Background. Spontaneous bacterial peritonitis (SBP) is a fatal complication of liver cirrhosis wi... more Background. Spontaneous bacterial peritonitis (SBP) is a fatal complication of liver cirrhosis with high mortality rates. Objective: The aim of this study is to investigate the diagnostic utility of absolute neutrophil count (ANC) as a non-invasive marker for SBP diagnosis. Methods. Six hundred patients with cirrhotic ascites were included in the study. All patients underwent abdominal paracentesis and the ascitic fluid was processed for cell count and culture. Results. Absolute neutrophil count was significantly higher in SBP versus non-SBP and in culture positive SBP versus culture negative SBP. ANC at cutoff value > 2.804 has 84% sensitivity and 78% specificity for diagnosis of SBP with positive and negative predictive values (79.4% and 83.6 respectively). At a cut-off point > 5.6, ANC is capable of differentiating culture positive SBP from culture negative SBP cases with 62.07% sensitivity and 60.87 % specificity. Increased ANC, WBC, CRP, creatinine and decreased platelet ...
Hepatocellular carcinoma (HCC) is the most prevalent malignancy affecting developing populations ... more Hepatocellular carcinoma (HCC) is the most prevalent malignancy affecting developing populations Aflatoxin B1 (AFB1), an established carcinogen produced by certain strains of fungi, particularly Aspergillus parasiticus and Aspergillus flavus. The carcinogenic effects of AFB1 in hepatocellular carcinoma (HCC) are ascribed to AFB1-DNA adduct formation with p53 gene mutation. Objective: The present study aimed was to investigate the prevalence of single nucleotide polymorphism (SNP) in rs 25487 of X-ray cross complementing group 1 protein (XRCC1) in association with AFB1 in patients with hepatocellular carcinoma (HCC). Methodology: The study included 100 patients with HCC and 100 healthy control subjects. Blood samples were withdrawn from each subject and SNP in rs 25487 XRCC1 was estimated by real time polymerase chain reaction (PCR) and determination of blood levels of AFB1. Results: There was a dramatic increase in the level of aflatoxin B1 in patients (1.02±0.7ng/gm) compared to control subjects (0.8±0.6ng/gm), P=0.01. A significant increase in mutant genotypes CT and TT was found in HCC patients (43% and 7%, respectively) compared to control subjects (27% and 1%, respectively), with a notable increase in the dominant genotype CC in healthy controls (72%) compared to patients with HCC (50%), P=0.002. There was also a statistically significant increase in C allele (85.5%) in the control subjects compared to patients with HCC (71.5%) with a significant increase in T allele in patients (28.5%) compared to control subjects (14.5%), P=0.001. Furthermore, a significant difference in level of aflatoxin B1 was detected in patients with different genotypes of rs25487 XRCC1, with high levels of aflatoxin B1 found in patients with CT genotype (1.2±0.5), P=0.002. Conclusion: This study revealed the relationship of SNP of XRCC1 rs25487 with hepatocellular carcinoma, showing a significant association between this SNP and the increased level of aflatoxin B1 in patients with HCC.
It has been suggested that insulin resistance may play a role in pathogenesis of NASH, with hepat... more It has been suggested that insulin resistance may play a role in pathogenesis of NASH, with hepatocyte apoptosis believed to be the main factor involved in disease progression from simple steatosis to NASH. During apoptosis, cytokeratin-18 (CK-18) is cleaved by caspases and released into serum, a finding that was shown to correlate with the existence of inflammation and fibrosis in patients with NASH. The present study aims to differentiate patients with simple steatosis from those with NASH using CK-18 assessment both in liver tissue and in serum. The present study was conducted on two groups of patients, the first including 44 patients with simple steatosis and the second comprising 106 patients with steatohepatitis. Serum fasting insulin was measured and serum CK-18 was estimated. No significant differences were found between steatohepatitis patients and patients with simple steatosis regarding fasting insulin levels, or HOMA-IR index (P > 0.05 for each). Comparison of serum CK-18 levels between simple and advanced fatty liver patients showed significantly higher concentrations in patients with steatohepatitis than in patients with simple steatosis (P < 0.001). Serum level of CK-18 demonstrated a satisfactory relationship with all pathological variables that allowed differentiation between both entities of nonalcoholic fatty liver disease.
