The impact of the timely birth dose vaccine on the global elimination of hepatitis B.

In 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.

Hepatitis Testing Performance of an Analyzer Integrated into Another Manufacturer's Automation System.

BACKGROUND: The capacity to integrate platforms across vendors and disciplines has become an essential feature in the design of total laboratory automation (TLA) due space and test menu constraints. However, data on its performance are lacking. We aim to evaluate an integrated third-party immunoassay platform to the TLA system for the performance of hepatitis testing using turnaround time (TAT). METHODS: We use the Beckman Power Express (PE) system with linked 2 Beckman AU5800, 2 Beckman DxI 800, 2 Abbott Architect i2000, and other accessory components. The PE system is managed and interfaced to the laboratory information system (LIS) through Beckman Remisol (middleware) and Cennexus (track software). The hepatitis tests are performed on the Abbott Architect i2000 using Abbott Instrument Manager (middleware) for test results and this is interfaced with LIS and Cennexus. Using Viewics and Microsoft Excel, the test volumes and TAT of hepatitis results were analyzed before (February 2017 to January 2018) and after (February 2018 to January 2019) integration. RESULTS: The TAT for each hepatitis test has decreased significantly, ranging from 13 to 81-minute reductions (P value <0.0001 for all tests) after instrument integration. The standard deviations of the TAT also decreased for each test. In addition, savings in labor expenditure of around 2 hours per day were observed. There were no laboratory space savings identified. Instead, 47.6 square foot more of space was utilized by the track connection lines. CONCLUSIONS: Our findings show significant improvement of TAT of hepatitis testing with the integration of the third-party Abbott Architect i2000 to Beckman PE system. In addition, the synchronization of multiple middleware for specimen management and result reporting allow the laboratory to achieve new efficiencies handling reflex tests and managing human resources.

In silico designing of peptide based vaccine for Hepatitis viruses using reverse vaccinology approach.

Five different Hepatitis virus from different viral species cause viral-hepatitis, which is a life threatening disease leading to a high number of loss of lives every year. The mode of infection and transmission is different for each species and mostly spreads by direct contact and body fluids (for HBV and HCV). No such vaccine is available that can cure all types of Hepatitis with cross-protection. Thus our study involves a peptide based vaccine design with the help of Immunoinformatics approach. We focused only on the secretory and extracellular proteins of each types and identified their epitopes. Epitopes were examined for antigenicity, allergenicity, toxicity, anti-inflammatory property and IFN-γ induction. The short-listed peptides were stitched using linkers and TLR4 adjuvant. This final vaccine was proven to have good physico-chemical and structural properties. Simulation study to determine structural stability of the vaccine showed good result. Docking structure of vaccine with TLR4 has high affinity binding. Immune-simulation reveals favourable induction of immune response with high level of interleukins production important for immunity. Periplasmic expression in E.coli K12 strain was quite satisfactory. This study of designing recombinant chimeric vaccine using reverse vaccinology method provides some idea about the vaccine production against Hepatitis virus.

Seroprevalence of viral hepatitis A, B, C, D and E viruses in the Hormozgan province southern Iran.

BACKGROUND: Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both surveillance and disease control programs. This study is aimed to determine the seroprevalence of markers for viral hepatitis (A, B, C, D and E) and the epidemiology of such infections in the general population of southern Iran's Hormozgan province. METHODS: Between 2016 and 2017, a total of 562 individuals with ages ranging from 1 to 86 years, who visited governmental public laboratories for routine check-ups, were tested for the presence of serological markers to hepatitis virus types A to E using enzyme-linked immunosorbent assays. RESULTS: The overall anti-hepatitis A virus (HAV) antibody seroprevalence was 93.2% (524/562). The prevalence of anti-hepatitis E virus (HEV) antibodies was 15.8% (89/562) among which 1.6% (9/562) of the seropositive individuals also had evidence of recent exposure to the virus (IgM positivity). Two and a half percent (14/562) were positive for hepatitis B surface (HBs) antigen, whereas 11.6% (65/562) tested positive for anti-hepatitis B core (HBc) antibodies. Among anti-HBc positive patients, 11% (7/65) had HBs Ag and 5% (3/65) were positive for anti-hepatitis D virus (HDV) antibodies. The prevalence of anti-hepatitis C virus (HCV) antibodies was 0.7% (4/562). The seroprevalence of anti-HAV, HEV IgG, anti-HBc antibodies, and HBs Ag increased with age. CONCLUSION: The present study confirms a high seroprevalence of HAV infection among the examined population and reveals high levels of endemicity for HEV in the region. Planned vaccination policies against HAV should be considered in all parts of Iran. In addition, improvements on public sanitation and hygiene management of drinking water sources for the studied area are recommended.

