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McDonald SA, Hickman M, Dillon JF, Yeung A, McAuley A, Fraser A, Hayes PC, Hutchinson SJ. A transient positive association between direct-acting antiviral therapy for hepatitis C infection and drug-related hospitalization among people who inject drugs: Self-controlled case-series analysis of national data. Addiction 2024; 119:369-378. [PMID: 37726951 DOI: 10.1111/add.16344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 08/03/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND AND AIMS Direct-acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra-hepatic' outcomes of drug-related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post-treatment to baseline periods using a within-subjects design to minimize selection bias concerns with cohort or case-control designs. DESIGN This was a self-controlled case-series study. SETTING Scotland, 1 January 2015-30 November 2020. PARTICIPANTS The study population of non-cirrhotic, DAA-treated PWID was identified using a data set linking Scotland's hepatitis C diagnosis, HCV clinical databases, national inpatient/day-case hospital records and the national deaths register. Three principal outcomes (drug overdose admission, non-viral injecting related admission and drug-related mortality) were defined using ICD codes. MEASUREMENTS Self-controlled case-series methodology was used to estimate the relative incidence (RI) of each outcome associated with time on treatment and up to six 90-day exposure risk periods thereafter. FINDINGS A total of 6050 PWID were treated with DAAs in the sampling time-frame. Compared with the baseline period, there was a significantly lowered risk of a drug overdose hospital admission in the second to fifth exposure risk periods only [relative incidence (RI) = 0.86, 95% confidence interval (CI) = 0.80-0.99; 0.89, 95% CI = 0.80-0.99; 0.86, 95% CI = 0.77-0.96; 0.88, 95% CI = 0.78-0.99, respectively]. For non-viral injecting-related admission, there was a reduced risk in the first, third and fourth exposure risk periods (RI = 0.76, 95% CI = 0.64-0.90; 0.75, 95% CI = 0.62-0.90; 0.79, 95% CI = 0.66-0.96, respectively). There was no evidence for reduced DRM risk in any period following treatment end. CONCLUSIONS Among people who inject drugs in Scotland, direct-acting antiviral treatment appears to be associated with a small, non-durable reduction in the risk of drug-related hospital admission, but not drug-related mortality. Direct-acting antiviral therapy, despite high effectiveness against liver disease, does not appear to offer a panacea for reducing other drug-related health harms.
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Affiliation(s)
- Scott A McDonald
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
| | - Matthew Hickman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - John F Dillon
- School of Medicine, University of Dundee, Dundee, UK
| | - Alan Yeung
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
| | - Andrew McAuley
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
| | | | | | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
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Johnson A, Shearer J, Thompson C, Jelley R, Aldridge J, Allsop C, Kerry J, Jones D, McCullough F, Miller C, Valappil M, Taha Y, Masson S, Jefferson T, Lawton C, Christensen L, McPherson S. Impact of 5 years of hepatitis C testing and treatment in the North East of England prisons. J Viral Hepat 2023; 30:914-921. [PMID: 37700492 DOI: 10.1111/jvh.13887] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/25/2023] [Accepted: 09/02/2023] [Indexed: 09/14/2023]
Abstract
Hepatitis C virus infection (HCV) is prevalent in prisons. Therefore, effective prison HCV services are critical for HCV elimination programmes. We aimed to evaluate the efficacy of a regional HCV prison testing and treatment programme. Between July 2017 and June 2022, data were collected prospectively on HCV test offer and uptake rates, HCV Antibody (HCV-Ab) and HCV-RNA positivity, treatment starts and outcomes for new inmates incarcerated in three prisons. Rates of HCV-Ab and RNA positivity at reception, incidence of new HCV infections and reinfection following treatment were determined. From a total of 39,652 receptions, 33,028 (83.3%) were offered HCV testing and 20,394 (61.7%) completed testing. Including all receptions, 24.5% of tests (n = 4995) were HCV-Ab positive and 8.4% of tests (n = 1713) were HCV-RNA positive. When considering the first test for each individual (median age 34 years; 88.1% male), 14.8% (n = 1869) and 7.2% (n = 905) were HCV-Ab and HCV-RNA positive, respectively. The incidence of new HCV-Ab and RNA positivity was 5.1 and 3.3 per 100 person-years, respectively. Of 1145 HCV viraemic individuals, 18 died within 6 months and 150 were rapidly transferred out of area, leaving 977 individuals with outcomes. Of these, 835 (85.5%) received antivirals and 47 spontaneously cleared the infection, leaving 95 (9.7%) untreated. 607 (72.7%) achieved SVR. 95 patients had reinfection post-treatment (rate 10.1 cases per 100 person-years). Testing for HCV has increased in our prisons and the majority with viraemia are initiated on antiviral treatment. Reassuringly, a significant fall in frequency of HCV-RNA positivity at prison reception was observed suggesting progress towards HCV elimination.
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Affiliation(s)
- Amy Johnson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Jessica Shearer
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | - Ryan Jelley
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | - Caroline Allsop
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Jenna Kerry
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Dee Jones
- Spectrum Community Health, Wakefield, UK
| | - Francesca McCullough
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Carolyn Miller
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Manoj Valappil
- Department of Microbiology and Virology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Yusri Taha
- Department of Microbiology and Virology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Steven Masson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | | | | | | | - Stuart McPherson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
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3
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Hamill V, Wong S, Benselin J, Krajden M, Hayes PC, Mutimer D, Yu A, Dillon JF, Gelson W, Velásquez García HA, Yeung A, Johnson P, Barclay ST, Alvarez M, Toyoda H, Agarwal K, Fraser A, Bartlett S, Aldersley M, Bathgate A, Binka M, Richardson P, Morling JR, Ryder SD, MacDonald D, Hutchinson S, Barnes E, Guha IN, Irving WL, Janjua NZ, Innes H. Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study. BMJ 2023; 382:e074001. [PMID: 37532284 PMCID: PMC10394680 DOI: 10.1136/bmj-2022-074001] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/26/2023] [Indexed: 08/04/2023]
Abstract
OBJECTIVES To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population. DESIGN Population based cohort study. SETTING British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only). PARTICIPANTS 21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019. MAIN OUTCOME MEASURES Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates. RESULTS 1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates. CONCLUSION Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals.
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Affiliation(s)
- Victoria Hamill
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
- Joint first authors
| | - Stanley Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Joint first authors
| | - Jennifer Benselin
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, UK
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | | | - David Mutimer
- Liver and Hepatology Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, UK
| | - William Gelson
- Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Hector A Velásquez García
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Alan Yeung
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
| | - Philip Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | | | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Andrew Fraser
- Aberdeen Royal Infirmary, Aberdeen, UK
- Queen Elizabeth University Hospital, Glasgow, UK
| | - Sofia Bartlett
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Mark Aldersley
- Leeds Liver Unit, St James's University Hospital, Leeds, UK
| | | | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Paul Richardson
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Joanne R Morling
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, UK
- Lifespan and Population Health, University of Nottingham, Nottingham, UK
| | - Stephen D Ryder
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Douglas MacDonald
- Gastroenterology and Hepatology, Royal Free London NHS Foundation Trust, London, UK
| | - Sharon Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
| | - Eleanor Barnes
- Nuffield Department of Medicine and the Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Indra Neil Guha
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, UK
| | - William L Irving
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, UK
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
- Centre for Health Evaluation and Outcome Sciences, St Paul's Hospital Vancouver, British Columbia, Canada
| | - Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
- Lifespan and Population Health, University of Nottingham, Nottingham, UK
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4
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Krüger K, Rossol S, Krauth C, Buggisch P, Mauss S, Stoehr A, Klinker H, Böker K, Teuber G, Stahmeyer J. Real-world experience for the outcomes and costs of treating hepatitis C patients: Results from the German Hepatitis C-Registry (DHC-R). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:489-503. [PMID: 35839795 PMCID: PMC10162862 DOI: 10.1055/a-1852-5713] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
BACKGROUND & AIMS With long-term consequences like the development of liver cirrhosis and hepatocellular carcinoma, chronic hepatitis C virus (HCV) infection is associated with a significant health burden. Information on HCV treatment outcomes and costs in routine care is still rare, especially for subgroups. The aim of this study was to analyse the treatment outcomes and costs of subgroups in routine care and to compare them over time with previous analyses. METHODS Data were derived from a noninterventional study including a subset of 10298 patients receiving DAAs with genotypes 1 and 3. Sociodemographic, clinical parameters and costs were collected using a web-based data recording system. The total sample was subdivided according to treatment regimen, cirrhosis status as well as present HIV infection and opioid substitution treatment (OST). RESULTS 95% of all patients achieved SVR. Currently used DAA showed higher SVR-rates and less adverse events (AE) compared to former treatments. Concerning subgroups, cirrhotic patients, HIV-coinfected patients and OST patients showed lower but still high SVR-rates. In comparison, cirrhotic had considerably longer treatment duration and more frequent (serious) AE. Overall, average treatment costs were €48470 and costs per SVR were €51129; for currently used DAAs costs amounted to €30330 and costs per SVR to €31692. After the end of treatment, physical health is similar to the general population in all patients except cirrhotic. Mental health remains far behind in all subgroups, even for currently used DAA. CONCLUSIONS Over time, some relevant factors developed positively (SVR-rates, costs, treatment duration, adverse events, health-related quality of life (HRQoL)). Further research on HRQoL, especially on mental health, is necessary to evaluate the differences between subgroups and HRQoL over time and to identify influencing factors.
