Mahmoud El-Bendary

Role of Helicobacter pylori in patients with HCV-related chronic hepatitis and cirrhosis with or without hepatocellular carcinoma: possible association with disease progression.

Summary.  The discovery of Helicobacter hepaticus as a causal agent of hepatitis and hepatocellular carcinoma (HCC) in mice has stimulated interest in looking for Helicobacter species in human liver samples. In this study, we searched for association between H. pylori and HCV‐related liver disease. Liver specimens were collected from eighty‐five patients; they were divided into five different groups according to liver pathology (METAVIR system). Group I (the 1st control group) consisted of 16 patients with chronic hepatitis C without histological activity. Group II consisted of 25 patients with chronic active hepatitis C, Group III, 17 patients with HCV‐related cirrhosis and Group IV, 16 patients with HCV‐related cirrhosis and HCC. Group V (2nd control group) consisted of 11 patients suffering from gastro duodenal and gall bladder diseases but negative for HCV. All cases were tested by polymerase chain reaction on liver samples for the presence of H. pylori DNA Cag A gene. Routine biochemical, radiological and RT‐PCR for HCV RNA were also performed for all cases. The positivity of H. pylori PCR CagA gene in liver tissue was directly proportional to the severity of liver pathology, this being 75%, 52.9% and 32% in groups IV, III and II, respectively, which was more significant than the 1st and 2nd control groups (P < 0.001). There was a significant difference between H. pylori PCR values when compared to METAVIR staging (F) in different groups (P = 0.001). Helicobacter pylori PCR (Cag A gene) was positive in about 28.2% cases of late fibrosis (F3 + F4) while positivity was (5.9%) in early fibrosis (F1 + F2) (P = 0.0001). There was significant difference between H. pylori PCR (Cag A gene) in liver tissue and METAVIR activity in different groups (P = 0.002) as most of H. pylori PCR–positive cases were METAVIR activity A1 and A2 (15.3% and 12.9%, respectively). There was no association between H. pylori PCR and quantitative HCV RNA (P = 0.531). Also there was no significant difference of Child‐Pugh staging in the H. pylori PCR–positive group when compared to the negative group (P = 0.996). There may be an association between the presence of H. pylori (Cag A gene) in the liver and disease progression in HCV‐related chronic hepatitis and cirrhosis with and without HCC.

Development of a novel score for liver fibrosis staging and comparison with eight simple laboratory scores in large numbers of HCV-monoinfected patients.

BACKGROUND This study aimed to develop and evaluate a predictive score named Fibrosis Routine Test (FRT) for liver fibrosis staging and to compare FRT with APRI, Lok, GUCI, FI, FibroQ, FCI, FIB-4 and 4RLB scores in large numbers of untreated HCV-monoinfected patients. METHODS Large numbers of estimation (N=2045) and validation patients (N=3212) were included in this study. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score comprising age, AFP, APRI and albumin. RESULTS In the estimation study, FRT produced AUCs 0.84, 0.85 and 0.86 for significant (F2-F4), advanced fibrosis (F3-F4) and cirrhosis (F4), respectively. FRT > 4 was 83% specific and 73% sensitive for F2-F4, FRT > 5 was 83% specific and 71% sensitive for F3-F4 and FRT > 5.5 was 81% specific and 73% sensitive for F4. In the validation study, FRT produced AUCs 0.81, 0.89 and 0.95 for F2-F4, F3-F4 and F4, respectively. The above eight scores demonstrated lower AUCs than FRT. CONCLUSION While liver biopsy is invasive, costly and associated with complications, Fibrosis Routine Test (FRT) is a non-invasive, inexpensive, simple and may reduce the need of liver biopsy.

Non-invasive predictive score of fibrosis stages in chronic hepatitis C patients based on epithelial membrane antigen in the blood in combination with routine laboratory markers

Aim:  The epithelial membrane antigen (EMA) could detect small deposits of liver malignant cells. However, no information exists regarding the use of EMA in patients with chronic hepatitis C (CHC). Therefore, we attempted to evaluate the diagnostic performance of EMA to distinguish patients with different liver fibrosis stages.

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.

Associations of human leucocyte antigen class II‐DQB1 alleles with hepatitis C virus infection in Egyptian population: a multicentre family‐based study

