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Recently, the active management of the third stage of labor hasbecome a routine practice. In this study we compared two different ecobolics which were oxytocin and methyl ergometrinethrough intra-umbilical route. The method: the trial divided theincluded pregnant full term (>37 weeks) women in two groupsrandomly; one for 0.2 mg methyl ergometrine and the second 10units oxytocin. The outcomes were on the short term; estimatedblood loss (EBL), the need to add another ecobolic, vomiting,blood pressure changes and the duration of the third stage, andthe long-term outcomes were hemoglobin levels and the needfor surgical or medical uterine evacuation. The results: the meanblood loss was 155± 50.45ml and 167± 45.76 in the methyl ergometrine and the oxytocin groups respectively. Three cases inthe oxytocin group (3%) required additional methyl ergometrinewhile in the ergometrine group only one case was given an additional oxytocin (1%). No vomiting was reported in both groupsand there were trivial changes in blood pressure. In the oxytocin group, the third stage duration was average 3.03± 1.02 minin comparison to 2.98± 1.54min in the ergometrine group. Neither did those cases who were injected methyl ergometrine havesignificant changes in the hemoglobin levels nor did they needuterine evacuation. However, only one case in the oxytocin siderequired blood transfusion due to uterine atony. Conclusion: intra-umbilical methyl ergometrine should be considered as an effective safe ecobolic in the third stage of labor. more...

Purpose: There is debatable data regarding the addition of azithromycin to the routine antibiotic prophylaxis of post-cesarean section (CS)infection. In this work, we tried to evaluate its potential benefit to protect against both post-cesarean maternal and fetalinfections.Methods: The study included 230 women who were intended to haveselective CS at Mansoura university hospital. They were randomlysubdivided into115 women that received azithromycin plus standardcephalosporin and another115 women that received standard cephalosporin alone. The main outcome is evaluation of post-cesarean sectioninfection as endometritis, wound sepsis, etc… across the puerperal period. Results: In comparison between the test group and the control group,there was significant reduction of re-admission during puerperium(0%vs 6.5%, p=0.01). Endometritis manifestations were significantly reduced, including: puerperal Fever >38OC (4.3% versus 15.2%), uterine tenderness (3.2% versus 11.9%), abdominal pain (1.1% versus14.1%), offensive vaginal discharge (2.1% versus 13%) and purulentdrainage from uterus (2.1% versus 9.8%). Wound infection manifestations were significantly reduced, including; erythema around incision(2.1%versus 8.7), induration around incision (3.2 versus 12%) and purulent discharge from incision site (1.1% versus 9.8%). Also, the needfor further antibiotic during puerperium was significantly reduced(3.2% versus 11.9%). There was no significant difference between the2 groups regarding neonatal outcomes.Conclusion: Azithromycin plus the standard cephalosporin administered to women in selective CS reduces maternal infections and maternal episodes of fever, with no clear benefit on the neonatal outcome more...

Objective: To assess the role of vitamin D deficiency and early pregnancy loss.Patient and Method: A nested case control study conducted in outpatient antenatal care clinic under supervision of Ain Shams University Maternity hospital from the period of March 2020 to June2020. Pregnant ladies in the first trimester were screened for eligibility criteria.Blood samples were taken from the participants at thetime of presentation. All participants were followed till the end of thefirst trimester to report cases of miscarriage. Vitamin d was assessedfor the 40 women who suffered from miscarriage (cases) and for 40selected controls.The primary outcome was the relation between vitamin d level and early pregnancy loss. Secondary outcome was therelation between vitamin d deficiency and obesity.Results: Our findings showed that the miscarriage groupwas significantly olderthan control group as p (42.5%) had 25(OH)D deficiency while (40.0%)&(17.5%) of caseshad either 25(OH)D insufficiencyor sufficiency which significantlydifferent than control group (p=0.049).25(OH)D ≤24.5 (ng/mL) wasa significant factor that increased the likelihood of first-trimestricmiscarriage with sensitivity 80%.No significant differences according to BMI grades regarding 25(OH)D grades.Conclusion: Vitamin d deficiency is one of modifiable risk factors forfirst trimestric abortion. . Preconceptional vitamin D supplementationis an easy method for decreasing incidence of early pregnancy loss. more...

Aim: To determine the optimum time for endometrial scratching in patients with unexplained primary infertility undergoing ICSI-ET cycles after one or more implantation failure. Methods: A randomized clinical trial wasconducted at fertility care unit, Mansoura University Hospital and 2 private fertility centers, Egypt, fromNovember 2016 tillJune 2018. Eligible participants [142] had unexplained primary infertility, were prepared and sched- uled to obligate for ICSIcycles. Patients were randomly allocated into two equal groups using computer-generated tables and sealed opaque envelopes. Endometrial scratching was done either just af- ter oocyte retrieval in (group 1) or mid-luteal in the cycle before induction (group 2). Patients, investigators, and data analysts were not masked to group assignment. The primary outcome measure was implantation rate while the clinical pregnancy rate was settled as the secondary outcome measure. Results: one hundred forty two clients were included (71 in each group). Baseline characteristics did not differ between both groups as regard the age, BMI, duration of infertility and basic laboratory inves- tigations (p>0.05). The mean estimated day of triggering (14.2 ± 2.1 in G1 vs 13.6 ± 2.2 in G2) together with the mean follicular size (19.3 ± 0.8 in G1 vs 18.5 ± 1.8 in G2) showed also no statistical significance (p values 0.690 and 0.751 respectively). Again, the mean estimated number of ova retrieved (7.4+ 2.1 in G1 vs 7.1+ 1.3 in G2) and zy- gote transferred (2 in each group) presented no significant differences together with the chemical pregnancy rates (54 in G1 vs 52 in G2, p>0.05). On the other hand, IR and CPR are found significantly high- er in group 1 compared to group 2, (IR 53.5% vs, 40.8%; whilst CPR 49.3% vs 35.2%, p more...

