Hatem Elalfy

Association of Human Leucocyte Antigen Class I (HLA-A and HLA-B) With Chronic Hepatitis C Virus Infection in Egyptian Patients

Egypt has the highest prevalence of hepatitis C virus (HCV) in the world, ranging from 6% to 28% with an average of approximately 13.8% in the general population. It has been reported that human leucocyte antigen (HLA) alleles are associated with the outcome of HCV infection, but this associations showed ethnic and geographical differences. The objective of this study is to investigate the association between the frequencies of HLA Class I and chronic HCV infection in Egyptian patients and to find out whether there is a relation between certain HLA Class I antigens and HCV viral load, degree of fibrosis, activity and alanine aminotransferase (ALT) level. A case control study was conducted on 100 patients with chronic HCV infection and 150 healthy controls. HLA‐A and HLA‐B typing by complement‐dependent micro‐lympho‐cytotoxicity assay was performed for both groups. HLA‐A11 antigen was significantly increased in patients with chronic HCV infection versus controls (OR 3.98; 95% CI = 1.85–8.89; P = 0.001; and Pc = 0.021). HLA‐B12, HLA‐B13, HLA‐B17 and HLA‐B40 were higher in patients, and HLA‐A32 and HLA‐B14 were higher in controls, although the significance was lost after correction for multiple testing. HLA‐A9 was significantly associated with low viral load (P = 0.008, Pc = 0.048). The results of this work implicate that HLA‐A11 antigen may influence chronic HCV infection and may play a role in viral persistence. Different HLA Class I antigens are not associated with degree of liver fibrosis, grades of activity or level of ALT. However, HLA‐A9 is associated with low HCV viral load in chronic HCV Egyptian patients.

Does steatosis affect the performance of diffusion-weighted MRI values for fibrosis evaluation in patients with chronic hepatitis C genotype 4?

BACKGROUND/AIMS To evaluate the effect of hepatic steatosis on the apparent diffusion coefficient (ADC) of hepatic fibrosis in patients with HCV genotype 4-related chronic hepatitis. MATERIALS AND METHODS Overall, 268 chronic hepatitis C patients (164 males and 104 females) underwent liver biopsy for fibrosis assessment by the METAVIR score and grading for hepatic steatosis. They were classified into early fibrosis stage (F1, F2) and advanced fibrosis stage (F3, F4). Diffusion-weighted MRI (DWI) of the liver was performed using 1.5-Tesla scanners, and the ADC value of the patients with and without steatosis in different stages of fibrosis was estimated and compared. RESULTS In patients with early fibrosis, the ADC value significantly decreased in patients with steatosis (1.52±0.17×10-3 mm2/s) compared to that in patients without steatosis (1.65±0.11×10-3 mm2/s) (p<0.001). In those with an advanced stage of fibrosis, the ADC value was also significantly decreased in patients with steatosis (1.07±0.16×10-3 mm2/s) compared with that in patients without steatosis (1.35±0.11×10-3 mm2/s) (p≤0.001). The cutoff value for ADC for steatosis prediction in the early fibrosis group was 1.585 according to the AUROC curve, with a sensitivity of 76.8% and a specificity of 73.5%. The cutoff value for ADC for steatosis prediction in patients with an advanced stage of fibrosis was 1.17×10-3 mm2/s, with a sensitivity of 97% and a specificity of 88.5%. CONCLUSION Histologically detected hepatic steatosis should always be considered when assessing hepatic fibrosis using diffusion-weighted MRI to avoid the underestimation of the ADC value in patients with chronic hepatitis C genotype 4.

Association of interferon gamma gene polymorphism and susceptibility to hepatitis C virus infection in Egyptian patients: A multicenter, family-based study: Interferon gamma genetic polymorphism

Polymorphisms in some genes may influence the persistence of hepatitis C virus (HCV) infection, clinical outcome, HCV replication, and liver damage. This study was conducted to investigate the role of the interferon gamma (IFN‐γ) gene at (+874 T/A, −764 G/C, −179 C/A) single‐nucleotide polymorphisms (SNPs) and its receptor (IFN‐γR2) at (rs 2786067 A/C) SNP in the susceptibility of Egyptian families to HCV infection with high‐resolution techniques.