Prevalence of hepatitis E virus and reassessment of HIV and other hepatitis virus seroprevalences among French prison inmates.

BACKGROUND: Prison inmates are considered a high-risk population for blood-borne and enterically transmitted infections before and during their imprisonment. Hepatitis E virus (HEV) prevalence is unknown among French inmates, whereas a reassessment of human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalences is required to describe the epidemiologic evolution in this high-risk population. METHODS: A prospective survey was conducted from June to December 2017 in Fresnes prison, a penitentiary center with 2,581 inmates. In addition to HIV, HAV, HBV and HCV testing, which is offered to all patients at admission, we systematically offered HEV screening. Retrospective serological data for HIV, HBV and HCV, collected annually from 2014 to 2017, were also used to assess evolution. RESULTS: In 2017, 1,093 inmates were screened for HEV, HIV, HAV, HBV and HCV. Prevalences in this population were 8.2%, 1.3%, 62.7%, 1.9% and 2.9%, respectively. HEV seroprevalence increased with age (p<0.0001) and was higher among Eastern Europe born inmates (p<0.0001). Between 2014 and 2017, HIV seroprevalence remained steady, while a decrease in HBV and HCV seroprevalence was observed. CONCLUSIONS: Compared to the reported prevalence in French blood donors, HEV seroprevalence was remarkably low in French inmates. HIV, HAV, HBV and HCV prevalences among prisoners were higher than reported in the general population.

Electronic health record year and country of birth testing and patient navigation to increase diagnosis of chronic viral hepatitis.

The United States Preventive Services Task Force recommends hepatitis C testing people born from 1945 to 1965, "birth cohort" as well as hepatitis C and hepatitis B testing people from countries of birth with endemic infection risk. We automated the hospital electronic health record system to test birth cohort and those born in countries with endemic infection risk. A script is launched searching the laboratory database upon registration for any hepatitis C antibody, hepatitis C RNA and/or hepatitis B surface antigen result. If no positive result was found, a hepatitis C antibody/reflex RNA and/or hepatitis B surface antigen were ordered. A patient navigator received weekly results and assisted patients with positive serology to schedule an appointment with their primary care provider or treatment specialist. A total of 10 726 participants were hepatitis C antibody tested, with 6.9% antibody positive. Monthly hepatitis C testing from January to July 2016 compared to August 2016-August 2017 increased 342% as a result of "birth cohort" testing. Following country of birth testing, monthly hepatitis B and hepatitis C testing increased 91%, and 44%, respectively, during June-August 2017 compared to September 2017-March 2018. 67% of hepatitis C-positive patients were linked to care. If the navigator contacted the patient, 92% were linked to care, and 32% were treated. Of hepatitis B surface antigen-positive patients, 43% were linked to care, 5% were on treatment, and 15% started treatment. Automated electronic health record ordering of hepatitis C and/or hepatitis B testing is feasible and increases testing. In the population tested, much improvement is needed with linkage to care and treatment.

A Territorywide Prevalence Study on Blood-Borne and Enteric Viral Hepatitis in Hong Kong.

