Search results for: hepatitis B and C
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 145

Search results for: hepatitis B and C

85 Therapeutic Management of Toxocara canis Induced Hepatitis in Dogs

Authors: Milind D. Meshram

Abstract:

Ascarids are the most frequent worm parasite of dogs and cats. There are two species that commonly infect dogs: Toxocara canis and Toxascaris leonina. Adult roundworms live in the stomach and intestines and can grow to 7 inches (18 cm) long. A female may lay 200,000 eggs in a day. The eggs are protected by a hard shell. They are extremely hardy and can live for months or years in the soil. A dog aged about 6 years, from Satara was referred to Teaching Veterinary Clinical Complex (TVCC) with a complaint of abdominal pain, anorexia, loss of condition and dull body coat with mucous pale membrane. The clinical examination revealed Anaemia, palpation of abdomen revealed enlargement of liver, slimy feel of the intestine loop, diarrhea.

Keywords: therapeutic management, Toxocara canis, induced hepatitis, dogs

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84 Impact of Hepatitis C Virus Chronic Infection on Quality of Life in Egypt

Authors: Ammal M. Metwally, Ghada A. Abdel-Latif, Walaa A. Fouad, Thanaa M. Rabah, Amira Mohsen, Fatma A. Shaaban, Iman I. Salama

Abstract:

The study aimed at determining the impact of chronic hepatitis C virus (HCV) infection on patients’ Quality of Life (QoL) , its relation to geographical characteristics of patients, awareness of the disease, treatment regimen, co-morbid psychiatric or other diseases. 457 patients were randomly selected from ten National Treatment Reference Centers of Ministry of Health hospitals from four community locations representing Egypt. Health related QoL assessment questionnaire with the 36-item Short Form used for assessment of the enrolled patients. The study showed no significant difference between HCV patients in different governorates as regards total QoL. Females, illiterate patients and those had bilharziasis, diabetes mellitus, hypertension or were depressed had significantly the lowest QoL score. HCV patients who knew the danger of the disease had significant lower mean score of physical and mental health components. Optimal care of overall well-being of HCV patients requires adequate knowledge of their neurological and psychological status. It is important to know that any patient will need to take the time to know that his new physical limitations do not limit him as a person, as soul, no matter what other people are thinking as a positive hopeful attitude is essential for combating HCV.

Keywords: hepatitis C virus chronic infection - physical health component and mental health component of QoL– total quality of life

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83 Hepatitis B Prevalence in Institutionalized Intellectually Disabled Children

Authors: Maryam Vaezjalali, Foad Davoodbeglou, Mehrnaz Mesdaghi, Hossein Goudarzi, Fariba Shojaei, Hourieh Aram

Abstract:

Introduction: Hepatitis B virus (HBV) infection causes chronic infection in human population, with high mortality. Some people are more susceptible to this infection. One of the high risk communities is mentally retarded children, who are institutionalized. Special conditions in these centers predispose children for HBV infection and transmission to healthy people. In this study our objective was to determine the prevalence of HBV infection among institutionalized mentally retarded children and study its associated risk factors. Materials and methods: In this study, 250 mentally retarded children (younger than 14 years old) were included. They were living in 5 nursing institutions, located in different parts of Tehran. HBsAg was measured in the sera of these patients by ELISA method. Results: Among 250 children, 20 children (8%) were HBsAg positive. HBV infection in girls was more than boys (11% to 5.6%). Among the types of mental retardation, children with cerebral palsy had the highest positive result for HBsAg. The most HBV infection (28.5%) was seen in children with longest duration of being institutionalized (10 to 11 years). Vaccinated children were more HBsAg positive (8.7%) than non-vaccinated children (5.3%). However, no significant relationship was observed between any of these factors and HBsAg positivity. Conclusion: Despite improvement of people’s health condition and implementation of HBV vaccination, the prevalence of HBV infection is high in institutionalized mentally retarded children, which highlights the need for active measures to reduce this infection among this high risk population.

Keywords: hepatitis B virus, HBV vaccine, intellectually disabled children, mentally retarded

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82 Bioinformatics Identification of Rare Codon Clusters in Proteins Structure of HBV

Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

Abstract:

Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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81 Detection of Bcl2 Polymorphism in Patient with Hepatocellular carcinoma

Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud

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Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis

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80 Association of Transmission Risk Factors Among HCV-infected Bangladeshi Patients With Different Genotypes

Authors: Nahida Sultana

Abstract:

Globally, an estimated 58 million people have chronic hepatitis C virus infection, with about 1.5 million new infections occurring per year. The hepatitis C virus is a blood-borne virus, and most infections occur through exposure to blood from unsafe injection practices, unsafe health care, unscreened blood transfusion, injection drug use, and sexual practices that lead to exposure to blood. Hepatitis C virus (HCV) causes chronic infections that mainly affect the liver leading to liver diseases. This study aimed to determine whether there is any significant association between HCV transmission risk factors in relation to genotypes in HCV-infected Bangladeshi patients. After quantification of HCV viral load, 36 samples were randomly selected for HCV genotyping and risk factor measurement. A greater proportion of genotype 1 (p > 0.05) patients (40%) underwent blood transfusion compared to patients (22.6%) with genotype 3 infections. More genotype 1 patient underwent surgery and invasive procedures (20%), and rather than those with genotype 3 patients (16.1%). The history of IDUs (25.8%) and sexual exposure (3.2%) are only prevalent in genotype 3 patients and absent in patients with genotype 1 (p >0.05). There was no significant statistical difference found in HCV transmission risk factors (blood transfusion, IDUs, Surgery& interventions, sexual transmission) between patients infected with genotypes 1 and 3. In HCV infection, genotype may have no relation to transmission risk factors among Bangladeshi patients.

