The scope of this study is to analyze the risk classification of transmission of vaccine-preventable diseases (VPDs) in the 853 municipalities in the state of Minas Gerais (MG) two years after the onset of the COVID-19 pandemic. It is an epidemiological study with secondary data on vaccination coverage and dropout rate of ten immuno-biologicals recommended for under 2-year-old children in 2021 in MG. With respect to the dropout rate, this indicator was only evaluated for the multidose vaccines. After calculating all the indicators, the municipalities of the state were classified according to the transmission risk of VPDs into five categories: very low, low, medium, high, and very high risk. Minas Gerais had 80.9% of municipalities classified as high transmission risk for VPDs. Regarding the homogeneity of vaccination coverage (HCV), large municipalities had the highest percentage of HCV classified as very low, and 100% of these municipalities were classified as high or very high risk for transmission of VPDs, with statistical significance. The use of immunization indicators by municipality is effective for the classification of the scenario of each territory and the proposal of public policies seeking to increase vaccination coverage.
O objetivo é analisar a classificação de risco de transmissão de doenças imunopreveníveis nos 853 municípios de Minas Gerais (MG) após dois anos de início da pandemia de COVID-19. Estudo epidemiológico com dados secundários da cobertura vacinal e taxa de abandono de dez imunobiológicos recomendados para crianças menores de 2 anos, no ano de 2021, em MG. Em relação à taxa de abandono, este indicador foi avaliado somente para as vacinas multidoses. Após o cálculo de todos os indicadores, os municípios do estado foram classificados de acordo com o risco de transmissão de doenças imunopreveníveis em cinco estratos. Minas Gerais apresentou 80,9% dos municípios classificados como alto risco para transmissão de doenças imunopreveníveis. Em relação à homogeneidade das coberturas vacinais (HCV), os municípios de grande porte apresentaram a maior porcentagem de HCV classificada como muito baixa e 100% desses municípios foram classificados como de alto ou muito alto risco para transmissão de doenças imunopreveníveis, com significância estatística. A utilização de indicadores de imunização por município é efetiva para o delineamento do cenário de cada território e a proposição de políticas públicas em saúde visando o aumento das coberturas vacinais.
Subject(s)COVID-19 , Hepatitis C , Vaccine-Preventable Diseases , Humans , Child, Preschool , Brazil/epidemiology , Vaccine-Preventable Diseases/epidemiology , Vaccine-Preventable Diseases/prevention & control , Pandemics , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination
In July 2020, the Mexican Government initiated the National Program for Elimination of Hepatitis C (HCV) under a procurement agreement, securing universal, free access to HCV screening, diagnosis and treatment for 2020-2022. This analysis quantifies the clinical and economic burden of HCV (MXN) under a continuation (or end) to the agreement. A modelling and Delphi approach was used to evaluate the disease burden (2020-2030) and economic impact (2020-2035) of the Historical Base compared to Elimination, assuming the agreement continues (Elimination-Agreement to 2035) or terminates (Elimination-Agreement to 2022). We estimated cumulative costs and the per-patient treatment expenditure needed to achieve net-zero cost (the difference in cumulative costs between the scenario and the base). Elimination is defined as a 90% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage and 65% reduction in mortality by 2030. A viraemic prevalence of 0.55% (0.50-0.60) was estimated on 1st January 2021, corresponding to 745,000 (95% CI 677,000-812,000) viraemic infections in Mexico. The Elimination-Agreement to 2035 would achieve net-zero cost by 2023 and accrue 31.2 billion in cumulative costs. Cumulative costs under the Elimination-Agreement to 2022 are estimated at 74.2 billion. Under Elimination-Agreement to 2022, the per-patient treatment price must decrease to 11,000 to achieve net-zero cost by 2035. The Mexican Government could extend the agreement through 2035 or reduce the cost of HCV treatment to 11,000 to achieve HCV elimination at net-zero cost.
