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1.
Clin Microbiol Infect ; 28(4): 611.e1-611.e7, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1828108

ABSTRACT

OBJECTIVES: Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy. METHODS: Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection. RESULTS: HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47-1.46; 1.76, IQR 0.83-2.66; 0.78, IQR 0.28-1.77), non-classical monocytes (1.11, IQR 0.49-1.26; 0.9, IQR 0.18-0.99; 0.54, IQR 0.28-1.77), conventional dendritic cells type 2 (0.55, IQR 0.35-0.59; 0.31, IQR 0.16-0.38; 0.19, IQR 0.11-0.36) and CD56dim natural killer cells (8.08, IQR 5.34-9.79; 4.72, IQR 2.59-6.05) 3.61, IQR 2.98-5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06-0.10; 0.10, IQR 0.09-0.19; 0.19, IQR 0.12-0.25), activated CD4 T cells (0.28, IQR 0.21-0.36; 0.56, IQR 0.33-0.77; 0.40, IQR 0.22-0.53) and activated CD8 T cells (0.23, IQR 0.14-0.42; 0.74, IQR 0.30-1.65; 0.80, IQR 0.58-1.16) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12. CONCLUSIONS: Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.


Subject(s)
HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , CD8-Positive T-Lymphocytes , HIV Infections/complications , HIV Infections/drug therapy , Hepacivirus , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans
2.
3.
Curr Opin Organ Transplant ; 27(1): 64-69, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1794983

ABSTRACT

PURPOSE OF REVIEW: The aim of this study was to describe recent developments in renal transplantation for HIV-positive recipients, especially the HIV Organ Policy Equity (HOPE) trial results. RECENT FINDINGS: HOPE trial data show that HIV-positive D+/R+ results are excellent and similar to D-/R+ in patients controlled on antiretroviral therapy (ART). Patients coinfected with hepatitis C or B virus now have effective treatment available. As pretransplant evaluation and post-transplant management is more complex in HIV-positive individuals early referral is important and coordination of evaluation and care with an infectious disease specialist is critical. HIV coordinated care services should be involved for best outcomes. HIV-positive renal transplant recipients have an increased risk of rejection and evidence suggests that standard lymphocyte depletion induction and maintenance immunosuppression be employed. Cardiovascular risk reduction and surveillance and attention to metabolic bone disease are important for HIV-positive renal transplant recipients. SUMMARY: HIV-positive to HIV-positive renal transplantation has been established as well tolerated and successful. Further efforts are needed to expand access to transplantation in this population. VIDEO ABSTRACT: http://links.lww.com/MOT/A29.


Subject(s)
HIV Infections , Hepatitis C , Kidney Transplantation , Graft Rejection/epidemiology , Graft Rejection/prevention & control , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/drug therapy , Hepacivirus , Humans , Kidney Transplantation/adverse effects , Transplant Recipients
4.
Sci Rep ; 12(1): 5771, 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1778635

ABSTRACT

SARS-CoV-2 is still a health problem worldwide despite the availability of vaccines. Therefore, there is a need for effective and safe antiviral. SARS-CoV-2 and HCV necessitate RNA-dependent RNA polymerase (RdRp) for replication; therefore, it has been hypothesized that RdRp inhibitors used to treat HCV may be effective treating SARS-CoV-2. Accordingly, we evaluated the effect of the sofosbuvir/velpatasvir (SOF/VEL) combination in early SARS-CoV-2 infection. A multicenter case-control study was conducted, enrolling 120 patients with mild or moderate COVID-19, of whom 30, HCV coinfected or not, received SOF/VEL tablets (400/100 mg) once daily for 9 days within a median of 6 days from the beginning of infection and 90 controls were treated with standard care. The primary endpoint was the effect on viral clearance, and the secondary endpoint was the improvement of clinical outcomes. Nasal swabs for SARS-CoV-2 by PCR were performed every 5-7 days. Between 5-14 days after starting SOF/VEL treatment, SAS-CoV-2 clearance was observed in 83% of patients, while spontaneous clearance in the control was 13% (p < 0.001). An earlier SARS-CoV-2 clearance was observed in the SOF/VEL group than in the control group (median 14 vs 22 days, respectively, p < 0.001) also when the first positivity was considered. None of the patients in the SOF/VEL group showed disease progression, while in the control group, 24% required more intensive treatment (high flow oxygen or noninvasive/invasive ventilation), and one patient died (p < 0.01). No significant side effects were observed in the SOF/VEL group. Early SOF/VEL treatment in mild/moderate COVID-19 seems to be safe and effective for faster elimination of SARS-CoV-2 and to prevent disease progression.


