Incidence and characteristics of HBV reactivation in hematological malignant patients in south Egypt

AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen(HBsAg)before the start of and throughout the chemotherapy course.HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by realtime detection polymerase chain reaction(RTD-PCR).For detecting the serological markers of HBV infection,HBsAg as well as antibodies to the core antigen(antiHBc)and to the surface antigen were measured in the sera by CEIA.Nucleic acids were extracted from sera,and HBV DNA sequences spanning the S gene were amplified by RTD-PCR.The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancerⅡ/core promoter/pre-core/core regions(nt1628-2364).Amplicons were sequenced directly.RESULTS:Thirty-five(66%)of the 53 HBsAg-negative patients were found to be negative serologically for antiHBc,and the remaining 18(34%)patients were positive for anti-HBc.Five of the 53(9.4%)patients with hematologic malignancies experienced HBV reactivation.Genotype D1 was detected in all five patients.Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation:T/S120,L143,and I126.HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation.In this patient,sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100%homology.Furthermore,in the phylogenetic tree,the sequences were clustered together,thereby indicating that this patient developed reactivation from an occult HBV infection.CONCLUSION:Past infection with HBV is a risk factor for HBV reactivation in Egypt.Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.

Applicability and efficacy of a model for prevention of perinatal transmission of hepatitis B virus infection:Single center study in Egypt

AIM:To identify possible maternal risk factors for hepatitis B virus(HBV)acquisition and assess the efficacy of immunoprophylaxis given to infants born to hepatitis B virus surface antigen(HBs Ag)positive mothers.METHODS:Screening of 2000 pregnant females wascarried out using rapid test and confirmed by enzyme immunoassay.A questionnaire consisting of 20 questions about the possible risk factors for acquisition of HBV infection was filled for every pregnant HBs Ag positive female in addition to at least 2 pregnant HBs Ag negative females for each positive case.Infants of HBs Ag positive women were offered passive and active immunoprophylaxis within the 1st 48 h after birth,in addition to 2nd and 3rd doses of HBV vaccine after1 and 6 mo respectively.Infants were tested for HBs Ag and hepatitis B surface antibodies(HBs Ab)at six months of age.RESULTS:HBs Ag was confirmed positive in 1.2%of tested pregnant women.Risk factors significantly associated with HBV positivity were;history of injections(OR=5.65),history of seeking medical advice in a clinic(OR=7.02),history of hospitalization(OR=6.82),history of surgery(OR=4)and family history of hepatitis(OR=3.89)(P<0.05).Dropout rate was 28%for HBs Ag women whose rapid test was not confirmed and could not be reached to provide immunoprophylaxis for thier newborns.Immunoprophylaxis failure was detected in only one newborn(3.7%)who tested positive for HBs Ag at 6 mo of age;and vaccine failure(seronegative to HBs Ab after 4 doses of the vaccine)was detected in another one(3.7%).The success rate of the immunoprophylaxis regimen was 92.6%.CONCLUSION:This pilot study shows that a successful national program for prevention of perinatal transmission of HBV needs to be preceded by an awareness campaign to avoid a high dropout rate.

Treatment Outcome of Pharmacokinetics-Based Dosing of Docetaxel and Fluorouracil in Advanced Head and Neck Cancer Patients

Introduction: Docetaxel, Cisplatin and 5-Fluorouracil (DPF) became the standard induction chemotherapy in advanced Head and Neck Cancer (HNC) but associated with high toxicity rate. Several studies reported higher response rates with better tolerability when chemotherapy dose is calculated based on Pharmacokinetics (PK) versus conventional Body Surface Area (BSA). Patients and Methods: Thirty nine patients with stage III and IV HNC who received induction DPF were included in the study. Dose of cycle 1 was BSA-based then Docetaxel and 5-FU doses were PK-adjusted starting from cycle 2 whereas Cisplatin dose was BSA-based throughout the study. Results: After median follow up period of 14 months the median overall survival (OS) and progression free survival (PFS) were 15.1 and 10.6 months respectively. Twenty nine patients were available for response assessment. Seven patients (24.1%) achieved complete response while partial response encountered in 19 patients (65.5%) with and Overall response rate of 89.6%. Both treatment related side effects and mortality significantly decreased after the application of PK dose adjustments (p-value 0.007 and 0.01 respectively). Conclusion: PK-guided dose adjustments of 5-FU and Docetaxel in DPF regimen can significantly decrease the treatment related side effects and mortality without compromising the tumor response rate. A randomized clinical trial is needed to compare the PK-guided dose adjustment with the standard BSA based protocol.