Subject(s)Hepatitis C, Chronic , Hepatitis C , Humans , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/prevention & control , Cost-Benefit Analysis , Mexico/epidemiology , Health Care Costs , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C/prevention & control , Hepacivirus , Antiviral Agents/therapeutic use
Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Seven oncogenic viruses are known to promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV), human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. Herein, we summarize the main relationships known to date between virus infection and cancer, providing a summary of the proposed biochemical mechanisms behind the cellular transformation. Mechanistically, DNA viruses (such as HPV, HBV, EBV, and MCPyV) encode their virus oncogenes. In contrast, RNA viruses (like HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation leading to different types of cancer. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. However, these effects could be significant in particular scenarios like those linked to severe COVID-19 or long COVID. On the other hand, looking at the SARS-CoV-2âcancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases. In summary, our work aims to recall comprehensive attention from the scientific community to elucidate the effects of SARS-CoV-2 and, more in general, ß-coronavirus infection on cancer susceptibility for cancer prevention or supporting therapeutic approaches.
Subject(s)COVID-19 , Epstein-Barr Virus Infections , Hepatitis C , Neoplasms , Papillomavirus Infections , Humans , SARS-CoV-2 , Epstein-Barr Virus Infections/complications , Papillomavirus Infections/complications , Post-Acute COVID-19 Syndrome , Herpesvirus 4, Human , COVID-19/complications , Neoplasms/pathology , Oncogenic Viruses/genetics , Cell Transformation, Neoplastic , Hepatitis C/complications
BACKGROUND: China implemented a nationwide lockdown to contain COVID-19 from an early stage. Previous studies of the impact of COVID-19 on sexually transmitted diseases (STDs) and diseases caused by blood-borne viruses (BBVs) in China have yielded widely disparate results, and studies on deaths attributable to STDs and BBVs are scarce. OBJECTIVE: We aimed to elucidate the impact of COVID-19 lockdown on cases, deaths, and case-fatality ratios of STDs and BBVs. METHODS: We extracted monthly data on cases and deaths for AIDS, gonorrhea, syphilis, hepatitis B, and hepatitis C between January 2015 and December 2021 from the notifiable disease reporting database on the official website of the National Health Commission of China. We used descriptive statistics to summarize the number of cases and deaths and calculated incidence and case-fatality ratios before and after the implementation of a nationwide lockdown (in January 2020). We used negative binominal segmented regression models to estimate the immediate and long-term impacts of lockdown on cases, deaths, and case-fatality ratios in January 2020 and December 2021, respectively. RESULTS: A total of 14,800,330 cases of and 127,030 deaths from AIDS, gonorrhea, syphilis, hepatitis B, and hepatitis C were reported from January 2015 to December 2021, with an incidence of 149.11/100,000 before lockdown and 151.41/100,000 after lockdown and a case-fatality ratio of 8.21/1000 before lockdown and 9.50/1000 after lockdown. The negative binominal model showed significant decreases in January 2020 in AIDS cases (-23.4%; incidence rate ratio [IRR] 0.766, 95% CI 0.626-0.939) and deaths (-23.9%; IRR 0.761, 95% CI 0.647-0.896), gonorrhea cases (-34.3%; IRR 0.657, 95% CI 0.524-0.823), syphilis cases (-15.4%; IRR 0.846, 95% CI 0.763-0.937), hepatitis B cases (-17.5%; IRR 0.825, 95% CI 0.726-0.937), and hepatitis C cases (-19.6%; IRR 0.804, 95% CI 0.693-0.933). Gonorrhea, syphilis, and hepatitis C showed small increases in the number of deaths and case-fatality ratios in January 2020. By December 2021, the cases, deaths, and case-fatality ratios for each disease had either reached or remained below expected levels. CONCLUSIONS: COVID-19 lockdown may have contributed to fewer reported cases of AIDS, gonorrhea, syphilis, hepatitis B, and hepatitis C and more reported deaths and case-fatality ratios of gonorrhea, syphilis, and hepatitis C in China.