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Affiliation(s)
- Kathrin Krüger
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School, Hannover, Germany
| | - Siegbert Rossol
- Medizinische Klinik, Krankenhaus Nordwest, Frankfurt, Germany
| | - Christian Krauth
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School, Hannover, Germany
| | - Peter Buggisch
- ifi-Institut für interdisziplinäre Medizin, Hamburg, Germany
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Duesseldorf, Germany
| | - Albrecht Stoehr
- ifi-Institut für interdisziplinäre Medizin, Hamburg, Germany
| | | | | | | | - Jona Stahmeyer
- Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover Medical School, Hannover, Germany
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5
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Honma Y, Shibata M, Morino K, Koya Y, Hayashi T, Ogino N, Kusanaga M, Oe S, Miyagawa K, Abe S, Tabaru A, Harada M. Impact of Interferon-Free Direct-Acting Antivirals on the Incidence of Extrahepatic Malignancies in Patients with Chronic Hepatitis C. Dig Dis Sci 2023; 68:685-698. [PMID: 36100828 DOI: 10.1007/s10620-022-07686-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 08/29/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND The incidence of extrahepatic malignancies (EHMs) after hepatitis C virus (HCV) eradication by interferon (IFN)-based and IFN-free direct-acting antivirals (DAAs) treatment remains unclear. AIMS The aim was to evaluate the cumulative incidence of EHMs diagnosed for the first time after the antiviral treatments. METHODS We analyzed a total 527 patients with chronic HCV infection and without prior history of any malignancies who achieved sustained virological response by antiviral treatments, including IFN-based (n = 242) or IFN-free DAAs (n = 285). The baseline predictors for EHM occurrence were analyzed using Cox regression analysis. RESULTS Thirty-two patients were diagnosed with EHMs, 14 in IFN-based and 18 in IFN-free DAAs, respectively. The total duration of follow-up was 1,796 person-years in IFN-based and 823 person-years in IFN-free DAAs. The incidence of EHMs in IFN-based and IFN-free DAAs was 7.8 and 21.9 per 1,000 person-years, respectively. The cumulative incidence of EHMs was significantly higher in IFN-free DAAs than IFN-based (p = 0.002). IFN-free DAAs was a single independent predictor for incidence of EHMs (p = 0.012). As for gender, the incidence of EHMs was significantly higher in IFN-free DAAs only in the female cohort (p = 0.002). After propensity score matching, IFN-free DAAs was a single independent predictor for incidence of EHMs in the female patients (p = 0.045). CONCLUSIONS The incidence of EHMs after HCV eradication is higher in IFN-free DAAs than IFN-based regimens, especially in female patients. We should carefully follow-up not only HCC but also EHMs after IFN-free DAAs regimens.
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Affiliation(s)
- Yuichi Honma
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
| | - Michihiko Shibata
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Kahori Morino
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Yudai Koya
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
- Department of Gastroenterology, Moji Medical Center, 3-1 Higashiminato-machi, Moji-ku, Kitakyushu, 801-8502, Japan
| | - Tsuguru Hayashi
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Noriyoshi Ogino
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Masashi Kusanaga
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Shinji Oe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Koichiro Miyagawa
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Shintaro Abe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Akinari Tabaru
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
- Department of Gastroenterology, Wakamatsu Hospital of the University of Occupational and Environmental Health, 1-17-1 Hama-machi, Wakamatsu-ku, Kitakyushu, 800-0024, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
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6
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Burraway J, Helbert B, Schexnayder J, Knick T, Dillingham R, Scherz C. Reliving it All Over Again: Uncanny Temporalities of Injection Drug Use and Hepatitis C Diagnosis in Southwest Virginia, USA. Med Anthropol 2023; 42:21-34. [PMID: 35944242 PMCID: PMC9822844 DOI: 10.1080/01459740.2022.2110090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Clinicians typically view the intersection between hepatitis C and injection drug use in terms of simultaneity - with transmission occurring via shared needles - or sequentially - with some states requiring that people stop using drugs prior to treatment. Yet, for patients, the connection between substance use and HCV infection can follow a more complex temporal pathway. In this article, we explore the non-linear temporality of "reliving" as it shapes HCV illness experience, its complex intersection with injection drug use, and the barriers patients face as they reckon with existing healthcare system responses and treatment modalities.
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Affiliation(s)
| | - Bailey Helbert
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
| | - Julie Schexnayder
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
| | - Terry Knick
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
| | - Rebecca Dillingham
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
| | - China Scherz
- Department of Anthropology, University of Virginia, Charlottesville, Virginia, USA
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7
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Beydoun N, Feinstein MJ. Heart Failure in Chronic Infectious and Inflammatory Conditions: Mechanistic Insights from Clinical Heterogeneity. Curr Heart Fail Rep 2022; 19:267-278. [PMID: 35838874 PMCID: PMC9283814 DOI: 10.1007/s11897-022-00560-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/29/2022] [Indexed: 01/21/2023]
Abstract
PURPOSE OF REVIEW The balance between inflammation and its resolution plays an important and increasingly appreciated role in heart failure (HF) pathogenesis. In humans, different chronic inflammatory conditions and immune-inflammatory responses to infection can lead to diverse HF manifestations. Reviewing the phenotypic and mechanistic diversity of these HF presentations offers useful clinical and scientific insights. RECENT FINDINGS HF risk is increased in patients with chronic inflammatory and autoimmune disorders and relates to disease severity. Inflammatory condition-specific HF manifestations exist and underlying pathophysiologic causes may differ across conditions. Although inflammatory disease-specific presentations of HF differ, chronic excess in inflammation and auto-inflammation relative to resolution of this inflammation is a common underlying contributor to HF. Further studies are needed to phenotypically refine inflammatory condition-specific HF pathophysiologies and prognoses, as well as potential targets for intervention.
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Affiliation(s)
- Nour Beydoun
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Matthew J Feinstein
- Division of Cardiology, Department of Medicine, Northwestern University, Chicago, IL, USA.
- Department of Pathology, Northwestern University, Chicago, IL, USA.
- Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
- Northwestern University Feinberg School of Medicine, 300 E. Superior St, Tarry 3-703, Chicago, IL, 60611, USA.
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8
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Askar S, Jelley R, McQue K, Allsop C, McCullough F, Miller C, Taha Y, Masson S, McPherson S. Determining the frequency and characteristics of Hepatitis C reinfections in North East England. J Viral Hepat 2022; 29:685-690. [PMID: 35643915 DOI: 10.1111/jvh.13707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/13/2022] [Accepted: 05/04/2022] [Indexed: 12/09/2022]
Abstract
Hepatitis C virus infection (HCV) is common, and injecting drug use is the major risk factor for acquisition. Understanding HCV reinfection following treatment is an important consideration for HCV elimination programmes. The aim of this work was to assess the frequency and patterns of HCV reinfection in our region to develop avoidance strategies. All individuals who completed anti-HCV treatment with a known outcome in Tyne and Wear, England between January 2016 and May 2021 were included. This was a retrospective analysis of prospectively collected data. HCV reinfection was defined as positive HCV RNA after achieving sustained virological response 12 (SVR12). 788 of 840 patients (76% male; mean age 45.7 ± 11.9 years; 47% Genotype 1; 11% Cirrhosis; 20% started in prison) achieved SVR (94%). 443 patients (56%) had HCV RNA testing post-SVR after a median 0.82 (range 0.1-5.2) years. 56 reinfections (7.1% of all SVRs and 12.6% of SVRs who had post-SVR testing) were diagnosed. The median time to reinfection was 1.37 (range 0.1-4.0) years and the rate of reinfection was 10.5 /100 person years. 45 (80%) reinfections became chronic, 17 of whom were retreated and achieved SVR. 5 individuals developed a second reinfection. Younger age was the only factor independently associated with reinfection (HR 0.91 [0.88-0.94] p < .001). In conclusion, HCV reinfection is common and may slow our HCV elimination efforts. In order to address high reinfection rates, harm minimization approaches need improved, and we have implemented an 'HCV track and trace' pilot to try to reduce onwards HCV transmission.
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Affiliation(s)
- Sumar Askar
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Ryan Jelley
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Kate McQue
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Caroline Allsop
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Francesca McCullough
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Carolyn Miller
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Yusri Taha
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.,Department of Microbiology and Virology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Steven Masson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.,Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Stuart McPherson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.,Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
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9
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Moran CA, Collins LF, Beydoun N, Mehta PK, Fatade Y, Isiadinso I, Lewis TT, Weber B, Goldstein J, Ofotokun I, Quyyumi A, Choi MY, Titanji K, Lahiri CD. Cardiovascular Implications of Immune Disorders in Women. Circ Res 2022; 130:593-610. [PMID: 35175848 PMCID: PMC8869407 DOI: 10.1161/circresaha.121.319877] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including HIV and hepatitis C virus. Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female predominant), HIV (male-female equivalent), and hepatitis C virus (male predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.