Keywords: HCV genotype, alanine aminotransferase (ALT), HCV viral load, IDUs

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79 Assessing Psycho-Social Stressors for Chronically Infected Hepatitis C Virus Patients in Egypt

Authors: Ammal M. Metwally, Dalia M. Elmosalami, Walaa A. Fouad, Abla G. Khalifa, Lobna A. El Etreby, Mohamed AbdelRahman

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People with hepatitis C are likely to experience psychological distress related to adjustment issues following diagnosis. Objective: The study was conducted to determine the psycho-social stressors accompanying Hepatitis C virus (HCV) chronic infection. The study focused on immediate and later on reactions to being diagnosed as infected HCV patients. Effect of HCV on disruption of patients’ relationships in term of family relationship and friendship, employment and financial status was assessed. The magnitude and causes of the social stigma and its relation to awareness about illness, level of education were also assessed. Methods: During this study the subjective experiences of people having HCV was explored through a designed questionnaire targeted 540 cases; 359 males and 181 females from ten out of 21 National Treatment Reference Centers of National Hepatology and Tropical Medicine Research Institutes of Ministry of Health (MOH) hospitals. The study was conducted along a period of six months from September 2011 to March 2012. Results: The study revealed that the financial problems are the commonest problems faced by 75.5 % of the cases. More than 70% of the cases suffered from immediate sadness versus 67.4% suffered from worry. Social stigma was reported by 13 % of HCV +patients, the majority of which were females. Conclusions: Exploring the psychosocial consequences of HCV infection can act as pressing motivators for behavior change needed for limiting HCV endemicity in Egypt.

Keywords: Egypt, HCV infection, psycho-social adjustment, stigma

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78 Study of Circulatory MiR-122 and MiR-130a Expression among Chronic Hepatitis C Egyptian Patients

Authors: Hend K. Moosa, Eman A. Rashwan, Ezzat M. Hassan, Amany A. Ghazy, Amel G. Sheredy

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The stability of microRNA (miR) in the circulation can show a great progress toward the discovery of non-invasive diagnostic and prognostic biomarkers in many diseases. In the present study, circulatory miR-122 and miR-130a were analysed in chronic hepatitis C Egyptian patients in predicting the clinical outcome of interferon treatment. In addition, their expression levels were correlated to viral RNA levels, necro-inflammatory markers (AST, ALT) and to each other. This study was conducted on 51 subjects where 36 were chronic HCV patients in which they were divided into naive and interferon treated HCV patients (responders and non-responders) and 15 matched healthy controls. Serum quantification of miR-122 and miR-130a were performed by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The results showed a significant upregulation of miR-122 in non-responder patients (P=0.049). By receiver operating characteristic analysis curve, miR-122 revealed 65% sensitivity and 92.3% specificity in predicting non-responsiveness of patients to IFN treatment, while miR-130a showed a sensitivity of 100% and specificity of 53.85%. Remarkably, there was a significant positive correlation between miR-122 and miR-130a in naive HCV patients (r=0.714, p=0.003). However, there was no significant correlation between serum miR-122, miR-130a expression levels and necro-inflammatory markers (AST, ALT). To conclude, miR-122 and miR-130a have a significant association with viral RNA levels and accordingly, they may have a synergistic power in promoting viral replication. Interestingly, miR-122 and miR-130a have a predictive power in predicting clinical outcome of IFN treatment which can be further studied in currently used drugs in order to reduce the socio-economic burden of potentially non-responders.

Keywords: hepatitis C, microRNA, miR-122, miR-130a

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77 A Computer-Aided System for Detection and Classification of Liver Cirrhosis

Authors: Abdel Hadi N. Ebraheim, Eman Azomi, Nefisa A. Fahmy

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This paper designs and implements a computer-aided system (CAS) to help detect and diagnose liver cirrhosis in patients with Chronic Hepatitis C. Our system reduces the required features (tests) the patient is asked to do to tests to their minimal best most informative subset of tests, with a diagnostic accuracy above 99%, and hence saving both time and costs. We use the Support Vector Machine (SVM) with cross-validation, a Multilayer Perceptron Neural Network (MLP), and a Generalized Regression Neural Network (GRNN) that employs a base of radial functions for functional approximation, as classifiers. Our system is tested on 199 subjects, of them 99 Chronic Hepatitis C.The subjects were selected from among the outpatient clinic in National Herpetology and Tropical Medicine Research Institute (NHTMRI).