Background: Polymorphisms in the cytokine gene involving IFN gamma (IFN-γ) have been implicated i... more Background: Polymorphisms in the cytokine gene involving IFN gamma (IFN-γ) have been implicated in many infections including HCV. The aim of this study is to evaluate the association between IFN-γ polymorphism in three regions, (+2109A/G, +874A/T,-183G/T) and either chronicity or spontaneous viral clearance (SCV) in HCV infected patients. Materials and Methods: The study included 200 HCV-infected patients divided into Group I of 100 patients with spontaneous virus clearance (SVC) and Group II of 100 patients with persistent chronic hepatitis C infection (PI) who did not receive any therapy. These patients were subjected to history taking, full clinical examination and laboratory investigations included analysis of IFN-γ gene polymorphisms. Results: At locus +2109 of the IFN-γ gene, patients with A/A genotype had a significantly higher rate of spontaneous hepatitis C clearance while the G/G genotype was more prone to persistent infection. No statistically significant difference was found between both groups regarding loci +874 and-183 of the IFN-γ gene, but column proportion comparison using Bonferroni method at locus +874 revealed a higher proportion for T/A genotype in SVC group. Both haplotypes AAT and TGT were more susceptible to chronic HCV infection, as were heterozygote T/A at locus +874 and G/G genotype at locus +2109s. A/G and A/A genotypes at locus +2109, TLC at cut off value ≤7.15, and AST at cut off value ≤27.5 were considered independent predictors for development of SVC. Conclusions: Polymorphisms in the IFN-γ gene may play role in sequelae following HCV infection, possibly determining whether the virus will be cleared spontaneously or not. Polymorphisms in cytokine genes, including interferon gamma (IFN-γ), have been implicated in numerous infections 17,18 , autoimmune diseases, and chronic inflammatory conditions 18,19. Some polymorphisms reported in the regulatory and coding regions of IFN-γ gene include-183G/T,
The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated he... more The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated hemoglobin (HbA1c), and a number of routine biomarkers as noninvasive indicators of liver fibrosis in patients with chronic hepatitis C (CHC). One hundred patients with CHC were subjected to full medical history and examination, in addition to ultrasound‐guided liver biopsy and histopathological examination for assessment of liver fibrosis stage. GA and HbA1c values, GA/HbA1c ratio, liver function tests, complete blood count, and alpha fetoprotein (AFP) were determined. A novel noninvasive index, dubbed Fibrosis Prediction Score (FPS), was selected for predicting significant liver fibrosis based on total bilirubin, glycated albumin, platelet count, age, and AFP. A validation study for FPS was applied on archival data which include 66 diabetics' patients. The FPS had area under the curve (AUC) of 0.92 for classification of patients with significant fibrosis with 81% sensitivity and 95% specificity. The AUCs of FPS in predicting advanced fibrosis and cirrhosis were 0.86 and 0.82, respectively. Comparison of AST‐to‐platelet ratio index (APRI) and FIB‐4 with FPS indicated increased sensitivity and specificity of FPS over APRI and FIB4 in both significant and advanced fibrosis. FPS has a good sensitivity and specificity for prediction of significant and advanced liver fibrosis in patients with CHC.
Limited data exists on the role of Th17 cells in chronic HCV infected patients, particularly with... more Limited data exists on the role of Th17 cells in chronic HCV infected patients, particularly with regard to hepatic inflammation and fibrosis. We aimed to investigate the relationship between circulating and intrahepatic frequency of Th17 cells and IL-17 serum level and degrees of hepatic inflammation and fibrosis in chronic HCV patients, as well as to evaluate the effect of successful anti-viral therapy on these parameters. This nested longitudinal case control study included 30 treatment-naïve chronic HCV patients and 20 healthy individuals as control. All patients were investigated for circulating Th17 cell percentage (flow cytometry) and intrahepatic Th17 cell percentage (immunohistochemistry) and serum IL-17 (ELISA) at baseline and at week 12 after discontinuation of therapy. Circulating and intrahepatic Th17 cell percentage and serum IL17 level were found to be significantly higher in chronic HCV patients when compared with controls, with significant correlation with Metavir a...
Afro-Egyptian Journal of Infectious and Endemic Diseases, 2014
Background and study aim: Spontaneous bacterial peritonitis (SBP) is an important cause of morbid... more Background and study aim: Spontaneous bacterial peritonitis (SBP) is an important cause of morbidity and mortality in cirrhotic patients with ascites. The diagnosis of SBP is based on PMN leukocyte cell count exceeding 250/μL in ascitic fluid. However, this procedure is time consuming as well as subjective. C-reactive protein (CRP) has been reported to be a reliable predictor of SBP and an index of therapeutic effectiveness in adults. Ascitic fluid calprotectin reliably predicts PMN count >250/μL, which may prove useful in the diagnosis of SBP. This work was planned aiming to evaluate both ascitic fluid calprotectin and serum CRP as accurate diagnostic laboratory markers for detecting SBP Patients and Methods: From 140 patients; only 124 patients with ascites were included in this study. They were divided into SBP group including 70 patients (49 males and 21 females) and non-SBP group of 54 patients (25 males and 29 females). Serum CRP was determined by latex agglutination and ascitic fluid calprotectin was measured using an enzyme-linked immunosorbent assay. Results: Ascitic fluid calprotectin and serum CRP were significantly higher in SBP patients in comparison with the non-SBP group (754.67 ±256.06 vs. 280.77 ±230.97 and 62.4 ±28.39 vs. 9.81 ±8.98) respectively. In addition, both were positively correlated with ascitic fluid proteins and PMN count as well as with each other. At a cutoff value of 270 mg/dl, ascitic fluid calprotectin had 86% specificity and 97.5% sensitivity for detecting SBP [Area under the receiver operating characteristics curve (AUC) = 0.924 with negative and positive predictive values (NPV, PPV) for ascitic calprotectin 96% and 69% respectively. Conclusion: Ascitic fluid calprotectin and serum CRP may be used as accurate and reliable markers for the diagnosis of SBP.
ABSTRACT Background: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are lin... more ABSTRACT Background: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. Materials & methods: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. Results: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). Conclusion: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.
Background:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into... more Background:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into various subtypes. Post-infection IBS may be attributed to the release of cytolethal distending toxin B (CdtB), which cross-reacts with the adhesion protein vinculin responsible for normal intestinal contractility.Objective:This study aims to identify anti-CdtB and anti-vinculin levels in IBS patients compared to healthy control.Subjects and methods:This retrospective case-control study was conducted on 100 subjects with IBS, as determined by a questionnaire based on Rome III criteria, recruited from the outpatient clinics of the Tropical Medicine at Mansoura University Hospital from January 2019 to January 2020.Results:Anti-vinculin and anti-CdtB levels were significantly elevated in patients with IBS (1.58±0.496, 2.47±0.60) when compared to control subjects (1.13±0.249ng/ml, 2.1±0.24 ng/ml), respectively with P=0.001 for both. Anti-vinculin level was significantly higher in the IBS-D...
