HCV), the authors found that the presented histopathological features may be unusual for any of the known scoring systems. Therefore, they suggested a new system for grading and staging of liver diseases in Egyptian patients infected with HCV. Accordingly, the degrees of necroinflammations are classified into 3 grades (1-3) and the progression of fibrosis is classified into 3 stages (1-3). The reduced numbers of grades and stages proposed in this study may be attributed to the rapid course among Egyptians who differ in environmental circumstances from abroad.

Molecular cytogentic profiles of hepatitis C infection in patients at Sharkia Governorate, Egypt.

It has become apparent that hepatitis C virus (HCV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. The precise mechanism by which HCV causes HCC is not known. Unlike the hepatitis B virus (HBV), HCV is not a DNA virus and does not become integrated within the genome of hepatocytes. It is more likely that HCC occurs against a background of inflammation and regeneration, associated with liver injury due to chronic hepatitis. In this study, 40 of paraffin blocks liver tissues from HCV-PCR positive patients (HBV seronegative) were examined using DNA image cytometry to evaluate its role in diagnosing HCC associated with HCV infection. Fluorescent in situ hybridization (FISH) technique using LSIZNF 217 chromosome 20q 13.2 probe was applied as well. The results showed high percentage of S-phase fraction in cases of G2S2 and G3S3 with DNA diploidy. Only two cases of G3S3 showed DNA aneuploidy with severe amplification of chromosome 20q 13.2. Consequently, DNA imaging cytometry is a good approach in differentiating dysplasia from well-differentiated HCC on top of HCV infection. In conclusion HCV has an acquired role in development of HCC through amplification of the aggressive tumor behavior oncogene LSIZNF 217 at chromosome 20q 13.2.

Autoantibodies in HCV infected patients at Sharkia Governerate, Egypt.

It is not clear whether HCV induces an autoimmune disease in infected patients or not. The aim of this study is to evaluate some immunological manifestations in chronic heapatitis C patients and to find out its relationship to liver pathology. The study included 109 positive HCV-RNA patients. They were classified according to liver histopathology into three groups: Group I included 22 patients (G1S1), Group II included 67 patients (G2S2) & Group III included 20 patients (G3S3), where G=The degree of necro-inflammatory process & S=Stage of liver fibrosis. All patients were investigated for the presence of: cryo-globulin, anti-neutrophil cytoplasmic (ANCA), anti-liver kidney microsomes (LKM), anti-double stranded DNA, (ds-DNA), anti-nuclear (ANA), anti-mitochondrial (AMA) and anti-smooth muscle (ASMA) auto-antibodies. The following results were obtained: ANCA, LKM, ds-DNA, ANA, ASMA, AMA and cryoglobulin were detected in 83/109 (76.1%), 32/109 (29.4%), 23/109 (21.1%), 38/109 (34.9%), 25/109 (22.9%), 5/109 (4.6%) and 60/109 (55%) of chronic HCV respectively. A highly significant positive correlation was found only between ANCA auto-antibodies and cryoglobulin versus grades of liver cirrhosis. Using ANCA, cryoglobulin, age and gender as covariates and by logistic regression analysis, Odds ratio (OR) revealed that these covariates were significant predictors of cirrhosis that add significance to the model according to the sequence: ANCA, cryoglobulin, age and gender suggesting that these covariates associate significantly with development of cirrhosis in HCV patients and that they are significant predictors of liver cirrhosis in HCV patients. The high prevalence of autoantibodies in chronic HCV patients suggests that HCV may trigger an autoimmune reaction, but most probably do not indicate a distinct autoimmune mechanism. Cryoglobulins and ANCA may be a useful prognostic indicator for increased risk of cirrhosis in chronic HCV patients. Follow up studies are recommended.

HCV and associated concomitant infections at Sharkia Governorate, Egypt.

The natural history of hepatitis C virus (HCV) infection has a highly variable course. Many patients develop chronic infection, with its consequent risk of cirrhosis, liver failure and hepatocellular carcinoma. A key question is whether patients at high risk of disease progression can be distinguished from those with relatively benign disease course. The disease progression is influenced by other factors such as duration of infection, age at infection, sex, co-infection with hepatitis B virus (HBV), Epstein Bar virus (EBV), cytomegalovirus (CMV), the level of HCV viraemia and its type. Other endemic infections in the community as bilharziasis may have a role in progression of the condition to serious complications. These factors are correlated with newly proposed grades and stages of the disease. The studied (109) cases were divided into 6 groups according to the concomitant infection with HCV. The result proved that groups 1, 3 & 5 had a higher level of viraemia than other groups, and to be the high-risk groups as 56.4% and 34.6% were in G2S2 and G3S3, respectively. All cases of liver cell dysplasia and hepatocellular carcinoma in this study were seen in these groups. The conclusion showed that these factors play an important role in the progression of HCV infection. Death of the patients of this progressive condition occurs in younger age and is more due to liver failure than to HCC.