Keywords: liver cirrhosis, artificial neural network, support vector machine, multi-layer perceptron, classification, accuracy

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76 Surveillance of Hepatitis C Virus Genotype Circulating in North India

Authors: Shantanu Prakash, Suruchi Shukla, Amita Jain

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Introduction: The hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease. Injection drug use and individuals receiving blood and blood products are the primary modes of HCV transmission. Our study aims to establish the prevalent genotypes/ subtypes of HCV circulating in Uttar Pradesh, North India, as reported from a tertiary care hospital. Methods: It is a retrospective observational analysis of consecutive 404 HCV RNA positive cases referred to our hospital during September 2014 to April 2017. The study was approved by an institutional ethics committee. Written informed consent was taken from each participant. Clinical and demographic details of these patients were recorded using predesigned questionnaires. All the laboratory testing was carried on stored serum sample of enrolled cases. Genotyping of all 404 strains was done by Sanger’s sequencing of the core region. The phylogenetic analysis of 179 HCV strains with high -quality sequencing data was performed. Results: The distribution of prevalent genotypes/ subtypes as noted in the present study was; Genotype (GT)1a [n-101(25%)], GT1b [n-12(2.9%)], GT1c [1(0.25%)], GT3a [275(68.07%)], GT3b [9(2.2%)], GT3g [2(0.49%)], GT3i [3(0.74%)], and GT4a [1(0.24%)]. HCV genotypes GT2, GT5 and GT6 were not detected from our region. Sequence analysis showed high genotypic variability in HCV GT3. Phylogenetic analysis showed that HCV GT3 and GT1 circulating in our region were related to Indian strains reported earlier. Conclusions: HCV genotypes 3a and 1a are commonest circulating genotypes in Uttar Pradesh (UP), India.

Keywords: Hepatitis C virus, genetic variation, bioinformatics, genotype, HCV

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75 Evaluation of Existence of Antithyroid Antibodies, Anti-Thyroid Peroxidase and Anti-Thyroglobulin in Patients with Hepatitis C Viral Infections

Authors: Junaid Mahmood Alam, Sana Anwar, Sarah Sughra Asghar

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Chronic hepatitis or Hepatitis C viral (HCV) infection has been identified as one of the factors that could elicit autoimmune disease resulting in the development of auto-antibodies. Furthermore, HCV is implicated in contravening of forbearance to antigens, therefore, inciting auto-reactivity. In this regard, several near and past studies noted the prevalence of thyroid dysfunction and production of anti-thyroid antibodies (ATAb) such as anti-thyroid peroxidase (AntiTPO) and anti-thyroglobulin (AntiTG) in patients with HCV. Likewise, one of the etiologies of augmentation of thyroid disease is basically interferon therapy for HCV infections, for which a number of autoimmune diseases have been noted including Grave’s disease, Hishimoto thyroiditis. A prospectively case-control study was therefore carried out at department of clinical biochemistry lab services and chemical pathology in collaboration with department of clinical microbiology, at Liaquat National Hospital and Medical College, Karachi Pakistan for the period January 2015 to December 2017. Two control groups were inducted for comparison purpose, control group 1 = without HCV infection and with thyroid disorders (n = 20), control group 2 = with HCV infection and without thyroid disorders (n = 20), whereas HCV infected were n = 40 where more than half were noted to be positive for either of HCV IgG and Ag. In HCV group, patients with existing sub-clinical hypothyroidism and clinical hyperthyroidism were less than 5%. Analysis showed the presence of AntiTG in 12 HCV patients (30%), AntiTPO in 15 (37.5%) and both AntiTG and antiTPO in 10 patients (25%). Only 3 patients were found with the history of anti-thyroid auto-antibodies (7.5%) and one with parents and relatives with auto-immune disorders (2.5%). Patients that remained untreated were 12 (30%), under treatment 18 (45%) and with complete-course of treatment 10 (25%). As per review of the literature, meta-analysis of evident data and cross-sectional studies of selective cohorts (as studied in presented research), thyroid connection is designated as one of the most recurrent endocrine ailment associated with chronic HCV infection. Moreover, it also represents an extrahepatic disease in the continuum of HCV syndrome. In conclusion, HCV patients were more likely to encompass thyroid disorders especially related to development of either of ATAb or both antiTG and AntiTPO.

Keywords: Hepatitis C viral (HCV) infection, anti-thyroid antibodies, anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies

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74 Lentiviral-Based Novel Bicistronic Therapeutic Vaccine against Chronic Hepatitis B Induces Robust Immune Response

Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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73 Molecular Farming: Plants Producing Vaccine and Diagnostic Reagent

Authors: Katerina H. Takova, Ivan N. Minkov, Gergana G. Zahmanova

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Molecular farming is the production of recombinant proteins in plants with the aim to use the protein as a purified product, crude extract or directly in the planta. Plants gain more attention as expression systems compared to other ones due to the cost effective production of pharmaceutically important proteins, appropriate post-translational modifications, assembly of complex proteins, absence of human pathogens to name a few. In addition, transient expression in plant leaves enables production of recombinant proteins within few weeks. Hepatitis E virus (HEV) is a causative agent of acute hepatitis. HEV causes epidemics in developing countries and is primarily transmitted through the fecal-oral route. Presently, all efforts for development of Hepatitis E vaccine are focused on the Open Read Frame 2 (ORF2) capsid protein as it contains epitopes that can induce neutralizing antibodies. For our purpose, we used the CMPV-based vector-pEAQ-HT for transient expression of HEV ORF2 in Nicotiana benthamina. Different molecular analysis (Western blot and ELISA) showed that HEV ORF2 capsid protein was expressed in plant tissue in high-yield up to 1g/kg of fresh leaf tissue. Electron microscopy showed that the capsid protein spontaneously assembled in low abundance virus-like particles (VLPs), which are highly immunogenic structures and suitable for vaccine development. The expressed protein was recognized by both human and swine HEV positive sera and can be used as a diagnostic reagent for the detection of HEV infection. Production of HEV capsid protein in plants is a promising technology for further HEV vaccine investigations. Here, we reported for a rapid high-yield transient expression of a recombinant protein in plants suitable for vaccine production as well as a diagnostic reagent. Acknowledgments -The authors’ research on HEV is supported with grants from the Project PlantaSYST under the Widening Program, H2020 as well as under the UK Biotechnological and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Grant ‘Understanding and Exploiting Plant and Microbial Secondary Metabolism’ (BB/J004596/1). The authors want to thank Prof. George Lomonossoff (JIC, Norwich, UK) for his contribution.