Mohamed Ibrahem Eid,1 Mohamed Sayed Abdelhafez,1 Waleed El-refaie,2 Ahmed A El-Zayadi,1 Khaled Samir,1 Mahmoud Mohamed Abdelrazik,1 Mahmoud Thabet,1 Alaa Wageh,1 Emad Ahmed Fyala,1 Yasser Abdeldayem,1 Ahmed Badawy1 1Department of Obstetrics and Gynecology, Mansoura University, Mansoura, Egypt; 2Department of Obstetrics and Gynecology, Port Said University, Port Said, Egypt Objective: We aimed to evaluate the effect of different timing of initiation of low-molecular- weight heparin (LMWH) administration on the pregnancy outcomes in women with antiphospholipid syndrome (APS). Materials and methods: A randomized controlled study was conducted on women with obstetrical APS. All participants were randomly divided at documentation of positive pregnancy test into two groups; early initiation group in which LMWH therapy was started once positive pregnancy test was established (in the fifth week of gestation), and later initiation group in which LMWH therapy was started after sonographic confirmation of fetal cardiac pulsation (in the seventh week of gestation). In both groups, LMWH (enoxaparin) was given at a dose of 40 mg/day subcutaneously and the therapy continued until end of pregnancy. The primary outcome measure was ongoing pregnancy rate and the secondary outcome measures were fetal loss, live birth rate, preterm labor before 34 weeks of gestation, intrauterine growth restriction (IUGR), and congenital fetal malformations. Results: Ninety-four women (48 in the early initiation group and 46 in the later initiation group) were subjected to final analysis. The ongoing pregnancy rate was significantly higher in the early initiation group than in the later initiation group (81.2% vs 60.9%; P=0.040). However, both groups were similar in the incidences of fetal loss, preterm labor before 34 weeks of gestation, and IUGR, and live birth rate. No recorded congenital fetal malformations in both groups. Conclusion: Early administration of LMWH for pregnant women with obstetrical APS reduces early pregnancy loss, but does not affect the incidence of late obstetrical complications. Keywords: APS, LMWH, fetal loss more...

Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1β, and IL-6 have crucial role in the pathogenesis of endometriosis. In this study, we investigated the immune-modulatory role of humanized anti-IL-6 receptor monoclonal antibodies in the treatment of endometriosis. This is a prospective, randomized, controlled, blinded study in which Sprague Dawley rats were used as animal model of endometriosis. Animals were randomly divided into two groups, a test group which received tocilizumab (Actemra; Roche, Switzerland) and a control group which received saline. Afterwards, a comparison was done between the eutopic and ectopic endometrium that was excised from both groups, histopathologically and immune-histochemically. Histopathologic assessment and immune-histochemical staining were performed using antibodies against IL-6. Tocilizumab significantly suppressed the volume of endometriotic lesions compared with non-treated rats (P = 0.006) and atrophied the ectopic endometrial-like epithelium (in 42.8% of treated rats vs 0% in the control group). Tocilizumab also decreased the anti-IL-6 receptor immune-histochemical staining intensity in ectopic endometrium (from non to +++ in the test group vs ++ or more in the control group), with no apparent difference in the eutopic one reflecting the down-regulation of IL-6-producing cells in ectopic endometriotic lesions. In rats with induced endometriosis, anti-IL-6 receptor monoclonal antibodies could offer a new horizon of usage of this immune-modulatory biologic drug, used in other autoimmune diseases, in treatment of endometriosis. more...

Introduction The incidence of caesarean scar pregnancy (CSP) and cervical pregnancy (CP) has increased significantly in recent years. The related hemorrhage can be lethal and often needs hysterectomy. This study aims to assess the technical and clinical results of uterine artery embolization (UAE) combined with intra-arterial methotrexate (MTX) infusion for CSP and CP. Methods A retrospective study was conducted for 11 patients (age range from 25–40 years, mean; 31.8 y) with CSP (7/11) and CP (4/11). The diagnosis was confirmed by elevated b-hCG levels (mean 31.245 mIU/mL) with sonography and/or magnetic resonance imaging. They were treated with UAE using particulate embolic material. In all patients, the infusion of MTX (50 mg/m2) was performed before UAE. Follow-up periods after UAE ranged between 6-24 months included weekly sonography and b-hCG level assessment. A literature review was performed using standard online search tools. Results In 10 patients, UAE controlled active vaginal bleeding and reduced post-procedural b-hCG levels significantly by the second week. One patient presented with persistent elevated b-hCG level and vaginal rebleeding. The rebleeding was successfully controlled by second UAE procedure. The ectopic pregnancies were resolved, and the uterus was preserved in all patients. No major complications were detected. Normal menses resumed within 2 months after UAE. Two patients had subsequent natural successful intrauterine pregnancies. Conclusion UAE combined with intra-arterial MTX infusion resulted in resolution of ectopic pregnancies with control of hemorrhage and without hysterectomy in this small group of patients. more...

The purpose of this study is to compare the early outcome of tricuspid valve repair using prosthetic ring annuloplasty versus suture annuloplasty. Methods: In the period between March 2016 and September 2017, 40 patients with severe functional tricuspid regurgitation (TR) secondary to rheumatic mitral with or without aortic valve pathology divided into two equal groups underwent open heart surgery at Kasr Al-Aini Hospitals, Cardiothoracic surgery department. Group (1) had tricuspid valve repair using suture annuloplasty, while Group (2) had tricuspid valve repair using prosthetic ring annuloplasty. All patients were evaluated thoroughly preoperative, intra-operative, and post-operative. Particular attention was paid to clinical and echocardiographic findings of presence of tricuspid regurgitation (TR), its nature and degree, postoperative intensive care unit (ICU) events, ICU stay, hospital stay and follow up of the degree of TR post-operatively. more...

Objectives. The Spondyloarthropathies (SpAs) are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesised that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis.\ud \ud Methods. The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-け and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real time-polymerase chain reaction (qRTPCR) for MSC lineage markers and osteogenesis assays were used.\ud \ud Results. Combined treatment of MSC with IL-22, IFN-け and TNF resulted in increased MSC proliferation (p=0.008) and migration (p=0.04); an effect which was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic, adipogenic but not chondrogenic transcription factors were up-regulated by IL-22 alone (p more...

