Search results for: viral hepatitis

Authors: Alakija Temitope Olufunmilayo, Akinyemi, Yagba Joy

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Hepatitis is the inflammation of the liver tissue that can cause whiteness of the eyes (Jaundice), lack of appetite, vomiting, tiredness, abdominal pain, diarrhea. Hepatitis is acute if it resolves within 6 months and chronic if it last longer than 6 months. Acute hepatitis can resolve on its own, lead to chronic hepatitis or rarely result in acute liver failure. Chronic hepatitis may lead to scarring of the liver (Cirrhosis), liver failure and liver cancer. Modelling Hepatitis B may become necessary in order to reduce its spread. So, dynamic SIR model can be used. This model consists of a system of three coupled non-linear ordinary differential equation which does not have an explicit formula solution. It is an epidemiological model used to predict the dynamics of infectious disease by categorizing the population into three possible compartments. In this study, a five-compartment dynamic model of Hepatitis B disease was proposed and developed by adding control measure of sensitizing the public called awareness. All the mathematical and statistical formulation of the model, especially the general equilibrium of the model, was derived, including the nonlinear least square estimators. The initial parameters of the model were derived using nonlinear least square embedded in R code. The result study shows that the proportion of Hepatitis B patient in the study population is 1.4 per 1,000,000 populations. The estimated Hepatitis B induced death rate is 0.0108, meaning that 1.08% of the infected individuals die of the disease. The reproduction number of Hepatitis B diseases in Nigeria is 6.0, meaning that one individual can infect more than 6.0 people. The effect of sensitizing the public on the basic reproduction number is significant as the reproduction number is reduced. The study therefore recommends that programme should be designed by government and non-governmental organization to sensitize the entire Nigeria population in order to reduce cases of Hepatitis B disease among the citizens.

Keywords: hepatitis B, modelling, non-linear ordinary differential equation, sihar model, sensitization

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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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Authors: R. J. Kuo, W. C. Cheng, W. C. Lien, T. J. Yang

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Taiwan is a hyper endemic area for the Hepatitis B virus (HBV). The estimated total number of HBsAg carriers in the general population who are more than 20 years old is more than 3 million. Therefore, a case record review is conducted from January 2003 to June 2007 for all patients with a diagnosis of acute hepatitis who were admitted to the Emergency Department (ED) of a well-known teaching hospital. The cost for the use of medical resources is defined as the total medical fee. In this study, principal component analysis (PCA) is firstly employed to reduce the number of dimensions. Support vector regression (SVR) and artificial neural network (ANN) are then used to develop the forecasting model. A total of 117 patients meet the inclusion criteria. 61% patients involved in this study are hepatitis B related. The computational result shows that the proposed PCA-SVR model has superior performance than other compared algorithms. In conclusion, the Child-Pugh score and echogram can both be used to predict the cost of medical resources for patients with acute hepatitis in the ED.

Keywords: acute hepatitis, medical resource cost, artificial neural network, support vector regression

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Authors: Imeobong Joseph Inyang, Aniekan-Augusta Okon Eyo, Abel William Essien

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Hepatitis B virus (HBV) is one of the known human carcinogens. The presence of HBsAg in liver tissues indicates active viral replication. More than 85% of Hepatocellular Carcinoma (HCC) cases occur in countries with increased rates of chronic HBV infection. An evaluation study to determine the relationship between positivity for HBsAg and development of HCC and its distribution between age and gender of subjects was done. Shikata Orcein and Haematoxylin and Eosin (H&E) staining techniques were performed on liver sections. A total of 50 liver tissue specimens comprising 38 biopsy and 12 post-mortem specimens were processed. Thirty-five of the 50 specimens were positive for HBsAg with Orcein stain whereas only 16 were positive with H&E stain, and these were also positive with Orcein stain, giving an HBsAg prevalence of 70.0% (35/50). The prevalence of HCC in the study was 56.0% (28/50), of which 21 (75.0%) cases were positive for HBsAg, 18 (64.3%) were males while 10 (35.7%) were females distributed within the age range of 20-70 years. The highest number of HBsAg positive HCC cases, 7/21 (33.3%) occurred in the age group 40-49 years. There was no relationship in the pattern of distribution of HCC between age and gender using the Pearson correlation coefficient (r = 0.0474; P < 0.05). HBV infection predisposed to HCC. Orcein technique was more specific and is therefore recommended for screening of liver tissues where facilities for immunohistochemistry are inaccessible.