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Affiliation(s)
- Caitlin A. Moran
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
| | - Lauren F. Collins
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
| | - Nour Beydoun
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - Puja K. Mehta
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - Yetunde Fatade
- Emory University School of Medicine, Department of Medicine, Atlanta, GA, USA
| | - Ijeoma Isiadinso
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - Tené T Lewis
- Emory University, Rollins School of Public Health, Department of Epidemiology, Atlanta, GA, USA
| | - Brittany Weber
- Harvard Medical School, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - Jill Goldstein
- Massachusetts General Hospital, Department of Psychiatry, and Harvard Medical School, Departments of Psychiatry and Medicine, Boston, MA, USA
| | - Igho Ofotokun
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
| | - Arshed Quyyumi
- Emory University School of Medicine, Department of Medicine, Center for Heart Disease Prevention, Division of Cardiology and Emory Women’s Heart Center, Atlanta, GA, USA
| | - May Y. Choi
- Cumming School of Medicine, University of Calgary, Calgary, AB Canada
| | - Kehmia Titanji
- Emory University, Department of Medicine, Division of Endocrinology, Metabolism, and Lipids, Atlanta, GA, USA
| | - Cecile D. Lahiri
- Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
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10
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The Impact of Direct-Acting Antiviral Therapy on the Risk of Recurrence after Curative Resection in Patients with Hepatitis-C-Virus-Related Early Stage Hepatocellular Carcinoma. Medicina (B Aires) 2022; 58:medicina58020259. [PMID: 35208582 PMCID: PMC8875284 DOI: 10.3390/medicina58020259] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/03/2022] [Accepted: 02/07/2022] [Indexed: 11/17/2022] Open
Abstract
Background and Objectives: The impact of direct-acting antiviral (DAA)-based regimens on the recurrence of hepatocellular carcinoma (HCC) after successful curative hepatectomy is controversial. Aims: This study aimed to assess the association between DAAs treatment and recurrence risk in HCC after resection. Materials and Methods: We retrospectively assessed 152 cases of early stage (BCLC stage 0/A) hepatitis C virus (HCV)-related HCC (HCV-HCC) that underwent resection with curative intent between 2001 and 2019 at Kaohsiung Chang Gung Memorial Hospital; 48 cases achieved a sustained virological response (SVR) by DAA, and 104 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative resection was analyzed by using the log-rank test and Kaplan–Meier method. A Cox proportional hazards model was used to analyze the factors that impacted RFS and OS. Results: Five patients (10.4%) experienced HCC recurrence after DAA therapy. The cumulative HCC recurrence rate was significantly lower in the DAA group than the non-treatment group (p < 0.001). Multivariate analysis revealed a significant difference in RFS between the non-treatment group and DAA group (p = 0.001; hazard ratio (HR), 4.978; 95% CI, 1.976–12.542); liver cirrhosis (p = 0.005; HR, 2.062; 95% CI, 1.247–3.410), microvascular invasion (p = 0.001; HR, 2.331; 95% CI, 1.408–3.860) and AFP > 15 ng/mL (p = 0.022; HR, 1.799; 95% CI, 1.089–2.970) were also independent factors for HCC recurrence. ALBI stage II/III (p = 0.005; HR, 3.249; 95% CI, 1.418–7.443) and microvascular invasion (p < 0.001; HR, 4.037 95% CI, 2.071–7.869) were independent factors for OS; no significant difference in OS was observed between the DAA and no DAA treatment groups. Conclusions: DAA treatment could reduce the risk of recurrence after curative treatment for early stage HCC.
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11
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Shengir M, Elgara M, Sebastiani G. Metabolic and cardiovascular complications after virological cure in hepatitis C: What awaits beyond. World J Gastroenterol 2021; 27:1959-1972. [PMID: 34007133 PMCID: PMC8108037 DOI: 10.3748/wjg.v27.i17.1959] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/06/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023] Open
Abstract
The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers’ clinical practice.
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Affiliation(s)
- Mohamed Shengir
- Department of Medicine, McGill University, Montreal, Quebec H3A0G4, Canada
| | - Mohamed Elgara
- Department of Internal Medicine, Hamad Medical Corporation, Doha 3050, Qatar
| | - Giada Sebastiani
- Department of Medicine, McGill University Health Center, Montreal, Quebec H4A3J1, Canada
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12
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Ciancio A. Impact of Direct Antiviral Agents (DAAs) on B-cell Non Hodgkin's Lymphoma in patients with chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:227-233. [PMID: 33856146 DOI: 10.23736/s2724-5985.21.02834-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The relationship between HCV infection and extrahepatic manifestations has been demonstrated by epidemiological, clinical, immunological and pathological studies. Patients with HCV infection have an increased risk of morbidity and mortality related to these non-liver diseases. For these reasons, HCV chronic infection should be considered a systemic disease in which extrahepatic manifestations increase the severity of the disease. HCV-extrahepatic manifestations may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Over the past 5 years, treatment of chronic HCV infection in patients with hematologic malignancies has evolved rapidly and effective and safe direct-acting antivirals (DAAs) have become the standardof-care treatment. The choice of regimens with DAAs should be individualized after thorough assessment for potential hematologic toxic effects and drug-drug interactions. Elimination of HCV from infected cancer patients confers virologic, hepatic, and oncologic benefits.
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Affiliation(s)
- Alessia Ciancio
- Dipartimento di Scienze Mediche, Scuola di Medicina, Università degli Studi di Torino, Turin, Italy -
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13
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Su X, Zhao X, Deng JL, Li SN, Du X, Dong JZ, Ma CS. Antiviral treatment for hepatitis C is associated with a reduced risk of atherosclerotic cardiovascular outcomes: A systematic review and meta-analysis. J Viral Hepat 2021; 28:664-671. [PMID: 33452699 DOI: 10.1111/jvh.13469] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 01/04/2021] [Indexed: 12/13/2022]
Abstract
Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could reduce the risk of CVD events is inconsistent. The aim of this meta-analysis was to investigate the association between anti-HCV treatment and the risk of CVD. We searched PubMed, EMBASE and Cochrane Library databases from inception to 20 August 2020. The pooled hazard ratio (HR) with 95% confidence interval (CI) of the risk of CVD events [any CVD, coronary artery disease (CAD) and stroke] was calculated using the random-effects model. A total of eleven studies, including 309,470 subjects, were enrolled in this meta-analysis. Among those, four studies reported on any CVD between anti-HCV-treated and anti-HCV-untreated patients, five studies reported on CAD, and five studies reported on stroke. Also, five studies reported on any CVD between patients with sustained virological response (SVR) and without SVR. Overall, antiviral therapy for HCV was associated with a reduced risk of any CVD (HR = 0.64, 95% CI: 0.50-0.83), CAD (HR = 0.73, 95% CI: 0.55-0.96) and stroke (HR = 0.74, 95% CI: 0.64-0.86). Besides, we found that SVR was associated with a significant decrease in any CVD compared with non-SVR (HR = 0.74, 95% CI: 0.60-0.92). In conclusion, this meta-analysis demonstrated that antiviral therapy for HCV was associated with a reduced risk of CVD events. In addition, the risk of CVD events was lower in individuals with SVR compared with those without SVR.
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Affiliation(s)
- Xin Su
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Xin Zhao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Jia-Long Deng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Song-Nan Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Xin Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Jian-Zeng Dong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
| | - Chang-Sheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
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14
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Affiliation(s)
- Patrice Cacoub
- From the Department of Internal Medicine and Clinical Immunology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Centre de Référence des Maladies Auto-Immunes Systémiques Rares and Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose Inflammatoire, Institut National de la Santé et de la Recherche Médicale UMR S 959, Centre National de la Recherche Scientifique FRE3632, and the Inflammation-Immunopathology-Biotherapy Department, Sorbonne Université - all in Paris
| | - David Saadoun
- From the Department of Internal Medicine and Clinical Immunology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Centre de Référence des Maladies Auto-Immunes Systémiques Rares and Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose Inflammatoire, Institut National de la Santé et de la Recherche Médicale UMR S 959, Centre National de la Recherche Scientifique FRE3632, and the Inflammation-Immunopathology-Biotherapy Department, Sorbonne Université - all in Paris
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15
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Ridziauskas M, Zablockienė B, Jančorienė L, Samuilis A, Zablockis R, Jackevičiūtė A. Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs. ACTA ACUST UNITED AC 2021; 57:medicina57030210. [PMID: 33652777 PMCID: PMC7996730 DOI: 10.3390/medicina57030210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/20/2021] [Accepted: 02/22/2021] [Indexed: 11/23/2022]
Abstract
Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.
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Affiliation(s)
- Martynas Ridziauskas
- Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania;
- Correspondence: ; Tel.: +370-606-98744
| | - Birutė Zablockienė
- Center of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, LT-08406 Vilnius, Lithuania; (B.Z.); (L.J.)
- Clinic of Infectious Diseases and Dermatovenerology, Institute of Clinical Medicine, Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Ligita Jančorienė
- Center of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, LT-08406 Vilnius, Lithuania; (B.Z.); (L.J.)
- Clinic of Infectious Diseases and Dermatovenerology, Institute of Clinical Medicine, Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Artūras Samuilis
- Center of Radiology and Nuclear Medicine, Vilnius University Hospital Santaros Klinikos, LT-08661 Vilnius, Lithuania;
- Department of Radiology, Nuclear Medicine and Medical Physics, Faculty of Medicine, Vilnius University, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Rolandas Zablockis
- Center of Pulmonology and Allergology, Vilnius University Hospital Santaros Klinikos, Santariskiu 2, LT-08661 Vilnius, Lithuania;
- Clinic of Chest Diseases, Immunology and Allergology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Aušrinė Jackevičiūtė
- Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania;
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16
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Han R, François C, Toumi M. Systematic Review of Health State Utility Values Used in European Pharmacoeconomic Evaluations for Chronic Hepatitis C: Impact on Cost-Effectiveness Results. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2021; 19:29-44. [PMID: 32661846 DOI: 10.1007/s40258-020-00600-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
BACKGROUND Health state utility values (HSUVs) identified from utility elicitation studies are widely used in pharmacoeconomic evaluations for chronic hepatitis C (CHC) and are particularly instrumental in health technology assessment (HTA) evaluations such as those from the National Institute for Health and Care Excellence (NICE). OBJECTIVE The aim of this study was to identify HSUVs used in cost-utility analyses (CUAs) for CHC in Europe and to evaluate the impact of HSUV selection on cost-effectiveness results in terms of the incremental cost per quality-adjusted life-year (QALY) gained (ICER). METHODS A systematic search of pharmacoeconomic evaluations for CHC was updated in the MEDLINE and EMBASE databases for the periods 2012-2017 and 2017-2020. Data on health states, HSUVs, and utility elicitation studies were extracted. The difference in HSUVs of the same health state in different CUAs, and the difference between HSUVs of one health state and of the interlink health state in the same CUAs, were calculated. A quality assessment was performed to evaluate the selection of HSUVs in CUAs. Sets of HSUVs identified were used in a reconstructed CUA model to assess the impact on the ICER. RESULTS Twenty-six CUAs conducted in European countries and referring to 17 utility elicitation studies were included. The difference in HSUVs of the same health state in different CUAs ranged from 0.021 (liver transplant) to 0.468 (decompensated cirrhosis). The difference between HSUVs of one health state and of the interlink health state of the next disease severity level was calculated between the health states of F0-F1/mild and F2-F3/moderate (n = 11, 0.040-0.110), F2-F3/moderate and F4/compensated cirrhosis (n = 18, 0.027-0.130), compensated cirrhosis and decompensated cirrhosis (n = 22, 0.020-0.100), decompensated cirrhosis and hepatocellular carcinoma (n = 24, 0.000-0.200), hepatocellular carcinoma and liver transplant in the first year (n = 17, - 0.329 to 0.170) and liver transplant in the first and subsequent years (n = 17, - 0.340 to 0.000). The utility elicitation study selected by most CUAs (n = 11) was recommended as the source of HSUVs, at least for the CUAs conducted in the UK, based on the results of quality assessment. Seven sets of HSUVs were generated to fit the reconstructed model and changed the results of the incremental analysis from being cost effective to not being cost effective (ICER ranging from £2460 to £24,954 per QALY gained), and to being dominated in the UK setting. CONCLUSIONS The CUAs for CHC were found to apply to various HSUVs from different utility elicitation studies in the same health state. This variability in HSUVs has the potential to significantly affect ICER and ICER-based reimbursement decisions. A rigorous selection of HSUVs in CUAs to inform healthcare resource allocation is suggested for future studies of CUAs and for guideline development.