Keywords: hepatitis E virus, plant molecular farming, transient expression, vaccines

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72 Low Volume High Intensity Interval Training Effect on Liver Enzymes in Chronic Hepatitis C Patients

Authors: Aya Gamal Khattab

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Chronic infection with the hepatitis C virus (HCV) is now the leading cause of liver-related morbidity and mortality; Currently, alanine aminotransferase ALT measurement is not only widely used in detecting the incidence, development, and prognosis of liver disease with obvious clinical symptoms, but also provides reference on screening the overall health status during health check-ups. Exercise is a low-cost, reliable and sustainable therapy for many chronic diseases. Low-volume high intensity interval training HIT is time efficient while also having wider application to different populations including people at risk for chronic inflammatory diseases. Purpose of this study was to investigate the effect of low volume high intensity interval training on ALT, AST in HCV patients. All practical work was done in outpatient physiotherapy clinic of Suez Canal Authority Hospitals. Forty patients both gender (27 male, 13 female), age ranged (40-60) years old submitted to low volume high intensity interval training on treadmill for two months three sessions per week. Each session consisting of five min warming up, two bouts for 10 min each bout consisting of 30 sec - 1 min of high intensity (75%-85%) HRmax then two to four min active recovery at intensity (40%-60%) HRmax, so the sum of high intensity intervals was one to two min for each session and four to eight min active recovery, and ends with five min cooling down. ALT and AST were measured before starting exercise session and 2 months later after finishing the total exercise sessions through blood samples. Results showed significant decrease in ALT, AST with improvement percentage (18.85%), (23.87%) in the study, so the study concluded that low volume high intensity interval training had a significant effect in lowering the level of circulating liver enzymes (ALT, AST) which means protection of hepatic cells and restoration of its function.

Keywords: alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis C (HCV), low volume high intensity interval training

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71 Developing a Deep Understanding of the Immune Response in Hepatitis B Virus Infected Patients Using a Knowledge Driven Approach

Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

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Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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70 Tenofovir-Amino Acid Conjugates Act as Polymerase Substrates: Implications for Avoiding Cellular Phosphorylation in the Discovery of Nucleotide Analogs

Authors: Weijie Gu, Sergio Martinez, Hoai Nguyen, Hongtao Xu, Piet Herdewijn, Steven De Jonghe, Kalyan Das

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Nucleotide analogs are used for treating viral infections such as HIV, hepatitis B, hepatitis C, influenza, and SARS-CoV-2. To become polymerase substrates, a nucleotide analog must be phosphorylated by cellular kinases, which are rate-limiting. The goal of this study is to develop dNTP/NTP analogs directly from nucleotides. Tenofovir (TFV) analogs were synthesized by conjugating with natural or unnatural amino acids. It demonstrates that some conjugates act as dNTP analogs, and HIV-1 reverse transcriptase (RT) catalytically incorporates the TFV part as the chain terminator. X-ray structures in complex with HIV-1 RT/dsDNA showed binding of the conjugates at the polymerase active site, however, in different modes in the presence of Mg²⁺ vs. Mn²⁺ ions. The adaptability of the compounds is seemingly essential for catalytic incorporation of TFV by RT. 4d with a carboxyl sidechain demonstrated the highest incorporation. 4e showed weak incorporation and rather behaved as a dNTP-competitive inhibitor. This result advocates the feasibility of designing NTP/dNTP analogs by chemical substitutions to nucleotide analogs.

Keywords: dNTP analogs, nucleotide analogs, polymerase, tenofovir, X-ray structure

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69 Autoimmune Diseases Associated with Primary Biliary Cirrhosis: A Retrospective Study of 51 Patients

Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Primary biliary cirrhosis (PBC) is a cholestatic cholangitis of unknown etiology. It is frequently associated with autoimmune diseases, which explains their systematic screening. The aim of our study was to determine the prevalence and the type of autoimmune disorders associated with PBC and to assess their impact on the prognosis of the disease. Material and methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for PBC. In all these patients we have systematically researched: dysthyroidism (thyroid balance, antithyroid autoantibodies), type 1 diabetes, dry syndrome (ophthalmologic examination, Schirmer test and lip biopsy in case of Presence of suggestive clinical signs), celiac disease(celiac disease serology and duodenal biopsies) and dermatological involvement (clinical examination). Results: Fifty-one patients (50 women and one men) followed for PBC were collected. The Mean age was 54 years (37-77 years). Among these patients, 30 patients(58.8%) had at least one autoimmune disease associated with PBC. The discovery of these autoimmune diseases preceded the diagnosis of PBC in 8 cases (26.6%) and was concomitant, through systematic screening, in the remaining cases. Autoimmune hepatitis was found in 12 patients (40%), defining thus an overlap syndrome. Other diseases were Hashimoto's thyroiditis (n = 10), dry syndrome (n = 7), Gougerot Sjogren syndrome (n=6), celiac disease (n = 3), insulin-dependent diabetes (n = 1), scleroderma (n = 1), rheumatoid arthritis (n = 1), Biermer Anemia (n=1) and Systemic erythematosus lupus (n=1). The two groups of patients with PBC with or without associated autoimmune disorders were comparable for bilirubin levels, Child-Pugh score, and response to treatment. Conclusion: In our series, the prevalence of autoimmune diseases in PBC was 58.8%. These diseases were dominated by autoimmune hepatitis and Hashimoto's thyroiditis. Even if their association does not seem to alter the prognosis, screening should be systematic in order to institute an early and adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, primary biliary cirrhosis, prognosis