Keywords: Hepatitis B. surface antigen, hepatocellular carcinoma, orcein, pathology

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Authors: Khabat Barkhordari, Ali Mohammad Arabzadeh

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Hepatitis delta virus (HDV) is a RNA virus that needs the function of hepatitis B virus (HBV) for its propagation and assembly. Infection by HDV can occur spontaneously with HBV infection and cause acute hepatitis or develop as secondary infection in HBV suffering patients. Based on genome sequence analysis, HDV has several genotypes which show broad geographic and diverse clinical features. The aim of current study is determine the prevalence of hepatitis delta virus genotype in patients with positive HBsAg in Kerman province of Iran. This cross-sectional study a total of 400 patients with HBV infection attending the clinic center of Besat from 2012 to 2014 were included. We carried out ELISA to detect anti-HDV antibodies. Those testing positive were analyzed further for HDV-RNA and for genotyping using restriction fragment length polymorphism (RFLP) and RT-nested PCR- sequencing. Among 400 patients in this study, 67 cases (16.75 %) were containing anti-HDV antibody which we found HDV RNA in just 7 (1.75%) serum samples. Analysis of these 7 positive HDV showed that all of them have genotype I. According to current study the HDV prevalence in Kerman is higher than the reported prevalence of 6.6% for Iran as a whole and clade 1 (genotype 1) is the predominant clade of HDV in Kerman.

Keywords: genotyping, hepatitis delta virus, molecular epidemiology, Kerman, Iran

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Authors: S. Essa, H. Safar, R. Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications to immunologically immature and immune-compromised hosts. Effective CMV vaccine that diminishes CMV disease in transplant patients and avoids congenital infection remains of high importance as no approved vaccines exist. Though the exact links of defense mechanisms are unidentified, viral-specific antibodies and Th1/Th2 cytokine responses have been involved in controlling viral infections. CMV envelope glycoprotein B (UL55/gB), the matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and the assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. In this study, mice were immunized with five HCMV antigens (UL32/pp150, UL80a/pp38, UL99/pp28, and UL83/pp65), and serum samples were collected and evaluated for eliciting viral-specific antibody responses. Moreover, Splenocytes were collected, stimulated, and assessed for cytokine responses. The results demonstrated a CMV-antigen-specific antibody response to pp38 and pp65 (E/C >2.0). The highest titers were detected with pp38 (average E/C 16.275) followed by pp65 (average E/C 7.72). Compared to control cells, splenocytes from PP38 antigen immunized mice gave a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-5, and IL-17A (P<0.05). Also, splenocytes from pp65 antigen immunized mice resulted in a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF- α. The designation of target CMV peptides by identifying viral-specific antibodies and cytokine responses is vital for understanding the protective immune mechanisms during CMV infection and identifying appropriate viral antigens to develop novel vaccines.

Keywords: hepatitis C virus, peripheral blood mononuclear cells, neutrophils, cytokines

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Authors: Yasser Ahmed Mahmoud Ali Helal

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The use of CAD (Computer Aided Design) technology is ubiquitous in the architecture, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of architecture schools in Nigeria as an important part of the training module. This article examines the ethical issues involved in implementing CAD (Computer Aided Design) content into the architectural education curriculum. Using existing literature, this study begins with the benefits of integrating CAD into architectural education and the responsibilities of different stakeholders in the implementation process. It also examines issues related to the negative use of information technology and the perceived negative impact of CAD use on design creativity. Using a survey method, data from the architecture department of University was collected to serve as a case study on how the issues raised were being addressed. The article draws conclusions on what ensures successful ethical implementation. Millions of people around the world suffer from hepatitis C, one of the world's deadliest diseases. Interferon (IFN) is treatment options for patients with hepatitis C, but these treatments have their side effects. Our research focused on developing an oral small molecule drug that targets hepatitis C virus (HCV) proteins and has fewer side effects. Our current study aims to develop a drug based on a small molecule antiviral drug specific for the hepatitis C virus (HCV). Drug development using laboratory experiments is not only expensive, but also time-consuming to conduct these experiments. Instead, in this in silicon study, we used computational techniques to propose a specific antiviral drug for the protein domains of found in the hepatitis C virus. This study used homology modeling and abs initio modeling to generate the 3D structure of the proteins, then identifying pockets in the proteins. Acceptable lagans for pocket drugs have been developed using the de novo drug design method. Pocket geometry is taken into account when designing ligands. Among the various lagans generated, a new specific for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication

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Authors: Rizky Kusuma Cahyani

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Hepatitis B is a liver inflammatory disease caused by hepatitis B virus (HBV). This infection can be prevented by vaccination which contains HBV surface protein (sHBsAg). However, vaccine supply is limited. Several attempts have been conducted to produce local sHBsAg. However, the purity degree and protein yield are still inadequate. Therefore optimization of HBsAg purification steps is required to obtain high yield with better purification fold. In this study, optimization of purification was done in 2 steps, precipitation using variation of NaCl concentration (0,3 M; 0,5 M; 0,7 M) and PEG (3%, 5%, 7%); ion exchange chromatography (IEC) using NaCl 300-500 mM elution buffer concentration.To determine HBsAg protein, bicinchoninic acid assay (BCA) and enzyme-linked immunosorbent assay (ELISA) was used in this study. Visualization of HBsAg protein was done by SDS-PAGE analysis. Based on quantitative analysis, optimal condition at precipitation step was given 0,3 M NaCl and PEG 3%, while in ion exchange chromatography step, the optimum condition when protein eluted with NaCl 500 mM. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicates that the presence of protein HBsAg with a molecular weight of 25 kDa (monomer) and 50 kDa (dimer). The optimum condition for purification of sHBsAg produced in Pichia pastoris gave a yield of 47% and purification fold 17x so that it would increase the production of hepatitis B vaccine to be more optimal.