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Affiliation(s)
- Ru Han
- University of Aix-Marseille, Marseille, France.
- Creativ-Ceutical, 215, rue de Faubourg St-Honoré, 75008, Paris, France.
| | - Clément François
- University of Aix-Marseille, Marseille, France
- Creativ-Ceutical, 215, rue de Faubourg St-Honoré, 75008, Paris, France
| | - Mondher Toumi
- University of Aix-Marseille, Marseille, France
- Creativ-Ceutical, 215, rue de Faubourg St-Honoré, 75008, Paris, France
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17
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Hutchinson SJ, Valerio H, McDonald SA, Yeung A, Pollock K, Smith S, Barclay S, Dillon JF, Fox R, Bramley P, Fraser A, Kennedy N, Gunson RN, Templeton K, Innes H, McLeod A, Weir A, Hayes PC, Goldberg D. Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study. Gut 2020; 69:2223-2231. [PMID: 32217640 DOI: 10.1136/gutjnl-2019-320007] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 02/19/2020] [Accepted: 02/24/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Population-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis of population-based data from Scotland. DESIGN Through analysis of national surveillance data (involving linkage of HCV diagnosis and clinical databases to hospital and deaths registers), we determined i) the scale-up in the number of patients treated and achieving a sustained viral response (SVR), and ii) the change in the trend of new presentations with HCV-related DC, with the introduction of DAAs. RESULTS Approximately 11 000 patients had been treated in Scotland over the 8-year period 2010/11 to 2017/18. The scale-up in the number of patients achieving SVR between the pre-DAA and DAA eras was 2.3-fold overall and 5.9-fold among those with compensated cirrhosis (the group at immediate risk of developing DC). In the pre-DAA era, the annual number of HCV-related DC presentations increased 4.6-fold between 2000 (30) and 2014 (142). In the DAA era, presentations decreased by 51% to 69 in 2018 (and by 67% among those with chronic infection at presentation), representing a significant change in trend (rate ratio 0.88, 95% CI 0.85 to 0.90). With the introduction of DAAs, an estimated 330 DC cases had been averted during 2015-18. CONCLUSIONS National scale-up in interferon-free DAA treatment is associated with the rapid downturn in presentations of HCV-related DC at the population-level. Major progress in averting HCV-related DC in the short-term is feasible, and thus other countries should strive to achieve the same.
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Affiliation(s)
- Sharon J Hutchinson
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK .,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Heather Valerio
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Scott A McDonald
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Alan Yeung
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Kevin Pollock
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Shanley Smith
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Stephen Barclay
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Glasgow Royal Infirmary, Glasgow, UK
| | | | | | | | - Andrew Fraser
- Aberdeen Royal Infirmary, Aberdeen, UK.,Queen Elizabeth University Hospital, Glasgow, UK
| | | | - Rory N Gunson
- West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, UK
| | - Kate Templeton
- East of Scotland Specialist Virology Centre, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Hamish Innes
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Allan McLeod
- Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | - Amanda Weir
- Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
| | | | - David Goldberg
- Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Blood Borne Virus & Sexually Transmitted Infections Team, Health Protection Scotland, Glasgow, UK
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18
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Muzica CM, Stanciu C, Huiban L, Singeap AM, Sfarti C, Zenovia S, Cojocariu C, Trifan A. Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy: A debate near the end. World J Gastroenterol 2020; 26:6770-6781. [PMID: 33268960 PMCID: PMC7684455 DOI: 10.3748/wjg.v26.i43.6770] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/27/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
Direct acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, achieving high rates (≥ 95%) of sustained virological response, with a good safety profile and high compliance rates. Consequently, it had been expected that viral clearance will reduce morbidity and mortality rates, as well as the risk of hepatocellular carcinoma (HCC). However, since 2016, concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy, which led to an avalanche of studies with contradictory results. We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.
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Affiliation(s)
- Cristina Maria Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon Emergency Hospital, Iasi 700115, Romania
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19
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Mocroft A, Lundgren JD, Rockstroh JK, Aho I, Wandeler G, Nielsen L, Edwards S, Viard JP, Lacombe K, Fätkenheuer G, Guaraldi G, Laguno M, Llibre J, Elinav H, Flamholc L, Gisinger M, Paduta D, Khromova I, Jilich D, Rozplochowski B, Oprea C, Peters L. Influence of Hepatitis C Coinfection and Treatment on Risk of Diabetes Mellitus in HIV-Positive Persons. Open Forum Infect Dis 2020; 7:ofaa470. [PMID: 33409325 PMCID: PMC7772946 DOI: 10.1093/ofid/ofaa470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/30/2020] [Indexed: 11/13/2022] Open
Abstract
Background The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear. Methods Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment). Results A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNA-positive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6-13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7-8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global P = .33). Hypertension (22.2%; 95% CI, 17.5%-26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%-29.7%) had the largest population-attributable fractions for DM. Conclusions HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized.
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Affiliation(s)
- Amanda Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK
| | | | | | - Inka Aho
- Helsinki University Hospital, Helsinki, Finland
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | | | | | - Karine Lacombe
- Sorbonne Université, IPLESP Inserm UMR-S1136, AP-HP, Paris, France
| | | | | | | | - Josep Llibre
- University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
| | | | | | | | | | - Irina Khromova
- Centre for HIV/AIDS & Infectious Diseases, Kaliningrad, Russia
| | - David Jilich
- Charles University in Prague and Na Bulovce Hospital, Prague, Czech Republic
| | | | - Cristiana Oprea
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Lars Peters
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK
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20
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Hepatitis C: Does Successful Treatment Alter the Natural History and Quality of Life? Gastroenterol Clin North Am 2020; 49:301-314. [PMID: 32389364 DOI: 10.1016/j.gtc.2020.01.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The cure of chronic hepatitis C infection has a major impact on the morbidity and mortality of infected patients. It is now clear that sustained virologic response improves overall survival and significantly reduces the risk of liver failure, fibrosis progression, need of liver transplantation, and incidence of hepatocellular carcinoma. Moreover, hepatitis C eradication improves a broad range of extrahepatic manifestations, such as dermatologic, neoplastic, cardiovascular, and endocrine, and improves quality of life.
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21
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Peleg N, Issachar A, Sneh Arbib O, Cohen-Naftaly M, Harif Y, Oxtrud E, Braun M, Leshno M, Barsheshet A, Shlomai A. Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response. J Viral Hepat 2019; 26:1257-1265. [PMID: 31243878 DOI: 10.1111/jvh.13167] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/10/2019] [Accepted: 05/28/2019] [Indexed: 12/24/2022]
Abstract
Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all-cause mortality and HCC in CHC patients with SVR following direct-acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow-up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all-cause mortality and HCC at 2 years of follow-up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5-fold increased risk of all-cause mortality and HCC (HR 7.51, 95% C.I 3.61-13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97-6.59, P = 0.06). In conclusion, LS is a major predictor of all-cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.
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Affiliation(s)
- Noam Peleg
- The Division of Gastroenterology and Hepatology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
| | - Assaf Issachar
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Orly Sneh Arbib
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
| | - Michal Cohen-Naftaly
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Harif
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
| | - Evelin Oxtrud
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
| | - Marius Braun
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Moshe Leshno
- Coller School of Management, Tel Aviv University, Tel Aviv, Israel
| | - Alon Barsheshet
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Cardiology, Rabin Medical Center, Petach-Tikva, Israel
| | - Amir Shlomai
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Medicine D, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
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22
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Elshimi E, Sakr N, Morad W, Mohamad NE, Waked I. Direct-acting antiviral drugs improve the female sexual burden associated with chronic HCV infection. Expert Rev Anti Infect Ther 2019; 17:919-926. [PMID: 31625425 DOI: 10.1080/14787210.2019.1682551] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Background: The impact of patient cure by direct-acting antiviral agents (DAAs) on female sexual dysfunction (FSD) associated with HCV hasn't been studied.Aim: To study the impact of DAAs on associated FSD in patients with chronic HCV infection.Methods: In patients with chronic HCV infection who were eligible for DAAs, the self-administered female-sexual-function index (FSFI) questionnaire was completed by 300 sexually active females' patients before treatment and compared to equal number of age and socioeconomically matched controls. FSFI questionnaire results after treatment were compared to patients' baseline results.Results: The mean total score for the patients was significantly lower than that for controls (16.77 ± 1.36 versus 17.52 ± 0.99, P < 0.001). Patients after treatment with DAAs significantly scored better results than baseline results in the total score and all domains of the questionnaire and significantly less patients had FSD compared to baseline (2.7% versus 29.3% P < 0.05). Patients' mean FSFI score significantly improved after cure (18.8 ± 0.27 vs. 16.77 ± 1.36, P < 0.001).Conclusion: Hepatitis C has negative impacts on FSF and affecting all domains of FSFI. The DAAS improve the sexual burden associated with hepatitis C in patients who achieved sustained virologic response.