Subject(s)
COVID-19 , Hepatitis C , Antiviral Agents/adverse effects , COVID-19/drug therapy , Carbamates , Case-Control Studies , Disease Progression , Genotype , Hepacivirus/genetics , Hepatitis C/drug therapy , Heterocyclic Compounds, 4 or More Rings/adverse effects , Humans , RNA-Dependent RNA Polymerase , SARS-CoV-2 , Sofosbuvir , Treatment Outcome
5.
Gene ; 820: 146235, 2022 Apr 30.
Article in English | MEDLINE | ID: covidwho-1778131

ABSTRACT

The relationship of single nucleotide polymorphisms (SNPs) in patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, and membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 with outcomes in patients with hepatitis C infection (HCV) is unclear. This study aimed to evaluate the association of PNPLA3, TM6SF2, and MBOAT7 with the baseline fibrosis stage and progression of liver fibrosis after HCV eradication with direct antiviral agents (DAAs). A total of 171 patients who received the DAAs at the Peking University First Hospital between June 2015 and June 2020 were included in the retrospective cohort. Transient elastography was used to determine liver stiffness measurements (LSMs) at the baseline, the end of treatment (EOT), 24 weeks after treatment (W24), and the last follow-up (LFU) visit. We used the QIAamp Blood Mini Kit (Qiagen) for whole blood genomic DNA extraction and polymerase chain reaction for PNPLA3, TM6SF2, and MBOAT7 amplification of the target gene. The PNPLA3 rs738409 SNP was associated with the baseline fibrosis stage in multivariate logistic regression analysis adjusted for other factors, and the adjusted odds ratio (OR) for advanced fibrosis (≥F3) at baseline was 2.52 (95% confidence interval[CI] = 1.096-5.794, p = 0.03). The G and GG alleles were predictive of advanced fibrosis (OR = 1.98, 95% CI = 1.021-4.196, p = 0.015; OR = 3.12, 95% CI = 1.572-6.536, p = 0.005). Similarly, the OR of TM6SF2 rs58542926 at baseline was 2.608 (95% CI = 1.081-6.29, p = 0.033). T and TT alleles were predictive of advanced fibrosis (OR = 2.3, 95% CI = 1.005-5.98, p = 0.007; OR = 3.05, 95% CI = 1.32-6.87, p = 0.001). After adjustment, the MBOAT7 rs641738 T plus TT alleles were not independently associated with the baseline fibrosis stage (95% CI = 0.707-2.959, p = 0.312). At the EOT, there were 35 patients and 136 patients in the fibrosis improvement and fibrosis non-improvement group, respectively. Logistic regression analysis showed that the G allele in PNPLA3 rs738409 was associated with fibrosis progression (OR = 2.47, 95% CI = 1.125-5.89, p = 0.003). The GG alleles were predictive of fibrosis progression (OR = 2.95, 95% CI = 1.35-6.35, p = 0.005). Similarly, the ORs of the T and TT alleles in TM6SF2 rs58542926 for fibrosis progression were 1.82 and 2.21, respectively (95% CI = 1.006-5.373, p = 0.045; 95% CI = 1.18-5.75, p = 0.01). At the W24 visit, we found that there was an association between the G allele in PNPLA3 rs738409 and fibrosis progression (OR = 2.218, 95% CI = 1.095-5.631, p = 0.015). Moreover, GG alleles were also predictive for fibrosis progression (OR = 2.558, 95% CI = 1.252-5.15, p = 0.008). Similarly, the OR of T allele and TT alleles in TM6SF2 rs58542926 for fibrosis progression was 2.056 and 2.652 (95% CI = 1.013-5.592, p = 0.038; 95% CI = 1.25-5.956, p = 0.015). For additional affirmation, we surveyed fibrosis progression utilizing the Cox proportional hazards model. G and GG alleles in PNPLA3 rs738409 were associated with an increased risk of progression to advanced fibrosis in multivariate model (hazard ratio [HR]1.566, 95% CI = 1.02-2.575, p = 0.017; and HR2.109, 95% CI = 1.36-3.271, p = 0.001, respectively). Besides, T and TT alleles in TM6SF2 rs58542926 were associated with an increased risk of progression to advanced fibrosis in multivariate model (HR = 1.322, 95% CI = 1.003-1.857, p = 0.045; and HR = 1.855, 95% CI = 1.35-2.765, p = 0.006, respectively). In contrast, rs641738 in MBOAT7 did not show a significant trend in the univariate and multivariate models. The PNPLA3 CG/GG SNP at rs738409 and TM6SF2 CT/TT SNP at rs58542926 were associated with the baseline fibrosis stage and fibrosis progression after HCV eradication with DAAs.