Introduction: The highest estimated prevalence of HCV infection has been reported in Egypt, nearly 12% mostly type 4. Currently, a commercial vaccine to protect this high risk population as well as global HCV infected patients is not available. Objectives: In the present study, we aim at: (1) examining the viral binding capacities of purified monospecific polyclonal murine antibodies raised against genetically conserved viral protein sequences, i.e. synthetic peptides derived from those sequences located within envelope proteins and (2) assessment of immunogenic properties and safety parameters of those peptides individually and in a vaccine format in mice. Methods: Purified IgG Abs from immunized mice were used in immunocapture RT-PCR experiments to test viral neutralization by Abs raised against each of 4 peptides termed p35 (E1), p36 (E2), p37 (E2) and p38 (E2). Swiss mice were immunized with each of the 3 peptides (p35, p37 and p38) which generated neutralizing antibodies in immunocapture experiments. Antibody responses to corresponding peptides were determined using different routes of administration, different adjuvants, different doses and at different time points post-injection. To explore the dose range for future pharmacological studies, three doses namely 50 ng, 10g and 50g/25 gm mouse body weight were tested for biochemical and histopathological changes in several organs. Results: Murine Abs against p35, p37 and p38 but not p36 showed HCV neutralization in immunocapture experiments. Subcutaneous injection of peptides elicited higher responses than i.m. and i.p. Immunization with Multiple Antigenic Peptide (MAP) form or coupled to Al PO4 elicited the highest Ab responses. Peptide doses of 50 ng/25 gm body weight or less were effective and safe, however dose assessment still requires further study. Histopathological changes were observed in animals that received doses ∼1000 times higher than the potential therapeutic dose. Conclusion: Exploration of humoral immunogenicity, neutralization capacity and safety suggested that the peptides presented herein are candidate vaccine components for further preclinical assessment. © 2009 Elsevier Ltd. All rights reserved. more...

At each stage of the life cycle of the virus, hepatitis C virus (HCV) interferes with the cellular antiviral mechanisms of the host. Therefore, HCV infection represents a fencing match between the virus and the host cell. The host’s defense depends primarily on activation of the immune response, including activation of interferon (IFN) signalling, expression of cytokines (TNF-α, IL-12, IL-10, IFN-α) and stimulation of cellular immune response (CIR) and humoral immune response (HIR). HCV offense relies on envelope mutation, evasion of the host immune response and interference with the endogenous cellular antiviral factors. more...

Occult hepatitis B virus (HBV) in blood donors is considered as a potential risk for transmission of HBV infection. The aim of this study was to determine the prevalence of anti-hepatitis B core antibody (anti-HBC) positivity in Egyptian blood donations as well as to estimate the frequency of HBV-DNA in anti-HBc-positive donations. The study included 760 Egyptian healthy blood donors, representing 26 different Egyptian governorates screened according to routine practice for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Abs), HIV-1/2 Abs and Treponema Abs. The accepted blood units for donation were tested for the presence of total anti-HBc Abs by two tests. Positive units for anti-HBc were further tested for HBV-DNA by polymerase chain reaction. According to routine screening, a total of 48/760 units (6.3%) were rejected [38 (5%) HCV-Ab-positive units, 9 (1.18%) HbsAg-positive units and 1 (0.13%) Treponema-Ab-positive unit]. Among the accepted blood units for donation, prevalence of anti-HBc was 78/712 units (10.96%). HBV-DNA was detected in 9/78 (11.54%) of the anti-HBc-positive units, and thus, occult HBV infection was detected in 9/712 (1.26%) of the accepted blood donations. Implementing anti-HBc test to the routine assay for the forthcoming two decades would certainly eliminate possible HBV-infected units. Rejection of these units will be beneficial to decrease the risk of HBV transmission with its potential consequences particularly in immunocompromised recipients. more...

Currently, pegylated interferon is the most effective therapy for hepatitis C but its cost is out of reach of most patients in the developing countries. The aim of this study was to assess the response rate of genotype-4 patients to 24 wks of peg-interferon-alpha2b (Peg-IFN-alpha2b) and ribavirin (RBV) or interferon-alpha2b (IFN-alpha2b) with RBV and amantadine (AMD) as an alternative option.In a controlled study, 180 biopsy-proven naïve chronic hepatitis C patients were allocated into three groups based on their financial affordability to any of the study regimens. Group I (control) comprised 40 patients who received Peg-IFN-alpha2b in a flat dose of 100 mug/wk (the dose available in Egypt) plus RBV 1,000-1,200 mg per day based on body weight for 48 wks. Group II comprised 70 patients who received the same regimen for 24 wks. Group III comprised 70 patients who received induction-dose triple therapy (IDTT) in the form of IFN-alpha2b 3 MU once daily for the first 4 wks then reduced to TIW for 20 wks plus RBV 1,000-1,200 mg per day based on body weight and AMD 100 mg twice daily for 24 wks. Six patients from group I, eight patients from group II, and four from group III discontinued the study either due to financial limitations and/or intolerable adverse effects of the drugs.Intention-to-treat analysis revealed that sustained virological response (SVR) achieved in 22 (55.0%), 34 (48.6%), and 20 (28.6%) in groups I, II, and III, respectively. Adherence-to-treatment analysis (80/80/80) revealed that SVR achieved in 22 (64.7%), 34 (54.8%), and 20 (30.3%) in groups I, II, and III, respectively. In absence of eradication of hepatitis-C-virus-RNA at week 12, there was virtually no chance of achieving SVR. These data collectively may indicate that genotype 4 is "not difficult to treat" as previously reported.Response of genotype-4 patients to 24 wks of Peg-IFN-alpha2b/RBV did not significantly differ from 48 wks, but was significantly higher than IDTT. Although SVR achieved by IDTT is less than Peg-IFN-alpha, yet it might provide a second option when the latter is not affordable. Early virological response should be used as a predictor to SVR to avoid unnecessary expenses in nonresponders patients. more...

