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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.
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
4.
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
5.
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
6.
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
7.
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
8.
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
10.
Int J Drug Policy ; 101: 103570, 2022 03.
Article in English | MEDLINE | ID: covidwho-1587942

ABSTRACT

BACKGROUND: Healthcare delivery was disrupted during the COVID-19 pandemic, requiring minimized in-person contact between patients and clinicians. During the pandemic, people with opioid use disorder (OUD) were not only at elevated risk for COVID-19, but had markedly reduced access to treatment for OUD, Hepatitis C virus (HCV) and HIV due to recommended decreased in-person visits. METHODS: From March 15-June 15, 2020 at the syringe services program (SSP) in New Haven, Connecticut, USA, a differentiated care model evolved with reduced clinical demands on people who inject drugs (PWID) to ensure screening and treatment for HCV, HIV and OUD, with a focus on HCV treatment. This model involved a single, bundled screening, evaluation, testing (SET) and monitoring strategy for all three conditions, minimal in-person visits, followed by tele-health communication between patients, outreach workers and clinicians. In-person visits occurred only during induction onto methadone and phlebotomy at baseline and phlebotomy 12 weeks post-treatment for HCV to measure sustained virological response (SVR). Patients received supportive texts/calls from outreach workers and clinicians. RESULTS: Overall, 66 actively injecting PWID, all with OUD, underwent bundled laboratory screening; 35 had chronic HCV infection. Participants were 40 years (mean), mostly white (N = 18) men (N = 28) and 12 were unstably housed. Two were lost to-follow-up and 2 were incarcerated, leaving 31 who started pan-genotypic direct-acting antivirals (DAAs). The mean time from referral to initial phlebotomy and initiation of DAAs was 6.9 and 9.9 days, respectively. Fourteen additional patients were newly started on buprenorphine and 6 started on methadone; three and four, respectively, were on treatment at baseline. Overall, 29 (93.5%) PWID who initiated DAAs achieved SVR; among unstably housed persons the SVR was 83.3%. CONCLUSIONS: In response to COVID-19, an innovative differentiated care model for PWID at an SSP evolved that included successful co-treatment for HCV, HIV and OUD using a client-centered approach that reduces treatment demands on patients yet supports ongoing access to evidence-based treatments.


Subject(s)
COVID-19 , Drug Users , Hepatitis C, Chronic , Hepatitis C , Opioid-Related Disorders , Substance Abuse, Intravenous , Telemedicine , Antiviral Agents , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Humans , Male , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/therapy , Pandemics , Pharmaceutical Preparations , SARS-CoV-2 , Substance Abuse, Intravenous/epidemiology , Syringes
11.
World J Gastroenterol ; 27(47): 8199-8200, 2021 Dec 21.
Article in English | MEDLINE | ID: covidwho-1580315

ABSTRACT

In 2016, the World Health Assembly adopted a Global Health Sector Strategy on viral hepatitis, with targets set for the years 2020 and 2030 to achieve hepatitis elimination. The main target of hepatitis elimination strategy is to reduce the incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) by 90% and mortality by 65% in 2030. In last 5 years, the number of people receiving HCV treatment has increased from 1 million to 9.4 million; however, this number is far from the 2030 target of 40 million people receiving HCV treatment. HBV and HCV incidence rates are down from 1.4 million to 1.1 million annual deaths but this is far from the 2030 target of < 0.5 million deaths. The coronavirus disease 2019 pandemic has severely affected the efforts in the fight against hepatitis. No major donor has committed to investing in the fight against hepatitis. Time is running out. There is a need to speed up efforts in the fight against hepatitis to achieve hepatitis elimination by 2030.


Subject(s)
COVID-19 , Hepatitis B , Hepatitis C , Hepatitis, Viral, Human , Antiviral Agents/therapeutic use , Global Health , Hepacivirus , Hepatitis B/diagnosis , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis, Viral, Human/drug therapy , Humans , SARS-CoV-2
12.
BMJ Open ; 11(10): e053394, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1476608