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68 A Replicon-Baculovirus Model for Efficient Packaging of Hepatitis E Virus RNA and Production of Infectious Virions

Authors: Mohammad K. Parvez, Mohammed S. Al-Dosari

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Hepatitis E virus (HEV) is an emerging RNA virus that causes acute and chronic liver disease with a global mortality rate of about 2%. Despite milestone developments in understanding of HEV biology, there is still lack of a robust culture system or animal model. Therefore, in a novel approach, two recombinant-baculoviruses (vBac-ORF2 and vBac-ORF3) that could overexpress HEV ORF2 (structural/capsid) and ORF3 (nonstructural/regulatory) proteins, respectively were constructed. The established HEV-SAR55 (genotype 1) replicon that contained GFP gene, in place of ORF2/ORF3 sequences was in vitro transcribed, and GFP production in RNA transfected S10-3 cells was scored by FACS. Enhanced infectivity, if any, of nascent virions produced by exogenously-supplied ORF2 and viral RNA by co-expression of ORF3 was tested on naïve HepG2 cells. Co-transduction with vBac-ORF2/vBac-ORF3 (108 pfu/microL) produced high amounts of native ORF2/ORF3 in approximately 60% of S10-3 cells, determined by immunofluorescence microscopy and Western analysis. FACS analysis showed about 9% GFP positivity of S10-3 cells on day6 post-transfection (i.e, day5 post-transduction). Further, FACS scoring indicated that lysates from S10-3 cultures receiving the RNA plus vBac-ORF2 were capable of producing HEV particles with about 4% infectivity in HepG2 cells. However, lysates of cultures co-transduced with vBac-ORF3, were found to further enhance virion infectivity by approximately 17%. This supported a previously proposed role of ORF3 as a minor-structural protein in HEV virion assembly and infectivity. In conclusion, the present model for efficient genomic RNA packaging and production of infectious virions could be a valuable tool to study various aspects of HEV molecular biology, in vitro.

Keywords: chronic liver disease, hepatitis E virus, ORF2, ORF3, replicon

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67 Investigation of Suspected Viral Hepatitis Outbreaks in North India

Authors: Mini P. Singh, Manasi Majumdar, Kapil Goyal, Pvm Lakshmi, Deepak Bhatia, Radha Kanta Ratho

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India is endemic for Hepatitis E virus and frequent water borne outbreaks are reported. The conventional diagnosis rests on the detection of serum anti-HEV IgM antibodies which may take 7-10 days to develop. Early diagnosis in such a situation is desirable for the initiation of prompt control measures. The present study compared three diagnostic methods in 60 samples collected during two suspected HEV outbreaks in the vicinity of Chandigarh, India. The anti-HEV IgM, HEV antigen and HEV-RNA could be detected in serum samples of 52 (86.66%), 16 (26.66%) and 18 (30%) patients respectively. The suitability of saliva samples for antibody detection was also evaluated in 21 paired serum- saliva samples. A total of 15 serum samples showed the presence of anti HEV IgM antibodies, out of which 10 (10/15; 66.6%) were also positive for these antibodies in saliva samples (χ2 = 7.636, p < 0.0057), thus showing a concordance of 76.91%. The positivity of reverse transcriptase PCR and HEV antigen detection was 100% within one week of illness which declined to 5-10% thereafter. The outbreak was attributed to HEV Genotype 1, Subtype 1a and the clinical and environmental strains clustered together. HEV antigen and RNA were found to be an early diagnostic marker with 96.66% concordance. The results indicate that the saliva samples can be used as an alternative to serum samples in an outbreak situation.

Keywords: HEV-antigen, outbreak, phylogenetic analysis, saliva

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66 Expression of Interferon-Lambda Receptor-(IFN-λRα) in Mononuclear Phagocyte Cells (MPCs) Is Influenced by the Levels of Newly Discovered Type III IFN-λ4 in Vitro

Authors: Hashaam Akhtar

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IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.

Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression

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65 Human Par14 and Par17 Isomerases Bind Hepatitis B Virus Components Inside and Out

Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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64 Monitoring of Serological Test of Blood Serum in Indicator Groups of the Population of Central Kazakhstan

Authors: Praskovya Britskaya, Fatima Shaizadina, Alua Omarova, Nessipkul Alysheva