Ethnic differences in the outcome of hepatitis C have been described. Our aim was to investigate ethnic differences in the distribution of genotypes associated with polymorphisms of the tumor necrosis factor-alpha promoter, interleukin-10 promoter, and transforming growth factor-beta1 leader sequence in patients with hepatitis C. Genomic DNA was obtained from 71 Egyptians and 67 Caucasians (hepatitis C and control patients). Amplification of appropriate gene segments was followed by direct sequencing. Infrequently occurring polymorphisms were identified at positions -244 and -77 of the tumor necrosis factor-alpha promoter and at positions -851 and -657 of the interleukin-10 promoter. The G/A genotype associated with tumor necrosis factor-alpha promoter positions -376 and -244 was more frequent in Egyptians (P =0.001 and P =0.004, respectively). The -244 G/A genotype occurred only in healthy Egyptians (P =0.024). Thus, ethnic differences in the distribution of genotypes of the tumor necrosis factor-alpha promoter exist, which may have clinical implications on the outcome of hepatitis C. more...

A new RNA virus, designated GBV-C/hepatitis G virus (HGV) has been identified recently. To evaluate the prevalence of GBV-C/HGV infection among Egyptians, five groups were enrolled in this study: group I, healthy blood donors (82); group II, health care personnel (30); group III, chronic non-B non-C hepatitis patients (63); group IV, chronic hepatitis C patients (100); group V, renal dialysis patients (79). GBV-C/HGV-RNA was detected by nested reverse transcription-polymerase chain reaction (RT-PCR) using primers derived from 5'-non coding region of GBV-C/HGV. GBV-C/HGV-RNA was detected in 57 of 354 tested sera with an overall prevalence of 16.1%. Meanwhile, isolated GBV-C/HGV infection was detected in 16/57 (28.1%), GBV-C/HGV coinfection with hepatitis C virus (HCV) in 37/57 (64.9%) and with hepatitis B virus (HBV) in 4/57 (7.6%) of cases. The highest prevalence was encountered among dialysis patients reaching 30% followed by chronic hepatitis C (14%), blood donors (12.2%), chronic non-B non-C hepatitis (11.1%), whereas the lowest prevalence rate of 6.6% was detected among health care personnel. Nucleotide sequence analysis in three Egyptians confirmed that these PCR products were derived from GBV-C/HGV genome and all isolates classified into US/European type (type 2) of GBV-C/HGV genotypes. The risk factors of all cases were non-transfusion parenteral exposure, e.g. reusing syringes, dental treatment, surgery, invasive medical maneuvers, with an exception of renal dialysis patients who have had repeated blood transfusion. It is concluded that there is a relatively high prevalence of GBV-C/HGV-RNA among different Egyptian groups compared to international figures. The main risk factors were direct percutaneous exposure rather than blood transfusion. The Egyptian GBV-C/HGV isolates are very similar to the American isolate PNF 2161. more...

Nitazoxanide, a new broad-spectrum antiprotozoal/anthelmintic drug, was tested in 546 patients with single or multiple intestinal protozoan and helminthic infections. After inclusion in the study, patients at least 12 years of age were instructed to take one nitazoxanide 500-mg table every 12 hours for 3 consecutive days. The guardians of the children aged 4 to 11 years were instructed to give their children one nitazoxanide 20-mg dispersible table every 12 hours for 3 consecutive days. Guardians of children aged 1 to 3 years were instructed to give their children 5 mL of a 100 mg/5 mL suspension every 12 hours for 3 consecutive days. No fasting was required, and the drug was to be administered with food. Based on negative findings on one posttreatment fecal examination performed 4 days after the end of treatment (study day 7), eradication rates of 81% (127 of 156), 95% (130 of 139), and 77% (10 of 13) were recorded for intestinal amebiasis, giardiasis, and balantidiasis, respectively. Nitazoxanide also showed good anthelmintic activity, with eradication rates of 95% (106 of 112), 95% (147 of 155), 96% (44 of 46), 86% (25 of 29), and 94% (34 of 36) for enterobiasis, ascariasis, ancylostomiasis caused by Ancylostoma duodenale , trichuriasis, and strongyloidiasis, respectively. Against the dwarf tapeworm, Hymenolepis nana , nitazoxanide therapy produced an eradiction rate of 85% (53 of 62). Nitazoxanide was well tolerated; 14.5% of the patients reported minimal side effects, such as nausea, headache, dizziness, vomiting, abdominal pain, and diarrhea. Hematolog, clinical chemistry, and urinalysis performed before and after treatment were unaffected by treatment with nitazoxanide. Key words: nitazoxanide, treatment, protozoa, helminths. more...

Hepatitis C virus (HCV) genotype 4 is the principal HCV genotype found in Egypt and the Middle East. Little is known concerning its propensity to cause disease and the frequency with which infected individuals respond to interferon-alpha (IFN-alpha). We have investigated the response to treatment in a cohort of 100 chronic hepatitis C patients infected with genotype 4. All patients had biopsy-proven chronic active liver disease. Each was treated with 3 million units (MU) IFN-alpha, thrice weekly. Response was monitored, in 92 patients who completed treatment, by alanine aminotransferase (ALT) measurements and by polymerase chain reaction (PCR) for HCV. ALT levels remained abnormal in 64 patients during treatment (69.6%). Of the 28 patients who showed a biochemical response during treatment (30.4%), 18 maintained this over the 6-month posttreatment period. Amongst the sustained biochemical responders, HCV RNA was cleared from serum in only four of the 18 (22.2%) in this period. Histological improvement was observed in 26/51 (50.9%) of the patients who had a second biopsy. Hence, patients infected with HCV genotype 4 show a poor response to IFN-alpha therapy compared with genotypes 2 and 3, but a similar response to IFN-alpha compared with those infected with type 1b HCV. These findings have major implications for treatment strategies in the Middle East, including Egypt, where HCV genotype 4 is widely distributed. more...

The aim of this study was to establish if a correlation exists between the HBe antigen/anti-HBe-antibody profile (HBeAg/anti-HBe) and the hepatitis B virus DNA (HBV-DNA) among patients in Egypt with chronic liver disease induced by the hepatitis B virus. The results revealed that 44 out of 100 patients with chronic HBsAg-positive liver disease were also HBV-DNA-positive. Of these 44 cases, 5 (11.3%) were HBeAg-positive, 18 (41.0%) anti-HBe-positive and 21 (47.7%) negative for both markers. This finding showed that HBeAg-negative chronic hepatitis B represents more than 80% of chronic hepatitis B cases in Egypt, suggesting that the HBeAg-minus variant of the hepatitis B virus characterizes the major infective agent. more...