Background The circulatory system is the main mechanism for transmission of the Hepatitis C Virus... more Background The circulatory system is the main mechanism for transmission of the Hepatitis C Virus (HCV). A new class of HCV infections, Occult HCV infection (OCI), is defined as the presence of HCV-RNA in hepatocytes with the absence of HCV in the serum/plasma utilizing current laboratory assays. Different groups have reported the prevalence of OCI; however, its associated risk factors have not been established. In Mexico, there are no reports about OCI, so the objective of our study was to determine the prevalence of OCI in total blood donors in Mexico City, as well as its associated risk factors. Methods Blood donors that were considered eligible for donation, according to NOM 253-SSA1-2012, were randomly selected. Demographic data was collected from 1,037 donors. Plasma and peripheral blood mononuclear cells were assessed for HCV-RNA. The presence of HCV-RNA was determined by nested PCR for the 5'-UTR region. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95%CI) to determine the level of association. Results The prevalence of OCI was 3.4% among blood donors. Homosexual relationships (OR = 5.52, 95%CI: 1.53-19.92, p<0.05) and acupuncture (OR = 3.56, 95%CI: 1.41-8.98, p<0.05) were significantly associated with OCI. Conclusion There is a significant presence of OCI in the blood donor population in Mexico City. The main risk factors for OCI transmission are homosexual relationships and acupuncture. This
Background: There is a growing literature providing evidence on the importance of non-cognitive s... more Background: There is a growing literature providing evidence on the importance of non-cognitive skills for life outcomes. However, to date there is limited evidence on the gains from incorporating such measures into large-scale competence surveys. Methods: We investigate the relationship between personality traits and eight important life outcomes: educational attainment, labour market participation, employability, wages, job satisfaction, health, trust and life satisfaction measured in the Polish followup study to PIAAC. The study assesses two short scales: the Big Five Inventory and Grit. First, we compare explanatory power of personality traits to that of cognitive skills measured by PIAAC. Second, an incremental validity of Grit after controlling for the Big Five dimensions is assessed. Results: The analyses show that differences in personality traits are important in explaining differences in life outcomes. Educational attainment is more strongly related to cognitive skills, while for wages, the explanatory power of personality and cognitive skills is similar. For most of the subjective outcomes, the Big Five traits outperform cognitive skills in predictive power. Conscientiousness is positively related to most of the outcomes analysed while Neuroticism has a negative relationship. After controlling for sociodemographic characteristics and cognitive skills, Big Five traits add explanatory power to all models except for employability. Grit explains some additional variation in educational attainment and in a number of subjective outcomes: health, trust, job and life satisfaction, even after adjusting for the effects of cognitive skills and Big Five traits. Conclusions: Given the potential benefits and relatively small burden on respondents in terms of required time it seems advisable to incorporate measures of personality traits into competence surveys as they contribute to explaining the variability in policyrelevant outcomes. The use of the Big Five Inventory seems preferable to Grit when a broad range of life outcomes is of interest, as the former covers multiple aspects of personality. However, using both scales offers an improvement in explanatory power.
Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deat... more Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) may be considered as potential markers for HCC. The aim of this study is to evaluate the diagnostic and prognostic value of lncRNA ZFAS1 in HCC patients. Materials and methods: The current study included 100 cirrhotic patients with HCC, in addition to 100 cirrhotic patients without HCC as control group. RNA extraction was performed for quantification of ZFAS1 expression by real-time quantitative polymerase chain reaction. Results: ZFAS1 gene expression was significantly elevated in HCC group of patients compared to non-HCC group. The ability to distinguish HCC from cirrhotic controls by ZFAS1 was determined to be 1.00 (95% CI:1.00-1.00). Comparison between the diagnostic performance of ZFAS1 and AFP in differentiating HCC on top of cirrhosis from cirrhosis without HCC showed that, at cutoff values ≥-4.65 ZFAS1 gene had 100 % specificity and 99% sensitivity while, AFP at cutoff value ≥ 9.4 ng/ml had 100 % specificity and 76% sensitivity. Comparison of AUC for the two parameters demonstrated a significantly higher AUC for ZFAS1 than for AFP (Difference = 0.168, P <0.001). No statistically significant correlation between ZFAS1gene and any HCC characteristic however, a statistically significant correlation between AFP level and sex , BCLC staging was found. Conclusions: lncRNA ZFAS1 is a good diagnostic marker for HCC in cirrhotic patients with high sensitivity and specificity value, however ZFAS1has no prognostic importance in patients with HCC.s
Mansoura Journal of Forensic Medicine and Clinical Toxicology
Aflatoxin B1, Hepatocellular carcinoma, Cirrhosis, This study aimed to assess the role of micro-r... more Aflatoxin B1, Hepatocellular carcinoma, Cirrhosis, This study aimed to assess the role of micro-ribonucleic acid-24 (microRNA-24) expression in patients with cirrhosis and hepatocellular carcinoma (HCC) who have experienced high levels of aflatoxin B1 (AFB1) exposure. Fifty HCC and 24 hepatic cirrhosis patients, in addition to 20 healthy control subjects were included in this study. Aflatoxin B1 was measured by enzyme-linked immunosorbent assay (ELISA) and microRNA-24 was detected using real-time polymerase chain reaction (real-time PCR). Both aflatoxin B1 levels and microRNA-24 expression were found to be significantly increased in all patient groups in comparison to controls, more so in the HCC than cirrhotic group (p<0.0001). A highly significant correlation was detected between levels of AFB1 and amount of microRNA-24 expressed in both patient groups relative to their control counterparts (p<0.0001). Receiver Operating Characteristic (ROC) curve performed to evaluate the ability of microRNA-24 to differentiate between HCC and cirrhosis showed that it had sensitivity of 80% and specificity of 63% at cutoff 1.3, which was highly significant (p<0.0001). Increased aflatoxin B1 levels detected in patients with cirrhosis and HCC further support previous studies evaluating the level of exposure of the Egyptian population to this carcinogen and support the critical role of aflatoxin B1 in the appearance of HCC. In addition, microRNA-24 expression levels demonstrated in both cirrhosis and HCC might be valuable for use as a noninvasive diagnostic tool for diagnosis of HCC.