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Planned preventive vaccination, which is carried out in the Republic of Kazakhstan, promoted permanent decrease in the incidence of measles and viral hepatitis B. In the structure of VHB patients prevail people of young, working age. Monitoring of infectious incidence, monitoring of coverage of immunization of the population, random serological control over the immunity enable well-timed identification of distribution of the activator, effectiveness of the taken measures and forecasting. The serological blood analysis was conducted in indicator groups of the population of Central Kazakhstan for the purpose of identification of antibody titre for vaccine preventable infections (measles, viral hepatitis B). Measles antibodies were defined by method of enzyme-linked assay (ELA) with test-systems "VektoKor" – Ig G ('Vektor-Best' JSC). Antibodies for HBs-antigen of hepatitis B virus in blood serum was identified by method of enzyme-linked assay (ELA) with VektoHBsAg test systems – antibodies ('Vektor-Best' JSC). The result of the analysis is positive, the concentration of IgG to measles virus in the studied sample is equal to 0.18 IU/ml or more. Protective level of concentration of anti-HBsAg makes 10 mIU/ml. The results of the study of postvaccinal measles immunity showed that the share of seropositive people made 87.7% of total number of surveyed. The level of postvaccinal immunity to measles in age groups differs. So, among people older than 56 the percentage of seropositive made 95.2%. Among people aged 15-25 were registered 87.0% seropositive, at the age of 36-45 – 86.6%. In age groups of 25-35 and 36-45 the share of seropositive people was approximately at the same level – 88.5% and 88.8% respectively. The share of people seronegative to a measles virus made 12.3%. The biggest share of seronegative people was found among people aged 36-45 – 13.4% and 15-25 – 13.0%. The analysis of results of the examined people for the existence of postvaccinal immunity to viral hepatitis B showed that from all surveyed only 33.5% have the protective level of concentration of anti-HBsAg of 10 mIU/ml and more. The biggest share of people protected from VHB virus is observed in the age group of 36-45 and makes 60%. In the indicator group – above 56 – seropositive people made 4.8%. The high percentage of seronegative people has been observed in all studied age groups from 40.0% to 95.2%. The group of people which is least protected from getting VHB is people above 56 (95.2%). The probability to get VHB is also high among young people aged 25-35, the percentage of seronegative people made 80%. Thus, the results of the conducted research testify to the need for carrying out serological monitoring of postvaccinal immunity for the purpose of operational assessment of the epidemiological situation, early identification of its changes and prediction of the approaching danger.

Keywords: antibodies, blood serum, immunity, immunoglobulin

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63 Studies of Single Nucleotide Polymorphism of Proteosomal Gene Complex and Their Association with HBV Infection Risk in India

Authors: Jasbir Singh, Devender Kumar, Davender Redhu, Surender Kumar, Vandana Bhardwaj

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Single Nucleotide polymorphism (SNP) of proteosomal gene complex is involved in the pathogenesis of hepatitis B Virus (HBV) infection. Some of such proteosomal gene complex are large multifunctional proteins (LMP) and antigen associated transporters that help in antigen presentation. Both are involved in intracellular processing and presentation of viral antigens in association with Major Histocompatability Complex (MHC) Class I molecules. A total of hundred each of hepatitis B virus infected and control samples from northern India were studied. Genomic DNA was extracted from all studied samples and PCR-RFLP method was used for genotyping at different positions of LMP genes. Genotypes at a given position were inferred from the pattern of bands and genotype frequencies and haplotype frequencies were also calculated. Homozygous SNP {A>C} was observed at codon 145 of LMP7 gene and having a protective role against HBV as there was statistically significant high distribution of this SNP among controls than cases. Heterozygous SNP {A>C} was observed at codon 145 of LMP7 gene and made individuals more susceptible to HBV infection as there was statistically significant high distribution of this SNP among cases than control. SNP {T>C} was observed at codon 60 of LMP2 gene but statistically significant differences were not observed among controls and cases. For codon 145 of LMP7 and codon 60 of LMP2 genes, four haplotypes were constructed. Haplotype I (LMP2 ‘C’ and LMP7 ‘A’) made individuals carrying it more susceptible to HBV infection as there was statistically significant high distribution of this haplotype among cases than control. Haplotype II (LMP2 ‘C’ and LMP7 ‘C’) made individuals carrying it more immune to HBV infection as there was statistically significant high distribution of this haplotype among control than cases. Thus it can be concluded that homozygous SNP {A>C} at codon 145 of LMP7 and Haplotype II (LMP2 ‘C’ and LMP7 ‘C’) has a protective role against HBV infection whereas heterozygous SNP {A>C} at codon 145 of LMP7 and Haplotype I (LMP2 ‘C’ and LMP7 ‘A’) made individuals more susceptible to HBV infection.

Keywords: Hepatitis B Virus, single nucleotide polymorphism, low molecular weight proteins, transporters associated with antigen presentation

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62 Inducible Trans-Encapsidation System for Temporal Separation of Hepatitis C Virus Life Cycle

Authors: Ovidiu Vlaicu, Leontina Banica, Dan Otelea, Andrei-Jose Petrescu, Costin-Ioan Popescu

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Hepatitis C Virus (HCV) infects 170 million peoples worldwide. Major advances have been made recently in HCV standard of care with interferon-free therapy being already approved. Despite major progress in HCV therapy, the genotype associated treatment efficacy and toxicity still represent issues to address. To identify endogenous factors involved in different stages of HCV life cycle, we have developed a trans-packaging system for HCV subgenomic replicons lacking core protein gene. Huh7 cells were used to generate a packaging cell line expressing the core protein in an inducible manner. The core packaging cell line was able to trans-complemented various subgenomic replicons to secret infectious trans-complemented HCV particles (HCV-TCP). Further, we constructed subgenomic replicons with foreign epitopes suitable for immunoaffinity purification or fluorescence microscopy studies. We have shown that the insertion has not effects on the efficacy of trans-complementation yielding similar titers to the control subgenomic replicon. This system will be a valuable tool in studying pre- and post-assembly events in HCV life cycle and for the fast identification of HCV assembly inhibitors.

