Prevent Hepatitis C Virus Infection Research Articles

Contemporary Insights into Hepatitis C Virus: A Comprehensive Review.

Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.

Induction of neutralizing antibodies against hepatitis C virus by a subviral particle-based DNA vaccine

Direct-acting antivirals (DAAs) have been introduced for the treatment of hepatitis C virus (HCV); however, there is still no available vaccine for preventing HCV infection. We previously reported on a Japanese encephalitis virus (JEV) subviral particle (SVP)-based vaccine with insertion of the HCV E2 neutralization epitope at three positions (SVP-E2/Tri). In this study, we utilized this SVP platform for DNA immunization. In addition, we explored further sites permitting the insertion of HCV epitopes without impairing viral assembly and secretion to elicit higher titers of neutralizing antibodies, and we identified three new positions for foreign epitope insertion. Successful secretion of SVPs with the insertion of HCV epitopes at five positions (SVP-E2/Pent) was seen from transfected cells. Compared to SVP-E2/Tri, sera from mice immunized with the plasmid expressing SVP-E2/Pent showed more neutralization activity against HCV, and less neutralization activity against JEV, suggesting that the additional insertion of HCV epitopes contributed to the induction of antibodies against the inserted peptide, whereas the neutralizing epitopes against JEV were disrupted. This study provides a potentially effective novel DNA vaccine platform.

Association Between Prescription Opioid Therapy for Noncancer Pain and Hepatitis C Virus Seroconversion

Initiation of injection drug use may be more frequent among people dispensed prescription opioid therapy for noncancer pain, potentially increasing the risk of hepatitis C virus (HCV) acquisition. To assess the association between medically dispensed long-term prescription opioid therapy for noncancer pain and HCV seroconversion among individuals who were initially injection drug use-naive. A population-based, retrospective cohort study of individuals tested for HCV in British Columbia, Canada, with linkage to outpatient pharmacy dispensations, was conducted. Individuals with an initial HCV-negative test result followed by 1 additional test between January 1, 2000, and December 31, 2017, and who had no history of substance use at baseline (first HCV-negative test), were included. Participants were followed up from baseline to the last HCV-negative test or estimated date of seroconversion (midpoint between HCV-positive and the preceding HCV-negative test). Episodes of prescription opioid use for noncancer pain were defined as acute (<90 days) or long-term (≥90 days). Prescription opioid exposure status (long-term vs prescription opioid-naive/acute) was treated as time-varying in survival analyses. In secondary analyses, long-term exposure was stratified by intensity of use (chronic vs. episodic) and by average daily dose in morphine equivalents (MEQ). Multivariable Cox regression models were used to assess the association between time-varying prescription opioid status and HCV seroconversion. A total of 382 478 individuals who had more than 1 HCV test were included, of whom more than half were female (224 373 [58.7%]), born before 1974 (201 944 [52.8%]), and younger than 35 years at baseline (196 298 [53.9%]). Participants were followed up for 2 057 668 person-years and 1947 HCV seroconversions occurred. Of the participants, 41 755 people (10.9%) were exposed to long-term prescription opioid therapy at baseline or during follow-up. The HCV seroconversion rate per 1000 person-years was 0.8 among the individuals who were prescription opioid-naive/acute (1489 of 1947 [76.5%] seroconversions; 0.4% seroconverted within 5 years) and 2.1 with long-term prescription opioid therapy (458 of 1947 [23.5%] seroconversions; 1.1% seroconverted within 5 years). In multivariable analysis, exposure to long-term prescription opioid therapy was associated with a 3.2-fold (95% CI, 2.9-3.6) higher risk of HCV seroconversion (vs prescription opioid-naive/acute). In separate Cox models, long-term chronic use was associated with a 4.7-fold higher risk of HCV seroconversion (vs naive/acute use 95% CI, 3.9-5.8), and long-term higher-dose use (≥90 MEQ) was associated with a 5.1-fold higher risk (vs naive/acute use 95% CI, 3.7-7.1). In this cohort study of people with more than 1 HCV test, long-term prescription opioid therapy for noncancer pain was associated with a higher risk of HCV seroconversion among individuals who were injection drug use-naive at baseline or at prescription opioid initiation. These results suggest injection drug use initiation risk is higher among people dispensed long-term therapy and may be useful for informing approaches to identify and prevent HCV infection. These findings should not be used to justify abrupt discontinuation of long-term therapy, which could increase risk of harms.