Keywords: hepatitis B virus, HBsAg, hepatitis B surface antigen, Pichia pastoris, purification

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Authors: Mohammad J. J. Taha, Mohammad T. Abuawwad, Warda A. Alrubasy, Shams Khalid Sameer, Taleb Alsafi, Yaqeen Al-Bustanji, Luai Abu-Ismail, Abdulqadir J. Nashwan

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Viral pandemics often take the world by storm, urging the medical community to prioritize the most evident systemic manifestations, often causing ocular manifestations to go unnoticed. This literature review aims to highlight the ocular complications of monkeypox, SARS-CoV-2, MERS, ebola, H1N1, and zika viruses as the most recent viral pandemics. Since the emergence of the newly resurfacing monkeypox and the novel SARS-CoV-2, research aiming to uncover the effects of these pandemics began right away. Moreover, it also discusses the ocular complications of the vaccines and treatments that were used in the scope of the viral pandemics. To add, this work discussed the role of the eye as an important route of viral transmission, and thereafter, the American Academy of Ophthalmology (AAO) recommendations to reduce the incidence of viral transmission were mentioned. Finally, this paper aims to outline a platform for researchers who are interested in further investigating eye-related viral manifestations.

Keywords: ophthalmology, monkeypox, ebola, zika, MERS, H1N1, influenza, COVID-19

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Authors: Khabat Barkhordari

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Hepatitis delta virus (HDV) is a RNA virus that needs the function of hepatitis B virus (HBV) for its propagation and assembly. Infection by HDV can occur spontaneously with HBV infection and cause acute hepatitis or develop as secondary infection in HBV suffering patients. Based on genome sequence analysis, HDV has several genotypes which show broad geographic and diverse clinical features. The aim of current study is determine the molecular epidemiology of hepatitis delta virus genotype in patients with positive HBsAg among different ethnic groups of Iran. This systematic review study reviews the results of different studies which examined 2000 Iranian patients with HBV infection from 2010 to 2015. Among 2000 patients in this study, 16.75 % were containing anti-HDV antibody and HDV RNA was found in just 1.75% cases. All of positive cases also have genotype I.

Keywords: HDV, genotype, epidemiology, distribution

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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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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

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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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Authors: Jihene Bettaieb, Kaouther Ayouni, Ghassen Kharroubi, Rym Mallekh, Walid Hammemi, Afif Ben Salah, Henda Triki

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In Tunisia, the hepatitis A virus (HAV) represents a public health concern. Due to the progress in sanitation and socio-economic conditions, the epidemiology of HAV has shown dynamic changes over the past years. This study aimed to investigate the current seroprevalence of HAV antibodies (anti-HAV) among the residents of Thala, a rural setting in central-west Tunisia, to determine the age-specific seroprevalence for HAV infection and co-infection with hepatitis C and B virus. A total of 1379 subjects (mean age: 25.0 ± 17.3 years, 555 males/ 824 females) were recruited between January and June 2014. The study population included 95 individuals previously known as hepatitis C positive. Serum samples were collected and screened for the detection of IgG anti-HAV, HBsAg, and HBcAb by the Elisa Test. The overall anti- HAV seroprevalence was about 84.7%. There was no statistically significant difference between males and females. On the 1379 tested individual, 219 were positive for HBcAb, and 67 were positive for HBsAg. IgG anti- HAV were positive in 80.6% of HBsAg-positive patients (54 out of 67), 81.3% of HBcAb-positive patients (178 out of 219), and in 95.8% of HCV-positive patients (91 out of 95). HBV infection and HCV infection were statistically associated with a greater risk of positive anti-HAV antibody (p < 0.001). Our study revealed that Thala represents an intermediate endemicity level and that the introduction of vaccination against HAV in this region is recommended, especially for the hepatitis B or C infected person seronegative for HAV.