To build a diagnostic non-invasive model for screening of large varices in cirrhotic hepatitis C ... more To build a diagnostic non-invasive model for screening of large varices in cirrhotic hepatitis C virus (HCV) patients.
European journal of gastroenterology & hepatology, Jan 6, 2016
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality among men world... more Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, which may be involved in the tumorigenesis of HCC. We aimed to determine whether serotonin is a dependable marker for the diagnosis of HCC in cirrhotic patients in comparison with α-fetoprotein protein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II). Serum serotonin, AFP, and PIVKA-II were measured in 262 patients with chronic hepatitis C (CHC): 82 cirrhotic patients with HCC (group I), 80 cirrhotic patients without HCC (group II), and 100 CHC-infected patients without cirrhosis (group III); in addition, 60 healthy controls were studied (group IV). AFP showed significant statistical differences among the groups studied (P<0.001). PIVKA-II and serotonin levels showed no statistically significant differences between the patients with CHC group and the healthy controls (P1=0.614 and P1=0.13, respectively), whereas their levels were st...
Background/Aims: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a polymorph... more Background/Aims: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a polymorphonuclear leukocytes (PMNs) exceeding 250/μL in ascitic fluid. The aim of the study was to evaluate serum procalcitonin and ascitic fluid calprotectin as accurate diagnostic markers for detecting SBP. Methods: Seventy-nine patients with cirrhotic ascites were included. They were divided into a SBP group, including 52 patients, and a non-SBP group of 27 patients. Serum procalcitonin, ascitic calprotectin, and serum and ascitic levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured using an enzyme-linked immunosorbent assay. Results: Serum procalcitonin and ascitic calprotectin were significantly higher in SBP patients than in non-SBP patients. Significant increases in both serum and ascitic levels of TNF-α and IL-6 were observed in SBP patients versus non-SBP patients. At a cutoff value of 0.94 ng/mL, serum procalcitonin had 94.3% sensitivity and 91.8% specificity for detecting SBP. In addition, at a cutoff value of 445 ng/mL, ascitic calprotectin had 95.4% sensitivity and 85.2% specificity for detecting SBP. Both were positively correlated with ascitic fluid proteins, PMN count, TNF-α, and IL-6. Conclusions: According to our findings, determination of serum procalcitonin levels and ascitic calprotectin appears to provide satisfactory diagnostic markers for the diagnosis of SBP. (Gut Liver 2016;10:624-631)
To document Toxoplasma gondii (T. gondii) antibody status in patients with liver disease, blood s... more To document Toxoplasma gondii (T. gondii) antibody status in patients with liver disease, blood samples were taken from 180 hepatic patients and 180 healthy controls. Toxoplasma IgG antibody was detected using enzyme-linked immunosorbent assay and histopathological assessment of liver biopsy METAVIR score was applied. Anti-T. gondii IgG antibodies were found in 32.8% of patients and in 22.2% of controls (P = 0.02). Toxoplasma seropositivity was significantly associated with lymphadenopathy, history of blood transfusion and reflex impairment in patients. Chronic hepatitis C virus (HCV) and chronic HCV-related cirrhosis groups compared to chronic HBV and chronic HBV-related cirrhosis groups expressed significantly higher prevalence of T. gondii seropositivity (odds ratio (OR) = 4; 95% confidence interval (CI): 1.3-12.6; P = 0.013, OR = 4.8; 95% CI: 1.5-14.9; P = 0.006, respectively). Within the chronic HCV group, T. gondii seropositivity significantly associated disease evolution as regards to METAVIR histopathological system for fibrosis and inflammation (OR = 19.4; 95% CI: 2.3-165.2; P = 0.0008, OR = 0.29; 95% CI: 0.1-0.8; P = 0.01, respectively). Albumin, international normalized ratio (INR) and platelets count were the laboratory parameters significantly altered in Toxoplasma-positive chronic HCV patients (P = 0.001, 0.03, 0.04, respectively). Child-Pugh scoring for cirrhosis in chronic HCV group placed the majority of seropositive patient in class C with significant statistical difference compared to Child A reference group (OR = 0.08; 95% CI: 0.01-0.5; P = 0.003). Toxoplasma seropositivity was high in patients with cirrhosis and associated higher grades of inflammation and necrosis signifying disease evolution, suggesting that cirrhotic patients may thus form a risk group for toxoplasmosis.