Keywords: assembly inhibitors, core protein, HCV, trans-complementation

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61 Pegylated Interferon in HCV Genotype 3 Relapser to Conventional Interferon in Pakistani Population

Authors: Saad Khalid Niaz, Arif Mahmood Siddiqui, Afzal Haqi

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Background: Estimated prevalence of Hepatitis C in Pakistan is 5% of which 78 % are Genotype 3, in which Response to conventional interferon is reported to be 70%. Objective: To determine the efficacy of pegylated interferon 20 kDa (Unipeg) plus ribavirin (Ribazole) in HCV genotype 3 patients who relapsed to conventional interferon. Methods: This is an ongoing study of 20 enrolled patients. Pegylated interferon alfa-2a 20 kDa 180 mcg weekly with ribavirin, were administered for a period of 24 weeks. Virological Responses were measured by Qualitative HCV RNA at weeks 4, 12, 24 and 48 to determine Rapid Virological Response (RVR), Early Virological Response (EVR), End of Treatment (ETR) and Sustained Virological Response (SVR), respectively. EVR was done for those who didn’t achieve RVR. Results: Males were 12 (60%) and mean age was 38.5 ±7.62 years. Out of 20 recruited patients, all completed 4 weeks therapy; RVR was achieved in 8 (40%) patients. One patient was lost to follow up and one yet to visit at 12 weeks. From 10 patients, 8 (80%) patients achieved EVR. Out of intent-to-treat patients, 15 completed 24 weeks therapy, ETR was achieved in 14 (93%) patients and 9 patients completed post therapy follow-up, of which, 8 (89%) patients achieved SVR. Conclusion: Our interim data demonstrates that Pegylated Interferon alfa-2a 20 kDa 180 mcg (Unipeg) in combination with Ribavirin (Ribazole) has shown promising results in treating HCV Genotype 3 patients who relapsed to conventional interferon. We recommend use of Pegylated Interferon in Relapsers with Genotype 3 when financial constraints limit the use of oral antivirals.

Keywords: pegylated interferon (unipeg), hepatitis c, relapsers, Pakistan

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60 Higher Freshwater Fish and Sea Fish Intake Is Inversely Associated with Liver Cancer in Patients with Hepatitis B

Authors: Maomao Cao

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Background and aims While the association between higher consumption of fish and lower liver cancer risk has been confirmed, however, the association between specific fish intake and liver cancer risk remains unknown. We aimed to identify the association between specific fish consumption and the risk of liver cancer. Methods: Based on a community-based seropositive hepatitis B cohort involving 18404 individuals, face to face interview was conducted by a standardized questionnaire to acquire baseline information. Three common fish types in this study were analyzed, including freshwater fish, sea fish, and small fish (shrimp, crab, conch, and shell). All participants received liver cancer screening, and possible cases were identified by CT or MRI. Multivariable logistic models were applied to estimate the odds ratio (OR) and 95% confidence intervals (CI). Multivariate multiple imputations were utilized to impute observations with missing values. Results: 179 liver cancer cases were identified. Consumption of freshwater fish and sea fish at least once a week had a strong inverse association with liver cancer risk compared with the lowest intake level, with an adjusted OR of 0.53 (95% CI, 0.38-0.75) and 0.38 (95% CI, 0.19-0.73), respectively. This inverse association was also observed after the imputation. There was no statistically significant association between intake of small fish and liver cancer risk (OR=0.58, 95%, CI 0.32-1.08). Conclusions: Our findings suggest that consumption of freshwater fish and sea fish at least once a week could reduce liver cancer risk.

Keywords: cross-sectional study, fish intake, liver cancer, risk factor

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59 Estrogen Controls Hepatitis C Virus Entry and Spread through the GPR30 Pathway

Authors: Laura Ulitzky, Dougbeh-Chris Nyan, Manuel M. Lafer, Erica Silberstein, Nicoleta Cehan, Deborah R. Taylor

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Hepatitis C virus (HCV)-associated hepatocellular carcinoma, fibrosis and cirrhosis are more frequent in men and postmenopausal women than in premenopausal women and women receiving hormone replacement therapy, suggesting that β-estradiol (estrogen) plays an innate role in preventing viral infection and liver disease. Estrogen classically acts through nuclear estrogen receptors or, alternatively, through the membrane-bound G-protein-coupled estrogen receptor (GPR30 or GPER). We observed a marked decrease in detectable virus when HCV-infected human hepatoma cells were treated with estrogen. The effect was mimicked by both Tamoxifen (Tam) and G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. Through GPR30, estrogen-mediated the down-regulation of occludin; a tight junction protein and HCV receptor, by promoting activation of matrix metalloproteinases (MMPs). Activated MMP-9 was secreted in response to estrogen, cleaving occludin in the extracellular Domain D, the motif required for HCV entry and spread. This pathway gives new insight into a novel innate immune pathway and the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral properties for HCV-infected postmenopausal women and show promise for new antiviral treatments for both men and women.