Keywords: coinfection, hepatitis A, seroprevalence, Tunisia

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Authors: Yanhua Zhao, Yu Gou, Shu Feng, Dongdong Li, Chuanmin Tao

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The natural history of HBV infection could experience immune tolerant (IT), immune clearance (IC), HBeAg-negative inactive/quienscent carrier (ENQ), and HBeAg-negative hepatitis (ENH). As current biomarkers for discriminating these four phases have some weaknesses, additional serological indicators are needed. Hepatits B core-related antigen (HBcrAg) encoded with precore/core gene contains denatured HBeAg, HBV core antigen (HBcAg) and a 22KDa precore protein (p22cr), which was demonstrated to have a close association with natural history of hepatitis B infection, but no specific cutoff values and diagnostic parameters to evaluate the diagnostic efficacy. This study aimed to clarify the distribution of HBcrAg levels and evaluate its diagnostic performance during the natural history of infection from a Western Chinese perspective. 294 samples collected from treatment-naïve chronic hepatitis B (CHB) patients in different phases (IT=64; IC=72; ENQ=100, and ENH=58). We detected the HBcrAg values and analyzed the relationship between HBcrAg and HBV DNA. HBsAg and other clinical parameters were quantitatively tested. HBcrAg levels of four phases were 9.30 log U/mL, 8.80 log U/mL, 3.00 log U/mL, and 5.10 logU/mL, respectively (p < 0.0001). Receiver operating characteristic curve analysis demonstrated that the area under curves (AUCs) of HBcrAg and quantitative HBsAg at cutoff values of 9.25 log U/mL and 4.355 log IU/mL for distinguishing IT from IC phases were 0.704 and 0.694, with sensitivity 76.39% and 59.72%, specificity 53.13% and 79.69%, respectively. AUCs of HBcrAg and quantitative HBsAg at cutoff values of 4.15 log U/mlmL and 2.395 log IU/mlmL for discriminating between ENQ and ENH phases were 0.931 and 0.653, with sensitivity 87.93% and 84%, specificity 91.38% and 39%, respectively. Therefore, HBcrAg levels varied significantly among four natural phases of HBV infection. It had higher predictive performance than quantitative HBsAg for distinguishing between ENQ-patients and ENH-patients and similar performance with HBsAg for the discrimination between IT and IC phases, which indicated that HBcrAg could be a potential serological marker for CHB.

Keywords: chronic hepatitis B, hepatitis B core-related antigen, hepatitis B surface antigens, hepatitis B virus

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Authors: Tatyana Savchuk, Yelena Grinvald, Mohamed Ali, Ramune Sepetiene, Dinara Sadvakassova, Saniya Saussakova, Kuralay Zhangazieva, Dulat Imashpayev

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Introduction. The problem of viral hepatitis B (HBV) takes a vital place in the global health system. The existing risk of HBV transmission through blood transfusions is associated with transfusion of blood taken from infected individuals during the “serological window” period or from patients with latent HBV infection, the marker of which is anti-HBcore. In the absence of information about other markers of hepatitis B, the presence of anti-HBcore suggests that a person may be actively infected or has suffered hepatitis B in the past and has immunity. Aim. To study the risk factors influencing the positive anti-HBcore indicators among the donor population. Materials and Methods. The study was conducted in 2021 in the Scientific and Production Center of Transfusiology of the Ministry of Healthcare in Kazakhstan. The samples taken from blood donors were tested for anti-HBcore, by CLIA on the Architect i2000SR (ABBOTT). A special questionnaire was developed for the blood donors’ socio-demographic characteristics. Statistical analysis was conducted by the R software (version 4.1.1, USA, 2021). Results.5709 people aged 18 to 66 years were included in the study, the proportion of men and women was 68.17% and 31.83%, respectively. The average age of the participants was 35.7 years. A weighted multivariable mixed effects logistic regression analysis showed that age (p<0.001), ethnicity (p<0.05), and marital status (p<0.05) were statistically associated with anti-HBcore positivity. In particular, analysis adjusting for gender, nationality, education, marital status, family history of hepatitis, blood transfusion, injections, and surgical interventions, with a one-year increase in age (adjOR=1.06, 95%CI:1.05-1.07), showed an 6% growth in odds of having anti-HBcore positive results. Those who were russian ethnicity (adjOR=0.65, 95%CI:0.46-0.93) and representatives of other nationality groups (adjOR=0.56, 95%CI:0.37-0.85) had lower odds of having anti-HBcore when compared to Kazakhs when controlling for other covariant variables. Among singles, the odds of having a positive anti-HBcore were lower by 29% (adjOR = 0.71, 95%CI:0.57-0.89) compared to married participants when adjusting for other variables. Conclusions.Kazakhstan is one of the countries with medium endemicity of HBV prevalence (2%-7%). Results of the study demonstrated the possibility to form a profile of risk factors (age, nationality, marital status). Taking into account the data, it is recommended to increase attention to donor questionnaires by adding leading questions and to improve preventive measures to prevent HBV. Funding. This research was supported by a grant from Abbott Laboratories.