Background. Spontaneous bacterial peritonitis (SBP) is a fatal complication of liver cirrhosis wi... more Background. Spontaneous bacterial peritonitis (SBP) is a fatal complication of liver cirrhosis with high mortality rates. Objective: The aim of this study is to investigate the diagnostic utility of absolute neutrophil count (ANC) as a non-invasive marker for SBP diagnosis. Methods. Six hundred patients with cirrhotic ascites were included in the study. All patients underwent abdominal paracentesis and the ascitic fluid was processed for cell count and culture. Results. Absolute neutrophil count was significantly higher in SBP versus non-SBP and in culture positive SBP versus culture negative SBP. ANC at cutoff value > 2.804 has 84% sensitivity and 78% specificity for diagnosis of SBP with positive and negative predictive values (79.4% and 83.6 respectively). At a cut-off point > 5.6, ANC is capable of differentiating culture positive SBP from culture negative SBP cases with 62.07% sensitivity and 60.87 % specificity. Increased ANC, WBC, CRP, creatinine and decreased platelet ...
Hepatocellular carcinoma (HCC) is the most prevalent malignancy affecting developing populations ... more Hepatocellular carcinoma (HCC) is the most prevalent malignancy affecting developing populations Aflatoxin B1 (AFB1), an established carcinogen produced by certain strains of fungi, particularly Aspergillus parasiticus and Aspergillus flavus. The carcinogenic effects of AFB1 in hepatocellular carcinoma (HCC) are ascribed to AFB1-DNA adduct formation with p53 gene mutation. Objective: The present study aimed was to investigate the prevalence of single nucleotide polymorphism (SNP) in rs 25487 of X-ray cross complementing group 1 protein (XRCC1) in association with AFB1 in patients with hepatocellular carcinoma (HCC). Methodology: The study included 100 patients with HCC and 100 healthy control subjects. Blood samples were withdrawn from each subject and SNP in rs 25487 XRCC1 was estimated by real time polymerase chain reaction (PCR) and determination of blood levels of AFB1. Results: There was a dramatic increase in the level of aflatoxin B1 in patients (1.02±0.7ng/gm) compared to control subjects (0.8±0.6ng/gm), P=0.01. A significant increase in mutant genotypes CT and TT was found in HCC patients (43% and 7%, respectively) compared to control subjects (27% and 1%, respectively), with a notable increase in the dominant genotype CC in healthy controls (72%) compared to patients with HCC (50%), P=0.002. There was also a statistically significant increase in C allele (85.5%) in the control subjects compared to patients with HCC (71.5%) with a significant increase in T allele in patients (28.5%) compared to control subjects (14.5%), P=0.001. Furthermore, a significant difference in level of aflatoxin B1 was detected in patients with different genotypes of rs25487 XRCC1, with high levels of aflatoxin B1 found in patients with CT genotype (1.2±0.5), P=0.002. Conclusion: This study revealed the relationship of SNP of XRCC1 rs25487 with hepatocellular carcinoma, showing a significant association between this SNP and the increased level of aflatoxin B1 in patients with HCC.
It has been suggested that insulin resistance may play a role in pathogenesis of NASH, with hepat... more It has been suggested that insulin resistance may play a role in pathogenesis of NASH, with hepatocyte apoptosis believed to be the main factor involved in disease progression from simple steatosis to NASH. During apoptosis, cytokeratin-18 (CK-18) is cleaved by caspases and released into serum, a finding that was shown to correlate with the existence of inflammation and fibrosis in patients with NASH. The present study aims to differentiate patients with simple steatosis from those with NASH using CK-18 assessment both in liver tissue and in serum. The present study was conducted on two groups of patients, the first including 44 patients with simple steatosis and the second comprising 106 patients with steatohepatitis. Serum fasting insulin was measured and serum CK-18 was estimated. No significant differences were found between steatohepatitis patients and patients with simple steatosis regarding fasting insulin levels, or HOMA-IR index (P > 0.05 for each). Comparison of serum CK-18 levels between simple and advanced fatty liver patients showed significantly higher concentrations in patients with steatohepatitis than in patients with simple steatosis (P < 0.001). Serum level of CK-18 demonstrated a satisfactory relationship with all pathological variables that allowed differentiation between both entities of nonalcoholic fatty liver disease.