Subject(s)Acquired Immunodeficiency Syndrome , COVID-19 , Gonorrhea , Hepatitis B , Hepatitis C , Sexually Transmitted Diseases , Syphilis , Humans , Syphilis/epidemiology , Gonorrhea/epidemiology , Acquired Immunodeficiency Syndrome/epidemiology , Interrupted Time Series Analysis , Communicable Disease Control , Sexually Transmitted Diseases/epidemiology , Hepatitis B/epidemiology , Hepatitis C/epidemiology
The year 2021 marked both successes and challenges for the field of kidney transplantation, in the context of the ongoing COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 25,487, driven by growth in deceased donor kidney transplants. The total number of candidates listed for deceased donor kidney transplant rose slightly in 2021 but remained below 2019 listing levels, with nearly 10% of candidates having been waiting 5 years or longer. Pretransplant mortality declined slightly among candidates of Black, Hispanic, and other races, in parallel with increasing numbers of Black and Hispanic transplant recipients. In the context of broader organ sharing, there is growing disparity in pretransplant mortality among non-metropolitan compared with metropolitan residents. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 24.6% overall, with greater nonuse among biopsied kidneys (35.9%), kidneys from donors aged 55 years or older (51.1%), and kidneys with kidney donor profile index (KDPI) of 85% or greater (66.6%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant persists, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 24% of adult kidney transplants in 2021. Five-year graft survival after living compared with deceased donor transplant was 88.6% versus 80.7% for recipients aged 18-34 years, and 82.1% versus 68.0% for recipients aged 65 years or older. The total number of pediatric kidney transplants performed increased to 820 in 2021, the highest number since 2010. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients, with continued racial disparities. The rate of deceased donor transplants among pediatric candidates recovered in 2021 from a low in 2020. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates. Most pediatric deceased donor recipients receive a kidney from a donor with KDPI less than 35%. Graft survival continues to improve, with superior outcomes for living donor transplant recipients.
Subject(s)COVID-19 , Hepatitis C , Tissue and Organ Procurement , Adult , Humans , Child , United States/epidemiology , Pandemics , COVID-19/epidemiology , Tissue Donors , Living Donors , Graft Survival , Kidney
INTRODUCTION: We aimed to evaluate access to diagnosis, treatment and follow-up in patients with viral hepatitis during the COVID-19 pandemic. METHODOLOGY: Patients who started treatment for hepatitis B and hepatitis C were included in the study and analyzed in two periods: before-pandemic and during-pandemic. Indication for treatment and frequency of laboratory follow-up was obtained from hospital records. A telephone survey was administered to evaluate treatment access and compliance. RESULTS: Four centers with 258 patients were included in the study. Of these 161 (62.4%) were male, median age was 50 years. The number of patients, admitted to outpatient clinics was 134647 in the before-pandemic period and 106548 in the during-pandemic period. Number of patients who started treatment for hepatitis B were significantly high during-pandemic period compared with before-pandemic (78 (0.07%); 73 (0.05%) respectively; p = 0.04). The number who received treatment for hepatitis C was similar in both periods: 43 (0.04%); 64 (0.05%), respectively (p = 0.25). Prophylactic treatment for hepatitis B, due to immunosuppressive agents was significantly higher in during-pandemic period (p = 0.001). In the laboratory follow-ups at 4th, 12th and 24th weeks of treatment, worse adherence was detected in during-pandemic (for all p < 0.05). Access to treatment and compliance of all patients was over 90% and did not differ in the two periods. CONCLUSIONS: During-pandemic, hepatitis patients' access to diagnosis, treatment initiation and follow-up had worsened in Turkey. The health policy implemented during the pandemic had a positive impact on patients' access to and compliance to treatment.