Keywords: anti-HBcore, blood donor, donation, hepatitis B virus, occult hepatitis

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Authors: Shahabeddin Sotudian, M. H. Fazel Zarandi, I. B. Turksen

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Hepatitis is one of the most common and dangerous diseases that affects humankind, and exposes millions of people to serious health risks every year. Diagnosis of Hepatitis has always been a challenge for physicians. This paper presents an effective method for diagnosis of hepatitis based on interval Type-II fuzzy. This proposed system includes three steps: pre-processing (feature selection), Type-I and Type-II fuzzy classification, and system evaluation. KNN-FD feature selection is used as the preprocessing step in order to exclude irrelevant features and to improve classification performance and efficiency in generating the classification model. In the fuzzy classification step, an “indirect approach” is used for fuzzy system modeling by implementing the exponential compactness and separation index for determining the number of rules in the fuzzy clustering approach. Therefore, we first proposed a Type-I fuzzy system that had an accuracy of approximately 90.9%. In the proposed system, the process of diagnosis faces vagueness and uncertainty in the final decision. Thus, the imprecise knowledge was managed by using interval Type-II fuzzy logic. The results that were obtained show that interval Type-II fuzzy has the ability to diagnose hepatitis with an average accuracy of 93.94%. The classification accuracy obtained is the highest one reached thus far. The aforementioned rate of accuracy demonstrates that the Type-II fuzzy system has a better performance in comparison to Type-I and indicates a higher capability of Type-II fuzzy system for modeling uncertainty.

Keywords: hepatitis disease, medical diagnosis, type-I fuzzy logic, type-II fuzzy logic, feature selection

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Authors: T. G. Kassem, A. K. Adunchezor, J. P. Chollom

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This paper describes a mathematical model developed to predict the dynamics of Hepatitis B virus (HBV) infection and to evaluate the potential impact of vaccination and treatment on its dynamics. We used a compartmental model expressed by a set of differential equations based on the characteristic of HBV transmission. With these, we find the threshold quantity R0, then find the local asymptotic stability of disease free equilibrium and endemic equilibrium. Furthermore, we find the global stability of the disease free and endemic equilibrium.

Keywords: hepatitis B virus, epidemiology, vaccination, mathematical model

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Authors: Ying-Jung Hsieh, Angela S. Huang, Chu-Ming Chiu, Yu-Min Chou, Chin-Hui Yang

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Background and Objectives: Hepatitis A is primarily acquired by the fecal-oral route through person-to-person contact or ingestion of contaminated food or water. During 2010 to 2014, an average of 83 cases of locally-acquired disease was reported to Taiwan’s notifiable disease system. Taiwan Centers for Disease Control (TCDC) identified an outbreak of acute hepatitis A which began in June 2015. Of the 126 cases reported in 2015, 103 (82%) cases were reported during June–December and 95 cases (92%) of them were male. The average age of all male cases was 31 years (median, 29 years; range, 15–76 years). Among the 95 male cases, 49 (52%) were also infected with HIV, and all reported to have had sex with other men. To control this outbreak, TCDC launched a free hepatitis A vaccination program in January 2016 for close contacts of confirmed hepatitis A cases, including family members, sexual partners, and household contacts. Effect of the vaccination program was evaluated. Methods: All cases of hepatitis A reported to the National Notifiable Disease Surveillance System were included. A case of hepatitis A was defined as a locally-acquired disease in a person who had acute clinical symptoms include fever, malaise, loss of appetite, nausea or abdominal discomfort compatible with hepatitis, and tested positive for anti-HAV IgM during June 2015 to June 2016 in Taiwan. The rate of case accumulation was calculated using a simple regression model. Results: During January–June 2016, there were 466 cases of hepatitis A reported; of the 243 (52%) who were also infected with HIV, 232 (95%) had a history of having sex with men. Of the 346 cases that were followed up, 259 (75%) provided information on contacts but only 14 (5%) of them provided the name of their sexual partners. Among the 602 contacts reported, 349 (58%) were family members, 14 (2%) were sexual partners, and 239 (40%) were other household contacts. Among the 602 contacts eligible for free hepatitis A vaccination, 440 (73%) received the vaccine. There were 87 (25%) cases that refused to disclose their close contacts. The average case accumulation rate during January–June 2016 was 21.7 cases per month, which was 6.8 times compared to the average case accumulation rate during June–December 2015 of 3.2 cases per month. Conclusions: Despite vaccination program aimed to provide free hepatitis A vaccine to close contacts of hepatitis A patients, the outbreak continued and even gained momentum in transmission. Refusal by hepatitis A patients to provide names of their close contacts and rejection of contacts to take the hepatitis A vaccine may have contributed to the poor effect of the program. Targeted vaccination efforts of all MSM may be needed to control the outbreak among this population in the short term. In the long term, universal vaccination program is needed to prevent the infection of hepatitis A.

