Raghda E. Farag

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.

Clinical significance of antibody to hepatitis B core antigen in multitransfused hemodialysis patients.

Background: In spite of the progress made in the prevention of transfusion transmitted infections over the last few years, transmission of HBV infection through transfusion of HBsAg negative blood has been documented. Objectives: To assess the frequency and clinical significance of anti-HBc in multitransfused hemodialysis patients. Materials and Methods: One hundred and forty-three hemodialysis patients who had been receiving blood regularly with an average of 39.4 ± 7.579 months on hemodialysis were enrolled in this study. HBV markers (HBsAg, anti-HBc, anti-HBs) were measured in these patients and in 100 healthy controls by the ELISA technique. The following data were obtained for all patients: socio demographic data, number of blood transfusions and some laboratory investigations. Results: In our patients, anti-HBc was positive in 9%, anti HBs in 7%, coexistant HbsAg/anti-HBc in 2.8% and anti HBc/anti HBs in 18.9%, meanwhile no patients were positive for HBsAg alone. In patients with only positive anti-HBc, the levels of anti-HBc were significantly related to abnormal results of liver function. In patients with positive anti-HBs/anti-HBc (n = 27), 18 patients had abnormal liver function, and 9 patients had normal liver function with no significant difference between them. Conclusions: This study suggests that hepatitis B prevalence in our multitransfused hemodialysis patients is far in excess of that anticipated on the basis of HBsAg prevalence. Absence of HBsAg in the blood of hemodialyzed patients may not be sufficient to ensure lack of circulating HBV, and isolated positivity of anti-HBc may be a possible indicator of active hepatitis B infection.

Toxoplasma gondii infection among chronic hepatitis C patients: a case-control study.

OBJECTIVE To determine the detection rate of anti-Toxoplasma gondii (T. gondii) IgG and IgM in chronic HCV patients attending the Department of Tropical Medicine Mansoura University hospital in Egypt. METHODS This study included 120 adult chronic HCV patients, 81 decompensate cirrhosis (late-stage) and 39 chronic HCV non cirrhotic patients (early-stage) and 40 healthy blood donors as controls. Serum samples were examined for anti-Toxoplasma IgM and anti-Toxoplasma IgG antibodies by ELISA. Real-time RT-polymerase chain reaction assay was done for quantitation of hepatitis C virus. RESULTS Anti-T. gondii IgG antibodies were detected in 75 (92.6%) of 81 late-stage cirrhotic patients, 30 (76.9%) of the 39 chronic HCV non cirrhotic patients (early-stage) and in 6 (15%) of 40 controls with statistically significant difference (P<0.001). Anti-T. gondii IgM antibodies were found in 11 (13.6%) in late stage patients, 5 (12.8%) in early stage and in 3 (7.5%) of controls with no statistical significant difference (P=0.610). There was no correlation between stage of fibrosis and IgM or IgG antibodies positivity in our studied groups (P=0.526). High IgG levels significantly correlated with high viral load (P=0.026). CONCLUSIONS Our findings suggest that the serious opportunistic T. gondii infection represent a potential significant risk for chronic HCV patients. So, toxoplasmosis should be considered in their investigations and follow-up.

Colorectal schistosomiasis: Is it still endemic in delta Egypt, early in the third millennium?

Background: Several governmental efforts have been exerted toward controlling schistosomiasis during the last decades in Egypt. This work was designed to study the prevalence of colorectal schistosomiasis in patients with different gastrointestinal symptoms. Materials and Methods: Patients presented to the gastroenterology unit with different gastrointestinal symptoms were endoscopically examined, where three to six tiny biopsies were taken from those with visible, suspected schistosomal lesions for histopathological examination and two additional rectal biopsies were taken from the apparently normal colonic mucosa. Form each patient, at least three stool samples were examined by the formal-ether concentration method for schistosoma ova. Results: Colonic abnormalities were detected in 510 out of 984 patients presented with different gut symptoms. Schistosoma mansoni was detected in 205 patients (180 males, 25 females) with an age range (18-65years). Six patients only had schistosomal polyps and excised successfully by snare polypectomy. The squash technique established the diagnosis of schistosomiasis in all endoscopically normal 118 (50.75%) cases by demonstrating the schistosomiasis ova and their associated histopathological findings showed no or minimal reaction in 96 (46.82%) cases and variable degrees of submucosal granulomata in the remaining cases. Stool examination detected the schistosomiasis ova in 25 (9.83%) patients only of the biopsy-positive cases. Conclusions: Our data revealed that despite governmental efforts, the prevalence of colorectal schistosomiasis (20.83%) is significant among patients with gut symptoms. Gaps in health care services should be detected and filled appropriately.