Subject(s)
Acyltransferases/economics , Acyltransferases/genetics , Liver Cirrhosis/genetics , Membrane Proteins/economics , Membrane Proteins/genetics , Phospholipases A2, Calcium-Independent/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Alleles , Disease Progression , Female , Genetic Predisposition to Disease , Hepacivirus , Hepatitis C/complications , Hepatitis C/virology , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/genetics , Prognosis , Retrospective Studies
6.
Front Public Health ; 9: 735572, 2021.
Article in English | MEDLINE | ID: covidwho-1775874

ABSTRACT

Background: The WHO has defined international targets toward the elimination of hepatitis C by 2030. Most countries cannot be on track to achieve this goal unless many challenges are surpassed. The Let's End HepC (LEHC) tool aims to contribute to the control of hepatitis C. The innovation of this tool combines the modelling of public health policies (PHP) focused on hepatitis C with epidemiological modelling of the disease, obtaining a unique result that allows to forecast the impact of policy outcomes. The model was applied to several countries, including Spain. Methods: To address the stated objective, we applied the "Adaptive Conjoint Analysis" for PHP decision-making and Markov Chains in the LEHC modelling tool. The tool also aims to be used as an element of health literacy for patient advocacy through gamification mechanisms and country comparability. The LEHC project has been conducted in several countries, including Spain. The population segments comprised in the project are: People Who Inject Drugs (PWID), prisoners, blood products, remnant population. Results: A total of 24 PHP related to hepatitis C were included in the LEHC project. It was identified that Spain had fully implemented 14 of those policies to control hepatitis C. According to LEHC's model forecast, the WHO's Hepatitis C elimination goal on reducing the number of patients living with Hepatitis C to 10% can be achieved in Spain by 2026 if current policies are maintained. The model estimates that the total population in Spain, by 2026, is expected to comprise 26,367 individuals living with hepatitis C. Moreover, if the 24 PHP considered for this study are fully implemented in Spain, the elimination goal may be achieved in 2024, with 29,615 individuals living with hepatitis C by that year. Conclusion: The findings corroborate the view that Spain has set great efforts in directing PHP toward Hepatitis C Virus (HCV) elimination by 2030. However, there is still room for improvement, namely in further implementing 10 of the 24 PHP considered for the LEHC project. By maintaining the 14 PHP in force, the LEHC model estimates the HCV elimination in the country by 2026, and by 2024 if further measures are employed to control the disease.


Subject(s)
Hepatitis C , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C/epidemiology , Humans , Public Health , Public Policy , Spain/epidemiology
8.
Lancet Glob Health ; 10 Suppl 1: S6, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1773859