Keywords: hepatitis A, HIV, men who have sex with men, vaccination

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Authors: Umme Shahera, Saifullah Munshi, Munira Jahan, Afzalun Nessa, Shahinul Alam, Shahina Tabassum

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The development of HCC is a multi-stage process. Several extrinsic factors, such as aflatoxin, HBV, nutrition, alcohol, and trace elements are thought to initiate or/and promote the hepatocarcinogenesis. Alteration of p53 status is an important intrinsic factor in this process as p53 is essential for preventing inappropriate cell proliferation and maintaining genome integrity following genotoxic stress. This study was designed to assess the correlation of p53 gene expression with HBV-DNA and serum Alanine transaminase (ALT) in patients with cirrhosis and HCC. The study was conducted among 60 patients. The study population were divided into four groups (15 in each groups)-HBV positive cirrhosis, HBV negative cirrhosis, HBV positive HCC and HBV negative HCC. Expression of p53 gene was observed using real time PCR. P53 gene expressions in the above mentioned groups were correlated with serum ALT level and HBV viral load. p53 gene was significantly higher in HBV-positive patients with HCC than HBV-positive cirrhosis. Similarly, the expression of p53 was significantly higher in HBV-positive HCC than HBV-negative HCC patients. However, the expression of p53 was reduced in HBV-positive cirrhosis in comparison with HBV-negative cirrhosis. P53 gene expression in liver was not correlated with the serum levels of ALT in any of the study groups. HBV- DNA load also did not correlated with p53 gene expression in HBV positive HCC and HBV positive cirrhosis patients. This study shows that there was no significant change with the expression of p53 gene in any of the study groups with ALT level or viral load, though differential expression of p53 gene were observed in cirrhosis and HCC patients.

Keywords: P53, ALT, HBV-DNA, liver cirrhosis, hepatocellular carcinoma

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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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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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Authors: G. Shiha, S. Seif, W. Samir, K. Zalata

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Prospective Validation of the FibroTest Score in assessing Liver Fibrosis in Hepatitis C Infection with Genotype 4 FibroTest (FT) is non-invasive score of liver fibrosis that combines the quantitative results of 5 serum biochemical markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma glutamyl transpeptidase (GGT) and bilirubin) and adjusted with the patient's age and sex in a patented algorithm to generate a measure of fibrosis. FT has been validated in patients with chronic hepatitis C (CHC) (Halfon et al., Gastroenterol. Clin Biol.( 2008), 32 6suppl 1, 22-39). The validation of fibro test ( FT) in genotype IV is not well studied. Our aim was to evaluate the performance of FibroTest in an independent prospective cohort of hepatitis C patients with genotype 4. Subject was 122 patients with CHC. All liver biopsies were scored using METAVIR system. Our fibrosis score(FT) were measured, and the performance of the cut-off score were done using ROC curve. Among patients with advanced fibrosis, the FT was identically matched with the liver biopsy in 18.6%, overestimated the stage of fibrosis in 44.2% and underestimated the stage of fibrosis in 37.7% of cases. Also in patients with no/mild fibrosis, identical matching was detected in 39.2% of cases with overestimation in 48.1% and underestimation in 12.7%. So, the overall results of the test were identical matching, overestimation and underestimation in 32%, 46.7% and 21.3% respectively. Using ROC curve it was found that (FT) at the cut-off point of 0.555 could discriminate early from advanced stages of fibrosis with an area under ROC curve (AUC) of 0.72, sensitivity of 65%, specificity of 69%, PPV of 68%, NPV of 66% and accuracy of 67%. As FibroTest Score overestimates the stage of advanced fibrosis, it should not be considered as a reliable surrogate for liver biopsy in hepatitis C infection with genotype 4.

Keywords: fibrotest, chronic Hepatitis C, genotype 4, liver biopsy

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

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Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown cause. Concomitant autoimmune disorders have been described in 30–50% of patients with AIH. The aim of our study is to determine the prevalence and the type of autoimmune disorders associated with AIH. Material and Methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for AIH. The diagnosis of AHI was based on the criteria of the revised International AIH group scoring system (IAIHG). Results: Twenty-for patients (21 women and 3 men) followed for AIH were collected. The mean age was 39 years (17-65 years). Among these patients, 11 patients(45.8%) had at least one autoimmune disease associated to AIH. These diseases were Hashimoto's thyroiditis (n = 5), Gougerot Sjogren syndrome (n=5), Primary biliary cirrhosis (n=2), Primitive sclerosant Cholangitis (n=1), Addison disease (n = 1) and systemic sclerosis (n=1). Patients were treated with corticosteroids alone or with azathioprine associated to the specific treatment of associated diseases with complete remission of AIH in 90% of cases and clinical improvement of other diseases. Conclusion: In our study, the prevalence of autoimmune diseases in AIH patients was 45.8%. These diseases were dominated by autoimmune thyroiditis and Gougerot Sjogren syndrome. The investigation of autoimmune diseases in autoimmune hepatitis must be systematic because of their frequency and the importance of adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, autoimmune thyroiditis, gougerot sjogren syndrome

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Authors: M. Shemis, O. Maher, G. Casterou, F. Gauffre