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Affiliation(s)
- Esam Elshimi
- Hepatology Department, National Liver Institute, Menoufia University, Shebeen Elkom, Egypt
| | - Neamat Sakr
- Hepatology Department, National Liver Institute, Menoufia University, Shebeen Elkom, Egypt
| | - Wesam Morad
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebeen Elkom, Egypt
| | - Noha Ezzat Mohamad
- Dermatology and Venerology Department, Faculty of Medicine, Fayoum University, Egypt
| | - Imam Waked
- Hepatology Department, National Liver Institute, Menoufia University, Shebeen Elkom, Egypt
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23
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Pereira Guedes T, Fragoso P, Lemos C, Garrido M, Silva J, Falcão D, Maia L, Moreira T, Manuel Ferreira J, Pedroto I. Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2019; 27:149-159. [PMID: 32509920 DOI: 10.1159/000503074] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 09/01/2019] [Indexed: 12/12/2022]
Abstract
Background Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment, with high sustained virological response (SVR) rates reported, even in historically difficult-to-treat groups. SVR is associated with a decreased risk of hepatocellular carcinoma (HCC), need for transplantation, and overall and liver-related mortality. Data from real-life cohorts on the medium- to long-term outcomes of patients with advanced liver disease and DAA-induced SVR are still missing. Objectives To report and analyze the long-term outcomes of DAA-induced SVR in a real-life cohort of patients with advanced liver disease. Method In this retrospective, longitudinal, single-center study, we collected data from patients with chronic hepatitis C infection and advanced liver disease (cirrhosis or advanced fibrosis) that had initiated DAA treatment between February 2015 and January 2017. Results A total of 237 patients were included. A treatment completion rate of 98.7% and an SVR rate of 97.8% (intention to treat: 96.6%) were found. Of the 229 patients with SVR, 67.2% were cirrhotic (64.2% Child-Pugh class A; 3.1% Child-Pugh class B) and 32.8% had stage F3 fibrosis, with an average follow-up of 28 months. The overall mortality rate was 19/1,000 person-years and the liver-related mortality rate was 9.5/1,000 person-years. The hepatic decompensation incidence rate was 25/1,000 person-years and the HCC incidence rate was 11.6/1,000 person-years. There was a sustained increase in serum platelet values during up to 2 years of follow-up. A history of pretreatment decompensation and baseline platelet and albumin values were significantly associated with the occurrence of adverse liver events after the end of treatment. Conclusions A DAA-induced SVR remains durable and is associated with an excellent clinical prognosis in patients with compensated advanced liver disease and with improvement or disease stabilization in decompensated patients. SVR is associated with a low risk of - yet does not prevent - HCC occurrence or disease progression, especially in the presence of other causes of liver injury. It is recommended that these patients be kept under surveillance.
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Affiliation(s)
- Tiago Pereira Guedes
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Pedro Fragoso
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Carolina Lemos
- UnIGENe, Instituto de Biologia Molecular e Celular (IBMC) and Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.,Department of Population Studies, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Mónica Garrido
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Joana Silva
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Daniela Falcão
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Luís Maia
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Teresa Moreira
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - José Manuel Ferreira
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Isabel Pedroto
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto, Porto, Portugal
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24
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Hickman M, Dillon JF, Elliott L, De Angelis D, Vickerman P, Foster G, Donnan P, Eriksen A, Flowers P, Goldberg D, Hollingworth W, Ijaz S, Liddell D, Mandal S, Martin N, Beer LJZ, Drysdale K, Fraser H, Glass R, Graham L, Gunson RN, Hamilton E, Harris H, Harris M, Harris R, Heinsbroek E, Hope V, Horwood J, Inglis SK, Innes H, Lane A, Meadows J, McAuley A, Metcalfe C, Migchelsen S, Murray A, Myring G, Palmateer NE, Presanis A, Radley A, Ramsay M, Samartsidis P, Simmons R, Sinka K, Vojt G, Ward Z, Whiteley D, Yeung A, Hutchinson SJ. Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) - a natural experiment (protocol). BMJ Open 2019; 9:e029538. [PMID: 31551376 PMCID: PMC6773339 DOI: 10.1136/bmjopen-2019-029538] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 07/25/2019] [Accepted: 07/29/2019] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID. METHODS AND ANALYSIS We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes. ETHICS AND DISSEMINATION Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.
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Affiliation(s)
- Matthew Hickman
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - John F Dillon
- Hepatology & Gastroenterology, Clinical & Molecular Medicine, School of Medicine, University of Dundee, Dundee, UK
| | | | - Daniela De Angelis
- MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Peter Vickerman
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Graham Foster
- Blizard Institute, Queen Mary University of London, London, UK
- Barts Health NHS Trust, London, UK
| | - Peter Donnan
- Dundee Epidemiology and Biostatistics Unit, University of Dundee, Dundee, UK
| | | | | | - David Goldberg
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | | | - Samreen Ijaz
- National Infection Service, Public Health England, London, UK
| | | | - Sema Mandal
- National Infection Service, Public Health England, London, UK
| | - Natasha Martin
- Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, UK
| | - Lewis J Z Beer
- Tayside Clinical Trials Unit, Tayside Medical Science Centre, University of Dundee, Dundee, UK
| | - Kate Drysdale
- Blizard Institute, Queen Mary University of London, London, UK
- Barts Health NHS Trust, London, UK
| | - Hannah Fraser
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Rachel Glass
- National Infection Service, Public Health England, London, UK
| | | | - Rory N Gunson
- West Of Scotland Specialist Virology Centre, NHS Greater Glasgow & Clyde Board, Glasgow, UK
| | | | - Helen Harris
- National Infection Service, Public Health England, London, UK
| | | | - Ross Harris
- National Infection Service, Public Health England, London, UK
| | | | - Vivian Hope
- Liverpool John Moores University, Liverpool, UK
| | - Jeremy Horwood
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Sarah Karen Inglis
- Tayside Clinical Trials Unit, Tayside Medical Science Centre, University of Dundee, Dundee, UK
| | - Hamish Innes
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Athene Lane
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Jade Meadows
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Andrew McAuley
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Chris Metcalfe
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | | | | | - Gareth Myring
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Norah E Palmateer
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Anne Presanis
- MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Andrew Radley
- Hepatology & Gastroenterology, Clinical & Molecular Medicine, School of Medicine, University of Dundee, Dundee, UK
- Directorate of Public Health, NHS Tayside, Dundee, UK
| | - Mary Ramsay
- National Infection Service, Public Health England, London, UK
| | - Pantelis Samartsidis
- MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Ruth Simmons
- National Infection Service, Public Health England, London, UK
| | - Katy Sinka
- National Infection Service, Public Health England, London, UK
| | | | - Zoe Ward
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | | | - Alan Yeung
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Sharon J Hutchinson
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
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25
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Shah H, Bilodeau M, Burak KW, Cooper C, Klein M, Ramji A, Smyth D, Feld JJ. The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver. CMAJ 2019; 190:E677-E687. [PMID: 29866893 DOI: 10.1503/cmaj.170453] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Hemant Shah
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
| | - Marc Bilodeau
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
| | - Kelly W Burak
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
| | - Curtis Cooper
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
| | - Marina Klein
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
| | - Alnoor Ramji
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
| | - Dan Smyth
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
| | - Jordan J Feld
- Toronto Centre for Liver Disease (Shah, Feld), Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Ont.; Department of Medicine, Liver Unit (Bilodeau), Centre hospitalier de l'Université de Montréal, Montréal, Que.; Department of Medicine, Liver Unit, Division of Gastroenterology and Hepatology (Burak), University of Calgary, Calgary, Alta.; Division of Infectious diseases (Cooper), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ont.; Division of Infectious Diseases and Chronic Viral Illness Service Glen site (Klein), McGill University Health Centre Montréal, Que.; Department of Medicine, Division of Gastroenterology (Ramji), University of British Columbia, Vancouver, BC; Division of Infectious Disease (Smyth), Dalhousie University, Moncton Hospital, Moncton, NB
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26
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Lapumnuaypol K, Thongprayoon C, Wijarnpreecha K, Cheungpasitporn W. Impact of hepatitis C sustained viral response on cardiovascular diseases: a meta-analysis. Hosp Pract (1995) 2019; 47:105-110. [PMID: 31018721 DOI: 10.1080/21548331.2019.1612066] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background: Hepatitis C virus-infected patients are found to have increased risks of cardiovascular disease (CVD)-related morbidity and mortality. However, the effect of treatment on cardiovascular risk remains unknown. We performed a systematic review and meta-analysis to assess the effect of Sustained Virologic Response (SVR) on cardiovascular outcome in chronic HCV-infected patients. Methods: A systematic review was conducted in MEDLINE, EMBASE, Cochrane databases from inception through November 2018 to identify studies that assessed the effect of SVR on CVDs. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Results: Seven cohort studies with a total of 53,841 HCV-infected patients with average follow-up time of 5 years were enrolled. When compared with HCV-infected patients who do not achieve SVR, patients with SVR have a reduced risk of overall CVDs with the pooled hazard ratio of 0.76 (95% confidence interval 0.61-0.94). Egger's regression asymmetry test was performed and showed no publication bias. Conclusions: Our study demonstrates a significant association between SVR after HCV treatment and reduced risk of overall CVDs.