Hepatitis C infection is a global pandemic. HLA‐DQB1 alleles are believed to have an effective role in immune response against HCV including susceptibility to or protection from this infection. The aim of this study was to investigate the contribution of HLA‐DQB1 alleles in the outcome of HCV genotype‐4 infection through a family‐based association study. Egyptian families with HCV (324) were recruited for this study (324 index positive for RNA‐HCV, 225 positive relatives representing chronic hepatitis C cases and 582 family members negative for HCV‐RNA [control], 63 of whom spontaneously cleared the virus. All subjects were genotyped for HLA‐DQB1 alleles by sequence‐specific primers (SSP‐PCR) and sequence‐based typing (SBT) methods. The frequency of DQB1*02:01:01 carriage was significantly higher in infected patients when compared to controls and those who spontaneously cleared virus (OR=5.47, P<.0001 and OR= 6.5234, P<.0001, respectively), and the carriage of the DQB1*03:01:01:01 allele was significantly higher in those who cleared and controls when compared to the infected patients (OR=0.2889, P<.0001 and OR=0.3016, P<.0001, respectively). On the other hand, the frequency of DQB1*06:01:01 and QB1*05:01:01:01 alleles was not associated with infection (comparison of infected and cleared patients showed OR of 2.1598 [P<.01]), but it becomes nonsignificant after adjustments with the Bonferroni formula (PC>0.05) and OR= 1.3523, P>.05, respectively. This study shows that clearance of HCV is associated with DQB1*03:01:01:01 allele and chronicity of HCV infection associated with the risk allele: DQB1*02:01:01.

Expression of Fas (CD95) and Bcl-2 in peripheral blood mononuclear cells in patients with chronic HCV and schistosomiasis

Abstract A high incidence of viral persistence and progression to chronic hepatitis are characteristic features of HCV infection. The aim of this case control study was to investigate the expression of the apoptosis related proteins Fas (CD95) and Bcl-2 in peripheral blood mononuclear cells (PBMCs) from patients with chronic HCV and schistosomiasis, and to evaluate their contribution in the development and maintenance of the different clinical forms of these diseases. The level of Fas and Bcl-2 expression in PBMCs was detected using flow cytometry in 85 cases in this study, including chronic HCV (40 patients) and schistosomiasis (25 patients) in addition to 20 healthy controls. Results showed that the increased apoptotic level correlated with increased Fas expression on the surface of PBMCs in chronic HCV patients (p = 0.001) which did not show increased expression of the anti-apoptotic factor Bcl-2 (p = 0.19). Apoptotic PBMCs in intestinal schistosomiasis patients showed increased expression of Fas (p = 0.001) but again did not exhibit a difference in Bcl-2 expression (p = 0.61) when compared to either hepatoplenic schistosomiasis or control patients. The Fas expression was highly significant in HCV > schistosomiasis > control (p < 0.002) while non-significant difference was found between the 3 groups as regards to Bcl-2 expression (p > 0.12). It was concluded that the detection of apoptosis of PBMCs in patients with chronic HCV was associated with increased expression of apoptotic markers in comparison with schistosomiasis patients, which may be an indicator of disease progression and severity. Modulation of this process may offer valuable methods of HCV therapy.

640 EPIDERMAL GROWTH FACTOR GENETIC POLYMORPHISM PREDICTS RISK OF HEPATOCELLULAR CARCINOMA IN EGYPTIAN PATIENTS WITH HCV (GENOTYPE 4)-RELATED CIRRHOSIS

and microwave ablation) (p = 0.15), whereas there was significant increased basal CK18 level in patients with recurrent local lesion versus nonrecurrent (p < 0.01). Interestingly there was marked significant increased in serum CK 18 with macroscopic vascular invasion level versus those without (p < 0.001). Conclusion: CK18 M30 could be used as a prognostic marker Predicts early local recurrence of HCC and macroscopic vascular invasion but it was of no value in detection successful ablation.

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.

Serum Levels of Heavy Metals in Cholangiocarcinoma Patients from the Nile Delta Region of Egypt: A Single Centre Study

Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt Department of Tropical Medicine, College of Medicine, Mansoura University, Mansoura, Egypt Department of Public Health and Community Medicine,College of Medicine, Mansoura University, Mansoura, Egypt Serum Levels of Heavy Metals in Cholangiocarcinoma Patients from the Nile Delta Region of Egypt: A Single Centre Study

Profile of expression of certain markers of apoptosis in chronic hepatitis C and hepatitis B patients in an Egyptian population.

Increased peripheral blood mononuclear cell (PBMC) apoptosis during viral hepatitis has been suggested to cause impaired regulation of the immune response and maintenance of the infection. The purpose of this work was to study the expression of some apoptotic markers in chronic hepatitis B (CHB) and C (CHC) infections in order to understand the underlying mechanisms of immune failure and viral persistence. This study aims to evaluate the level of PBMC apoptosis and the expression of the apoptosis-related proteins Fas and Bcl-2 in CHB and CHC patients. This case control study was carried out on 38 cases (group I: 20 chronic HCV patients; group II: 18 chronic HBV patients) attending the Tropical Medicine Clinic, Mansoura University Hospital, in addition to 10 healthy controls. Morphological assessment of apoptosis of cultured PBMCs was done. The level of Fas and Bcl-2 expression by PBMCs was detected using flow cytometry. An increased level of apoptosis correlated with increased Fas expression, but no increase in Bcl-2 expression was found on the surface of PBMCs in CHC and CHB patients compared to controls. No significant difference in the level of apoptosis, Fas, or Bcl2 expression between CHC and CHB patients was detected. Modulation of apoptosis, particularly by manipulation of Fas receptor activation, may be of therapeutic benefit in chronic CHB and CHC.