Background: Polymorphisms in the cytokine gene involving IFN gamma (IFN-γ) have been implicated i... more Background: Polymorphisms in the cytokine gene involving IFN gamma (IFN-γ) have been implicated in many infections including HCV. The aim of this study is to evaluate the association between IFN-γ polymorphism in three regions, (+2109A/G, +874A/T,-183G/T) and either chronicity or spontaneous viral clearance (SCV) in HCV infected patients. Materials and Methods: The study included 200 HCV-infected patients divided into Group I of 100 patients with spontaneous virus clearance (SVC) and Group II of 100 patients with persistent chronic hepatitis C infection (PI) who did not receive any therapy. These patients were subjected to history taking, full clinical examination and laboratory investigations included analysis of IFN-γ gene polymorphisms. Results: At locus +2109 of the IFN-γ gene, patients with A/A genotype had a significantly higher rate of spontaneous hepatitis C clearance while the G/G genotype was more prone to persistent infection. No statistically significant difference was found between both groups regarding loci +874 and-183 of the IFN-γ gene, but column proportion comparison using Bonferroni method at locus +874 revealed a higher proportion for T/A genotype in SVC group. Both haplotypes AAT and TGT were more susceptible to chronic HCV infection, as were heterozygote T/A at locus +874 and G/G genotype at locus +2109s. A/G and A/A genotypes at locus +2109, TLC at cut off value ≤7.15, and AST at cut off value ≤27.5 were considered independent predictors for development of SVC. Conclusions: Polymorphisms in the IFN-γ gene may play role in sequelae following HCV infection, possibly determining whether the virus will be cleared spontaneously or not. Polymorphisms in cytokine genes, including interferon gamma (IFN-γ), have been implicated in numerous infections 17,18 , autoimmune diseases, and chronic inflammatory conditions 18,19. Some polymorphisms reported in the regulatory and coding regions of IFN-γ gene include-183G/T,
The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated he... more The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated hemoglobin (HbA1c), and a number of routine biomarkers as noninvasive indicators of liver fibrosis in patients with chronic hepatitis C (CHC). One hundred patients with CHC were subjected to full medical history and examination, in addition to ultrasound‐guided liver biopsy and histopathological examination for assessment of liver fibrosis stage. GA and HbA1c values, GA/HbA1c ratio, liver function tests, complete blood count, and alpha fetoprotein (AFP) were determined. A novel noninvasive index, dubbed Fibrosis Prediction Score (FPS), was selected for predicting significant liver fibrosis based on total bilirubin, glycated albumin, platelet count, age, and AFP. A validation study for FPS was applied on archival data which include 66 diabetics' patients. The FPS had area under the curve (AUC) of 0.92 for classification of patients with significant fibrosis with 81% sensitivity and 95% specificity. The AUCs of FPS in predicting advanced fibrosis and cirrhosis were 0.86 and 0.82, respectively. Comparison of AST‐to‐platelet ratio index (APRI) and FIB‐4 with FPS indicated increased sensitivity and specificity of FPS over APRI and FIB4 in both significant and advanced fibrosis. FPS has a good sensitivity and specificity for prediction of significant and advanced liver fibrosis in patients with CHC.
Limited data exists on the role of Th17 cells in chronic HCV infected patients, particularly with... more Limited data exists on the role of Th17 cells in chronic HCV infected patients, particularly with regard to hepatic inflammation and fibrosis. We aimed to investigate the relationship between circulating and intrahepatic frequency of Th17 cells and IL-17 serum level and degrees of hepatic inflammation and fibrosis in chronic HCV patients, as well as to evaluate the effect of successful anti-viral therapy on these parameters. This nested longitudinal case control study included 30 treatment-naïve chronic HCV patients and 20 healthy individuals as control. All patients were investigated for circulating Th17 cell percentage (flow cytometry) and intrahepatic Th17 cell percentage (immunohistochemistry) and serum IL-17 (ELISA) at baseline and at week 12 after discontinuation of therapy. Circulating and intrahepatic Th17 cell percentage and serum IL17 level were found to be significantly higher in chronic HCV patients when compared with controls, with significant correlation with Metavir a...
Afro-Egyptian Journal of Infectious and Endemic Diseases, 2014
Background and study aim: Spontaneous bacterial peritonitis (SBP) is an important cause of morbid... more Background and study aim: Spontaneous bacterial peritonitis (SBP) is an important cause of morbidity and mortality in cirrhotic patients with ascites. The diagnosis of SBP is based on PMN leukocyte cell count exceeding 250/μL in ascitic fluid. However, this procedure is time consuming as well as subjective. C-reactive protein (CRP) has been reported to be a reliable predictor of SBP and an index of therapeutic effectiveness in adults. Ascitic fluid calprotectin reliably predicts PMN count >250/μL, which may prove useful in the diagnosis of SBP. This work was planned aiming to evaluate both ascitic fluid calprotectin and serum CRP as accurate diagnostic laboratory markers for detecting SBP Patients and Methods: From 140 patients; only 124 patients with ascites were included in this study. They were divided into SBP group including 70 patients (49 males and 21 females) and non-SBP group of 54 patients (25 males and 29 females). Serum CRP was determined by latex agglutination and ascitic fluid calprotectin was measured using an enzyme-linked immunosorbent assay. Results: Ascitic fluid calprotectin and serum CRP were significantly higher in SBP patients in comparison with the non-SBP group (754.67 ±256.06 vs. 280.77 ±230.97 and 62.4 ±28.39 vs. 9.81 ±8.98) respectively. In addition, both were positively correlated with ascitic fluid proteins and PMN count as well as with each other. At a cutoff value of 270 mg/dl, ascitic fluid calprotectin had 86% specificity and 97.5% sensitivity for detecting SBP [Area under the receiver operating characteristics curve (AUC) = 0.924 with negative and positive predictive values (NPV, PPV) for ascitic calprotectin 96% and 69% respectively. Conclusion: Ascitic fluid calprotectin and serum CRP may be used as accurate and reliable markers for the diagnosis of SBP.
ABSTRACT Background: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are lin... more ABSTRACT Background: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. Materials & methods: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. Results: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). Conclusion: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.
Background:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into... more Background:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into various subtypes. Post-infection IBS may be attributed to the release of cytolethal distending toxin B (CdtB), which cross-reacts with the adhesion protein vinculin responsible for normal intestinal contractility.Objective:This study aims to identify anti-CdtB and anti-vinculin levels in IBS patients compared to healthy control.Subjects and methods:This retrospective case-control study was conducted on 100 subjects with IBS, as determined by a questionnaire based on Rome III criteria, recruited from the outpatient clinics of the Tropical Medicine at Mansoura University Hospital from January 2019 to January 2020.Results:Anti-vinculin and anti-CdtB levels were significantly elevated in patients with IBS (1.58±0.496, 2.47±0.60) when compared to control subjects (1.13±0.249ng/ml, 2.1±0.24 ng/ml), respectively with P=0.001 for both. Anti-vinculin level was significantly higher in the IBS-D...