ABSTRACT

INTRODUCTION: The hepatitis C virus (HCV) is a highly infectious and deadly disease, affecting some 58 million people worldwide. Of the 1.13 million people living in the Balearic Islands, Spain, about 1350 individuals have untreated HCV. Of these, about 1120 (83%) are estimated to be people who use drugs (PWUD), who are one of the key at-risk groups for HCV infection globally. Carrying out micro-elimination approaches focused on this population is crucial to achieve the WHO goal of eliminating HCV by 2030. Thus, the primary objective of this study is to validate a model of care that simplifies the screening and linkage to HCV care pathways for PWUD on the Balearic Islands. METHODS AND ANALYSIS: This intervention study will be implemented across 17 sites, in 4 different settings: addiction service centres (n=12), non-governmental organisation centres (n=3), a mobile methadone unit and a prison, with an estimated 3725 participants. Together with the healthcare staff at each centre, the intervention protocols will be adapted, focusing on four phases: recruitment and testing; linkage to care; treatment for those who test positive; and monitoring of sustained virological response 12 weeks after treatment and reinfection. The primary outcomes will be the number of tested and treated individuals and the secondary outcomes will include individuals lost at each step in the cascade of care. Descriptive analysis and multivariable logistic regression of the data will be undertaken. ETHICS AND DISSEMINATION: The Hospital Clínic Barcelona, Spain, Ethics Committee approved this study on 18 February 2021 (HCB/2020/2018). Findings will be disseminated through peer-reviewed publications, conference presentations and social media. The results of this study could provide a model for targeting PWUD for HCV testing and treatment in the rest of Spain and in other settings, helping to achieve the WHO HCV elimination goal.


Subject(s)
Hepatitis C , Pharmaceutical Preparations , Substance Abuse, Intravenous , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Humans , Spain/epidemiology , Substance Abuse, Intravenous/drug therapy , Substance Abuse, Intravenous/epidemiology , World Health Organization
13.
PLoS One ; 16(10): e0257437, 2021.
Article in English | MEDLINE | ID: covidwho-1456086

ABSTRACT

INTRODUCTION: This article presents the Louisiana Hepatitis C Elimination Program's evaluation protocol underway at the Louisiana State University Health Sciences Center-New Orleans. With the availability of direct-acting antiviral (DAA) agents, the elimination of Hepatitis C (HCV) has become a possibility. The HCV Elimination Program was initiated by the Louisiana Department of Health (LDH) Office of Public Health (OPH), LDH Bureau of Health Services Financing (Medicaid), and the Louisiana Department of Public Safety and Corrections (DPSC) to provide HCV treatment through an innovative pricing arrangement with Asegua Therapeutics, whereby a fixed cost is set for a supply of treatment over five years. MATERIALS AND METHODS: A cross-sectional study design will be used. Data will be gathered from two sources: 1) an online survey administered via REDCap to a sample of Medicaid members who are receiving HCV treatment, and 2) a de-identified data set that includes both Medicaid claims data and OPH surveillance data procured via a Data Use Agreement between LSUHSC-NO and Louisiana Medicaid. DISCUSSION: The evaluation will contribute to an understanding of the scope and reach of this innovative treatment model, and as a result, an understanding of areas for improvement. Further, this evaluation may provide insight for other states considering similar contracting mechanisms and programs.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Cross-Sectional Studies , Health Services Accessibility , Hepacivirus/drug effects , Humans , Louisiana/epidemiology , Medicaid , New Orleans/epidemiology , United States/epidemiology
14.
Gastroenterol Hepatol ; 45(4): 256-264, 2022 Apr.
Article in English, Spanish | MEDLINE | ID: covidwho-1450112

ABSTRACT

AIMS: To evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients. METHOD: Transversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection. RESULTS: In this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0-104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19). CONCLUSION: Screening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.


Subject(s)
COVID-19 , Hepatitis B , Hepatitis C , Aged , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Humans , Male , Prospective Studies , SARS-CoV-2 , Virus Activation
15.
J Viral Hepat ; 28(10): 1474-1483, 2021 10.
Article in English | MEDLINE | ID: covidwho-1440781