914. The Relationship Between Buprenorphine Maintenance Therapy and Hepatitis C Virus Infection, Testing, and Treatment in Southern Appalachian Ohio

Abstract Background The hepatitis C virus (HCV) epidemic in the United States is primarily among young people who use drugs (PWUD), especially in rural and Appalachian regions. Buprenorphine maintenance therapy (BMT) may indirectly prevent HCV infection by reducing injection drug use. We aim to assess the relationship between BMT and HCV infection, testing, and treatment among rural PWUD. Methods We conducted a cross-sectional respondent driven sampling survey of 243 PWUD adults in southern Appalachian Ohio from May to November 2019. Participants completed audio computer-assisted self-interview and were tested for HCV antibodies. We defined recent BMT use as self-reported BMT in the past 30 days and prior BMT use as self-reported BMT any time prior to the past 30 days. HCV antibody positive participants were incentivized to receive confirmatory HCV RNA testing. We fit log-binomial regression models to assess the relationship between BMT and HCV infection, testing, and treatment. Results 72% of participants were HCV antibody positive (n=175). 31% (n=54) of antibody positive participants received an RNA test; of those, 96% (n=52) were HCV RNA positive. Compared to participants with no history of BMT, those with prior BMT were more likely to be HCV antibody positive (PR=1.3, 95% CI: 1.1-1.6) and to have been tested for HCV (PR=1.3 95% CI: 1.1-1.5); they were somewhat more likely to have been treated for HCV (PR=1.3 95% CI: 0.5-3.4). Compared to participants with no history of BMT, those reporting recent BMT had similar HCV antibody positivity (PR=1.1 95% CI: 0.9-1.5) but were more likely to have been tested (PR=1.3 95% CI: 1.1-1.6) and possibly more likely to have been treated for HCV (PR=2.0 95% CI: 0.6-5.9). Compared to those with a prior BMT, people with recent BMT use had slightly lower HCV antibody positivity (PR=0.8 95% CI: 0.7-1.1) and possibly higher prevalence of HCV treatment (PR=1.5 95% CI: 0.6-3.8) but had similar prevalence of HCV testing (PR=1.0 95% CI: 0.9-1.2). Conclusion Participants with a recent history of BMT were more likely to have been tested for HCV and possibly to have received prior treatment. Participants with prior BMT were more likely to be antibody positive and to have tested for HCV. Improved coordination between BMT and HCV care may increase HCV treatment among rural PWUD. Disclosures All Authors: No reported disclosures

New hepatitis C virus infection, re-infection and associated risk behaviour in male Irish prisoners: a cohort study, 2019

BackgroundPrisoners are recognised as a high-risk population and prisons as high-risk locations for the transmission of hepatitis c virus (HCV) infection. Injecting drug use (IDU) is the main driver of HCV infection in prisoners and harm reduction services are often suboptimal in prison settings. HCV prevalence and incident data in prisoners is incomplete which impacts the public health opportunity that incarceration provides in identifying, treating and preventing HCV infection. The aim of this study is to identify new HCV infection and associated risk factors in an Irish male prison.MethodsWe conducted a follow up (18-month) cohort study on prisoners who had previously tested negative, self-cleared or had been successfully treated for HCV infection. We conducted the study in a male medium security prison located in Dublin Ireland (Mountjoy Prison) using HCV serology, a review of medical records and a researcher-administered questionnaire.Results99 prisoners with a mean age of 33.2 yrs. participated in the study and 82(82.8%) completed a research-administered questionnaire. Over half (51%) had a history of drug use from a young age (14.8 yrs.), 49.9% a history of heroin use and 39% a history of IDU. The prevalence of HIV and hepatitis B virus core antibody was 3% and HCV antibody was 22.2%. No new HCV infections were identified in those who had never been infected (n = 77), had self-cleared (n = 9) or achieved sustained virological response (n = 12). Small numbers of prisoners continued to engage in risk-behaviour including, IDU both in the prison (n = 2) and the community (n = 3), sharing syringes (n = 1) and drug taking paraphernalia (n = 6) and receiving non-sterile tattoos (n = 3).ConclusionDespite the high numbers of Irish prisoners with a history of IDU and HCV infection, new HCV infection is low or non-existent in this population. Small numbers of prisoners continue to engage in risk behaviour and larger studies are required to further understand HCV transmission in this cohort in an Irish and international context.