Several studies have demonstrated that the outcome of chronic hepatitis C (CHC) infection is profoundly influenced by a variety of comorbidities. Many of these comorbidities have a significant influence on the response to antiviral therapy. These comorbidities negatively affect the course and outcome of liver disease, often reducing the chance of achieving a sustained virological response with PEGylated interferon and ribavirin treatments. Comorbidities affecting response to antiviral therapy reduce compliance and adherence to inadequate doses of therapy. The most important comorbidities affecting the course of CHC include hepatitis B virus coinfection, metabolic syndrome, and intestinal bacterial overgrowth. Comorbidities affecting the course and response to therapy include schistosomiasis, iron overload, alcohol abuse, and excessive smoking. Comorbidities affecting response to antiviral therapy include depression, anemia, cardiovascular disease, and renal failure. more...

Egyptian hepatocellular carcinoma (HCC) patients present at advanced stages. We aimed to study the influence of surveillance versus non-surveillance on HCC staging and the potential therapeutic options.A retrospective study to evaluate the effect of surveillance on early detection of HCC among cirrhotic patients from 2003 to 2008. Patients examined every 6 months using ultrasound and α-fetoprotein (α-FP) (group A) and those diagnosed with those that present for the first time symptomatically or incidentally (group B). Groups were compared for α-FP level, tumour characteristics, severity of liver disease; tumour staging was evaluated by Okuda, CLIP and BCLC staging systems, in addition to the potential therapeutic options.Group A comprised 122 HCC cases and group B 473. Surveillance improved HCC detection: at the stage of single nodule in 62.3% in group A versus 52.2% in group B, (P = 0.046) and reduced the percentage of HCC with portal vein thrombosis in 16.4 versus 33.8%, (P = 0.000) and the percentage of α-FP400 ng/ml in 19.5 versus 32.6%, (P = 0.006) in groups A and B, respectively. Surveillance doubled the detection of HCC at early stage of BCLC (25.4 vs. 11.9% P = 0.000) and doubled the patients' chance for loco-regional ablation (12.3 vs. 5.9%, P = 0.015) and liver transplantation (10.7 vs. 3.2%, P = 0.001) in groups A and B, respectively.HCC surveillance increases early detection of HCC and doubled the chances for curative options. Implementation of both HCC surveillance and cadaveric liver transplantation programs should be recommended in Egypt. more...

A subgroup of HBeAg-negative chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) and/or hepatitis B virus (HBV)-DNA levels below the cutoff values of international guidelines may have significant liver disease and miss the opportunity for early treatment. Histopathological changes of HBeAg-negative CHB patients at initial presentation irrespective of HBV-DNA and/or ALT levels to increase the likelihood of patients for treatment are evaluated.CHB patients attending Cairo Liver Center from January 2006 to May 2008 had biochemical, serological, and virological screening as well as liver biopsy that was assessed by Metavir score.Fifty-two HBeAg-negative CHB patients (46 male and 6 female) with a median age of 37.5 years were included in the study. Significant fibrosis (or=F2) was found in 26% (5/19) of patients with serum HBV-DNA2,000 IU/ml, and 53% (21/40) of patients with ALT level2xULN. Liver biopsy increased candidacy for treatment by nearly 25% before implementation of the recommended lower ALT levels (30 U/l for male and 19 U/l for female patients), and by 21.2% after implementation of the lower ALT level. Implementation of the lower ALT level increased the candidacy of patients for treatment by 4% (two patients), whereas liver biopsy increased eligibility for treatment by 55.8 % (27/49).Liver biopsy is more reliable than either ALT or HBV-DNA levels in the decision to treat Egyptian HBeAg-negative CHB patients, even with the implementation of the recommended lower ALT levels. more...

Steatosis is a common feature of many liver diseases, namely non-alcoholic steatohepatitis (NASH) and hepatitis C virus (HCV) infection, but the pathogenic mechanisms differ. Insulin resistance (IR), a key feature of metabolic syndrome, is crucial for NASH development, associated with many underlying genetically determined or acquired mitochondrial and metabolic defects and culminates to inflammation and progression to fibrosis. This may have potential implications for new drug therapy. In HCV-related disease, steatosis impacts both fibrosis progression and response to treatment. Steatosis in HCV-related disease relates to both viral factors (HCV genotype 3), and host factors (alcohol consumption, overweight, hyperlipidemia, diabetes). Among others, IR is a recognized factor. Hepatic steatosis is reported to be associated with disturbance in the signaling cascade of interferon and downregulation of its receptors. Thus, hepatic steatosis should not be considered a benign feature, but rather a silent killer. more...

Background and objectives The human spondyloarthropathies (SpA) are associated with single nucleotide polymorphisms (SNPs) in the IL-23 pathway and IL-23/17 axis therapy is effective in SpA. The SpAs are also associated with new bone formation that is to a degree independent of TNF blockade. Given that IL-23R receptor signalling in lymphoid cells is associated with IL-22 production and since IL-22 is a pivotal cytokine that maintains gut and skin stem cell function,1,2 we hypothesised that IL-22 might also drive skeletal stem cells and hence contribute to the SpA bone phenotype. Therefore we explored the effect of IL-22 on bone marrow mesenchymal stem cells (MSCs). Materials and methods Human Bone marrow MSCs were expanded and tested by flow cytometry for IL-22R expression. MSC proliferation and migration were tested by colorimetric XTT assay and chamber migration assays. MSC osteogenic functional differentiation was performed with and without cytokines. Results MSCs expressed low level IL22RA1 which was significantly up-regulated (1.8 ± 0.12 fold) in combination with IFNG and TNFa. MSCs proliferation and migration dramatically increased following IL-22 exposure after IFNG and TNFa combined priming compared to IL-22 alone or no cytokine. MSCs migration function was enhanced by IL-22 after priming with IFNG and TNFa compared to no cytokine. Osteogenic differentiation was significantly higher in MSCs exposed to IL-22 alone, but decreased when IL-22 combined with IFNG and TNFa. Conclusion IL-22 is exclusively produced by immune cells and acts on non-immune cells including stem cells; our findings confirm that IL-22 can drive bone marrow MSC osteogenesis. Furthermore, IL-22 boosted MSCs proliferation and migration after priming with IFNG & TNFa in vitro and had variable effects depending on the inflammatory milieu. Given that the IL-23 axis association with SpA this work opens up a novel pathway for exploring new bone formation in SpA related disease. References Eyerich et al. J Clin Invest. 2009;119(12):3573–3585 Serafini et al. J Exp Med. 2014;211(2):199–208 more...

Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. It induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects and oncogenic effects. Smoking yields chemical substances with cytotoxic potential which increase necro-inflammation and fibrosis. In addition, smoking increases the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF- alpha) that would be involved in liver cell injury. It contributes to the development of secondary polycythemia and in turn to increased red cell mass and turnover which might be a contributing factor to secondary iron overload disease promoting oxidative stress of hepatocytes. Increased red cell mass and turnover are associated with increased purine catabolism which promotes excessive production of uric acid. Smoking affects both cell-mediated and humoral immune responses by blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking also increases serum and hepatic iron which induce oxidative stress and lipid peroxidation that lead to activation of stellate cells and development of fibrosis. Smoking yields chemicals with oncogenic potential that increase the risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are independent of viral infection as well. Tobacco smoking has been associated with suppression of p53 (tumour suppressor gene). In addition, smoking causes suppression of T-cell responses and is associated with decreased surveillance for tumour cells. Moreover, it has been reported that heavy smoking affects the sustained virological response to interferon (IFN) therapy in hepatitis C patients which can be improved by repeated phlebotomy. Smoker's syndrome is a clinico-pathological condition where patients complain of episodes of facial flushing, warmth of the palms and soles of feet, throbbing headache, fullness in the head, dizziness, lethargy, prickling sensation, pruritus and arthralgia. more...

Objectives: Interferon (IFN) therapy is not affordable by the majority of Egyptian patients. Our aim was to tailor an effective and inexpensive regimen that ameliorates hepatic necro-inflammatory activity among chronic hepatitis C (CHC) patients. Methods: One hundred and seventy naive CHC patients with elevated alanine aminotransferase (ALT) (>1.5-fold) and detectable hepatitis C virus (HCV)-RNA by polymerase chain reaction, who cannot afford IFN-based therapy were randomly allocated either to non-interferon-based therapy (N-IFN-BT) (group I) or silymarin therapy (group II). Group I comprised 87 patients (biopsy proved chronic hepatitis in 62 patients) who were administered a daily combination of ribavirin (600–800 mg) plus amantadine (200 mg) and ursodeoxycholic acid (UDCA) (500 mg) for 24 weeks. Group II comprised 83 patients who were administered Silymarin 450 mg/day for 24 weeks. Results: Statistical evaluation was conducted on 82 patients from group I and 72 from group II because of the withdrawal of five and 11 patients from Groups I and II, respectively. Age, sex, social status and biochemical parameters were comparable in both groups. Normalization of ALT at the end of treatment was achieved in 58.5% and 15.3% (P more...

Heavy cigarette smoking induces hypoxic polycythemia (erythrocytosis) and hyperuricemia in chronic hepatitis C patients with reversal of clinical symptoms and laboratory parameters with therapeutic phlebotomy more...

Background: The studies carried out on hepatocellular carcinoma (HCC) are scarce in Egypt. Nevertheless, they presumed an upward trend for HCC among chronic liver disease (CLD) patients. The objectives of this research were to determine the trend of HCC, the possible risk factors implicated in its development and the population attributable risk of HCVAb and HBsAg positivity for HCC. Methods: Medical records of all patients attending Cairo Liver Center during the years 1992-1995 were reviewed to determine the sociodemographic characteristics, HCVAb, HBsAg and HCC status. Prospectively, 200 HCC cases' stored sera as well as 120 healthy control were tested for aflatoxin B(1) quantitatively and qualitatively. Results: HCC accounted for 4.7% (321/6850) of CLD patients included in the study. HCVAb positive cases were strikingly high (71.1%) and HBsAg positive cases were reported in 22.4% of patients. There was an annual significant rise of HCC ranging from 3.6% in 1992 to 5.3% in 1995. HCC was significantly more prevalent among old age groups (60 years) than younger age groups. The impact of gender and past history of schistosomiasis on HCC was not proved by this study. HCVAb and HBsAg positivity were the two significant independent risk factors for HCC. The population attributable risk percent has shown that HCC cases attributed to HCVAb positivity accounted for 51.1%; while HBsAg positivity only explained 21.3% of cases. Aflatoxin B(1) was detected in 17% of HCC cases compared to 9.4% of healthy control. Risk ratio=2(95%). Conclusion: HCC is showing an increasing trend among our patients. Its development is mainly due to high rates of HCVAb and HBsAg positivity. HBsAg positive patients were at double risk to develop HCC and HCVAb positive patients were at 1.6 more risk. The high prevalence of HCVAb positivity renders its contribution to the development of HCC over seven-fold higher than HBsAg positivity. Short and long term health strategies are crucial to prevent and control HCC in Egypt. more...

By PCR screening, we found an extremely high prevalence of TT virus (TTV) in the general populations from different geographic regions. This suggests that TTV may be a common DNA virus with no clear disease association in humans. TTV genotyping by phylogenetic analysis was also performed. more...

Hepatitis C infection is considered the leading cause of chronic liver disease in Egypt. Hepatitis C virus (HCV) genotype 4 is the predominant genotype in the Middle East including Egypt.1 A striking feature of HCV infection is its association with fat accumulation within hepatocytes,2 which is defined by the presence of hepatic steatosis with or without steatohepatitis.3 Hepatic steatosis has been reported in 30–70% of patients with HCV infection, even when the most common causes of steatosis are excluded.4 A causal relationship between infection with HCV genotype 3 and the incidence of hepatic steatosis has been elicited.5 In Egypt the true prevalence of non-alcoholic fatty liver disease is unknown among patients with HCV who are commonly infected with genotype 4. Our aim was to … more...