ABSTRACT

BACKGROUND: The prevalence of hepatitis C in people who use injectable drugs along the USA-Mexico border is very high (>90%). In 2019, the Mexican government committed to providing hepatitis C treatment with priority for people who use injectable drugs, people living with HIV, and people living in prison or jail, yet the immediate plan for prioritized treatment allocation and rollout remained unclear prior to the COVID-19 pandemic. Understanding which prevention and intervention strategies and at what level of scale-up can achieve the WHO goal of 80% incidence reduction by 2030 along the border is needed. METHODS: We adapted our previously published dynamic, deterministic model of hepatitis C transmission among people who use injectable drugs to determine the direct-acting antiviral treatment allocations in combination with harm-reduction interventions (opiate agonist therapy and needle and syringe programmes) needed to achieve the WHO elimination goal between 2021 and 2030. Our model is calibrated and parameterised to epidemiological data from Ciudad Juarez (where approximately 10 000 people who use injectable drugs reside and the seroprevalence of hepatitis C among people who use injectable drugs is 92%) and minimal harm reduction. FINDINGS: To reduce hepatitis C incidence by 80% between 2021 and 2030, 910 direct-acting antiviral treatments per 10 000 people who use injectable drugs in Ciudad Juarez per year are needed. Overall, fewer treatments are required if combined with harm reduction. If opiate agonist therapy and needle and syringe programmes are scaled-up to 50%, approximately 30-40% fewer people who use injectable drugs would need to be treated each year (650 direct-acting antiviral treatments per 10 000 people who use injectable drugs per year). Between 2021 and 2030, using direct-acting antivirals alone, an estimated total of 8190 people who use injectable drugs in Ciudad Juarez would need to be treated, compared with 6255 (nearly 25%) fewer people who use injectable drugs overall if treatment is scaled-up alongside 50% of opiate agonist therapy and needle and syringe programmes combination intervention coverage. INTERPRETATION: Hepatitis C treatment with direct-acting antivirals should be prioritised for people who use injectable drugs along the USA-Mexico border and progress towards hepatitis C elimination should be monitored. Regional hepatitis C micro-elimination among people who use injectable drugs could be possible if national treatment allocations are prioritised and distributed to people who use injectable drugs as planned and in the presence of essential harm-reduction programmes. FUNDING: National Institutes of Health; Fogarty International Center grant D43TW009343; and National Institute of Allergy and Infectious Diseases and National Institute on Drug Abuse grant R01AI147490.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Hepatitis C , Substance Abuse, Intravenous , Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C/prevention & control , Hepatitis C, Chronic/epidemiology , Humans , Mexico/epidemiology , Pandemics , Seroepidemiologic Studies , Substance Abuse, Intravenous/epidemiology , World Health Organization
9.
Public Health ; 205: 182-186, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1751168

ABSTRACT

OBJECTIVES: In 2015, the Republic of Georgia initiated a National Hepatitis C Elimination Program, with a goal of 90% reduction in prevalence of chronic hepatitis C virus (HCV) infections by 2020. In this article, we explore the impact of the COVID-19 pandemic on the 2020 hepatitis C cascade of care in Georgia. STUDY DESIGN: Retrospective analytic study. METHODS: We used a national screening registry that includes hospitals, blood banks, antenatal clinics, harm reduction sites, and other programs and services to collect data on hepatitis C screening. A separate national treatment database was used to collect data on viremia and diagnostic testing, treatment initiation, and outcome including testing for and achieving sustained virologic response (SVR). We used these databases to create hepatitis C care cascades for 2020 and 2019. Bivariate associations for demographic characteristics and screening locations per year and care cascade comparisons were assessed using a chi-squared test. RESULTS: In 2020 compared to 2019, the total number of persons screened for HCV antibodies decreased by 25% (from 975,416 to 726,735), 59% fewer people with viremic infection were treated for HCV infection (3188 vs. 7868), 46% fewer achieved SVR (1345 vs. 2495), a significantly smaller percentage of persons with viremic infection initiated treatment for HCV (59% vs. 62%), while the percentage of persons who achieved SVR (99.2% vs. 99.3%) remained stable. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the hepatitis C elimination program in Georgia. To ensure Georgia reaches its elimination goals, mitigating unintended consequences of delayed diagnosis and treatment of hepatitis C due to the COVID-19 pandemic are paramount.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Female , Georgia/epidemiology , Georgia (Republic)/epidemiology , Hepacivirus , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Pandemics , Pregnancy , Retrospective Studies
10.
J Interferon Cytokine Res ; 42(1): 39-41, 2022 01.
Article in English | MEDLINE | ID: covidwho-1746968

Subject(s)
Hepacivirus , Hepatitis C , Humans
11.
J Virol ; 96(7): e0199521, 2022 Apr 13.
Article in English | MEDLINE | ID: covidwho-1745826