Subject(s)COVID-19 , Hepatitis B , Hepatitis C , Humans , Male , Middle Aged , Female , Pandemics , Turkey/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Hepacivirus , COVID-19 Testing
We conducted a mixed-methods study to understand current drug use practices and access to healthcare services for people who use injection drugs in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who used injection drugs within the past 6 months from KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP. None of the participants ever tested for Hepatitis C.
Subject(s)Drug Users , HIV Infections , Hepatitis C , Humans , South Africa/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C/prevention & control , Hepacivirus
Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.
Subject(s)Diabetes Mellitus , Hepatitis C, Chronic , Hepatitis C , Humans , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C, Chronic/drug therapy , Hepatitis C/drug therapy , Diabetes Mellitus/drug therapy
To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.
Subject(s)Coinfection , HIV Infections , Hepatitis C , Humans , Hepacivirus/genetics , Myanmar/epidemiology , Coinfection/diagnosis , Prospective Studies , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/drug therapy , Hepatitis C/complications , Hepatitis C/diagnosis , Hepatitis C/drug therapy
Subject(s)COVID-19 , Hepatitis C , Humans , Hepatitis B virus , Confounding Factors, Epidemiologic , Prevalence , Hepacivirus
BACKGROUND: The care provided in general practice to intravenous drug users (IDUs) with hepatitis C (HCV) extends beyond opioid substitution therapy. An aggregated analysis of HCV service utilization within general practice specifically related to diagnosis and treatment outcomes remains unknown from previous literature. AIMS: This study aims to estimate the prevalence of HCV and analyze data related to the diagnosis and treatment-related outcomes of HCV patients with a history of intravenous drug use in the general practice setting. DESIGN AND SETTING: A systematic review and meta-analysis in general practice. METHODS: This review included studies published in the following databases: EMBASE, PubMed, and Cochrane Central Register of Controlled Trials. Two reviewers independently extracted data in standard forms in Covidence. A meta-analysis was done using a DerSimonian and Laird random-effects model with inverse variance weighting. RESULTS: A total of 20,956 patients from 440 general practices participated in the 18 selected studies. A meta-analysis of 15 studies showed a 46% (95% confidence interval (CI), 26-67%) prevalence rate of hepatitis C amongst IDUs. Genotype information was available in four studies and treatment-related outcomes in 11 studies. Overall, treatment uptake was 9%, with a cure rate of 64% (95% CI, 43-83%). However, relevant information, such as specific treatment regimens, treatment duration and doses, and patient comorbidities, was poorly documented in these studies. CONCLUSION: The prevalence of HCV in IDUs is 46% in general practice. Only ten studies reported HCV-related treatment outcomes; however, the overall uptake rate was below 10%, with a cure rate of 64%. Likewise, the genotypic variants of HCV diagnoses, medication types, and doses were poorly reported, suggesting a need for further research into this aspect of care within this patient group to ensure optimal treatment outcomes.
Subject(s)Drug Users , Hepatitis C , Substance Abuse, Intravenous , Humans , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C/diagnosis , Substance Abuse, Intravenous/epidemiology , Hepacivirus , Family Practice , Prevalence
Community-based screening for the hepatitis C virus (HCV) decreased during the COVID-19 pandemic. We developed a collaborative referral model between a primary clinic (Liouguei District Public Health Center, LDPHC) and a tertiary referral center to increase HCV screening and treatment uptake in a mountainous region of Taiwan. Once-in-a-lifetime hepatitis B and C screening services established by the Taiwan National Health Insurance were performed at LDPHC. Antibody-to-HCV (anti-HCV)-seropositive patients received scheduled referrals and took a shuttle bus to E-Da hospital for HCV RNA testing on their first visit. Direct-acting antiviral agents (DAAs) were prescribed for HCV-viremic patients on their second visit. From October 2020 to September 2022, of 3835 residents eligible for HCV screening in Liouguei District, 1879 (49%) received anti-HCV testing at LDPHC. The overall HCV screening coverage rate increased from 40% before referral to 69.4% after referral. Of the 79 anti-HCV-seropositive patients, 70 (88.6%) were successfully referred. Of the 38 HCV-viremic patients, 35 (92.1%) received DAA therapy, and 32 (91.4%) achieved sustained virological response. The collaborative referral model demonstrates a good model for HCV screening and access to care and treatment in a Taiwan mountainous region, even during the COVID-19 pandemic. Sustained referral is possible using this routine referral model.
