Nadia Elwan

Clinical significance of plasma osteopontin level in Egyptian patients with hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies worldwide. Osteopontin (OPN) is a secreted glycoprotein frequently associated with various tumors. This study aimed to investigate the clinical usefulness of plasma OPN level as a biomarker for HCC among high-risk patients compared to alpha-fetoprotein (AFP) and to evaluate its relationship with clinicopathological features of HCC patients. METHODS Plasma levels of OPN and AFP were measured in 60 Egyptian patients with hepatitis C virus-related liver cirrhosis (30 with HCC, 30 without HCC) and 20 healthy controls. RESULTS Plasma OPN levels in cirrhotic patients with HCC were significantly higher than in those without HCC and controls (p <0.001). Among HCC patients, plasma levels of OPN increased significantly with advanced Child-Pugh class (B-C, p <0.001), late tumor stage (III-IV, p <0.001), larger tumor size (≥5 cm, p <0.01), and high tumor grade (p <0.01). The sensitivity and specificity of OPN for HCC were 88.3% and 85.6%, respectively, at a cut-off value of 9.3 ng/mL. OPN had a greater area under curve value (0.918) than AFP (0.712), suggesting superior diagnostic accuracy of OPN. Moreover, no significant correlation was found between OPN and AFP levels in HCC patients. CONCLUSIONS Plasma OPN can be regarded as a promising diagnostic biomarker for HCC in the surveillance of Egyptian patients with HCV infection. It could also serve as an adverse prognostic factor for HCV-related HCC patients.

Serum Soluble Fas in Patients with Schistosomal Cor pulmonale

Background: Schistosomal cor pulmonale is considered an important pathological condition in endemic areas. Few recent studies have reported the role of apoptosis in pulmonary hypertension. Objectives: The aim of this study was to assess serum levels of soluble Fas (sFas), an inhibitor of apoptosis, in patients with schistosomal cor pulmonale as compared to patients with cor pulmonale due to chronic obstructive pulmonary disease (COPD) and normal subjects. Methods: Serum sFas was assessed in 15 men with schistosomal cor pulmonale (age 32 ± 10 years), 15 men with chronic cor pulmonale secondary to COPD and 20 healthy men, matched for age. Results: Serum levels of sFas were significantly higher in patients with schistosomal cor pulmonale (74 ± 80 U/ml) than in patients with cor pulmonale due to COPD (15 ± 10 U/ml) and normal subjects (19 ± 11 U/ml, p < 0.001 in both). In patients with schistosomal cor pulmonale, sFas was significantly higher in patients with mean pulmonary artery pressure >30 mm Hg as compared to patients with pressure ≤30 mm Hg (109 ± 97 vs. 34 ± 20 U/ml, p = 0.01). There was a significant correlation between serum sFas and the mean pulmonary artery pressure in patients with bilharzial cor pulmonale (r = 0.4, p < 0.01), but not in patients with COPD (r = 0.1, p = NS). Conclusions: Serum sFas levels are elevated in patients with schistosomal cor pulmonale and they are related to the severity of pulmonary hypertension. These findings suggest a role of apoptosis in schistosomal cor pulmonale.

High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients

ABSTRACT Background: Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related death worldwide. It has evolved different immune escape mechanisms, which might include emergence of lymphoid and myeloid regulatory cells. Aim of this work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN-γ and α-fetoprotein (α-FP). Patients and methods: Sixty individuals were enrolled in this study; forty cirrhotic patients with ascites; twenty without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy individuals as a control group (group III). The phenotype and numbers of MDSCs were analyzed in peripheral blood of all the individuals and ascitic fluid of the patients using flow cytometry. Intracellular IFN-γ and serum alfa-fetoprotein were measured. Results: Significant increases in the relative and the mean number of peripheral blood MDSCs were found in the cirrhosis and HCC groups than in the control group, with the HCC group showing the highest number. MDSC count was negatively correlated with IFN-γ levels, while α-FP was positively correlated with MDSC% in the HCC group. MDSC count was low in ascitic fluid of both HCC and cirrhosis groups with no significant difference between the 2 groups. Conclusion: A high frequency of MDSCs was detected in the peripheral blood of cirrhotic and HCC patients, indicating presence of immunosuppressive arms. These cells could be targeted to develop a new effective immunotherapy or an adjuvant to current therapies.

Evaluation of portal pressure by doppler ultrasound in patients with cirrhosis before and after simvastatin administration – a randomized controlled trial

Background: Portal hypertension is one of the most frequent complications of cirrhosis. β-adrenergic blockers, with or without organic nitrates, are currently used as hypotensive agents. Statins such as simvastatin seem to be safe for patients with chronic liver diseases and exert multiple pleiotropic actions. This study aimed to assess PTH using Doppler ultrasound in patients with cirrhosis before and after simvastatin administration. Methods: This randomized controlled clinical trial was conducted on 40 patients with cirrhosis who were randomized into 2 groups: group I included 20 patients with cirrhosis who were administered 20 mg of simvastatin daily for 2 weeks and then 40 mg daily for another 2 weeks, and group II included 20 patients with cirrhosis who did not receive simvastatin as a control group. All patients underwent full clinical examination, laboratory investigations, and abdominal Doppler ultrasound at baseline and after 30 days to evaluate portal vein diameter, blood flow volume, direction and velocity of portal vein blood flow, hepatic artery resistance and pulsatility indices, splenic artery resistance index, portal hypertension index (PHI), liver vascular index, and modified liver vascular index (MLVI). Results: There was a highly significant decrease in the hepatic artery resistance index in group I, from 0.785 ± 0.088 to 0.717 ± 0.086 (P < 0.001). There was a significant decrease in the PHI in group I , from 3.915 ± 0.973 m/sec to 3.605 ± 1.168 m/sec (P = 0.024). Additionally, there was a significant increase in the MLVI in group I from 11.540 ± 3.266 cm/sec to 13.305 ± 3.222 cm/sec, an increase of 15.3% from baseline (P = 0.009). No significant adverse effects were detected. Conclusions: Simvastatin is safe and effective in lowering portal hypertension. [ClinicalTrials.gov Identifier: NCT02994485]