ABSTRACT

C-type lectin domain-containing proteins (CTLDcps) shape host responses to pathogens and infectious disease outcomes. Previously, we identified the murine CTLDcp Cd302 as restriction factor, limiting hepatitis C virus (HCV) infection of murine hepatocytes. In this study, we investigated in detail the human orthologue's ability to restrict HCV infection in human liver cells. CD302 overexpression in Huh-7.5 cells potently inhibited infection of diverse HCV chimeras representing seven genotypes. Transcriptional profiling revealed abundant CD302 mRNA expression in human hepatocytes, the natural cellular target of HCV. Knockdown of endogenously expressed CD302 modestly enhanced HCV infection of Huh-7.5 cells and primary human hepatocytes. Functional analysis of naturally occurring CD302 transcript variants and engineered CD302 mutants showed that the C-type lectin-like domain (CTLD) is essential for HCV restriction, whereas the cytoplasmic domain (CPD) is dispensable. Coding single nucleotide polymorphisms occurring in human populations and mapping to different domains of CD302 did not influence the capacity of CD302 to restrict HCV. Assessment of the anti-HCV phenotype at different life cycle stages indicated that CD302 preferentially targets the viral entry step. In contrast to the murine orthologue, overexpression of human CD302 did not modulate downstream expression of nuclear receptor-controlled genes. Ectopic CD302 expression restricted infection of liver tropic hepatitis E virus (HEV), while it did not affect infection rates of two respiratory viruses, including respiratory syncytial virus (RSV) and the alpha coronavirus HVCoV-229E. Together, these findings suggest that CD302 contributes to liver cell-intrinsic defense against HCV and might mediate broader antiviral defenses against additional hepatotropic viruses. IMPORTANCE The liver represents an immunoprivileged organ characterized by enhanced resistance to immune responses. However, the importance of liver cell-endogenous, noncytolytic innate immune responses in pathogen control is not well defined. Although the role of myeloid cell-expressed CTLDcps in host responses to viruses has been characterized in detail, we have little information about their potential functions in the liver and their relevance for immune responses in this organ. Human hepatocytes endogenously express the CTLDcp CD302. Here, we provide evidence that CD302 limits HCV infection of human liver cells, likely by inhibiting a viral cell entry step. We confirm that the dominant liver-expressed transcript variant, as well as naturally occurring coding variants of CD302, maintain the capacity to restrict HCV. We further show that the CTLD of the protein is critical for the anti-HCV activity and that overexpressed CD302 limits HEV infection. Thus, CD302 likely contributes to human liver-intrinsic antiviral defenses.


Subject(s)
Hepacivirus , Hepatitis C , Animals , Antiviral Agents/metabolism , Asialoglycoprotein Receptor/metabolism , Hepacivirus/physiology , Hepatitis C/metabolism , Hepatocytes , Humans , Lectins, C-Type/genetics , Lectins, C-Type/metabolism , Mice , Receptors, Cell Surface/metabolism , Virus Replication
13.
Viruses ; 14(3)2022 02 28.
Article in English | MEDLINE | ID: covidwho-1715780

ABSTRACT

Following the availability of highly effective direct-acting antivirals (DAAs) to treat hepatitis C infection, the uptake of treatment by people living with hepatitis C rose dramatically in high- and middle-income countries but has since declined. To achieve the World Health Organization's (WHO) 2030 target to eliminate hepatitis C as a public health threat among people who inject drugs, an increase in testing and treatment is required, together with improved coverage of harm reduction interventions. The population that remains to be treated in high- and middle-income countries with high hepatitis C prevalence are among the most socially disadvantaged, including people who inject drugs and are involved in the criminal justice system, a group with disproportionate hepatitis C prevalence, compared with people in the wider community. Imprisonment provides an unrivalled opportunity for screening and treating large numbers of people for hepatitis C, who may not access mainstream health services in the community. Despite some implementation challenges, evidence of the efficacy, acceptability, and cost-effectiveness of in-prison hepatitis treatment programs is increasing worldwide, and evaluations of these programs have demonstrated the capacity for treating people in high numbers. In this Perspective we argue that the scale-up of hepatitis C prevention, testing, and treatment programs in prisons, along with the investigation of new and adapted approaches, is critical to achieving WHO elimination goals in many regions; the Australian experience is highlighted as a case example. We conclude by discussing opportunities to improve access to prevention, testing, and treatment for people in prison and other justice-involved populations, including harnessing the changed practices brought about by the COVID-19 pandemic.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Australia/epidemiology , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C/prevention & control , Humans , Pandemics , Prisons
14.
Viruses ; 14(3)2022 02 26.
Article in English | MEDLINE | ID: covidwho-1715776

ABSTRACT

In 2016, the WHO announced a plan to eliminate viral hepatitis as a public health threat by 2030. In this narrative review, experts from Bulgaria, Croatia, the Czech Republic, Hungary, Latvia, Lithuania, Poland and Slovakia assessed the feasibility of achieving the WHO 2030 target for HCV infections in Central Europe. They focused mainly on HCV micro-elimination in prisons, where the highest incidence of HCV infections is usually observed, and the impact of the COVID-19 pandemic on the detection and treatment of HCV infections. According to the presented estimates, almost 400,000 people remain infected with HCV in the analyzed countries. Interferon-free therapies are available ad libitum, but the number of patients treated annually in the last two years has halved compared to 2017-2019, mainly due to the COVID-19 pandemic. None of the countries analyzed had implemented a national HCV screening program or a prison screening program. The main reason is a lack of will at governmental and prison levels. None of the countries analyzed see any chance of meeting the WHO targets for removing viral hepatitis from the public threat list by 2030, unless barriers such as a lack of political will and a lack of screening programs are removed quickly.