Background The circulatory system is the main mechanism for transmission of the Hepatitis C Virus... more Background The circulatory system is the main mechanism for transmission of the Hepatitis C Virus (HCV). A new class of HCV infections, Occult HCV infection (OCI), is defined as the presence of HCV-RNA in hepatocytes with the absence of HCV in the serum/plasma utilizing current laboratory assays. Different groups have reported the prevalence of OCI; however, its associated risk factors have not been established. In Mexico, there are no reports about OCI, so the objective of our study was to determine the prevalence of OCI in total blood donors in Mexico City, as well as its associated risk factors. Methods Blood donors that were considered eligible for donation, according to NOM 253-SSA1-2012, were randomly selected. Demographic data was collected from 1,037 donors. Plasma and peripheral blood mononuclear cells were assessed for HCV-RNA. The presence of HCV-RNA was determined by nested PCR for the 5'-UTR region. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95%CI) to determine the level of association. Results The prevalence of OCI was 3.4% among blood donors. Homosexual relationships (OR = 5.52, 95%CI: 1.53-19.92, p<0.05) and acupuncture (OR = 3.56, 95%CI: 1.41-8.98, p<0.05) were significantly associated with OCI. Conclusion There is a significant presence of OCI in the blood donor population in Mexico City. The main risk factors for OCI transmission are homosexual relationships and acupuncture. This
Background: There is a growing literature providing evidence on the importance of non-cognitive s... more Background: There is a growing literature providing evidence on the importance of non-cognitive skills for life outcomes. However, to date there is limited evidence on the gains from incorporating such measures into large-scale competence surveys. Methods: We investigate the relationship between personality traits and eight important life outcomes: educational attainment, labour market participation, employability, wages, job satisfaction, health, trust and life satisfaction measured in the Polish followup study to PIAAC. The study assesses two short scales: the Big Five Inventory and Grit. First, we compare explanatory power of personality traits to that of cognitive skills measured by PIAAC. Second, an incremental validity of Grit after controlling for the Big Five dimensions is assessed. Results: The analyses show that differences in personality traits are important in explaining differences in life outcomes. Educational attainment is more strongly related to cognitive skills, while for wages, the explanatory power of personality and cognitive skills is similar. For most of the subjective outcomes, the Big Five traits outperform cognitive skills in predictive power. Conscientiousness is positively related to most of the outcomes analysed while Neuroticism has a negative relationship. After controlling for sociodemographic characteristics and cognitive skills, Big Five traits add explanatory power to all models except for employability. Grit explains some additional variation in educational attainment and in a number of subjective outcomes: health, trust, job and life satisfaction, even after adjusting for the effects of cognitive skills and Big Five traits. Conclusions: Given the potential benefits and relatively small burden on respondents in terms of required time it seems advisable to incorporate measures of personality traits into competence surveys as they contribute to explaining the variability in policyrelevant outcomes. The use of the Big Five Inventory seems preferable to Grit when a broad range of life outcomes is of interest, as the former covers multiple aspects of personality. However, using both scales offers an improvement in explanatory power.
Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deat... more Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) may be considered as potential markers for HCC. The aim of this study is to evaluate the diagnostic and prognostic value of lncRNA ZFAS1 in HCC patients. Materials and methods: The current study included 100 cirrhotic patients with HCC, in addition to 100 cirrhotic patients without HCC as control group. RNA extraction was performed for quantification of ZFAS1 expression by real-time quantitative polymerase chain reaction. Results: ZFAS1 gene expression was significantly elevated in HCC group of patients compared to non-HCC group. The ability to distinguish HCC from cirrhotic controls by ZFAS1 was determined to be 1.00 (95% CI:1.00-1.00). Comparison between the diagnostic performance of ZFAS1 and AFP in differentiating HCC on top of cirrhosis from cirrhosis without HCC showed that, at cutoff values ≥-4.65 ZFAS1 gene had 100 % specificity and 99% sensitivity while, AFP at cutoff value ≥ 9.4 ng/ml had 100 % specificity and 76% sensitivity. Comparison of AUC for the two parameters demonstrated a significantly higher AUC for ZFAS1 than for AFP (Difference = 0.168, P <0.001). No statistically significant correlation between ZFAS1gene and any HCC characteristic however, a statistically significant correlation between AFP level and sex , BCLC staging was found. Conclusions: lncRNA ZFAS1 is a good diagnostic marker for HCC in cirrhotic patients with high sensitivity and specificity value, however ZFAS1has no prognostic importance in patients with HCC.s
Mansoura Journal of Forensic Medicine and Clinical Toxicology
Aflatoxin B1, Hepatocellular carcinoma, Cirrhosis, This study aimed to assess the role of micro-r... more Aflatoxin B1, Hepatocellular carcinoma, Cirrhosis, This study aimed to assess the role of micro-ribonucleic acid-24 (microRNA-24) expression in patients with cirrhosis and hepatocellular carcinoma (HCC) who have experienced high levels of aflatoxin B1 (AFB1) exposure. Fifty HCC and 24 hepatic cirrhosis patients, in addition to 20 healthy control subjects were included in this study. Aflatoxin B1 was measured by enzyme-linked immunosorbent assay (ELISA) and microRNA-24 was detected using real-time polymerase chain reaction (real-time PCR). Both aflatoxin B1 levels and microRNA-24 expression were found to be significantly increased in all patient groups in comparison to controls, more so in the HCC than cirrhotic group (p<0.0001). A highly significant correlation was detected between levels of AFB1 and amount of microRNA-24 expressed in both patient groups relative to their control counterparts (p<0.0001). Receiver Operating Characteristic (ROC) curve performed to evaluate the ability of microRNA-24 to differentiate between HCC and cirrhosis showed that it had sensitivity of 80% and specificity of 63% at cutoff 1.3, which was highly significant (p<0.0001). Increased aflatoxin B1 levels detected in patients with cirrhosis and HCC further support previous studies evaluating the level of exposure of the Egyptian population to this carcinogen and support the critical role of aflatoxin B1 in the appearance of HCC. In addition, microRNA-24 expression levels demonstrated in both cirrhosis and HCC might be valuable for use as a noninvasive diagnostic tool for diagnosis of HCC.