Evaluating the Role of Interleukin-12 B gene polymorphism in prediction of disease progression in patients with chronic hepatitis C virus infection.

Background & Aims: Cell-mediated immunity plays a critical role in viral clearance and disease progression during Hepatitis C virus (HCV) infection. Interleukin (IL)-12 is a cytokine that has been shown to be a potent antiviral cytokine. The aim of this work is to investigate the association of IL-12 B gene polymorphism with the progression of liver disease in chronic HCV patients. Methods: This cross sectional study was carried out in tropical medicine department, Tanta university hospital, Egypt, on 120 chronic HCV patients with various stages of liver disease and 30 healthy subjects served as control. All the participants were tested for IL- 12 B (p40) gene polymorphism. Results: the frequency of AA genotype was higher in HCV patients with decompensated cirrhosis and in HCV patients with Hepatocellular carcinoma (HCC). However, the CC genotype was less detected in all groups, with the lowest percentage (6.6%) detected in decompensated cirrhotics and HCC patients. Conclusions: AA genotype presented more frequently in late stages of HCV chronically ill patients, while, CC genotype had no significant association with the severity of liver disease and had low frequency especially in late stages of liver disease.BACKGROUND & AIMS Cell-mediated immunity plays a critical role in viral clearance and disease progression during Hepatitis C virus (HCV) infection. Interleukin (IL)-12 is a cytokine that has been shown to be a potent antiviral cytokine. The aim of this work is to investigate the association of IL-12 B gene polymorphism with staging of liver disease in chronic HCV patients. METHODS This cross sectional study was carried out in tropical medicine department, Tanta university hospital, Egypt, on 120 chronic HCV patients with various stages of liver disease and 30 healthy subjects served as control. All the participants were tested for IL- 12 B (p40) gene polymorphism. RESULTS the frequency of AA genotype was higher in HCV patients with decompensated cirrhosis and in HCV patients with Hepatocellular carcinoma (HCC). However, the CC genotype was less detected in all groups, with the lowest percentage (6.6%) detected in decompensated cirrhosis and HCC patients. CONCLUSIONS AA genotype presented more frequently in late stages of HCV chronically ill patients, while, CC genotype had no significant association with staging of liver disease and had low frequency especially in late stages of liver disease.

Genetic Susceptibility in Family Members of Egyptian Hepatitis C Virus Infected Patients: Role of Interleukin-12 B Gene Polymor-phism

AIM The research was conducted to study 1188 A\C polymorphism of Interleukin (IL)-12B gene for C/C, A/C and A/A genotypes in families of Hepatitis C virus (HCV) infected patients in Egypt. METHODS Three hundreds HCV patients, 860 family members and 100 healthy subjects were studied. All family members were screened for HCV antibodies by enzyme-linked immunosorbent assay (ELISA). Positive cases were examined using Real-Time polymerase chain reaction (PCR) to confirm the presence of HCV ribonucleic acid (RNA) and detect the viral load. Molecular study of IL-12B gene was carried out on all patients, family members and controls using PCR and restriction enzyme analysis. RESULTS HCV infection was confirmed in 10.6% of family members. The distribution of IL-12B gene polymorphism in patients was 2.3%, 45.7% and 52% for C/C, A/C and A/A genotypes respectively, in infected family members was 3.3%, 41.7%, 55%, in noninfected family members was 4.5%, 43.5% and 52% for C/C, A/C and A/A genotypes respectively and in control was 5%, 36% and 59% for C/C, A/C and A/A genotypes respectively. The frequency of the C/C, A/C and A/A genotype was not significantly different between the studied groups. CONCLUSION IL-12B gene polymorphism has no role in intrafamilial susceptibility of HCV transmission. The distribution of the functional 1188 A\C polymorphism of Interleukin (IL)-12B gene for C/C, A/C and A/A genotypes was not significantly different among the studied groups.

P6A: Role of IL-12B and IL-28B gene polymorphisms in families of HCV infected patients in the Nile Delta of Egypt

of them have IgG for HCV (10%) and two were positive for HBsAg (6.7%) none of them had antibodies for HEV or HAV. In children with hematological disorders 15 of children had HCV IgG (15%) and 12 had either positive HBsAg or/and positive core IgM (12%). For HEV eight children were positive for HEV IgG (8%) and five of them (5/ 8–62.5%) were positive for HEV IgM and none of those children had positive IgM for HAV. None of the control had any positive serological markers for any of the hepatotropic viruses. CONCLUSION: Hepatitis E virus can be responsible for acute viral hepatitis in multiple transfused children in endemic area like Egypt. Regular screening for those children for specific antibodies for HEV is recommended to exclude presence of acute hepatitis. Blood transfusion route of infection of hepatitis E may be present in high endemic region.