A new cutoff value for fecal calprotectin level in differentiating functional from organic causes of chronic diarrhea

Background The gold standard to establish inflammatory bowel disease diagnosis remains in the hands of endoscopists and pathologists. A challenge is thus to distinguish symptoms of inflammatory bowel disease from that of irritable bowel syndrome. Aim of this work The aim of this study was to evaluate the clinical usefulness of fecal calprotectin level as a noninvasive marker in order to distinguish patients with diarrhea in need of intensified follow-up from those who do not need further workup. Patients and methods From a total of 150 patients presented with chronic diarrhea with or without bleeding per-rectum in the outpatient clinic of Specialized Medical Hospital, only 60 were involved in this study. Stool analysis and culture were carried out. Measurement of fecal calprotectin was done using the ELISA kit. Inflammatory biomarkers, such as erythrocyte sedimentation rate and C-reactive protein and perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA), were tested. Full colonoscopy with histopathological examination was performed. Results The frequencies of diseases on the basis of diagnostic colonoscopy and pathological examination were as follows: 19 patients with irritable bowel syndrome (31.67%), 41 patients with nonorganic gastrointestinal (GIT) disease versus organic GIT diseases (68.33%), 32 patients with ulcerative colitis (53.33%), two patients with Crohn′s disease (3.33%), two patients with diverticulitis (3.33%), two patients with eosinophilic gastroenteritis (3.33%), and two patients with cancer colon (3.33%). There was a remarkable difference between organic GIT diseases versus nonorganic groups as regard fecal level of calprotectin (P < 0.001). Fecal calprotectin value of at least 350 μg/g with a receiver operating characteristic value of 0.931 [95% confidence interval (CI) 0.864-0.971] was diagnostic of ulcerative colitis with a sensitivity of 81.82% (95% CI 64.5-93), specificity of 85.19% (95% CI 66.3-95.8), positive predictive value of 86.32%, and negative predictive value of 80.39%. Conclusion Calprotectin, a fecal marker, is helpful as an adjunctive tool in overall evaluation of patients with nonspecific symptoms and as a diagnostic tool in those with inflammatory disease. It is less invasive than colonoscopy and can help to guide management in a more cost-effective manner.

Occult hepatitis C infection: the prevalence and profile of its immunoregulatory cytokines

Background/aim The immunopathogenesis of occult hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with proinflammatory and anti-inflammatory activity. This work aimed at studying the production of serum Th1 and Th2 cytokines in patients with occult HCV infection. Methods Serum levels of cytokines Th1 [interleukin-2 (IL-2) and interferon-&ggr; (IFN-&ggr;)] and Th2 (IL-4) were measured in 27 patients with occult HCV infection and in 28 patients with chronic hepatitis C infection. Results The levels of IL-2 and IFN-&ggr; were highly significantly increased in patients with chronic HCV infection (P<0.001). In contrast, IL-4 showed a highly significant increase in occult HCV infection (P<0.001). Significant increases were noted in chronic HCV infection with respect to bilirubin (P<0.001), alanine transaminase (P=0.009), aspartate transaminase (P=0.013) and alfa-fetoprotein (P<0.001) levels, whereas the level of serum albumin was significantly higher in occult HCV infection (P<0.001). The degree of necroinflammation (P<0.001), fibrosis (P<0.001) and cirrhosis (P=0.03) was significantly increased during chronic HCV infection. Conclusion Our data revealed a high prevalence of occult HCV infection (25%) in patients with unexplained persistently abnormal liver function test results. These patients exhibited a distinct immunoregulatory cytokine pattern, favouring viral persistence and explaining the less-aggressive course of this disease entity compared with chronic HCV infection.