Towards hepatitis C virus elimination:Egyptian experience,achievements and limitations

Worldwide, more than one million people die each year from hepatitis C virus(HCV) related diseases, and over 300 million people are chronically infected with hepatitis B or C. Egypt used to be on the top of the countries with heavy HCV burden. Some countries are making advances in elimination of HCV, yet multiple factors preventing progress; remain for the majority. These factors include lack of global funding sources for treatment, late diagnosis, poor data, and inadequate screening. Treatment of HCV in Egypt has become one of the top national priorities since 2007. Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients. Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014. Yet, with the development of highly-effective direct acting antivirals(DAAs) for HCV, elimination of viral hepatitis has become a real possibility. The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs. Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV. This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols. Also, it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt

AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV) infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen(HBs Ag), and antibodies to HBV core(anti-HBc) and surface antigens. Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23(42.6%) of 54 patients with hematological malignancies who were HBsA g negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120 T and S143 L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations. 120 T mutation impairs the detection of HBsA g by CLEIA.

Predictive value of serum lactate dehydrogenase in diagnosis of septic shock in critical pediatric patients:A cross-sectional study

Objectives:To determine the predictive value of lactate dehydrogenase(LDH)in the diagnosis of septic shock and its association with other prognostic scores in critical pediatric patients.Methods:A cross-sectional study was performed at Children’s Hospital of Cairo University between June 2019 and December 2019.A total of 200 pediatric patients were divided into the septic shock group[100 critically ill patients with septic shock from the pediatric intensive care unit(PICU)]and the control group(100 patients with only sepsis).LDH was determined in the first 24 hours of admission.The sensitivity and specificity of LDH in diagnosis of septic shock were assessed;the levels of related indicators of patients with different etiologies were compared;correlations between LDH,Paediatric Index of MortalityⅡ,and Pediatric Sequential Organ Failure Assessment(pSOFA)were analyzed.Results:Median LDH was 512μL(406.50-663.00)in the septic shock group and was significantly higher than that[190μL(160.00-264.50)]in the control group(P<0.001).Besides,median LDH in children with chest infecion was higher than that in children with other diagnoses(P=0.047).A good positive correlation was found between pSOFA and LDH(r=0.503,P<0.001).Conclusions:LDH could be a potential inflammatory marker in the diagnosis of septic shock and is valuable for PICU admission decisions.

Serum Resistin Level and Polymorphonuclear Leukocytes Dysfunctions in Children on Regular Hemodialysis

Resistin is a secretory adipocytoine, which is expressed mainly in humans by inflammatory cells especially macrophages. Resistin serum levels are elevated in end-stage renal diseases of people having an increased risk of infections as a result of impaired polymorphonuclear leukocytes (PMNLs) functions. Objectives: To evaluate neutrophil functions (phagocytosis and oxidative burst) in children with end-stage renal disease (ESRD) on regular hemodialysis and to shed light on the contribution of resistin on neutrophil functions. Patients and Methods: The study included 40 children with ESRD on regular hemodialysis. Their ages ranged from 6 to 12 years, and they were selected from children attending the pediatric hemodialysis unit of AL-Zahraa Hospital, Al-Azher University during the period from October 2012 to December 2013. Another group of 40 apparently healthy children with matched age and sex with the patient group served as a control. Serum resistin, phagocytic index and nitro blue tetrazolium test (NBT%) were assessed in both groups. Results: There was a statistically more significant increase in resistin serum levels in cases than in controls;it was (3.25 ± 0.86 ng/ml) and (0.25 ± 0.16 ng/ml) respectively

Assessment of Liver Fatty Acid Binding Protein (L-FABP) as a Diagnostic Marker in Non-Alcoholic Fatty Liver Disease