Subject(s)COVID-19 , Hepatitis C, Chronic , Hepatitis C , Humans , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Taiwan/epidemiology , Pandemics , COVID-19/diagnosis , COVID-19/epidemiology , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepacivirus/genetics , Referral and Consultation
Subject(s)Carcinoma, Hepatocellular , Hepatitis C , Liver Neoplasms , Humans , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Mass Screening
Members of the Numb-associated kinase family of serine/threonine kinases play an essential role in many cellular processes, such as endocytosis, autophagy, dendrite morphogenesis, osteoblast differentiation, and the regulation of the Notch pathway. Numb-associated kinases have been relevant to diverse diseases, including neuropathic pain, Parkinson's disease, and prostate cancer. Therefore, they are considered potential therapeutic targets. In addition, it is reported that Numb-associated kinases have been involved in the life cycle of multiple viruses such as hepatitis C virus (HCV), Ebola virus (EBOV), and dengue virus (DENV). Recently, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten global health. Studies show that Numb-associated kinases are implicated in the infection of SARS-CoV-2 which can be suppressed by Numb-associated kinases inhibitors. Thus, Numb-associated kinases are proposed as potential host targets for broad-spectrum antiviral strategies. We will focus on the recent advances in Numb-associated kinases-related cellular functions and their potential as host targets for viral infections in this review. Questions that remained unknown on the cellular functions of Numb-associated kinases will also be discussed.
Subject(s)COVID-19 , Hepatitis C , Male , Humans , SARS-CoV-2/metabolism , Protein Serine-Threonine Kinases/metabolism , Endocytosis , Antiviral Agents , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism
BACKGROUND & OBJECTIVES: Screening for hepatitis C virus is the first critical decision point for preventing morbidity and mortality from HCV cirrhosis and hepatocellular carcinoma and will ultimately contribute to global elimination of a curable disease. This study aims to portray the changes over time in HCV screening rates and the screened population characteristics following the 2020 implementation of an electronic health record (EHR) alert for universal screening in the outpatient setting in a large healthcare system in the US mid-Atlantic region. METHODS: Data was abstracted from the EHR on all outpatients from 1/1/2017 through 10/31/2021, including individual demographics and their HCV antibody (Ab) screening dates. For a limited period centered on the implementation of the HCV alert, mixed effects multivariable regression analyses were performed to compare the timeline and characteristics of those screened and un-screened. The final models included socio-demographic covariates of interest, time period (pre/post) and an interaction term between time period and sex. We also examined a model with time as a monthly variable to look at the potential impact of COVID-19 on screening for HCV. RESULTS: Absolute number of screens and screening rate increased by 103% and 62%, respectively, after adopting the universal EHR alert. Patients with Medicaid were more likely to be screened than private insurance (ORadj 1.10, 95% CI: 1.05, 1.15), while those with Medicare were less likely (ORadj 0.62, 95% CI: 0.62, 0.65); and Black (ORadj 1.59, 95% CI: 1.53, 1.64) race more than White. CONCLUSIONS: Implementation of universal EHR alerts could prove to be a critical next step in HCV elimination. Those with Medicare and Medicaid insurance were not screened proportionately to the national prevalence of HCV in these populations. Our findings support increased screening and re-testing efforts for those at high risk of HCV.