Hepatitis C Virus Glycan-Dependent Interactions and the Potential for Novel Preventative Strategies.

Chronic hepatitis C virus (HCV) infections continue to be a major contributor to liver disease worldwide. HCV treatment has become highly effective, yet there are still no vaccines or prophylactic strategies available to prevent infection and allow effective management of the global HCV burden. Glycan-dependent interactions are crucial to many aspects of the highly complex HCV entry process, and also modulate immune evasion. This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights glycan-focused advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.

Factors associated with phylogenetic clustering of hepatitis C among people who inject drugs in Baltimore

BackgroundThe availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID).MethodsSequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster.ResultsOf 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2–4.5]) and HIV infection (OR 5.7 [CI 2.7–11.9]) remained independently associated with being in an HCV infection cluster.ConclusionsMolecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.

Level of knowledge of prevention of hepatitis C virus infection among nursing students

Introduction. Infection with hepatitis C virus (HCV) may lead to the severe form of chronic hepatitis C. According to the relevant literature, the percentage of infected population worldwide is approximately 2-3%, while in Poland it is about 1.4%. The incidence of hepatitis C is showing an upward tendency. The routes of infection with HCV are mainly associated with the disruption of tissue continuity, contact with infected blood, and via contact with infected medical equipment. The prevention of HCV infection in medical facilities is conditioned by non-specific prophylaxis, the essence of which is the cutting-off of transmission routes. Objective. The aim of the study was assessment of the level of knowledge concerning prevention of infection with hepatitis C virus among students of nursing at the Higher School in Radom. Material and Methods. The study was conducted in the first half of 2018, among 141 licentiate students of nursing at the Higher School in Radom. The research method was a diagnostic survey using a questionnaire technique. Results. The majority of respondents (98.6%) indicated the correct answer and reported that HCV is the ‘hepatitis C virus’. A large group of the examined students (94.3%) knew that ‘contact with infected blood’ may be the source of infection with HCV. The vast majority of respondents (87.9%) reported that infection with HCV may take place ‘for example, during a visit to a hairdresser or beautician, when there occurs damage to the skin’. The majority of adolescents (86.5%) knew that ‘everyone’ is exposed to HCV infection. More than a half of the students in the study (56.0%) knew that approximately 700,000 people in Poland are infected with HCV. In the opinions of the majority of respondents (88.7%) the best diagnostic method in infection with hepatitis C virus is ‘blood test for anti-HCV antibodies’. The largest number of students (61.0%) knew that there is no vaccine against hepatitis C, because the efforts to develop this vaccine have failed due to the high variability of the virus. A small group of the examined students (39.0%) had knowledge concerning the possibilities of curing a patient infected with HCV, as long as the disease is diagnosed early. The collected research material was statistically analyzed using the software StatSoft Statistica 13.1 PL and Microsoft Office software package. Non-parametric Pearson's chi-squared test was used. The p values p&lt;0.05 were considered statistically significant. Conclusions. The examined students had a high level of knowledge concerning the essence and situations of risk of infection with HCV. Students at the specialty of nursing should be motivated to expand their knowledge pertaining to prophylaxis of infection with hepatitis C virus. The risk of infection with HCV associated with occupational exposure should be considered while educating students of the specialty of nursing.