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common liver disease worldwide, it causes chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. We aimed to assess the value of liver fatty acid binding protein (L-FABP) in the diagnosis of non-alcoholic fatty liver disease in comparison to ultrasonography. Patients and Methods: Ninty subjects were enrolled in this study who attended the Hepatology, Gastroenterology and Internal medicine clinics in Benha University Hospitals between January 2017 and January 2018 and divided into group I included 70 consecutive patients with non-alcoholic fatty liver disease who were diagnosed by ultrasound with or without elevated liver enzymes and group II included 20 healthy control subjects without NAFLD (by ultrasound) with normal liver enzymes. Serum levels of L-FABP were determined by enzyme-linked immunosorbent assay. Results: NAFLD patients were slightly older than healthy subjects as mean age in group I was (37.74 ± 11.7) while in group II was (36.5 ± 11.31). There was a slight increase in NAFLD in males, there was a high prevalence of NAFLD in the urban population. L-FABP levels in NAFLD patients were higher than in the control group (levels were 188.6 ± 34.94 and 137.7 ± 13.05 ng/l respectively). A strong correlation was found between L-FABP and ALT, AST, BMI and glucose levels. Analysis of ROC curve revealed that at a level 151.1 ng/sensitivity, specificity, PPV, NPV and accuracy were 83.3%, 71.8%, 31.3%, 96.6% and 73.3% respectively with AUC 0.839 and at a level 189.5 ng/sensitivity, specificity, PPV, NPV and accuracy were 90%, 90%, 95.4%, 95.4%, 88.9% with AUC was 0.950. Conclusion: Serum L-FABP could be used as a new diagnostic biomarker for detecting NAFLD.

Incidence of Helicobacter Pylori Infection in Cases of Hyperemesis Gravidarum

Background: One of the serious problems affecting pregnant females is Hyperemesis gravidarum. Different theories were suggested. But the main etiology is still unknown. Objectives: To determine the incidence of Helicobacter pylori infection in cases of Hyperemesis gravidarum. Patients and methods: Case control study of 80 cases (40 cases of Hyperemesis gravidarum (HEG) and 40 cases of normal pregnant females). Determination of Helicobacter pylori antibodies was done in serum and stool for the two studied groups. Results: 75% of cases of HEG were positive of Helicobacter pylori in stool samples and 37.50% of normal pregnant females. These results were statistically significant (P = 0.001). The prevalence of HpIgG AB and HpSAB was 77.5% in the patients group with HEG, and 55.0% in control studied group (P = 0.05). There was a significant difference between HEG cases and normal pregnancy as regards serum sodium (0.042). Conclusions: Infection by Helicobacter pylori may be one of the risk factors for HEG. Helicobacter pylori AB in both serum and stool is higher in HEG cases than in normal pregnant females.

Inherited Thrombophilia and Early Recurrent Pregnancy Loss among Egyptian Women

Inherited thrombophilia has been implicated as a possible cause of recurrent pregnancy loss. Although numerous studies are available in literature, thrombophilia rate seems to vary fromstudy to another. The aim of our study was to determine the frequency of FII Prothrombin(G20210A), Factor V Leiden (G1691A), as well as methyl tetrahydrofolate reductase (MTHFR?C677T) polymorphisms, protein C, protein S and antithrombin III deficiency in a series of patients with unexplained RPL compared to control. Patients and Methods: 100 patients of unexplained RPL and 43 age-matched healthy controls were investigated for inherited thrombophilia. Results: MTHFR and Factor V Leiden were the commonest gene defects among cases studied (63%, 60% respectively) and control groups (41.9%, 41.9% respectively) (p = 0.019, p = 0.046 respectively). The least common deficiencies were protein S and protein C deficiency in cases (3%, 2% respectively) as well as in controls (1%, 0% respectively). 4 cases were homozygous for MTHFR and 2 cases homozygous for Factor V Leiden mutation. Odds ratio for MTHFR and Factor V mutation was 2.36 and 2.08 respectively (CI 95%). Combined defects were seen in cases and controls (p < 0.05). Conclusion: Our study found an association between MTHFR and Factor V Leiden mutations in patients with unexplained RPL among Egyptian women. Further studies are needed to define the management of genetic thrombophilia in cases of recurrent pregnancy loss.