Assays that detect antibody to hepatitis C virus (HCV) are used to screen blood donors and patients with hepatitis. Current enzyme-linked immunosorbent assay (ELISA)-based methods are invariably based upon antigens from expressed recombinant proteins or oligopeptides from HCV type 1. Some HCV antigens used in screening assays are coded by regions of the HCV genome that show extensive variability; therefore, HCV type 1-based assays may be less effective for the detection of antibody elicited by infection with other genotypes. In this study, we have measured antibody reactivity of sera from 110 hepatitis C patients infected with type 1b, 3a, or 4a to genotype-specific and cross-reactive epitopes present in recombinant proteins from HCV genotypes 1b (core, NS3, and NS5), 3a (NS3, NS5), and 4a (core, NS3), corresponding to those used in current third-generation screening ELISAs. By comparing the serological reactivities of sera to type-homologous and type-heterologous antigens, we detected a significant type-specific component to the reactivity to NS3 (61 to 77% of the total reactivity) and NS5 (60% of the total reactivity). Furthermore, despite the similarities in the amino acid sequences of the core antigens of type 1b and type 4a, we also found significantly greater reactivity to type-homologous antigens, with approximately 25% of reactivity being type specific. These findings are consistent with previous findings of fivefold weaker reactivity of sera from HCV type 2- and HCV type 3-infected blood donors in the currently used third-generation ELISAs and suggest that these assays are suboptimal for screening populations in which the predominant genotype is not type 1. more...

The 5' end of the NS-4 protein of different genotypes of hepatitis C virus (HCV) is highly variable in nucleotide and inferred amino acid sequence, with frequent predicted amino acid substitutions between all six of the major HCV genotypes described to date. This region has been shown to be antigenic by epitope mapping, and elicits antibody in HCV-infected individuals with a detectable type-specific component. We have used this sequence data to specify branched peptides for an indirect binding/competition assay to detect type-specific antibody to each major genotype. A total of 183 out of 210 samples (87%) from blood donors and patients with chronic hepatitis C infected with genotypes 1 to 6 showed detectable type-specific antibody to NS-4 peptides that in almost all cases (> 97 %) corresponded to the genotype detected by a PCR typing method. These findings demonstrate the existence of major antigenic differences between genotypes of HCV, and indicate how infection with different variants of HCV may be detected by a serological test. more...

Background and Aim: Diabetes was associated with twoto threefolds more with Hepatocellular carcinoma (HCC). We investigate the impact of comorbidity of diabetes on HCC presentation, progression and treatment outcome. Patients and Methods: Over 3 years, 1049 consecutive patients of HCC were evaluated; of them 347 patients were diabetics. The age, clinical features, aetiology of HCC and staging of the tumour at presentation, treatment decision and ultimate outcome were compared in diabetic to non-diabetic HCC patients. Results: HCC patients with DM (Group A, n =347, age = 60.3±7.3 years, sex (M:F) = 299:48) were compared with patient of HCC without DM (Group B, n = 702, age = 61.7±11.8 years, sex (M:F) = 608:94). Non alcoholic steatohepatitis was significantly more prevalent in Group A than Group B (p 0.05). Advanced HCC lesions were prevalent in group A than Group B (74.3 vs. 39.4%) – p < 0.05). During one year follow up, mortality rate was higher in Group A than Group B (60.2 vs. 45.3% – P < 0.05). more...

Schistosomiasis is a chronic parasitic disease caused by a trematode blood fluke of the genus schistosoma that belongs to the schistosomatidae family. The ancient Egyptians contracted the disease more than 4 000 years ago. It was recognized through haematuria, the main sign of urinary bilharziasis was recorded in the Kahun papyrus 1900 B.C. as “â-a-â” disease[1]. One of the milestone events in the history of bilharziasis occurred in 1851, Theodor Bilharz, a German physician working at Cairo Medical School, saw the fluke in the mesenteric veins of post-mortem of an Egyptian boy[2,3], then described two types of ova, one with a terminal spine, and the other with a lateral spine, which he considered to be the mature and immature ova, respectively, produced by the female worms of the same species[2]. The controversy was finally settled by Leiper (1915-1918), when he demonstrated the presence of two species of Bilharzia that were different with regard to the morphology of the adult worms, the type of ova, the molluscan intermediate host, and the human habitat (i.e. the urogenital versus the intestinal tract)[4]. Another milestone was the introduction by McDonagh (1918), of antimony as an antibilharzial agent, and the popularization of the drug by Christopherson (1918) in Egypt[5,6]. In the life cycle, the adult worms live in terminal venules of the bowel (S mansoni, S japonicum) or bladder (S. haematobium). When eggs passed in feces or urine reach fresh water, a larval form is released that subsequently infects snails, the intermediate host. After development, infective larvae (cercariae) leave the snails, enter water, and infect exposed persons through the skin or mucous membranes. After penetration, the cercariae become “schistosomula” that reach the portal circulation in the liver, where they rapidly mature. After a few weeks, adult worms pair, mate, and migrate mainly to terminal venules of specific veins, where females deposit their eggs. By means of lytic secretions, some eggs reach the lumen of the bowel or bladder and are passed with feces or urine. Others are retained in the bowel or bladder wall, while still others are carried in the circulation to the liver, lung, and (less often) to other tissues. more...

AIM: Smoking may affect adversely the response rate to interferon-α . Our objective was to verify this issue among chronic hepatitis C patients. METHODS: Over the year 1998, 138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into: group I which comprised 38 smoker patients ( > 30 cigarettes/d) and group II which included 84 non-smoker patients. Irregular and mild smokers (16 patients) were excluded. Non eligible patients for interferon-α therapy were excluded from the study and comprised 3/38 (normal ALT) in group I and 22/84 in group II (normal ALT, advanced cirrhosis and thrombocytopenia). Group I was randomly allocated into 2 sub-groups: group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy. In sub-group Ia, 3 patients with normal ALT after repeated phlebotomies were excluded from the study. Interferon-α 2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia, 17 patients in group Ib and 62 patients in group II. Biochemical, virological end-of- treatment and sustained responses were evaluated. RESULTS: At the end of interferon-α treatment, ALT was normalized in 3/15 patients (20%) in group Ia and 2/17 patients (11.8%) in group Ib compared to17/62 patients (27.4%) in group II (P = 0.1). Whereas 2/15 patients (13.3%) in group Ia. and 2/17 patients (11.8%) in group Ib lost viraemia compared to 13/62 patients (26%) in group II (P = 0.3). Six months later, ALT was persistently normal in 2/15 patients (13.3%) in group 1a and 1/17 patients (5.9%) in group Ib compared to 9/62 patients (14.5%) in group II (P = 0.47). Viraemia was eliminated in 1/15 patients (6.7%) in group Ia and 1/17 patients (5.9%) in group Ib compared to 7/62 patients (11.3%) in group II, but the results did not mount to statistical significance (P = 0.4). CONCLUSION: Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-α compared to non-smokers. Therapeutic phlebotomy improves the response rate to interferon-α therapy among this group. more...