Subject(s)
COVID-19 , Hepatitis C , COVID-19/epidemiology , COVID-19/prevention & control , Europe/epidemiology , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C/prevention & control , Humans , Pandemics/prevention & control , Prisons
15.
Viruses ; 14(2)2022 02 02.
Article in English | MEDLINE | ID: covidwho-1715769

ABSTRACT

A hepatitis C virus (HCV) screening and treatment program was conducted in Hungarian prisons on a voluntary basis. After HCV-RNA testing and genotyping for anti-HCV positives, treatments with direct-acting antiviral agents were commenced by hepatologists who visited the institutions monthly. Patients were supervised by the prisons' medical staff. Data were retrospectively collected from the Hungarian Hepatitis Treatment Registry, from the Health Registry of Prisons, and from participating hepatologists. Eighty-four percent of Hungarian prisons participated, meaning a total of 5779 individuals (28% of the inmate population) underwent screening. HCV-RNA positivity was confirmed in 317/5779 cases (5.49%); 261/317 (82.3%) started treatment. Ninety-nine percent of them admitted previous intravenous drug use. So far, 220 patients received full treatment and 41 patients are still on treatment. Based on the available end of treatment (EOT) + 24 weeks timepoint data, per protocol sustained virologic response rate was 96.8%. In conclusion, the Hungarian prison screening and treatment program, with the active participation of hepatologists and the prisons' medical staff, is a well-functioning model. Through the Hungarian experience, we emphasize that the "test-and-treat" principle is feasible and effective at micro-eliminating HCV in prisons, where infection rate, as well as history of intravenous drug usage, are high.


Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/isolation & purification , Hepatitis C/drug therapy , Adolescent , Adult , Female , Hepacivirus/drug effects , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis C/blood , Hepatitis C/diagnosis , Hepatitis C/virology , Humans , Hungary , Male , Mass Screening , Middle Aged , Prisons/statistics & numerical data , Retrospective Studies , Sustained Virologic Response , Young Adult
16.
Int J Drug Policy ; 96: 103438, 2021 10.
Article in English | MEDLINE | ID: covidwho-1712559

ABSTRACT

BACKGROUND: People who use drugs (PWUD), and especially those who inject drugs, are at increased risk of acquiring bloodborne infections (e.g., HIV and HCV), experiencing drug-related harms (e.g., abscesses and overdose), and being hospitalized and requiring inpatient parenteral antibiotic therapy delivered through a peripherally inserted central catheter (PICC). The use of PICC lines with PWUD is understood to be a source of tension in hospital settings but has not been well researched. Drawing on theoretical and analytic insights from "new materialism," we consider the assemblage of sociomaterial elements that inform the use of PICCs. METHODS: This paper draws on n = 50 interviews conducted across two related qualitative research projects within a program of research about the impact of substance use on hospital admissions from the perspective of healthcare providers (HCPs) and people living with HIV/HCV who use drugs. This paper focuses on data about PICC lines collected in both studies. RESULTS: The decision to provide, maintain, or remove a PICC is based on a complex assemblage of factors (e.g., infections, bodies, drugs, memories, relations, spaces, temporalities, and contingencies) beyond whether parenteral intravenous antibiotic therapy is clinically indicated. HCPs expressed concerns about the risk posed by past, current, and future drug use, and contact with non-clinical spaces (e.g., patient's homes and the surrounding community), with some opting for second-line treatments and removing PICCs. The majority of PWUD described being subjected to threats of discharge and increased monitoring despite being too ill to use their PICC lines during past hospital admissions. A subset of PWUD reported using their PICC lines to inject drugs as a harm reduction strategy, and a subset of HCPs reported providing harm reduction-centred care. CONCLUSION: Our analysis has implications for theorizing the role of PICC lines in the care of PWUD and identifies practical guidance for engaging them in productive and non-judgemental discussions about the risks of injecting into a PICC line, how to do it safely, and about medically supported alternatives.