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Hepatitis C virus (HCV) is a major cause of chronic liver disease with a global 170 million chronic carriers at risk of developing liver cirrhosis and/or liver cancer. Egypt reports the highest prevalence of HCV worldwide. Currently, two classes of assays are used in the diagnosis and management of HCV infection. Despite the high sensitivity and specificity of the available diagnostic assays, they are time-consuming, labor-intensive, expensive, and require specialized equipment and highly qualified personal. It is therefore important for clinical and economic terms to develop a low-tech assay for the direct detection of HCV RNA with acceptable sensitivity and specificity, short turnaround time, and cost-effectiveness. Such an assay would be critical to control HCV in developing countries with limited resources and high infection rates, such as Egypt. The unique optical and physical properties of gold nanoparticles (AuNPs) have allowed the use of these nanoparticles in developing simple and rapid colorimetric assays for clinical diagnosis offering higher sensitivity and specificity than current detection techniques. The current research aims to develop a detection assay for HCV RNA using gold nanoparticles (AuNPs). Methods: 200 anti-HCV positive samples and 50 anti-HCV negative plasma samples were collected from Egyptian patients. HCV viral load was quantified using m2000rt (Abbott Molecular Inc., Des Plaines, IL). HCV genotypes were determined using multiplex nested RT- PCR. The assay is based on the aggregation of AuNPs in presence of the target RNA. Aggregation of AuNPs causes a color shift from red to blue. AuNPs were synthesized using citrate reduction method. Different sets of probes within the 5’ UTR conserved region of the HCV genome were designed, grafted on AuNPs and optimized for the efficient detection of HCV RNA. Results: The nano-gold assay could colorimetrically detect HCV RNA down to 125 IU/ml with sensitivity and specificity of 91.1% and 93.8% respectively. The turnaround time of the assay is < 30 min. Conclusions: The assay allows sensitive and rapid detection of HCV RNA and represents an inexpensive and simple point-of-care assay for resource-limited settings.

Keywords: HCV, gold nanoparticles, point of care, viral load

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Authors: Ananya Pal, Neelakshi Sarkar, Debraj Saha, Dipanwita Das, Subhashish Kamal Guha, Bibhuti Saha, Runu Chakravarty

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Presently, tenofovir disoproxil fumurate (TDF) is the most effective anti-viral agent for the treatment of hepatitis B virus (HBV) in individuals co-infected with HIV and HBV as TDF has activity to suppress both wild-type and lamivudine (3TC)-resistant HBV. However, suboptimal response to TDF was reported in HIV-HBV co-infected individuals with prior 3TC therapy from different countries recently. The incidence of 3TC-resistant HBV strains is quite high in HIV-HBV co-infected patients experiencing long-term anti-retroviral therapy (ART) in eastern India. In spite of this risk, most of the patients with long-term 3TC treatment are continued with the same anti-viral agent in this country. Only a few have received TDF in addition to 3TC in the ART regimen since TDF has been available in India for the treatment of HIV-infected patients in 2012. In this preliminary study, we investigated the virologic and biochemical parameters among HIV-HBV co-infected patients who are non-responders to 3TC treatment during the continuation of 3TC or TDF add-on to 3TC in their ART regimen. Fifteen HIV-HBV co-infected patients who experienced long-term 3TC (mean duration months 36.87 ± 24.08 months) were identified with high HBV viremia ( > 20,000 IU/ml) or harbouring 3TC-resistant HBV. These patients receiving ART from School of Tropical Medicine Kolkata, the main ART centre in eastern India were followed-up semi-annually for next three visits. Different virologic parameters including quantification of plasma HBV load by real-time PCR, detection of hepatitis B e antigen (HBeAg) by commercial ELISA and anti-viral resistant mutations by sequencing were studied. During three follow-up among study subjects, 86%, 47%, and 43% had 3TC-mono-therapy (mean treatment-duration 41.54±18.84, 49.67±11.67, 54.17±12.37 months respectively) whereas 14%, 53%, and 57% experienced TDF in addition to 3TC (mean treatment duration 4.5±2.12, 16.56±11.06, and 23±4.07 months respectively). Mean CD4 cell-count in patients receiving 3TC was tended to be lower during third follow-up as compared to the first and the second [520.67±380.30 (1st), 454.8±196.90 (2nd), and 397.5±189.24 (3rd) cells/mm3) and similar trend was seen in patients experiencing TDF in addition to 3TC [334.5±330.218 (1st), 476.5±194.25 (2nd), and 461.17±269.89 (3rd) cells/mm3]. Serum HBV load was increased during successive follow-up of patients with 3TC-mono-therapy. Initiation of TDF lowered serum HBV-load among 3TC-non-responders at the time of second visit ( < 2,000 IU/ml), interestingly during third follow-up, mean HBV viremia increased >1 log IU/ml (mean 3.56±2.84 log IU/ml). Persistence of 3TC-resistant double and triple mutations was also observed in both the treatment regimens. Mean serum alanine aminotransferase remained elevated in these patients during this follow-up study. Persistence of high HBV viraemia and 3TC-resistant mutation in HBV during the continuation of 3TC might lead to major public health threat in India. The inclusion of TDF in the ART regimen of 3TC non-responder HIV-HBV co-infected patients showed adverse treatment response in terms of virologic and biochemical parameters. Therefore, serious attention is necessary for proper management of long-term 3TC experienced HIV-HBV co-infected patients with high HBV viraemia or 3TC-resistant HBV mutants in India.