BACKGROUND: Viral hepatitis epidemiological data are important for the World Health Organization plan of eliminating viral hepatitis. We aimed to document the prevalence of viral hepatitis A to E in Hong Kong. METHODS: This community-based study was open to all Hong Kong Chinese citizens aged ≥18 years. Baseline data and risk factors were collected. Hepatitis A-E serology was measured, including hepatitis B e antigen, antibodies to hepatitis B e antigen, antibodies to hepatitis D, hepatitis B virus (HBV) DNA for hepatitis B surface antigen (HBsAg)-positive participants, and antibodies to hepatitis B surface antigen and antibodies to hepatitis B core antigen (anti-HBc) in HBsAg-negative participants. Hepatitis C virus (HCV) RNA and genotypes were determined in anti-HCV-positive participants. RESULTS: A total of 10 256 participants were recruited from February 2015 to July 2016. Overall HBsAg seroprevalence was 7.8% (95% confidence interval [CI], 7.3%-8.3%), which was reduced significantly with HBV vaccination (odds ratio, 0.15 [95% CI, .11-.21]). Among HBsAg-negative participants, anti-HBc seroprevalence increased from 5.4% (<26 years) to 60.1% (>65 years). No hepatitis D virus (HDV) cases were detected. Anti-HCV positivity was 0.5% (95% CI, .3%-.6%). Prevalence of antibodies to hepatitis A virus (anti-HAV) and hepatitis E virus (anti-HEV) was 65.2% (95% CI, 64.2%-66.1%) and 33.3% (95% CI, 32.4%-34.2%), respectively, and were influenced by age, family income, and being born in mainland China. CONCLUSIONS: HBV seroprevalence remained high despite universal vaccination. High anti-HBc seroprevalence underlines the potential issue of HBV reactivation during profound immunosuppression. HCV and HDV remained uncommon. Anti-HAV seroprevalence had decreased whereas anti-HEV seroprevalence had risen.

Seroprevalence of antibodies and antigens against hepatitis A-E viruses in refugees and asylum seekers in Germany in 2015.

BACKGROUND: Migration because of miscellaneous political crises in countries in the Middle East and Africa is a global challenge for whole Europe from an economic, social, and public health view. There is an urgent need to generate comprehensive, evidence-based data to expedite further screening and vaccination strategies. METHODS: A total of 604 individuals ranging in age from 2 to 68 years who enrolled at a single reception center were tested for the prevalence of serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV), respectively. RESULTS: Anti-HAV antibody prevalence was 91.2 and 70.3% in children younger than 18 years of age. The prevalence of anti-HEV antibodies was 20.1% among the individuals. 3.0% were positive for hepatitis B surface antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated against hepatitis B and had a protective anti-hepatitis B surface level of at least 10 mIU/ml. Significant differences in vaccination status were found between the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence interval=12.7-19.3%) versus African Region with 1/55 (1.8%; 95% confidence interval=0-5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7% HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals were HCV coinfected (n=3). CONCLUSION: The prevalence of refugees with previous exposure to hepatitis viruses was higher than that in the general German population, but lower than in other migrant populations in Germany. The vaccination status against hepatitis B was poor.

Direct-Acting Antiviral Therapy Restores Immune Tolerance to Patients With Hepatitis C Virus-Induced Cryoglobulinemia Vasculitis.

BACKGROUND & AIMS: Interferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular immunity. METHODS: We performed a prospective study of 27 consecutive patients with HCV-CV (median age, 59 y) treated with DAA therapy (21 patients received sofosbuvir plus ribavirin for 24 weeks, 4 patients received sofosbuvir plus daclatasvir for 12 weeks, and 2 patients received sofosbuvir plus simeprevir for 12 weeks) in Paris, France. Blood samples were collected from these patients before and after DAA therapy, and also from 12 healthy donors and 12 individuals with HCV infection without CV. HCV load, cryoglobulins, and cytokines were quantified by flow cytometry, cytokine multiplex assays, and enzyme-linked immunosorbent assay. RESULTS: Twenty-four patients (88.9%) had a complete clinical response of CV to DAA therapy at week 24, defined by improvement of all the affected organs and the absence of relapse. Compared with healthy donors and patients with HCV infection without CV, patients with HCV-CV, before DAA therapy, had a lower percentage of CD4+CD25hiFoxP3+ regulatory T cells (P < .01), but higher proportions of IgM+CD21-/low memory B cells (P < .05), CD4+IFNγ+ cells (P < .01), CD4+IL17A+ cells (P < .01), and CD4+CXCR5+interleukin 21+ follicular T-helper (Tfh) cells (P < .01). In patients with HCV-CV, there was a negative correlation between numbers of IgM+CD21-/low memory B cells and T-regulatory cells (P = .03), and positive correlations with numbers of Tfh cells (P = .03) and serum levels of cryoglobulin (P = .01). DAA therapy increased patients' numbers of T-regulatory cells (1.5% ± 0.18% before therapy vs 2.1% ± 0.18% after therapy), decreased percentages of IgM+CD21-/low memory B cells (35.7% ± 6.1% before therapy vs 14.9% ± 3.8% after therapy), and decreased numbers of Tfh cells (12% ± 1.3% before therapy vs 8% ± 0.9% after therapy). Expression levels of B lymphocyte stimulator receptor 3 and programmed cell death 1 on B cells increased in patients with HCV-CV after DAA-based therapy (mean fluorescence units, 37 ± 2.4 before therapy vs 47 ± 2.6 after therapy, P < .01; and 29 ± 7.3 before therapy vs 48 ± 9.3 after therapy, P < .05, respectively). CONCLUSIONS: In a prospective clinical trial of patients with HCV-CV, DAA-based therapy restored disturbances in peripheral B- and T-cell homeostasis.