Subject(s)COVID-19 , Hepatitis C , Liver Neoplasms , United States/epidemiology , Humans , Aged , Hepacivirus , Electronic Health Records , Medicare , Hepatitis C/diagnosis , Hepatitis C/epidemiology
Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called "replication factories"), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA synthesis. In the current study, we investigate pan-viral similarities and virus-specific differences in the life cycle of this highly relevant group of viruses. We first measured the kinetics of viral RNA, viral protein, and infectious virus particle production of hepatitis C virus (HCV), dengue virus (DENV), and coxsackievirus B3 (CVB3) in the immuno-compromised Huh7 cell line and thus without perturbations by an intrinsic immune response. Based on these measurements, we developed a detailed mathematical model of the replication of HCV, DENV, and CVB3 and showed that only small virus-specific changes in the model were necessary to describe the in vitro dynamics of the different viruses. Our model correctly predicted virus-specific mechanisms such as host cell translation shut off and different kinetics of replication organelles. Further, our model suggests that the ability to suppress or shut down host cell mRNA translation may be a key factor for in vitro replication efficiency, which may determine acute self-limited or chronic infection. We further analyzed potential broad-spectrum antiviral treatment options in silico and found that targeting viral RNA translation, such as polyprotein cleavage and viral RNA synthesis, may be the most promising drug targets for all plus-strand RNA viruses. Moreover, we found that targeting only the formation of replicase complexes did not stop the in vitro viral replication early in infection, while inhibiting intracellular trafficking processes may even lead to amplified viral growth.
Subject(s)Hepatitis C , RNA Viruses , Humans , Antiviral Agents/pharmacology , Virus Replication/physiology , RNA, Viral/genetics , Models, Theoretical
Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.
Subject(s)COVID-19 , Carcinoma, Hepatocellular , Coinfection , Drug Users , HIV Infections , Hepatitis A , Hepatitis B, Chronic , Hepatitis B , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Sexual and Gender Minorities , Substance Abuse, Intravenous , Male , Humans , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Hepatitis B, Chronic/complications , Homosexuality, Male , Coinfection/drug therapy , Coinfection/epidemiology , Coinfection/complications , Substance Abuse, Intravenous/complications , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , COVID-19/complications , Hepatitis C, Chronic/complications , Hepatitis C/drug therapy , Liver Cirrhosis/complications , Tenofovir/therapeutic use , Hepatitis B/drug therapy
Subject(s)Birth Cohort , Hepatitis C , Humans , Mass Screening , Cost-Benefit Analysis , Hepacivirus
CONTEXT: Birth cohort ("baby boomer") screening represents a well-validated strategy for the identification of asymptomatic hepatitis C-infected patients. However, successful linkage of newly diagnosed patients to antiviral therapy has been more difficult to accomplish. OBJECTIVE: To analyze the results of a systemwide birth cohort screening program in a US community health care system. DESIGN: We analyzed the data from an ongoing hepatitis C virus (HCV) screening and treatment program that was established at NorthShore University Health System in 2015. Hepatitis C virus screening by primary care providers was prompted through automated Best Practice and Health Maintenance alerts. Patient visits and screening orders were tracked using a customized HCV dashboard. Virologic, demographic, and treatment data were assessed and compared with those of a cohort of patients with previously established HCV infection. RESULTS: Since program inception, 61 8161 (64.3%) of the entire NorthShore baby boomer population of 96 001 patients have completed HCV antibody testing, and 160 patients (0.26%) were antibody positive. Of 152 antibody-positive patients who underwent HCV RNA testing, 53 (34.2%) were viremic. A total of 39 of 53 patients (73.6%) underwent antiviral therapy and achieved a sustained virologic response. Compared with patients identified through screening, a comparison cohort of patients with previously established HCV had more advanced fibrosis and significantly lower dropout rates. The COVID-19 pandemic was associated with a decrease in the number of outpatient visits of screening-eligible patients and with a reduction in HCV screening rates. CONCLUSION: Our data demonstrate the electronic medical records-assisted systemwide implementation of HCV birth cohort screening and successful linkage to antiviral therapy in a community-based US multihospital system.