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Affiliation(s)
- Kamolyut Lapumnuaypol
- Department of Internal Medicine, Albert Einstein Medical Center , Philadelphia , PA , USA
| | - Charat Thongprayoon
- Department of Nephrology and Hypertension, Mayo Clinic , Rochester , MN , USA
| | - Karn Wijarnpreecha
- Department of Gastroenterology, Mayo Clinic Hospital , Jacksonville , FL , USA
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center , Jackson , MS , USA
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Implementation of Value-based Medicine (VBM) to Patients With Chronic Hepatitis C (HCV) Infection. J Clin Gastroenterol 2019; 53:262-268. [PMID: 30681638 DOI: 10.1097/mcg.0000000000001174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION With the significant clinical and economic burden of chronic HCV, effective treatment must be provided efficiently and appropriately. VBM is predicated upon improving health outcomes (clinical and quality) while optimizing the cost of delivering these outcomes. This review explores the concepts of VBM and how it can be used as a strategy for HCV eradication, using the United States as a case example. Once treated with interferon-based regimens, patients with HCV experienced low cure rates, very poor health-related quality of life (HRQoL), decreased work productivity and significant costs. In this context, the old treatment of HCV produced little value to the patient and the society. However, the development of new antiviral regimens for HCV which are free of interferon, has greatly improved treatment success rates as documented with very high cure rates and by improving patient-reported outcomes (PROs), including HRQoL. However, the short-term economic investment to deliver this curative treatment to all HCV-infected patients can be sizeable. In contrast, if one takes the long-term view from the societal perspective, these new treatment regimens can lead to savings by reducing the costs of long-term complications of HCV infection. CONCLUSIONS All of the necessary tools are now available to implement strategies to eradicate HCV. The new all oral direct acting antivirals brings value to the patients and the society because it leads to improvements of clinically important outcomes. Furthermore, the costs associated with these treatment regimens can be recovered by preventing the future economic burden of HCV-complications.
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Heffernan A, Cooke GS, Nayagam S, Thursz M, Hallett TB. Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model. Lancet 2019; 393:1319-1329. [PMID: 30704789 PMCID: PMC6484702 DOI: 10.1016/s0140-6736(18)32277-3] [Citation(s) in RCA: 196] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 08/13/2018] [Accepted: 09/12/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met. METHODS We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions. FINDINGS By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0-15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000-670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8-16·1) new infections and 1·5 million (1·4-1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78-82) reduction in incidence and a 61% (60-62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan. INTERPRETATION Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic. FUNDING Wellcome Trust.
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Affiliation(s)
- Alastair Heffernan
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK
| | - Graham S Cooke
- Division of Infectious Diseases, St Mary's Hospital, Imperial College London, London, UK
| | - Shevanthi Nayagam
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK; Division of Digestive Diseases, St Mary's Hospital, Imperial College London, London, UK
| | - Mark Thursz
- Division of Digestive Diseases, St Mary's Hospital, Imperial College London, London, UK
| | - Timothy B Hallett
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK.
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Butt AA, Yan P, Shuaib A, Abou-Samra AB, Shaikh OS, Freiberg MS. Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events. Gastroenterology 2019; 156:987-996.e8. [PMID: 30445009 DOI: 10.1053/j.gastro.2018.11.022] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 11/01/2018] [Accepted: 11/06/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Infection with hepatitis virus C (HCV) is associated with an increased risk of cardiovascular disease (CVD) events. It is not clear whether treatment with direct-acting antiviral (DAA) agents affects risk of CVD. METHODS We searched the Electronically Retrieved Cohort of HCV-Infected Veterans database for patients with chronic HCV infection (n = 242,680) and identified patients who had been treated with a pegylated interferon and ribavirin regimen (n = 4436) or a DAA-containing regimen (n = 12,667). Treated patients were matched for age, race, sex, and baseline values with patients who had never received treatment for HCV infection (controls). All subjects were free of any CVD event diagnosis of HCV infection at baseline. The primary outcome was incident CVD events, identified by International Classification of Diseases, Ninth Edition, Clinical Modification or International Classification of Diseases, Tenth Edition code, in the different groups and in patients with vs without a sustained virologic response to therapy. RESULTS There were 1239 (7.2%) incident CVD events in the treated groups and 2361 (13.8%) events in the control group. Incidence rates were 30.9 per 1000 patient-years (95% CI 29.6-32.1) in the control group and 20.3 per 1000 patient-years (95% CI 19.2-21.5) in the treated groups (P < .0001). Treatment with pegylated interferon and ribavirin (hazard ratio 0.78; 95% CI 0.71-0.85) or a DAA regimen (hazard ratio 0.57; 95% CI 0.51-0.65) was associated with a significantly lower risk of a CVD event compared with no treatment (controls). Incidence rates for CVD events were 23.5 per 1000 patient-years (95% CI 21.8-25.3) in the group treated with the pegylated interferon and ribavirin regimen, 16.3 per 1000 patient-years (95% CI 14.7-18.0) in the group treated with a DAA regimen, and 30.4 (95% CI 29.2-31.7) in the control group. A sustained virologic response was associated with a lower risk of incident CVD events (hazard ratio 0.87; 95% CI 0.77-0.98). CONCLUSIONS In an analysis of a cohort of HCV-infected veterans, treatment of HCV infection was associated with a significant decrease in risk of CVD events. Patients treated with a DAA regimen and patients who achieved sustained virologic responses had the lowest risk for CVD events.
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Affiliation(s)
- Adeel A Butt
- VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Weill Cornell Medical College, New York, New York and Doha, Qatar; Hamad Medical Corporation, Doha, Qatar.
| | - Peng Yan
- VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | | | - Abdul-Badi Abou-Samra
- Weill Cornell Medical College, New York, New York and Doha, Qatar; Hamad Medical Corporation, Doha, Qatar
| | - Obaid S Shaikh
- VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Elshimi E, Morad W, Mohamad NE. Male Sexual Dysfunction Among Egyptian Patients with Chronic Hepatitis C Virus Infection Before and After Direct-Acting Antiviral Drugs. J Sex Med 2019; 16:402-409. [DOI: 10.1016/j.jsxm.2019.01.309] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 01/18/2019] [Accepted: 01/21/2019] [Indexed: 02/06/2023]
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC University of Paris and Inflammation-Immunopathology-Biotherapy Department and INSERM, UMR_S 959 and CNRS FRE3632 and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
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Outcomes and costs of treating hepatitis C patients with second-generation direct-acting antivirals: results from the German Hepatitis C-Registry. Eur J Gastroenterol Hepatol 2019; 31:230-240. [PMID: 30325794 DOI: 10.1097/meg.0000000000001283] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Chronic hepatitis C virus infection is associated with a significant health burden. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of direct-acting antivirals (DAA) has led to an increase in sustained virologic response rates (SVR), but is accompanied by higher treatment costs. The aim of this study was to assess the outcomes and costs of treating hepatitis C virus infected patients with DAAs in clinical practice in Germany. PATIENTS AND METHODS Data were derived from a noninterventional study including a pharmacoeconomic subset of 2673 patients with genotypes 1 and 3 who initiated and completed treatment between February 2014 and February 2017. Sociodemographic and clinical parameters as well as resource utilization were collected using a web-based data recording system. Costs were calculated using official remuneration schemes. RESULTS The mean age of the patients was 54.6 years; 48% were men. 93.5% of all patients achieved an SVR. The average total treatment costs were &OV0556;67 979 (&OV0556;67 131 medication costs, &OV0556;824 ambulatory care, &OV0556;24 hospital costs). The average costs per SVR of &OV0556;72 705 were calculated. Differences in SVR and costs according to genotype, treatment regimen, treatment experience, and cirrhosis were observed. Quality-of-life data showed no or a minimal decrease during treatment. CONCLUSION This analysis confirms high SVR rates for newly introduced DAAs in a real-world setting. Costs per SVR estimated are comparable to first-generation DAA. Given the fact that the costs for the currently used treatment regimens have declined, it can be assumed that the costs per SVR have also decreased. Our insight into real-world outcomes and costs can serve as a basis for a comparison with the mentioned newly introduced treatment regimens.
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Fourati S, Rodriguez C, Hézode C, Soulier A, Ruiz I, Poiteau L, Chevaliez S, Pawlotsky JM. Frequent Antiviral Treatment Failures in Patients Infected With Hepatitis C Virus Genotype 4, Subtype 4r. Hepatology 2019; 69:513-523. [PMID: 30125371 DOI: 10.1002/hep.30225] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 08/10/2018] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus (HCV) genotype 4 is highly heterogeneous. HCV subtype 4r has been suggested to be less responsive to direct-acting antiviral (DAA) drug treatment than other genotype 4 subtypes. Among 537 DAA-treated patients who experienced a virological failure (VF) in France between 2015 and 2018, 121 (22.5%) were infected with genotype 4 and 27 of them (22.3%) with subtype 4r; subtype 4r was thus over-represented as compared to its prevalence in the French general population. Population sequencing of the nonstructural protein (NS) 3, NS5A, and NS5B genes was performed in all subtype 4r patients at treatment failure and in 6 at baseline, whereas full-length HCV genome sequencing was performed in two baseline and three treatment failure samples by means of an original shotgun metagenomics method based on deep sequencing. At treatment failure, all subtype 4r patients harbored two to three dominant NS5A resistance-associated substitutions (RASs), including at least L28A/C/I/M/V and L30R. Among 13 patients exposed to sofosbuvir and an NS5A inhibitor (daclatasvir, ledipasvir, or velpatasvir), 5 (38.5%) also harbored NS5B S282C/T RASs at treatment failure. An additional patient harbored S282C/T RASs at treatment failure by deep sequencing. Prevalence of S282C/T RASs at treatment failure was significantly higher in patients infected with genotype 4r than with other genotypes, including other subtypes of genotype 4. Conclusion: The lower rates of sustained virological response in patients infected with subtype 4r are related to the frequent preexistence at treatment baseline and subsequent selection by DAA treatment of both NS5A and NS5B S282 RASs. Our study suggests that these patients should be identified and receive a triple DAA combination regimen as first-line treatment.