Exploring HCV genome to construct multi-epitope based subunit vaccine to battle HCV infection: Immunoinformatics based approach.

Hepatitis C Virus (HCV) infection is a major cause of chronic liver disease, hepatocellular carcinoma, and the single most common indication for liver transplantation. HCV vaccines eliciting specific T-cell responses, have been considered as potent method to prevent HCV infection. Despite several reports on progress of vaccine, these vaccine failed in mediating clinical relevance activity against HCV in humans. In this study we integrated both immunoinformatic and molecular docking approach to present a multiepitope vaccine against HCV by designating 17 conserved epitopes from eight viral proteins such as Core protein, E1, E2, NS2, NS34A, NS4B, NS5A, and NS5B. The epitopes were prioritized based on conservation among epitopes of T cell, B cell and IFN-γ that were then scanned for non-homologous to host and antigenicity. The prioritized epitopes were then linked together by AAY linker and adjuvant (β-defensin) were attached at N-terminal to enhance immunogenic potential. The construct thus formed were subjected to structural modeling and physiochemical characteristics. The modeled structure were successfully docked to antigenic receptor TLR-3 and In-silico cloning confers the authenticity of its expression efficiency. However, the proposed construct need to be validate experimentally to ensure its safety and immunogenic profile.

Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study

An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors. HCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing. 30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 log10IU/mL (IQR 4·55-5·63) and at least three HCV genotypes were represented (nine [50%] donors with genotype 1, two [11%] with genotype 2, five [28%] with genotype 3, and two [11%] with unknown genotype). All 30 (100%) transplant recipients met the primary endpoint of undetectable HCV RNA at 12 weeks post-transplant, and were HCV RNA-negative at last follow-up (median 36 weeks post-transplant [IQR 25-47]). Low-level viraemia was transiently detectable in 21 (67%) of 30 recipients in the early post-transplant period but not after day 14. Treatment was well tolerated with no dose reductions or treatment discontinuations; 32 serious adverse events occurred in 20 (67%) recipients, with one grade 3 elevation in alanine aminotransferase (ALT) possibly related to treatment. Non-serious transient elevations in ALT and creatine kinase during the study dosing period resolved with treatment completion. Among the serious adverse events were two recipient deaths due to causes unrelated to study drug treatment (sepsis at 49 days and subarachnoid haemorrhage at 109 days post-transplant), with neither patient ever being viraemic for HCV. Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors. Canadian Institutes of Health Research; the Organ Transplant Program, University Health Network.

Risk of hepatitis C virus infection in injecting and noninjecting drug users receiving opioid substitution therapy.

Hepatitis C virus (HCV) is the most common viral infection among illicit drug users in the world. Although intervention of needle and syringe program and opioid substitution therapy had engaged to prevent HCV infection, the prevalence of HCV infection does not seem to decline. The aim of this study was to estimate the risk of HCV infection in injecting drug users (IDUs) and noninjecting drug users (NIDUs) receiving opioid substitution therapy. We recruited 1179 heroin-dependent patients (age: 20-66 years) under opioid substitution therapy from 2012 to 2015 in a Psychiatric Center, Southern Taiwan. The data of HCV, hepatitis B virus and HIV infection and liver biochemical examination were obtained. We used multivariate logistic regression analysis to predict the risk of HCV infection. There were 93.1% of IDUs and 68.1% of NIDUs positive for HCV infection. In IDUs, HIV infection, age of heroin initiation, duration and dose of heroin use, frequency of detoxification, and number of criminal conviction were significantly associated with HCV infection. In NIDUs, snort/sniff heroin exhibited a significantly increased risk of HCV infection. Intravenous injecting (odds ratio [OR] = 23.10, 95% CI = 8.04-66.40, p < 0.001), intravenous injecting combined snort/sniff (OR = 12.95, 95% CI = 3.90-42.97, p < 0.001), and snort/sniff (OR = 4.14, 95% CI = 1.30-13.18, p = 0.016) were significantly associated with increased risk of HCV infection compared with smoking. The trend was significant (p for trend <0.001). In Taiwan, IDUs had harmful characteristics compared with NIDUs and both had extremely high prevalence of HCV infection. We provided evidence that snort/sniff is a possible way of leak in HCV infection despite needle-syringes supplement program been provided. Opioid substitution therapy program should include HCV assessment and treatment in the new direct-acting antiviral therapy era.