A prospective controlled trial was conducted at Ain-Shams and Benha University Hospitals. One-hundred and eighteen chronic liver disease patients, mostly schistosomal in origin and presenting with recent proven variceal hemorrhage, were randomly allocated to injection sclerotherapy or medical therapy. The follow-up period extended to 21 months. Sixty-three patients received injection sclerotherapy using ethanolamine oleate (5% wt/vol) paravariceally while 55 received medical treatment in the form of general resuscitative measures, blood transfusion, vasopressin intravenous drip, and insertion of a Sengstaken-Blakemore tube if bleeding continued. The first 30-day mortality was 7 (11%) in the injection sclerotherapy group compared with 11 (20%) in the medical treatment group. This difference was not statistically significant. During the entire observation period 9 (14.3%) died in the sclerosed group and 16 (29%) died in the medically treated group, and this difference was statistically significant at the 5% level. Comparison of recurrent bleeding among both groups revealed that the difference was statistically not significant. It was concluded that injection sclerotherapy was no better than medical treatment in the control of acute variceal bleeding, but injection sclerotherapy did increase significantly long-term survival of sclerosed patients. more...

The incidence of malnutrition and immunocompetence in 156 patients admitted to hospital with liver disease was investigated. Expected weight/height was within the normal range for all groups except those with carcinoma. Triceps skinfold thickness (TSF) was reduced in 49% of patients with cirrhosis and 55% with alcoholic disease. Hypoalbuminaemia was common in all groups, with 66% of those with chronic disease having concentrations below 35 g/dl. Lymphopenia was equally common, 65% of patients with fulminant hepatic failure (FHF) having counts below 1000 cells/mm3. Incidence of total anergy to standard skin tests was 54% overall: 93% in FHF and 60% in cirrhosis and alcoholic disease. There were significant links between reduced TSF and hypoalbuminaemia, lymphopenia and anergy, hypoalbuminaemia and anergy, and anergy and mortality. Reduced TSF was only associated with anergy in patients with chronic disease. The high incidence of immuno-incompetence may underlie the frequent occurrence of spontaneous infections in patients with liver disease, and the association between anergy and malnutrition in patients with chronic liver disease suggests that the anergy may be partly reversible by dietary measures. more...

There is considerable controversy as regards the exact cause of bleeding from esophageal varices. This study examined changes in the mucosa of such patients in an effort to understand the underlying mechanisms. Fifty patients were studied, 20 with a history of variceal bleeding and 30 without who served as controls. Endoscopic biopsies were taken from the inter-variceal mucosa within 5 cm from the cardia and were examined histopathologically. The results showed dilated intra-epithelial blood-filled channels within the squamous epithelium and the lamina propria in all bleeders, and in 50% of the non-bleeders. Evidence of esophagitis was also more pronounced in bleeders (50%) than in non-bleeders (23.3%). It is our opinion that esophagitis and the presence of dilated blood-filled channels may play a role in the initiation of variceal bleeding. more...

The manner in which a gastroenterologist is trained will reflect the national program for undergraduate and postgraduate education and also particularly the degree to which speciality medicine is practised in a country. At the one end of the spectrum (as is seen in much of the United Kingdom's specialist medicine) the gastroenterologist both practises as a general physician and exhibits his special clinical, technical, and intellectual skills in gastroenterology; at the other extreme is the gastroenterologist who sees no other type of medicine (or surgery) than gastroenterology. This latter pattern is probably a less common method of gastroenterologic practice. There is continuing argument about the benefits and disadvantages of the two systems. The gastroenterologist with a narrow field of interest will be an expert in this particular field but not have the capacity to manage the total medical problems of his patient. The gastroenterologist with a general medical interest may well be deficient in the dep... more...

Background To understand the complex and largely not well-understood apoptotic pathway and immune system evasion mechanisms in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and HCV associated chronic hepatitis (CH), we studied the expression patterns of a number of pro-apoptotic and anti-apoptotic genes (Fas, FasL, Bcl-2, Bcl-xL and Bak) in HepG2 cell line harboring HCV- genotype-4 replication. For confirmation, we also assessed the expression levels of the same group of genes in clinical samples obtained from 35 HCC and 34 CH patients. Methods Viral replication was assessed in the tissue culture medium by RT-PCR, quantitative Real-Time PCR (qRT-PCR); detection of HCV core protein by western blot and inhibition of HCV replication with siRNA. The expression level of Fas, FasL, Bcl-2, Bcl-xL and Bak was assessed by immunohistochemistry and RT-PCR whereas caspases 3, 8 and 9 were assessed by colorimetric assay kits up to 135 days post infection. Results There was a consistent increase in apoptotic activity for the first 4 weeks post-CV infection followed by a consistent decrease up to the end of the experiment. The concordance between the changes in the expression levels of Fas, FasL, Bcl-2, Bcl-xL and Bak in vitro and in situ was statistically significant (p < 0.05). Fas was highly expressed at early stages of infection in cell lines and in normal control liver tissues followed by a dramatic reduction post-HCV infection and an increase in the expression level of FasL post HCV infection. The effect of HCV infection on other apoptotic proteins started very early post-infection, suggesting that hepatitis C modulating apoptosis by modulating intracellular pro-apoptotic signals. Conclusions Chronic HCV infection differently modulates the apoptotic machinery during the course of infection, where the virus induces apoptosis early in the course of infection, and as the disease progresses apoptosis is modulated. This study could open a new opportunity for understanding the various signaling of apoptosis and in the developing a targeted therapy to inhibit viral persistence and HCC development. more...