Immune responses and immunopathology in acute and chronic viral hepatitis.

Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this Review, we discuss the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct courses and outcomes of each hepatitis virus infection.

Molecular characterization of woodchuck IFI16 and AIM2 and their expression in woodchucks infected with woodchuck hepatitis virus (WHV).

IFI16 and AIM2 are important DNA sensors in antiviral immunity. To characterize these two molecules in a woodchuck model, which is widely used to study hepatitis B virus (HBV) infection, we cloned and analyzed the complete coding sequences (CDSs) of woodchuck IFI16 and AIM2, and found that AIM2 was highly conserved in mammals, whereas the degree of sequence identity between woodchuck IFI16 and its mammalian orthologues was low. IFI16 and IFN-ß were upregulated following VACV ds 70 mer transfection, while AIM2 and IL-1ß were upregulated following poly (dA:dT) transfection, both in vitro and in vivo; IFI16-targeted siRNA decreased the transcription of IFI16 and IFN-ß stimulated by VACV ds 70 mer, and AIM2 siRNA interference downregulated AIM2 and IL-1ß transcripts stimulated by poly (dA:dT), in vitro, suggesting that woodchuck IFI16 and AIM2 may play pivotal roles in the DNA-mediated induction of IFN-ß and IL-1ß, respectively. IFI16 and AIM2 transcripts were upregulated in the liver and spleen following acute WHV infection, while IFI16 was downregulated in the liver following chronic infection, implying that IFI16 and AIM2 may be involved in WHV infection. These data provide the basis for the study of IFI16- and AIM2-mediated innate immunity using the woodchuck model.

Multiplex qPCR for serodetection and serotyping of hepatitis viruses: A brief review.

The present review describes the current status of multiplex quantitative real time polymerase chain reaction (qPCR) assays developed and used globally for detection and subtyping of hepatitis viruses in body fluids. Several studies have reported the use of multiplex qPCR for the detection of hepatitis viruses, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). In addition, multiplex qPCR has also been developed for genotyping HBV, HCV, and HEV subtypes. Although a single step multiplex qPCR assay for all six hepatitis viruses, i.e., A to G viruses, is not yet reported, it may be available in the near future as the technologies continue to advance. All studies use a conserved region of the viral genome as the basis of amplification and hydrolysis probes as the preferred chemistries for improved detection. Based on a standard plot prepared using varying concentrations of template and the observed threshold cycle value, it is possible to determine the linear dynamic range and to calculate an exact copy number of virus in the specimen. Advantages of multiplex qPCR assay over singleplex or other molecular techniques in samples from patients with co-infection include fast results, low cost, and a single step investigation process.

Status of hepatitis C virus vaccination: Recent update.

Hepatitis C virus (HCV) infection is still a major public health problem worldwide since its first identification in 1989. At the start, HCV infection was post-transfusion viral infection, particularly in developing countries. Recently, due to iv drug abuse, HCV infection became number one health problem in well-developed countries as well. Following acute HCV infection, the innate immune response is triggered in the form of activated coordinated interaction of NK cells, dendritic cells and interferon α. The acquired immune response is then developed in the form of the antibody-mediated immune response (ABIR) and the cell-mediated immune response (CMIR). Both are responsible for clearance of HCV infection in about 15% of infected patients. However, HCV has several mechanisms to evade these antivirus immune reactions. The current review gives an overview of HCV structure, immune response and viral evasion mechanisms. It also evaluates the available preventive and therapeutic vaccines that induce innate, ABIR, CMIR. Moreover, this review highlights the progress in recent HCV vaccination studies either in preclinical or clinical phases. The unsatisfactory identification of HCV infection by the current screening system and the limitations of currently available treatments, including the ineligibility of some chronic HCV patients to such antiviral agents, mandate the development of an effective HCV vaccine.

Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate.

The anti-hepatitis C virus (HCV) activity of a novel monoclonal antibody (mAb; AR4A) and epigallocatechin gallate (EGCG) were studied in vitro using a HCV cell culture system and in vivo using a humanized liver mouse model capable of supporting HCV replication. Alone, both exhibit reliable cross-genotype HCV inhibition in vitro, and combination therapy completely prevented HCV infection. In vitro AR4A mAb (alone and combined with EGCG) robustly protects against the establishment of HCV genotype 1a infection. EGCG alone fails to reliably protect against an HCV challenge. In conclusion, AR4A mAb represents a safe and efficacious broadly neutralizing antibody against HCV applicable to strategies to safely prevent HCV reinfection following liver transplantation, and it lends further support to the concept of HCV vaccine development. The poor bioavailability of EGCG limits HCV antiviral activity in vitro.

Administration of Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and Avian Beta Defensin as Adjuvants in Inactivated Inclusion Body Hepatitis Virus and its Hexon Protein-Based Experimental Vaccine Formulations in Chickens.

Inclusion body hepatitis (IBH) is one of the major infectious diseases adversely affecting the poultry industry of the United States and Canada. Currently, no effective and safe vaccine is available for the control of IBH virus (IBHV) infection in chickens. However, based on the excellent safety and immunogenic profiles of experimental veterinary vaccines developed with the use of new generation adjuvants, we hypothesized that characterization of vaccine formulations containing inactivated IBHV or its capsid protein hexon as antigens, along with poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and avian beta defensin 2 (ABD2) as vaccine adjuvants, will be helpful in development of an effective and safe vaccine formulation for IBH. Our data demonstrated that experimental administration of vaccine formulations containing inactivated IBHV and a mixture of PCEP with or without ABD2 as an adjuvant induced significantly higher antibody responses compared with other vaccine formulations, while hexon protein-based vaccine formulations showed relatively lower levels of antibody responses. Thus, a vaccine formulation containing inactivated IBHV with PCEP or a mixture of PCEP and ABD2 (with a reduced dosage of PCEP) as an adjuvant may serve as a potential vaccine candidate. However, in order to overcome the risks associated with whole virus inactivated vaccines, characterization of additional viral capsid proteins, including fiber protein and penton of IBHV along with hexon protein in combination with more new generation adjuvants, will be helpful in further improvements of vaccines against IBHV infection.

The Presence of Some Humoral Immunologic Indicators and Clinical Manifestations in Cryoglobulin Positive Heroin Addicts without Evidence of Hepatitis Virus Infection.

INTRODUCTION: Cryoglobulins are single or mixed immunoglobulins that are subject to reversible precipitation at low temperatures. OBJECTIVE: The aims of this paper were: 1. Comparison of cryoglobulin positive (CP), cryoglobulin negative (CN) heroin addicts and the control group (CG) in terms of serum immunoglobulins IgG, IgA and IgM and complement components C3 and C4; 2. Comparison of CP and CN heroin addicts in terms of rheumatoid factor (RF) and circulating immune complexes (CIC); 3. Assessment of clinical manifestations in CP heroin addicts. METHODS: This is a comparative study of cases (outpatients) treated at the University Clinic of Toxicology in Skopje over 3.5 years, from January 2009 to June 2012. In this study 140 heroin addicts without HbsAg were examined, seronegative for HCV and HIV infections.They were divided into 2 groups: 70 CP and 70 CN heroin addicts. A previously designed self-administered questionnaire was used as a data source on participants. All heroin addicts underwent the following analyses: urea and creatinine in serum; creatinine in urine; proteinuria; 24-hour proteinuria; IgM, IgG, IgA, C3, C4; RF; CIC; creatinine clearance; ECG; toxicological analyses for opioids in a urine sample; cryoglobulins. In addition to these 2 groups, IgG, IgA, IgM, C3 and C4 were also examined in 70 healthy subjects (CG). RESULTS: The study showed that there was no statistically significant difference between CP, CN heroin addicts and CG regarding the concentration of IgA, IgG, IgM, C3 and C4, and between CP and CN regarding the concentration of CIC. There was significant difference between CP and CN regarding the concentration of RF. The following conditions were significantly more frequently manifested in CP than in CN heroin addicts: arthralgia, Raynaud's phenomenon, respiratory difficulties, neurological disorders, manifested skin changes, hematuria, 24-hour proteinuria levels, and decreased renal clearance. CONCLUSION: There were no differences in concentrations of IgG, IgA, IgM, C3, C4 and CIC, while there was a difference in concentration of RF between CP and CN heroin addicts. Clinical manifestations (arthralgias, Raynaud's phenomenon, respiratory, neurologic, renal disorders and skin changes) were more common in CP heroin addicts.