Subject(s)
Catheterization, Central Venous , HIV Infections , Hepatitis C , Pharmaceutical Preparations , Catheterization, Central Venous/adverse effects , Catheters , HIV Infections/drug therapy , Hepatitis C/drug therapy , Hospitals , Humans , Retrospective Studies , Risk Factors
17.
BMC Public Health ; 22(1): 371, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1708042

ABSTRACT

BACKGROUND: While the availability of generic direct-acting antivirals (DAAs) opens the door for large-scale treatment, the care for people living with hepatitis C virus (HCV) in Malaysia is shifting toward a tripartite partnership between the public health system, correctional settings and civil society organizations (CSOs). This study aimed to explore the barriers to scaling up HCV treatment in Malaysia from the perspective of key stakeholders. METHODS: Eighteen focus-group discussions (FGDs) were conducted with 180 individuals, who actively engaged in coordinating, executing or supporting the implementation of the national strategic plan for HCV. An analytical framework was adapted to guide the data collection and thematic analysis. It covered four key aspects of HCV treatment: geographical accessibility, availability, affordability and acceptability. RESULTS: Movement restrictions in times of coronavirus disease 2019 (COVID-19) outbreaks and being marginalized translated into barriers to treatment access in people living with HCV. Barriers to treatment initiation in health and correctional settings included limited staffing and capacity; disruption in material supply; silos mentality and unintegrated systems; logistical challenges for laboratory tests; and insufficient knowledge of care providers. Although no-cost health services were in place, concerns over transportation costs and productivity loss also continued to suppress the treatment uptake. Limited disease awareness, along with the disease-related stigma, further lowered the treatment acceptability. CONCLUSIONS: This study disclosed a series of supply- and demand-side barriers to expanding the treatment coverage among people living with HCV in Malaysia. The findings call for strengthening inter-organizational collaborations to overcome the barriers.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Health Services , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Humans , Malaysia , SARS-CoV-2
18.
Lancet Gastroenterol Hepatol ; 7(5): 396-415, 2022 May.
Article in English | MEDLINE | ID: covidwho-1683802

ABSTRACT

BACKGROUND: Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. METHODS: This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. FINDINGS: Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7-0·9), corresponding to 56·8 million (95% UI 55·2-67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8-75·8) infections (0·9% [0·8-1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5-15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. INTERPRETATION: At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. FUNDING: John C Martin Foundation, Gilead Sciences, AbbVie, ZeShan Foundation, and The Hepatitis Fund.


Subject(s)
COVID-19 , Hepatitis A , Hepatitis C , COVID-19/epidemiology , Hepacivirus , Hepatitis C/epidemiology , Humans , Infant, Newborn , Pandemics , Prevalence , Viremia/epidemiology
19.
J Med Virol ; 94(5): 2296-2301, 2022 05.
Article in English | MEDLINE | ID: covidwho-1640755

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can generate a systemic inflammatory response, characterized by a cytokine storm and associated with an exaggerated release of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-17, all of which can affect the liver. Here, we aimed to evaluate the cytokine profiles of patients suffering from coronavirus disease (COVID)-19 and/or hepatitis. We subjected 87 patients to serology and/or polymerase chain reaction analysis for the hepatitis C virus. They were also tested for TNF-α, IL-6, and IL-17 using commercial immunoassay kits. The test results of the COVID-19/hepatitis C patients (n = 8) were compared with that of the negative controls (n = 28), hepatitis C patients (n = 29), and COVID-19 patients (n = 22). All COVID-19 patients (mono- and coinfected) expressed high levels of cytokines. The COVID-19/hepatitis patients exhibited higher levels of IL-6 (6.33 ± 3.9 pg/ml) and IL-17 (102.23 ± 2.7 pg/ml); however, TNF-α values were lower (68.08 ± 15.88 pg/ml), as compared with that of the hepatitis patients (p < 0.001), and lower than that of the COVID-19 patients and exceptionally for TNF-α (p < 0.05). These data highlight the importance of monitoring patients with hepatitis and COVID-19.


Subject(s)
COVID-19 , Hepatitis C , Cytokine Release Syndrome , Cytokines , Hepacivirus , Humans , SARS-CoV-2
20.
Kaohsiung J Med Sci ; 38(4): 394-395, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1633584
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