ABSTRACT

The number of patients diagnosed with hepatitis C virus (HCV) is markedly higher than the number initiating treatment indicating gaps in the care cascade, likely centred around reaching at-risk populations. Understanding changing characteristics of patients with HCV allows for targeted programs that increase linkage to care. We investigated changes in demographic and clinical characteristics of patients registered in the German Hepatitis C-Registry (DHC-R) from 1 January 2014 to 31 December 2019. The DHC-R is an ongoing, noninterventional, multicentre, prospective, observational cohort registry including 327 German centres. Patient characteristics were analysed over time in 7 phases for all patients completing a screening visit. Overall, 14,357 patients were enrolled. The percentage of treatment-naïve/non-cirrhotic patients increased from 34.4% in phase 1 (1 January-31 December 2014) to 68.2% in phase 7 (1 August-31 December 2019). The proportion of migrants, alcohol users, people who inject drugs, and those receiving opiate substitution therapy increased in later registry phases. Most patients (60.1%) were receiving comedication at baseline. The most prescribed comedications were drugs used to treat opioid dependence which increased from 9.2% in phase 1 to 24.0% in phase 7. The patients' mean age decreased from 52.3 years in phase 1 to 48.7 years in phase 7. From 2014 to 2019, the proportion of at-risk patients enrolling in the registry increased. To eliminate viral hepatitis as a major public health threat, a continued commitment to engaging underserved populations into the HCV care cascade is needed.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Substance Abuse, Intravenous , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Middle Aged , Prospective Studies , Registries , Substance Abuse, Intravenous/drug therapy
17.
Rev Esp Enferm Dig ; 113(8): 623-624, 2021 08.
Article in English | MEDLINE | ID: covidwho-1395476

ABSTRACT

Hepatitis C (HCV) management has dramatically changed with the advent of direct-acting antivirals. Their high efficacy and safety are changing the paradigm of detection and treatment of patients with an active HCV infection. Following the latest guidelines, the path to elimination of hepatitis C will be achieved by simplifying management.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Telemedicine , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans
19.
Antimicrob Agents Chemother ; 65(9): e0268020, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1360543

ABSTRACT

Antivirals targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could improve treatment of COVID-19. We evaluated the efficacy of clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PIs) against SARS-CoV-2 and their interactions with remdesivir, the only direct-acting antiviral approved for COVID-19 treatment. HCV PIs showed differential potency in short-term treatment assays based on the detection of SARS-CoV-2 spike protein in Vero E6 cells. Linear PIs boceprevir, telaprevir, and narlaprevir had 50% effective concentrations (EC50) of ∼40 µM. Among the macrocyclic PIs, simeprevir had the highest (EC50, 15 µM) and glecaprevir the lowest (EC50, >178 µM) potency, with paritaprevir, grazoprevir, voxilaprevir, vaniprevir, danoprevir, and deldeprevir in between. Acyclic PIs asunaprevir and faldaprevir had EC50s of 72 and 23 µM, respectively. ACH-806, inhibiting the HCV NS4A protease cofactor, had an EC50 of 46 µM. Similar and slightly increased PI potencies were found in human hepatoma Huh7.5 cells and human lung carcinoma A549-hACE2 cells, respectively. Selectivity indexes based on antiviral and cell viability assays were highest for linear PIs. In short-term treatments, combination of macrocyclic but not linear PIs with remdesivir showed synergism in Vero E6 and A549-hACE2 cells. Longer-term treatment of infected Vero E6 and A549-hACE2 cells with 1-fold EC50 PI revealed minor differences in the barrier to SARS-CoV-2 escape. Viral suppression was achieved with 3- to 8-fold EC50 boceprevir or 1-fold EC50 simeprevir or grazoprevir, but not boceprevir, in combination with 0.4- to 0.8-fold EC50 remdesivir; these concentrations did not lead to viral suppression in single treatments. This study could inform the development and application of protease inhibitors for optimized antiviral treatments of COVID-19.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Hepatitis C , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Chlorocebus aethiops , Hepacivirus , Hepatitis C/drug therapy , Humans , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vero Cells , Viral Protease Inhibitors
20.
Viruses ; 13(7)2021 07 19.
Article in English | MEDLINE | ID: covidwho-1344395

ABSTRACT

OBJECTIVES: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. METHODS: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. RESULTS: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). CONCLUSIONS: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.


Subject(s)
Disease Eradication/statistics & numerical data , HIV Infections/virology , Hepacivirus/genetics , Hepatitis C/prevention & control , Lipid Metabolism , Antiviral Agents/therapeutic use , Cholesterol/blood , Cholesterol, LDL/blood , Cohort Studies , Female , Genotype , Hepacivirus/classification , Hepacivirus/drug effects , Hepatitis C/drug therapy , Humans , Italy , Male , Middle Aged , Sustained Virologic Response
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