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Affiliation(s)
- Slim Fourati
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France.,INSERM U955, Créteil, France
| | - Christophe Rodriguez
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France.,INSERM U955, Créteil, France
| | - Christophe Hézode
- INSERM U955, Créteil, France.,Department of Hepatology, Henri Mondor Hospital, University of Paris-Est, Créteil, France
| | - Alexandre Soulier
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France.,INSERM U955, Créteil, France
| | - Isaac Ruiz
- INSERM U955, Créteil, France.,Department of Hepatology, Henri Mondor Hospital, University of Paris-Est, Créteil, France
| | - Lila Poiteau
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France.,INSERM U955, Créteil, France
| | - Stéphane Chevaliez
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France.,INSERM U955, Créteil, France
| | - Jean-Michel Pawlotsky
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France.,INSERM U955, Créteil, France
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Morey S, Hamoodi A, Jones D, Young T, Thompson C, Dhuny J, Buchanan E, Miller C, Hewett M, Valappil M, Hunter E, McPherson S. Increased diagnosis and treatment of hepatitis C in prison by universal offer of testing and use of telemedicine. J Viral Hepat 2019; 26:101-108. [PMID: 30315691 DOI: 10.1111/jvh.13017] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Revised: 08/30/2018] [Accepted: 09/03/2018] [Indexed: 12/18/2022]
Abstract
With recent advances in antiviral therapy, there is an opportunity to eliminate hepatitis C virus (HCV) from the UK population. HCV is common in incarcerated individuals, with previous estimates suggesting ~7% of the UK prison population is anti-HCV antibody positive. Increasing diagnosis and treatment of HCV in prison is a priority in seeking to eliminate transmission in the general population. Thus the study aimed to assess the impact implementation of: (a) A universal offer of blood borne virus testing (UOBBVT) using dry blood spot testing for prisoners at reception to increase diagnosis; (b) Telemedicine clinics (TC) within North East England (NEE) prisons to increase HCV treatment rates. UOBBVT was initially implemented at Her Majesty's Prison (HMP) Durham, commencing March 2016. From March 2016 to February 2017, 2831 of 4280 (66%) new receptions were offered blood borne virus (BBV) testing. Of these, 1495 (53% of offered) accepted BBV testing, of whom 95 (6.4%) were HCV antibody positive, with 47 of those 95 (49.5%) HCV RNA positive, suggesting a prevalence of active infection in the tested population of 3.1% (95% CI 2.4%-4.2%). Between August 2015 and October 2017, 80 individuals were seen in the TC and 57 (71%) commenced antiviral therapy. Of those with known outcome (n = 29), 100% achieved sustained virological response. In the year prior to implementation, only four patients received HCV treatment. In conclusion, a universal offer of BBV testing to inmates presenting at HMP reception coupled with linkage into specialist care via TC can substantially increase rates of testing, diagnosis and treatment of HCV in this high-prevalence population.
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Affiliation(s)
- Sarah Morey
- Viral Hepatitis Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.,Northumbria University, Newcastle upon Tyne, UK
| | - Abi Hamoodi
- Public Health England, Newcastle upon Tyne, UK
| | | | - Tina Young
- Viral Hepatitis Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | | | - Julie Dhuny
- NHS England (Cumbria and the North East), Darlington, UK
| | - Emma Buchanan
- Viral Hepatitis Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Carolyn Miller
- Viral Hepatitis Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Margaret Hewett
- Viral Hepatitis Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Manoj Valappil
- Viral Hepatitis Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Ewan Hunter
- Department of Infection and Tropical Medicine, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
| | - Stuart McPherson
- Viral Hepatitis Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Cacoub P, Comarmond C. Considering hepatitis C virus infection as a systemic disease. Semin Dial 2018; 32:99-107. [PMID: 30549107 DOI: 10.1111/sdi.12758] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus (HCV) infection has been demonstrated to result in several adverse hepatic outcomes and has been associated with a number of important extrahepatic manifestations. The scope of extrahepatic clinical possibilities includes systemic diseases such as vasculitis and lymphoproliferative disorders, cardiovascular disease, myalgia, arthritis, and sicca syndrome. These end-organ effects of HCV may dominate the clinical course beyond the hepatic complications and significantly worsen the long-term prognosis of infected patients. Until several years ago, the standard of care for the treatment of HCV infection had been interferon-alpha-based regimens, which not only had limited effectiveness in achieving a cure but were often poorly tolerated, especially in patients with kidney disease. In those HCV-infected patients with significant systemic manifestations, the interferon-based regimens were problematic given their association with a wide variety of toxicities. The development of highly effective direct-acting antiviral agents to treat HCV infection presented an opportunity to improve the HCV care cascade with the eradication of HCV in most infected patients and by reducing the burden of both hepatic and extrahepatic complications.
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Affiliation(s)
- Patrice Cacoub
- UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, Paris, France.,INSERM, UMR_S 959, Paris, France.,CNRS, FRE3632, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Cloé Comarmond
- UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, Paris, France.,INSERM, UMR_S 959, Paris, France.,CNRS, FRE3632, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
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36
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Bradley C, Scott RA, Cox E, Palaniyappan N, Thomson BJ, Ryder SD, Irving WL, Aithal GP, Guha IN, Francis S. Short-term changes observed in multiparametric liver MRI following therapy with direct-acting antivirals in chronic hepatitis C virus patients. Eur Radiol 2018; 29:3100-3107. [PMID: 30506214 PMCID: PMC6510871 DOI: 10.1007/s00330-018-5788-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 09/04/2018] [Accepted: 09/21/2018] [Indexed: 12/11/2022]
Abstract
Methods We applied multiparametric MRI to assess changes in liver composition, perfusion and blood flow in 17 patients before direct-acting antiviral (DAA) therapy and after treatment completion (within 12 weeks of last DAA tablet swallowed). Results We observed changes in hepatic composition indicated by a reduction in both liver longitudinal relaxation time (T1, 35 ± 4 ms), transverse relaxation time (T2, 2.5 ± 0.8 ms; T2* 3.0 ± 0.7 ms), and liver perfusion (28.1 ± 19.7 ml/100 g/min) which we suggest are linked to reduced pro-inflammatory milieu, including interstitial oedema, within the liver. No changes were observed in liver or spleen blood flow, splenic perfusion, or superior mesenteric artery blood flow. Conclusion For the first time, our study has shown that treatment of HCV with DAAs in patients with cirrhosis leads to an acute reduction in liver T1, T2 and T2* and an increase in liver perfusion measured using MR parameters. The ability of MRI to characterise changes in the angio-architecture of patients with cirrhosis after intervention in the short term will enhance our understanding of the natural history of regression of liver disease and potentially influence clinical decision algorithms. Key Points • DAAs have revolutionised the treatment of hepatitis C and achieve sustained virological response in over 95% of patients, even with liver cirrhosis. • Currently available non-invasive measures of liver fibrosis are not accurate after HCV treatment with DAAs, this prospective single-centre study has shown that MRI can sensitively measure changes within the liver, which could reflect the reduction in inflammation with viral clearance. • The ability of MRI to characterise changes in structural and haemodynamic MRI measures in the liver after intervention will enhance our understanding of the progression/regression of liver disease and could potentially influence clinical decision algorithms.
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Affiliation(s)
- C Bradley
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - R A Scott
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - E Cox
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.,NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - N Palaniyappan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - B J Thomson
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - S D Ryder
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - W L Irving
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - G P Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, the University Of Nottingham, Nottingham, UK
| | - I N Guha
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, the University Of Nottingham, Nottingham, UK
| | - S Francis
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK. .,NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
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Cacoub P, Bourliere M, Asselah T, De Ledinghen V, Mathurin P, Hézode C, Henry L, Stepanova M, Younossi ZM. French Patients with Hepatitis C Treated with Direct-Acting Antiviral Combinations: The Effect on Patient-Reported Outcomes. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2018; 21:1218-1225. [PMID: 30314623 DOI: 10.1016/j.jval.2018.01.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 01/03/2018] [Accepted: 01/14/2018] [Indexed: 06/08/2023]
Abstract
BACKGROUND In addition to high efficacy, new anti-hepatitis C virus (HCV) regimens improve patient-reported outcomes (PROs), which must be considered by policymakers in different countries when deciding upon treatment coverage. OBJECTIVE To assess PROs of French patients with HCV treated with different antiviral regimens. METHODS French patients with HCV from 11 clinical trials were included. PROs were measured before, during, and after treatment (Short Form-36 version 2, Functional Assessment of Chronic Illness Therapy-Fatigue, Chronic Liver Disease Questionnaire-HCV, and Work Productivity and Activity Index: Specific Health Problem). RESULTS A total of 931 subjects (age 54 ± 10 years, 60.3% males, 55% employed, 33.5% cirrhotic, 50% treatment-naive, and 45.6% genotype 1) were treated with a combination of interferon, ribavirin, and sofosbuvir (IFN + RBV + SOF) (N = 11; excluded from comparisons), SOF/RBV ± ledipasvir (LDV) (N = 202), IFN/RBV-free (LDV/SOF, SOF/velpatasvir, or SOF/velpatasvir/voxilaprevir) (N = 594), or placebo (N = 124). The sustained virologic response 12 (SVR-12) rates were 87.1% for IFN-free RBV-containing regimens, 97.6% for IFN/RBV-free regimens, and 0% for placebo. Baseline PRO scores were not different across the treatment groups (all P > 0.10). At the end of treatment, patients treated with IFN-free SOF/RBV ± LDV experienced moderate declines in their PRO scores (up to -7.9% of a PRO range size; P < 0.05), and placebo-treated group did not have significant changes in their PROs (P > 0.05). In contrast, the IFN/RBV-free group experienced significant on-treatment improvement in most PROs (up to +7.9%; P < 0.05). Despite those on-treatment differences, most PROs improved with SVR-12 and SVR-24 regardless of the regimen. In comparison with matched controls from the United States treated with the same regimens, French subjects had lower baseline PROs but similar or greater post-SVR PRO improvements. CONCLUSIONS The use of IFN- and RBV-free regimens leads to significant PRO improvement during treatment and after SVR in French patients with HCV.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology Biotherapy Department, Paris, France
| | | | | | - Victor De Ledinghen
- Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | | | | | - Linda Henry
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Maria Stepanova
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Zobair M Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
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Younossi ZM, Tanaka A, Eguchi Y, Henry L, Beckerman R, Mizokami M. Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan. J Viral Hepat 2018; 25:945-951. [PMID: 29478258 DOI: 10.1111/jvh.12886] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Accepted: 01/17/2018] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is a serious complication of hepatitis C virus (HCV) infection. Sustained virologic response (SVR) for HCV is associated with a reduction in cirrhosis, HCC and mortality and their associated costs. Japanese HCV patients are older with higher prevalence of HCC. Here we used a decision-analytic Markov model to estimate the economic benefit of HCV cure by reducing HCC and DCC burden in Japan. A cohort of 10 000 HCV genotype 1b (GT1b) Japanese patients was modelled with a hybrid decision tree and Markov state-transition model capturing natural history of HCV over a lifetime horizon. Treatment options were approved all-oral direct-acting anti-virals (DAAs) vs no treatment. Treatment efficacy was based on clinical trials and transition rates and costs obtained from Japan-specific data. Cases of HCC, decompensated cirrhosis (DCC) and quality-adjusted life years (QALYs) were projected for patients treated with DAAs vs NT. QALYs were monetized using a willingness-to-pay threshold of ¥4-to-¥6 million. Incremental savings with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. The model showed that DAA treatment vs no treatment, reduces 2057 cases of HCC and 1478 cases of decompensated cirrhosis and saves ¥850 446.73 and ¥338 229.90 per patient (ppt). Additionally, treatment can lead to additional 2.64 QALYs gained per patient. The indirect economic gains associated with treatment-related QALY improvements were ¥10 576 000, ¥13 220 000 and ¥15 864 000 ppt (willingness-to-pay thresholds of ¥4 million, ¥5 million and ¥6 million). Total economic savings of treatment with DAAs (vs no treatment) was ¥7 526 372.63, ¥10 170 372.63 and ¥12 814 372.63, at these different willingness-to-pay thresholds. In conclusion treatment of HCV GT1b with all-oral DAAs in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.