Diagnosis of cirrhosis in patients with chronic hepatitis C genotype 4: Role of ABCB11 genotype polymorphism and plasma bile acid levels

BACKGROUND/AIMS Chronic hepatitis C (CHC)-related mortality generally results from cirrhosis and subsequent complications. We aimed to investigate the potential role of plasma bile acid levels and ABCB11 1331T > C (V444A, rs2287622) (ATP-binding cassette subfamily B, member 11) gene polymorphism in fibrosis prediction in CHC genotype 4 patients. MATERIALS AND METHODS This case control study included 85 healthy control and the following 225 subjects: 170 adult patients infected with hepatitis C virus (HCV) and categorized into three groups according to liver biopsy; no fibrosis group (F0) (n=33), early fibrosis group (F1-F2) (n=61), and advanced fibrosis group (F3-F4) (n=76). Fasting bile acid levels, hepatitis C virus (HCV) genotyping, and ABCB11 1331T > C gene polymorphism were assessed. RESULTS The frequency of the variant homozygote genotype CC in advanced fibrosis was significantly higher than that in early fibrosis (48.7% vs. 36.1%) (odd ratio, OR =2.58; 95% confidence interval, CI=1.07-6.20; p=0.03). C allele was significantly represented in advanced fibrosis (65.8%) compared with that in early fibrosis (51.6%) (OR=1.80, 95% CI=1.10-2.93, p=0.01). A significant elevation of plasma bile acid levels in advanced fibrosis was observed compared with those in early fibrosis (p≤0.001). Receiver operating characteristic curve for plasma bile acid levels at cutoff value of 75.5 μmol/L had a 59% specificity and 97.4% sensitivity as a predictor of advanced hepatic fibrosis (AUROC=0.78%). CONCLUSION We concluded that Egyptian patients having chronic hepatitis C genotype 4 with CC genotype of ABCB11 SNP 1331T > C and high plasma bile acid levels at cutoff value of 75.5 μmol/L were associated with advanced hepatic fibrosis.

Predictors of hepatocyte proliferative activity in chronic hepatitis B and C vs. steatohepatitis as assessed by the monoclonal antibody MIB1-Ki-67.

BACKGROUND AND STUDY AIMS Chronic hepatitis is characterised by increased regenerative cell proliferation, a process that makes cells more susceptible to gene mutations and development of hepatocellular carcinoma (HCC). Evaluation of the proliferative index could be a useful tool for identifying patients at risk for HCC. The current study was planned to evaluate hepatocyte proliferation in predominant causes of chronic liver disease in an attempt to investigate predictors of proliferation. PATIENTS AND METHODS This study included 84 patients with chronic liver diseases, and they were classified into three groups: chronic hepatitis C (50 patients), non-alcoholic steatohepatitis (NASH) (20 patients) and chronic hepatitis B (14 patients). All cases were investigated by liver function tests, polymerase chain reaction (PCR) hepatitis C virus (HCV) and hepatitis B virus (HBV), routine abdominal ultrasound and liver biopsy with detection of the proliferative index using the monoclonal antibody MIBI-Ki-67. RESULTS The proliferative index was significantly higher in the chronic hepatitis C group than in the chronic hepatitis B group (P value=0.007). There were significant correlations of the Ki-67 index in both zone 1 and zones 2 and 3 with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and histological activity index (HAI) score. Using the multiple regression analysis on the variables affecting proliferation, it was found that predictors of zone 1 proliferation were the following variables: ALT, age, AST and aetiological factor, in that order. CONCLUSION HCV aetiology had significantly higher proliferation index, whereas NASH had the least. Increased HAI score is associated with higher proliferative index in either zone 1 or zones 2 and 3. Predictors of proliferation index in zone 1 were ALT, age, AST and aetiological factor.