Non-invasive markers and predictors of severity of hepatic fibrosis in HCV patients at Sharkia Governorate, Egypt.

Liver biopsy is thought mandatory for management in patients with hepatitis C virus infection (HCV) especially for histopathological grading and staging of the disease to assess suitability for treatment and monitoring disease progression. However, tracking of liver disease progression can't rely on repeated biopsies. The study aimed to evaluate two significant items, we try to develop and validate a non-invasive predictive tool to assess hepatic necro-inflammation and fibrosis. Also, to determine factors that associate severity of hepatic pathology in HCV infected Egyptian patients particularly at Sharkia G. The study included 109 patients with detectable HCV by Real Time-PCR. The patients were classified into three different pathological stages and grades according to the new concept of histopathoglical staging and grading. The different clinical, biochemical, virological and ultra-sonographic parameters were assessed and analyzed and the variables that showed significant association with histopathological staging and grading were included in multivariate logistic regression analysis. The regression model revealed that, platelet count, matrix metalloproteinase-9 (MMP-9), portal vein diameter, splenic longitudinal axis, alanine transaminase, aspartate transaminase and viral load were the factors that add significance to the model in decreasing order of significance. From these findings we generate a new score ranged from 0-9. The score model was applied to our patients to assess its validity where it proved to be accurate in discriminating patients with mild inflammation and fibrosis (sensitivity 81.8%, specificity 80.5% and accuracy 80.7%) and more accurate in detecting patients with cirrhosis (specificity 96.6%, sensitivity 80% & accuracy 93.6%) but less accurate in detecting patients with moderate to severe fibrosis (specificity 66.7%, sensitivity 68.7% & accuracy 67.9%). Also the results revealed that, co-infection with schistosomiasis, old age > or = 45 years and positive history of blood transfusion as a source of infection was significantly associated with severe hepatic pathology. It is concluded that, the score model can't completely replace liver biopsy but at least it could be used to substantially reduce the number of liver biopsies done in patients with HCV infection in assessing disease progression during follow up. Also, it can be used to make decisions about treatment in patients who have contraindications to or who refused liver biopsy. Co-infection with schistosomiasis, age > or = 45 and positive history of blood transfusion in patients with HCV warrant special attention with more intensive follow up. These factors may play a major role in forecasting the course of HCV as well as in determining the therapeutic approach in each case.

The role of aflatoxin-contaminated food materials and HCV in developing hepatocellular carcinoma in Al-Sharkia Governorate, Egypt.

Aflatoxins, particularly aflatoxin B1 (AFB1) have been recognized as one of the most potent chemical carcinogen. In Egypt, HCV is prevalent. The progressive nature of HCV-related liver diseases was found to be influenced by other factors. In this paper, the role of aflatoxin contamination in the onset of liver cancer in HCV-infected patients was studied. The quantitative identification of the possible aflatoxins contamination in six urban and eleven rural areas using high performance liquid chromatography technique, revealed that corn, wheat, pea nut, lupine "termis", white rice, cowpea "lobiya", fava bean and brown rice showed the prevalence of AFB1 to be 64.7%, 53%, 53%, 47%, 47%, 41%, 29.4% & 29.4% respectively. A positive correlation was found between aflatoxin and positive HCV-PCR together with liver disease progression to G3S3, the indicative of hepatocellular carcinoma. Such correlation was not fully understood, but the oncogene amplification caused by HCV-infection may be aggravated by the consumption of aflatoxin contaminated raw food materials or their products.

Experimental demonstration of hepatitis C virus (HCV) in an Egyptian strain of Culex pipiens complex.

Reverse transcriptase (RT) polymerase chain reaction (PCR) was used to detect hepatitis C Virus (HCV) RNA among heads, guts, larvae and eggs of Culex pipiens complex. The mosquitoes were trapped from homes of hepatitis C patients or among the same organs of symbiotic (normal gut bacteria) and aposymbiotic (without gut bacteria) mosquitoes fed HCV positive blood by an artificial membrane feeder. The eggs and larvae resulted from symbiotic females fed HCV positive blood was tested for HCV-RNA. Hepatitis C virus RNA was detected only in heads of symbiotic mosquitoes collected from homes of HCV positive patients at 3h and 6h after feeding. The virus was detected at 3d and 8d after being fed on HCV-RNA positive blood in guts of the same group. The virus was not detected in the eggs or larvae resulted from female mosquitoes fed on HCV-RNA positive blood. The results raise the possibility of the mechanical and/or biological transmission of HCV by Cx. pipiens, and pave the way to the ongoing study on the effect of gut bacteria of Cx. pipiens in a trial to identify an anti-HCV agent.