The Role of Ursodeoxycholic Acid in Acute Viral Hepatitis: an Evidence-based Case Report.

AIM: to review the role of ursodeoxycholic acid in acute viral hepatitis. METHODS: following literature searching according to the clinical question on Pubmed and Cochrane Library. After filtered with our inclusion and exclusion criteria, one meta-analysis and two randomized clinical trials are obtained. Through critical appraisal, it was concluded that the articles meet the criteria for validity and relevance. RESULTS: the article found that there is a positive effect of ursodeoxycholic acid on the activity of serum transaminases and cholestasis indexes. However, there is insufficient evidence to support or to refute effects of ursodeoxycholic acid on disease's course as well as the viral load. CONCLUSION: better method of clinical trials are needed to obtain a valid and applicable result for daily practice.

Coinfection of hepatitis E virus and other hepatitis virus in Colombia and its genotypic characterization.

INTRODUCTION: Hepatitis E virus has emerged as a public health problem, particularly in developing countries. The four genotypes identified in mammals include the G3 found in indigenous hepatitis in countries and regions with high porcine population, and the G1, associated with maternal deaths.  OBJECTIVE: To determine coinfection by hepatitis E virus and the circulating genotypes in Colombia in 1,097 samples using serological markers for hepatitis A, B and C.  MATERIALS AND METHODS: Serum samples of 1,097 patients from different regions of Colombia stored at the Laboratorio de Virología of the Instituto Nacional de Salud were selected to detect IgG and IgM anti-hepatitis E virus antibodies. The viral genomes of positive samples were amplified by RT-PCR, and the products were sequenced and phylogenetically analyzed by comparing ORF2 sequences deposited in the GenBank.  RESULTS: IgG anti-hepatitis E virus antibodies were found in 278 samples, IgM in 62, and both markers in 64. Hepatitis E virus and hepatitis A virus coinfection determined by IgG anti-hepatitis E virus was 33.6% and 16.1% by IgM; hepatitis E virus and hepatitis B virus coinfection was 23.4% and 8.1%, and hepatitis E virus and hepatitis C virus coinfection was 35.4% and 5.83%, respectively. Among the 52 positive samples by PCR nine were sequenced and grouped within genotype 3A of the American porcine strain.  CONCLUSIONS: The highest seropositivity was observed for hepatitis A and E. The incidence of hepatitis E virus coinfection with other hepatotropic viruses indicated that this pathogen is more frequent than expected. The circulation of genotype 3A implies that this disease may occur in outbreaks and as zoonosis in Colombia.

Mutational escape of CD8+ T cell epitopes: implications for prevention and therapy of persistent hepatitis virus infections.

Over the past two decades, much has been learned about how human viruses evade T cell immunity to establish persistent infection. The lessons are particularly relevant to two hepatotropic viruses, HBV and HCV, that are very significant global public health problems. Although HCV and HBV are very different, the natural history of persistent infections with these viruses in humans shares some common features including failure of T cell immunity. During recent years, large sequence studies of HCV have characterized intra-host evolution as well as sequence diversity between hosts in great detail. Combined with studies of CD8+ T cell phenotype and function, it is now apparent that the T cell response shapes viral evolution. In turn, HCV sequence diversity influences the quality of the CD8+ T cell response and thus infection outcome. Here, we review published studies of CD8+ T cell selection pressure and mutational escape of the virus. Potential consequences for therapeutic strategies to restore T cell immunity against persistent human viruses, most notably HBV, are discussed.