Keywords: HBV, HIV, TDF, 3TC-resistant

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Authors: Gamal Shiha, Seham Seif, Shahera Etreby, Khaled Zalata, Waleed Samir

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Background: Transient Elastography (TE; FibroScan®) is a non-invasive technique to assess liver fibrosis. Aim: To compare TE and liver biopsy in hepatitis C virus (HCV) patients, genotype IV and evaluate the effect of steatosis and schistosomiasis on FibroScan. Methods: The fibrosis stage (METAVIR Score) TE, was assessed in 519 patients. The diagnostic performance of FibroScan is assessed by calculating the area under the receiver operating characteristic curves (AUROCs). Results: The cut-off value of ≥ F2 was 8.55 kPa, ≥ F3 was 10.2 kPa and cirrhosis = F4 was 16.3 kPa. The positive predictive value and negative predictive value were 70.1% and 81.7% for the diagnosis of ≥ F2, 62.6% and 96.22% for F ≥ 3, and 27.7% and 100% for F4. No significant difference between schistosomiasis, steatosis degree and FibroScan measurements. Conclusion: Fibroscan could accurately predict liver fibrosis.

Keywords: chronic hepatitis C, FibroScan, liver biopsy, liver fibrosis

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Authors: Semaw A., Awet H., Yohannes M.

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Background: Hepatitis B Virus (HBV) is a major global public health problem. Individuals living in Sub-Sahara Africa have 60% lifetime risk of acquiring HBV infection. Evidences showed that 80-90% of those born from infected mothers developed chronic HBV. Perinatal HBV transmission is a major determinant of HBV carrier status, its chronic squeal and maintains HBV transmission across generations. Method: Institution based cross-sectional study was conducted among 406 pregnant mothers attending Antenatal clinics at Mekelle and Ayder referral hospital from January 30 to April 1/2014. Epidata version 3.1 was used for data entry and SPSS version 21 statistical software was used for data cleaning, management and finally determine associated factors of hepatitis B surface antigen adjusting important confounders using multivariable logistic regression analysis at 5% level of significance. Result: The overall prevalence of hepatitis B surface antigen among pregnant women was 33 (8.1%). The socio-demographic characteristic of the study population showed that there is high positivity among secondary school 189 (46.6%). In the multivariable logistic regression analysis, history of a contact with individuals who had history of hepatitis B infection or jaundice and lifetime number of multiple sexual partners were found to be significantly associated with HBsAg positivity at AOR = 3.73 95%C.I (1.373-10.182) and AOR = 2.57 95%C.I (1.173-5.654), respectively. Moreover, Human Immunodeficiency Virus (HIV) and HBV confection rate was found 3.6%. Conclusion: This study has shown that HBV prevalence in pregnant women is highly prevalent (8.1%) in the study area. Contact with individuals who had a history of hepatitis or have jaundice and report of multiple lifetime sexual partnership were associated with hepatitis B infection. Education about HBV transmission and prevention as well as screening all pregnant mothers shall be sought to reduce the serious public health crisis of HBV.

Keywords: HBsAg, hepatitis B, pregnant women, prevalence

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Authors: Zakieh Rostamzadeh Khameneh, Nariman Sepehrvand, Khalkhali-Zahra Shirmohamadi

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Background: Although the hepatitis E virus mostly causes a self-limited disease in general population, the disease is more severe in pregnant women. Hepatitis E accounts for about 10% of pregnancy-associated deaths in southern Asia. Methods: 136 pregnant women who referred to urban health centers of Urmia for pursuing pregnancy-related health services were selected randomly and enrolled in a descriptive, cross-sectional study. Each subject was tested for the presence of anti-HEV IgG antibody using an enzyme-linked immunosorbent assay (ELISA, Dia.Pro). Results: The mean age among 136 pregnant women was 25.12±4.91 years old (range of 14-39 years). Only five cases (3.6%) among all 136 subjects were demonstrated to be seropositive for anti-HEV IgG using ELISA method. There was no significant difference between age (P=0.88), income level (P=0.19) of two seropositive and seronegative groups. All seropositive cases were from urban areas. Conclusion: The seroprevalence of anti-HEV IgG is low in the population of pregnant women in Urmia, Iran. Because of limited sample size in this study, we recommend to perform further studies with larger sample size in other regions of Iran in order to be able to systematically generalize the findings of studies to the population of Iranian pregnant women.

Keywords: pregnancy, hepatitis E, women, ELISA

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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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