GSTP1 (Ile105Val) Gene Polymorphism: Risk and Treatment Response in Chronic Myeloid Leukemia

Background: Genetic variation influencing individual susceptibility to chemical carcinogens is one of the main factors leading to cancer development. The glutathione S-transferases (GSTs) are a family of enzymes belonging to phase II enzymes involved in detoxification of xenobiotics. A significant relationship is observed between the risk of developing cancer and genetic polymorphisms within GSTs. Methods: In this study, we investigated the influence of inherited GSTP1 (Ile105Val) gene polymorphism on the susceptibility to CML in Egypt in 40 CML patients (20 children and 20 adults), together with 40 healthy controls using a [PCR-RFLP] assay. Results: We found that the mutant type (IIe/Val, Val/Val) was significantly higher in CML patients (67.5%) compared to controls (35%) (p = 0.004);[odds ratio 3.9;95% CI: 1.5 - 9.7]. The mutant type was associated with more advanced phases in disease and with both worse hematological and cytogenetic responses when compared to the wild type (p = 0.03, p = 0.05, and p 0.001, respectively). Conclusion: GSTP1 (Ile105Val) gene polymorphism conferred a significant association with increased risk of CML and is associated with worse prognosis. Further studies on the functional consequences of this genetic polymorphism would pave the way to declare its role in the pathogenesis of CML or as a possible predictor for response to therapy.

An Observational Study on the Management of COVID-19 Patients in Limited-Resource Hospitals

Background:The purpose of this study was to evaluate the effectiveness of limited-resource hospitals in managing mild and moderate hospitalized cases of COVID-19 with comorbidities and in preventing their progression to severe illness.Methods:Data were obtained from 88 moderate COVID-19 patients with comorbidities who were admitted to limitedresource hospitals.The data were classified into several parts:comorbidities,chronic medication before hospital admission,symptoms of COVID-19 before and during hospitalization,clinical features,laboratory findings on hospital admission,complications during hospitalization,as well as worst laboratory values during hospitalization,hospital stay,and outcomes.The clinical features,laboratory results,type of oxygen therapy used,and the final treatment outcome were all evaluated to assess for any potential relationship.Results:All patients were alive upon discharge.Before admission,the majority of patients(60.2%)received COVID-19 treatment,and the average hospital stay was 12 days.The most common symptoms were fever(88.7%),cough(95.5%),shortness of breath(90.9%),myalgia(84.1%),confusion(63.6%),headache(62.5%),sore throat(88.7%),rhinorrhea(17%),chest pain(58%),diarrhea(19.3%),nausea and vomiting(38.6%),anosmia(62.5%),as well as dysgeusia(64.8%).Based on chest radiograph or computed tomography(CT)scan,9.1%of the patients had unilateral pneumonia,90.9% had bilateral pneumonia,and 96.6% had multiple mottling and ground-glass opacity.Age was found associated with a significant increase in headache(p=0.005),rhinorrhea(p=0.013),chest pain(p=0.007),and the need for positive airway pressure(p=0.008).Between pre-and post-hospital admissions,there was a significant increase in lactate dehydrogenase and ferritin but a decrease in platelet,D-dimer,hemoglobin,lymphocytes,neutrophils,and total leucocyte count(p<0.001).There was a significant association between hospital stay and D-dimer level(p=0.05).Conclusion:Limited-resource hospitals in Egypt were efficient in managing mild and moderate hospitalized cases of COVID-19 with comorbidities.Many of these cases did not escalate to severe illness and were all alive upon discharge.Early management of COVID-19 tends to delay the disease progression to severe illness and improves patients5 chances of survival.Treating COVID-19 or using oxygen therapy at home can also delay the need for hospitalization in mild or moderate cases.

Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

AIM: To correlate a genetic polymorphism of the low-density lipoprotein(LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus(HCV) patients.METHODS: Our study included 657 HCV-infected patients with genotype 4 who received interferonbased combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index(BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction(PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor(LDLR) genotype study of LDLR exon8 c.1171G>A and exon-10 c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases.RESULTS: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10 c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8 c.1171G>A genotype between cases(AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls(AA: 3.8%, GA: 53.1% and GG: 43.1%)(P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders(AA: 3.6%, GA: 15.2%, GG: 81.2%) and nonresponders(AA: 52.2%, GA: 30.6%, GG: 17.2%)(P < 0.001). The G allele of LDL receptor exon8 c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8 c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders(P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for nonresponse. There was a significant association between LDL receptors exon8 c.1171G>A and HAI(P < 0.011). There was a significant association between LDL receptors exon8 c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype(28.7 ± 4.7 kg/m2) followed by the GA genotype(28.1 ± 4.8 kg/m2). The lowest BMI was the GG genotype(26.6 ± 4.3 kg/m2)(P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis(P < 0.001).CONCLUSION: LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptiansinfected with chronic HCV.