Per-Contact Infectivity of Hepatitis C Virus Acquisition in Association With Receptive Needle Sharing Exposures in a Prospective Cohort of Young Adult People who Inject Drugs in San Francisco, California.

BackgroundSharing needles and ancillary injecting equipment is a primary risk exposure for hepatitis C virus (HCV) infection among people who inject drugs (PWID); however, infectivity of these exposures is not well quantified. We aimed to estimate per-event HCV infectivity associated with receptive needle sharing (RNS) among susceptible PWID.MethodsParticipants in a prospective cohort study of young adult PWID who were anti-HCV and HCV RNA negative at baseline and attended at least 2 follow-up study visits between 2003 and 2014 were eligible. Data were selected from the first HCV-negative through the first HCV-positive visit (or last HCV-negative among those uninfected). Anti-HCV and HCV-RNA tests were used to determine infection status. A probabilistic exposure model linking observed HCV infection outcomes to self-reported exposure events was applied to estimate infectivity.ResultsAmong 344 participants, a maximum likelihood estimate considering RNS yielded a pooled population per RNS event HCV probability of 0.25% (95% confidence interval [CI], 0.10%–0.43%), and 1.12% (95% CI, 0.48%–2.35%) among those who acquired any HCV infection (primary or reinfection).ConclusionsHCV is highly infectious in association with RNS, a primary injection-related risk exposure. Our infectivity estimate among participants who acquired any HCV infection is 1.7 times higher than that estimated for HIV infection in PWID and 2.24 times higher than that estimated among health care workers exposed through needle sticks. The strengths of this study include the assessment of receptive needle sharing events, the prospective design, and relatively short recall and testing periods. These results can inform transmission models and research to prevent HCV infection.

Hepatitis C Virus: Evading the Intracellular Innate Immunity.

Hepatitis C virus (HCV) infections constitute a major public health problem and are the main cause of chronic hepatitis and liver disease worldwide. The existing drugs, while effective, are expensive and associated with undesirable secondary effects. There is, hence, an urgent need to develop novel therapeutics, as well as an effective vaccine to prevent HCV infection. Understanding the interplay between HCV and the host cells will certainly contribute to better comprehend disease progression and may unravel possible new cellular targets for the development of novel antiviral therapeutics. Here, we review and discuss the interplay between HCV and the host cell innate immunity. We focus on the different cellular pathways that respond to, and counteract, HCV infection and highlight the evasion strategies developed by the virus to escape this intracellular response.

The Prevalence of Hepatitis C Infection in Blood Donors: A Meta-Analysis and Systematic Review

Context: Hepatitis C virus (HCV) infection is one of the major diseases worldwide. Although many screening tests were introduced and utilized for donations, as the main source of HCV transmission, it has still remained a global concern. Evidence Acquisition: The prevalence of HCV infection among donors in every country and every WHO region was investigated. A Comprehensive electronic systematic search algorithm in the international databases PubMed, ISI, Scopus, and ProQuest were adopted for articles published until October 2016, using the following keywords: (Blood Donors OR OR donor OR donation OR blood OR safety OR bloodborne OR residual risk OR transfusion-transmitted infections) AND (prevalence OR epidemiology) in combination with “hepatitis C” OR “HCV” for hepatitis C. Only cross-sectional studies, which had appropriate measurement and sampling methods, were selected. Results: The review of the literature showed that the global prevalence of HCV was 854.09 in 100,000. The highest and lowest rates of HCV among WHO divisions were seen in the African region by 2503.61 and the European region by 450.21 in 100,000, respectively. The highest and lowest rates among the countries were seen in Cambodia by 14,670 and Netherlands by 25.370 in 100,000. Conclusions: It seems that strategies for prevention of HCV infection in donations should be considered for the policymakers; low prevalence countries are suggested to share their knowledge and countries with lower socioeconomic status should be aided to control the HCV infection among their donors.