To build a diagnostic non-invasive model for screening of large varices in cirrhotic hepatitis C ... more To build a diagnostic non-invasive model for screening of large varices in cirrhotic hepatitis C virus (HCV) patients.
European journal of gastroenterology & hepatology, Jan 6, 2016
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality among men world... more Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, which may be involved in the tumorigenesis of HCC. We aimed to determine whether serotonin is a dependable marker for the diagnosis of HCC in cirrhotic patients in comparison with α-fetoprotein protein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II). Serum serotonin, AFP, and PIVKA-II were measured in 262 patients with chronic hepatitis C (CHC): 82 cirrhotic patients with HCC (group I), 80 cirrhotic patients without HCC (group II), and 100 CHC-infected patients without cirrhosis (group III); in addition, 60 healthy controls were studied (group IV). AFP showed significant statistical differences among the groups studied (P<0.001). PIVKA-II and serotonin levels showed no statistically significant differences between the patients with CHC group and the healthy controls (P1=0.614 and P1=0.13, respectively), whereas their levels were st...
Background/Aims: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a polymorph... more Background/Aims: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a polymorphonuclear leukocytes (PMNs) exceeding 250/μL in ascitic fluid. The aim of the study was to evaluate serum procalcitonin and ascitic fluid calprotectin as accurate diagnostic markers for detecting SBP. Methods: Seventy-nine patients with cirrhotic ascites were included. They were divided into a SBP group, including 52 patients, and a non-SBP group of 27 patients. Serum procalcitonin, ascitic calprotectin, and serum and ascitic levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured using an enzyme-linked immunosorbent assay. Results: Serum procalcitonin and ascitic calprotectin were significantly higher in SBP patients than in non-SBP patients. Significant increases in both serum and ascitic levels of TNF-α and IL-6 were observed in SBP patients versus non-SBP patients. At a cutoff value of 0.94 ng/mL, serum procalcitonin had 94.3% sensitivity and 91.8% specificity for detecting SBP. In addition, at a cutoff value of 445 ng/mL, ascitic calprotectin had 95.4% sensitivity and 85.2% specificity for detecting SBP. Both were positively correlated with ascitic fluid proteins, PMN count, TNF-α, and IL-6. Conclusions: According to our findings, determination of serum procalcitonin levels and ascitic calprotectin appears to provide satisfactory diagnostic markers for the diagnosis of SBP. (Gut Liver 2016;10:624-631)
To document Toxoplasma gondii (T. gondii) antibody status in patients with liver disease, blood s... more To document Toxoplasma gondii (T. gondii) antibody status in patients with liver disease, blood samples were taken from 180 hepatic patients and 180 healthy controls. Toxoplasma IgG antibody was detected using enzyme-linked immunosorbent assay and histopathological assessment of liver biopsy METAVIR score was applied. Anti-T. gondii IgG antibodies were found in 32.8% of patients and in 22.2% of controls (P = 0.02). Toxoplasma seropositivity was significantly associated with lymphadenopathy, history of blood transfusion and reflex impairment in patients. Chronic hepatitis C virus (HCV) and chronic HCV-related cirrhosis groups compared to chronic HBV and chronic HBV-related cirrhosis groups expressed significantly higher prevalence of T. gondii seropositivity (odds ratio (OR) = 4; 95% confidence interval (CI): 1.3-12.6; P = 0.013, OR = 4.8; 95% CI: 1.5-14.9; P = 0.006, respectively). Within the chronic HCV group, T. gondii seropositivity significantly associated disease evolution as regards to METAVIR histopathological system for fibrosis and inflammation (OR = 19.4; 95% CI: 2.3-165.2; P = 0.0008, OR = 0.29; 95% CI: 0.1-0.8; P = 0.01, respectively). Albumin, international normalized ratio (INR) and platelets count were the laboratory parameters significantly altered in Toxoplasma-positive chronic HCV patients (P = 0.001, 0.03, 0.04, respectively). Child-Pugh scoring for cirrhosis in chronic HCV group placed the majority of seropositive patient in class C with significant statistical difference compared to Child A reference group (OR = 0.08; 95% CI: 0.01-0.5; P = 0.003). Toxoplasma seropositivity was high in patients with cirrhosis and associated higher grades of inflammation and necrosis signifying disease evolution, suggesting that cirrhotic patients may thus form a risk group for toxoplasmosis.
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