Association between Toll-Like Receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and Chronic HCV

ABSTRACT Background: Inconsistent results were reported on the association of TLRs polymorphisms with the risk of HCV infection and HCV-related diseases. Objective: to assess the relation between TLR3 rs3775290, TLR7 rs17900 and TLR9 rs352140 SNPs and chronic HCV in the Egyptian cohort and to study their relation to interferon response. Methods: TLR3 rs3775290, TLR7 rs179008 and TLR9 rs352140 gene polymorphisms were typed by RFLP for 100 patients with chronic HCV and 25 with HCC in addition to 100 healthy controls. Results: A significant higher frequency has been found for the CT genotype of TLR3 rs3775290 in chronic HCV infection (p < 0.001) and CC genotype and the combined genotype CC-AT-GA ♀ in controls (p < 0.001). Non-significant associations have been found for studied SNPs and HCC and response to interferon and also the viral load or the degree of fibrosis, however, the higher HCV viral load and the higher grade of fibrosis were associated with treatment failure (p < 0.001). Conclusion: The heterozygous CT genotype of TLR3 rs3775290 may be a susceptibility risk factor for chronic HCV infection and the homozygous CC and the combined CC-AT-GA ♀ genotypes may be protective. The HCV viral load and the grades of liver fibrosis could be considered a risk factor for interferon treatment failure. It seems that the studied SNPs have no role in HCC development or failure of treatment. However, the small sample size is a limiting factor of the present study when interpreting the negative associations and that the current used cohort does not permit such conclusion. Abbreviations: cHCV=chronic Hepatitis C virus, HCC=hepatocellular carcinoma, TLR=Toll like Receptor, RFLP=Restriction Fragment Length Polymorphism, SNP=Single Nucleotide Polymorphism, IFN-α= interferon alpha

Assessment of auditory functions in chronic hepatitis C patients treated by sofosbuvir

Objective Evaluating the auditory function in patients with chronic hepatitis C treated with sofosbuvir and ribavirin. Methods This study involved 80 patients with chronic hepatitis C who agreed to receive sofosbuvir and ribavirin. All participants were subjected to baseline otological and audiological assessment just before treatment. The audiological assessment included standard pure tone audiometry, extended high-frequency audiometry, immitancemetry and otoacoustic emissions (OAEs) (transient and distortion product). According to baseline hearing threshold measurements, the study population was divided into 2 groups. Group 1 included 42 patients with normal hearing sensitivity (250–8000 Hz), and Group 2 included 38 patients with sensorineural hearing loss. After 24 weeks of therapy, otological and audiological assessments were repeated and compared between the two groups and before and after therapy. Results Post-treatment hearing threshold evaluation showed no significant difference from pretreatment evaluation at all tested frequencies. There was no statistically significant difference between pre and post-treatment otoacoustic emissions results. Conclusion Therapy with sofosbuvir and ribavirin in chronic hepatitis C has no noticeable effects on cochlear functions.

Do we need to screen for de-novo diabetes mellitus in chronic hepatitis C patients after a sustained virological response?

Background and aim There are millions of chronic hepatitis C (CHC) virus-infected patients who have been treated with a combination therapy (interferon and ribavirin) and have achieved a virological response (SVR) worldwide. The aim of this study is to evaluate the risk factors for de-novo diabetes mellitus in CHC patients treated with combination therapy (interferon and ribavirin) and have achieved an SVR. Patients and methods A total of 214 nondiabetic CHC patients with SVR and baseline homeostasis model assessment (HOMA) less than or equal to 2 were divided into group A, which included 108 patients with a BMI less than 25, and group B, which included 106 patients with a BMI of at least 25 and less than 30. HOMA insulin resistance (IR) and BMI were measured at the baseline, at achievement of an SVR, and 1 year after achievement of an SVR. Leptin levels were assessed at baseline and 1 year after achievement of an SVR in patients with increased BMI. Results One year after SVR, 36 (33.33%) patients from group A developed increasing BMI with no significant changes in HOMA versus that at SVR (P=0.53), but showed a significant reduction versus baseline HOMA (P=0.02). In group B, 68 (64.1%) patients showed increased BMI of at least 25, with a significant increase in HOMA versus that at SVR (P=0.02), and with no significant reduction versus baseline HOMA (P=0.44). In group B, serum leptin showed a significant reduction 12 months after achievement of an SVR versus baseline in patients with increased BMI. Six patients from group B with increased BMI after 1 year developed de-novo IR and type two diabetes mellitus. Conclusion In nondiabetic CHC patients with SVR and baseline BMI of at least 25, the post-SVR increase in BMI predisposed to an increase in HOMA-IR and could be considered a predisposing factor for diabetes mellitus.