Inhibitory Activity of a Scorpion Defensin BmKDfsin3 against Hepatitis C Virus.

Hepatitis C virus (HCV) infection is a major worldwide health problem which can cause chronic hepatitis, liver fibrosis and hepatocellular carcinoma (HCC). There is still no vaccine to prevent HCV infection. Currently, the clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) which are expensive and have side effects. Here, BmKDfsin3, a scorpion defensin from the venom of Mesobuthus martensii Karsch, is found to dose-dependently inhibit HCV infection at noncytotoxic concentrations and affect viral attachment and post-entry in HCV life cycle. Further experimental results show that BmKDfsin3 not only suppresses p38 mitogen-activated protein kinase (MAPK) activation of HCV-infected Huh7.5.1 cells, but also inhibits p38 activation of Huh7.5.1 cells stimulated by tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) or lipopolysaccharide (LPS). BmKDfsin3 is also revealed to enter into cells. Using an upstream MyD88 dimerization inhibitor ST2345 or kinase IRAK-1/4 inhibitor I, the inhibition of p38 activation represses HCV replication in vitro. Taken together, a scorpion defensin BmKDfsin3 inhibits HCV replication, related to regulated p38 MAPK activation.

Global Trends and Regional Differences in Hepatitis C Virus Infection Prevalence and Implications for Prevention - Worldwide, 1990-2017.

What is already known on this topic?The global prevalence of hepatitis C virus (HCV) infection in 2015 has been modeled to assess the disease burden in 21 Global Burden of Disease (GBD) regions. However, there is no study to clarify the global long-term trends and regional differences in HCV infection prevalence.What is added by this report?This report clarified the global temporal trends and regional differences in HCV infection prevalence. Global HCV infection age-standardized prevalence rate (ASR) gradually decreased from 1990 to 2017 except in Eastern Europe, and liver cancer due to hepatitis C ASR increased worldwide with drastic shifts in low-middle Socio-Demographic Index (SDI) regions in the last decade.What are the implications for public health practice?HCV is still prevalent worldwide despite the development of highly effective direct-acting antivirals (DAAs) and showed a reemergence concurrent with the opioid crisis. HCV infection prevention might involve at least 3 aspects: first, prohibiting HCV widespread transmission among general populations; second, increasing global DAAs coverage; and third, continuously investing in the development of the HCV vaccine.

Knowledge and Risk Behavior on Hepatitis C Virus Infection Among Laboratory Technicians in A Selected Army Medical Unit

Background: Hepatitis C virus (HCV) is a new virus identified in the year l989. Regarding the morbidity &amp; mortality and also for disease burden HCV infection is now an important disease phenomenon worldwide especially among the health care professionals. Laboratory technicians are at increased risk for acquiring blood-borne infections as they have to collect blood samples to find out the disease pathology. The aim of this study is to assess the knowledge and risk behavior on HCV infection among laboratory technicians in a selected army medical unit.&#x0D; Methods: A descriptive cross sectional study was conducted among laboratory technician in a selected army medical unit from 01September 2015 to 31 December 2016. Total 105 participants were interviewed by pretested structured questionnaire.&#x0D; Results: This study explored that 44.8% respondents were in between 31-40 years and 63.8% were educated up to HSC level. All the respondents had overall knowledge about the cause, high risk group and prevention of HCV infection and 20.95% were not aware that water did not transmit HCV infection, 55.24% had no information of vaccination for prevention of HCV infection. This knowledge was gained by majority (62%) of participants from their existing course curriculum. Use of disposable syringe, sterilize instruments, practice of recapping after using needles and their proper disposal were found among all of the respondents and 61% did not habit to use gloves during sample collection due to negligence and lack of time. This study showed that there is an association between level of education and risk behavior (use of gloves) (P&lt;.005).&#x0D; Conclusion: Adequate program on updating knowledge, strict use of gloves, sterile instrument during sample collection will be helpful in minimizing transmission of HCV infection.&#x0D; Anwer Khan Modern Medical College Journal Vol. 10, No. 1: Jan 2019, P 38-42

Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus.

Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing more therapeutic antiviral compounds. Hepatitis C virus (HCV) and dengue virus (DENV) belong to the Flaviviridae family and are an increasing global health threat. Our previous study reported that the crude venom of Scorpio maurus palmatus possessed anti-HCV and anti-DENV activities in vitro. We report here the characterization of a natural antiviral peptide (scorpion-like peptide Smp76) that prevents HCV and DENV infection. Smp76 was purified from S. m. palmatus venom and contains 76 amino acids with six residues of cysteine. Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). A potential antiviral activity of Smp76 was detected in culture cells with an approximate IC50 of 0.01 μg/ml. Moreover, Smp76 prevents HCV infection and suppresses secondary infection, by inactivating extra-cellular infectious particles without affecting viral replication. Interestingly, Smp76 is neither toxic nor hemolytic in vitro at a concentration 1000-fold higher than that required for antiviral activity. Conclusively, this report highlights novel anti-HCV and anti-DENV activities of Smp76, which may lay the foundation for developing a new therapeutic intervention against these flaviviruses.

Characterization of monoclonal antibodies recognizing each extracellular loop domain of occludin.

The tight junction protein occludin (OCLN) is a four-pass transmembrane protein with two extracellular loops (ELs), and also functions as a co-receptor for hepatitis C virus (HCV). Recently, we reported the establishment of monoclonal antibodies (mAbs) recognizing each intact EL domain of OCLN that can strongly prevent HCV infection in vitro and in vivo and these mAbs were applicable for flow cytometric analysis, immunocytochemistry, and cell-based enzyme-linked immunosorbent assay. In the present study, we further examined the application of these anti-OCLN mAbs and characterized their binding properties. All four mAbs were available for immunoprecipitation. The three first EL (EL1)-recognizing mAbs were applicable for immunoblotting, but the second EL (EL2)-recognizing one was not. Using site-directed mutagenesis, we also determined residues of OCLN critical for recognition by each mAb. Our findings showed that the small loop between two cysteines of the EL2 domain is essential for the binding to one EL2-recognizing mAb and that the recognition regions by three EL1-recognizing mAbs overlap, but are not the same sites of EL1. To obtain a deeper understanding of OCLN biology and its potential as a therapeutic target, specific mAbs to detect or target OCLN in intact cells should be powerful tools for future studies.

Human-rat chimeric anti-occludin monoclonal antibodies inhibit hepatitis C virus infection

Occludin (OCLN), an integral tetra-spanning plasma membrane protein, is a host entry factor essential for hepatitis C virus (HCV) infection, making it a promising host-targeting molecule for HCV therapeutic intervention. We previously generated rat anti-OCLN monoclonal antibodies (mAbs) that strongly prevented HCV infection in vitro and in vivo. In the present study, we attempted to improve the druggability of the extracellular loop domain-recognizing anti-OCLN mAbs, namely clones 1–3 and 37-5, using genetic engineering. To avoid adverse reactions induced by antibody-dependent cellular cytotoxicity and enhance the antibody stability, we developed human-rat chimeric immunoglobulin G4 S228P mutant (IgG4m) forms of clones 1–3 and 37-5 (named Xi 1–3 and Xi 37-5, respectively) by grafting the variable regions of the light and heavy chains of each rat anti-OCLN mAb into those of human IgG4m. The constructed Xi 1–3 and Xi 37-5 chimeras demonstrated levels of affinity and specificity similar to each parental rat anti-OCLN mAb, and the Fcγ receptor Ⅲa was not activated by the antigen-bound chimeric mAbs, as expected. Both chimeric mAbs inhibited in vitro infection with various HCV genotypes. These results indicate that the IgG4m forms of human-rat chimeric anti-OCLN mAbs may be potential candidate molecules of host-targeting antivirals with pan-genotypic anti-HCV activity.