Keywords: HCV, estrogen, occludin, MMPs

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58 Predictors of Response to Interferone Therapy in Chronic Hepatitis C Virus Infection

Authors: Ali Kassem, Ehab Fawzy, Mahmoud Sef el-eslam, Fatma Salah- Eldeen, El zahraa Mohamed

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Introduction: The combination of interferon (INF) and ribavirin is the preferred treatment for chronic hepatitis C viral (HCV) infection. However, nonresponse to this therapy remains common and is associated with several factors such as HCV genotype and HCV viral load in addition to host factors such as sex, HLA type and cytokine polymorphisms. Aim of the work: The aim of this study was to determine predictors of response to (INF) therapy in chronic HCV infected patients treated with INF alpha and ribavirin combination therapy. Patients and Methods: The present study included 110 patients (62 males, 48 females) with chronic HCV infection. Their ages ranged from 20-59 years. Inclusion criteria were organized according to the protocol of the Egyptian National Committee for control of viral hepatitis. Patients included in this study were recruited to receive INF ribavirin combination therapy; 54 patients received pegylated NF α-2a (180 μg) and weight based ribavirin therapy (1000 mg if < 75 kg, 1200 mg if > 75 kg) for 48 weeks and 53 patients received pegylated INF α-2b (1.5 ug/kg/week) and weight based ribavirin therapy (800 mg if < 65 kg, 1000 mg if 65-75 kg and 1200 mg if > 75kg). One hundred and seven liver biopsies were included in the study and submitted to histopathological examination. Hematoxylin and eosin (H&E) stained sections were done to assess both the grade and the stage of chronic viral hepatitis, in addition to the degree of steatosis. Modified hepatic activity index (HAI) grading, modified Ishak staging and Metavir grading and staging systems were used. Laboratory follow up including: HCV PCR at the 12th week to assess the early virologic response (EVR) and at the 24th week were done. At the end of the course: HCV PCR was done at the end of the course and tested 6 months later to document end virologic response (ETR) and sustained virologic response (SVR) respectively. Results One hundred seven patients; 62 males (57.9 %) and 45 females (42.1%) completed the course and included in this study. The age of patients ranged from 20-59 years with a mean of 40.39±10.03 years. Six months after the end of treatment patients were categorized into two groups: Group (1): patients who achieved sustained virological response (SVR). Group (2): patients who didn't achieve sustained virological response (non SVR) including non-responders, breakthrough and relapsers. In our study, 58 (54.2%) patients showed SVR, 18 (16.8%) patients were non-responders, 15 (14%) patients showed break-through and 16 (15 %) patients were relapsers. Univariate binary regression analysis of the possible risk factors of non SVR showed that the significant factors were higher age, higher fasting insulin level, higher Metavir stage and higher grade of hepatic steatosis. Multivariate binary regression analysis showed that the only independent risk factor for non SVR was high fasting insulin level. Conclusion: Younger age, lower Metavir stage, lower steatosis grade and lower fasting insulin level are good predictors of SVR and could be used in predicting the treatment response of pegylated interferon/ribavirin therapy.

Keywords: chronic HCV infection, interferon ribavirin combination therapy, predictors to antiviral therapy, treatment response

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57 The Potential Effect of Climate Changes on Food and Water Associated Infections

Authors: Mohammed A. Alhoot, Rathika A/P Nagarajan

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Climate change and variability are affecting human health and diseases direct or indirectly through many mechanisms. Change in rain pattern, an increase of temperature and humidity are showing an increased trend in Malaysia. This will affect the biological, physical and chemical component of water through different pathways and will enhance the risk of waterborne diseases. Besides, the warm temperature and humid climate provide very suitable conditions for the growth of pathogenic bacteria. This study is intended to highlight the relationship between the climate changes and the incidence food and water associated infections. Incidences of food and water associated infection and climate data were collected from Malaysian Ministry of health and Malaysian Metrological Department respectively. Maximum and minimum temperature showed high correlation with incidence of typhoid, hepatitis A, dysentery, food poisoning (P value <0.05 significant with 2 tailed / 0.5<[r]). Heavy rainfall does not associated with any outbreaks. Climate change brings out new challenges in controlling food and water associated infections. Adaptation strategies should involve all key stakeholders with a strong regional cooperation to prevent and deal with cross-boundary health crises. Moreover, the role of health care personnel at local, state and national levels is important to ensure the success of these programmes. As has been shown herein, climate variability is an important element influencing the food and water associated epidemiology in Malaysia. The results of this study are crucial to implementing climate changes as a factor to reduce any future outbreaks.

Keywords: climate change, typhoid, hepatitis A, dysentery, food poisoning

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56 A Sui Generis Technique to Detect Pathogens in Post-Partum Breast Milk Using Image Processing Techniques

Authors: Yogesh Karunakar, Praveen Kandaswamy

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Mother’s milk provides the most superior source of nutrition to a child. There is no other substitute to the mother’s milk. Postpartum secretions like breast milk can be analyzed on the go for testing the presence of any harmful pathogen before a mother can feed the child or donate the milk for the milk bank. Since breast feeding is one of the main causes for transmission of diseases to the newborn, it is mandatory to test the secretions. In this paper, we describe the detection of pathogens like E-coli, Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV), Cytomegalovirus (CMV), Zika and Ebola virus through an innovative method, in which we are developing a unique chip for testing the mother’s milk sample. The chip will contain an antibody specific to the target pathogen that will show a color change if there are enough pathogens present in the fluid that will be considered dangerous. A smart-phone camera will then be acquiring the image of the strip and using various image processing techniques we will detect the color development due to antigen antibody interaction within 5 minutes, thereby not adding to any delay, before the newborn is fed or prior to the collection of the milk for the milk bank. If the target pathogen comes positive through this method, then the health care provider can provide adequate treatment to bring down the number of pathogens. This will reduce the postpartum related mortality and morbidity which arises due to feeding infectious breast milk to own child.

Keywords: postpartum, fluids, camera, HIV, HCV, CMV, Zika, Ebola, smart-phones, breast milk, pathogens, image processing techniques

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