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Affiliation(s)
- Z M Younossi
- Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA.,Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA
| | - A Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Y Eguchi
- Liver Center, Saga University Hospital, Saga University, Saga, Japan
| | - L Henry
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | | | - M Mizokami
- National Center for Global Health and Medicine, Tokyo, Japan
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39
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McDonald SA, Innes HA, Aspinall EJ, Hayes PC, Alavi M, Valerio H, Goldberg DJ, Hutchinson SJ. Inpatient hospital burden of hepatitis C-diagnosed patients with decompensated cirrhosis. Liver Int 2018; 38:1402-1410. [PMID: 29288595 DOI: 10.1111/liv.13681] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 12/07/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS To describe the burden on inpatient hospital resources over time from patients diagnosed with hepatitis C virus (HCV) infection and who have reached the decompensated stage of cirrhosis (DC), as existing estimates of hospital stay in these patients are limited. METHODS A retrospective longitudinal dataset was formed via record-linkage between the national HCV diagnosis database and inpatient/daycase hospitalisation and death registers in Scotland. The study population consisted of HCV-diagnosed patients with a first DC admission in 1996-2013, with follow-up available until 31 May 2014. We investigated and quantified the mean cumulative length of hospital stay, distributions over discharge diagnosis categories, and trends in admission rates. RESULTS Among our study population (n = 1543), we identified 10 179 admissions with any diagnosis post-first DC admission. Between 1996 and 2013 there was a 16-fold rise in annual total admissions (from 112 to 1791) and an 11-fold rise in hospital stay (719-8045). When restricting minimum possible follow-up to 2 years, DC patients (n = 1312) had an overall admission rate of 7.3 per person-year, and spent on average 43 days (26 days during first 6 months) in hospital; for all liver-related, liver-related other than HCC/DC, and non-liver related only admissions, this was 39, 14, and 5 days respectively. CONCLUSIONS HCV-infected DC patients impose a considerable inpatient hospital burden, mostly from DC- and other liver-related admissions, but also from admissions associated with non-liver comorbidities. Estimates will be useful for monitoring the impact of prevention and treatment, and for computing the cost-effectiveness of new therapies.
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Affiliation(s)
- Scott A McDonald
- School of Health and Life Sciences, Glasgow Caledonian University, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| | - Hamish A Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| | - Esther J Aspinall
- School of Health and Life Sciences, Glasgow Caledonian University, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| | - Peter C Hayes
- Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK
| | - Maryam Alavi
- Health Protection Scotland, Glasgow, Scotland, UK
| | - Heather Valerio
- School of Health and Life Sciences, Glasgow Caledonian University, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| | - David J Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
| | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Scotland, UK.,Health Protection Scotland, Glasgow, Scotland, UK
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40
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Wong A, Tsien C, Mansour S, Cooper C. Remaining clinical issues in hepatitis C treatment. CANADIAN LIVER JOURNAL 2018; 1:66-77. [PMID: 35990713 PMCID: PMC9202793 DOI: 10.3138/canlivj.1.2.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 03/12/2018] [Indexed: 08/31/2024]
Abstract
Key advances in the evaluation and treatment of hepatitis C virus (HCV) infection have positively transformed the management and outcomes of those living with this chronic viral infection. Previously difficult-to-cure populations, including those coinfected with HIV infection, now enjoy similarly high success rates with interferon-free, orally administered direct-acting antiviral (DAA) therapies. Nonetheless, relevant unresolved clinical questions remain. The role and impact of viral resistance testing on treatment selection and outcome remain to be fully determined. The consequences of developing resistance while on DAA treatments that ultimately prove unsuccessful requires further evaluation. Optimal HCV management strategies in decompensated liver disease are unclear, and the role for ribavirin in DAA treatment-naïve and treatment-experienced patients is uncertain. A chief concern for those with cirrhosis relates to the risk for de novo and recurrent hepatocellular carcinoma among DAA recipients. In this article, we present and interpret current data and consider pragmatic, clinically useful options.
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Affiliation(s)
- Alexander Wong
- Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Cynthia Tsien
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Sarah Mansour
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Curtis Cooper
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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41
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Petta S, Adinolfi LE, Fracanzani AL, Rini F, Caldarella R, Calvaruso V, Cammà C, Ciaccio M, Di Marco V, Grimaudo S, Licata A, Marrone A, Nevola R, Pipitone RM, Pinto A, Rinaldi L, Torres D, Tuttolomondo A, Valenti L, Fargion S, Craxì A. Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis. J Hepatol 2018; 69:18-24. [PMID: 29505844 DOI: 10.1016/j.jhep.2018.02.015] [Citation(s) in RCA: 97] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 02/14/2018] [Accepted: 02/19/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Recent studies suggest an association between hepatitis C virus (HCV) infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct-acting antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS One hundred eighty-two consecutive patients with HCV and advanced fibrosis or compensated cirrhosis were evaluated. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT ≥1 mm) and carotid plaques, defined as focal thickening of ≥1.5 mm at the level of the common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy. Fifty-six percent of patients were male, mean age 63.1 ± 10.4 years, and 65.9% had compensated cirrhosis. One in five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. At baseline, mean IMT was 0.94 ± 0.29 mm, 42.8% had IMT ≥1 mm, and 42.8% had carotid plaques. RESULTS All patients achieved a 12-week sustained virological response. IMT significantly decreased from baseline to follow-up (0.94 ± 0.29 mm vs. 0.81 ± 0.27, p <0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p <0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p = 0.34). These results were confirmed in subgroups of patients stratified for cardiovascular risk factors and liver disease severity. CONCLUSION HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis with or without additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term. LAY SUMMARY Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy.
| | - Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Francesca Rini
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Rosalia Caldarella
- Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Calogero Cammà
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Marcello Ciaccio
- Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
| | - Vito Di Marco
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Stefania Grimaudo
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Anna Licata
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Aldo Marrone
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Riccardo Nevola
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | | | - Antonio Pinto
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Daniele Torres
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Antonino Tuttolomondo
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Antonio Craxì
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
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Lee MH. Risk of hepatocellular carcinoma for patients treated with direct-acting antivirals: steps after hepatitis C virus eradication to achieve elimination. Transl Gastroenterol Hepatol 2018; 3:15. [PMID: 29682622 DOI: 10.21037/tgh.2018.02.03] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 02/19/2018] [Indexed: 12/14/2022] Open
Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei
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43
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Innes H, Barclay ST, Hayes PC, Fraser A, Dillon JF, Stanley A, Bathgate A, McDonald SA, Goldberg D, Valerio H, Fox R, Kennedy N, Bramley P, Hutchinson SJ. The risk of hepatocellular carcinoma in cirrhotic patients with hepatitis C and sustained viral response: Role of the treatment regimen. J Hepatol 2018; 68:646-654. [PMID: 29155019 DOI: 10.1016/j.jhep.2017.10.033] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 10/18/2017] [Accepted: 10/30/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV clinical database. METHODS We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral therapy in Scotland from 1997-2016 resulting in a sustained virologic response. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free vs. IFN-containing. RESULTS A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48; p = 0.021). However, after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, p = 0.744). CONCLUSION These findings suggest that the higher incidence of HCC following sustained virologic response with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se. LAY SUMMARY We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer.
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Affiliation(s)
- Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
| | | | | | | | | | | | | | - Scott A McDonald
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK
| | - David Goldberg
- Health Protection Scotland, Glasgow, UK; School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
| | - Heather Valerio
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK
| | - Ray Fox
- The Brownlee Centre, Glasgow, UK
| | | | | | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK
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44
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Cacoub P, Nahon P, Layese R, Blaise L, Desbois AC, Bourcier V, Cagnot C, Marcellin P, Guyader D, Pol S, Larrey D, De Lédinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Riachi G, Calès P, Péron JM, Alric L, Bourlière M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grangé JD, Attali P, Bacq Y, Wartelle C, Dao T, Thabut D, Pilette C, Silvain C, Christidis C, Capron D, Thiefin G, Zucman D, Di Martino V, Bagnis CI, Ziol M, Sutton A, Letouze E, Roudot-Thoraval F, Audureau E. Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients. Am Heart J 2018; 198:4-17. [PMID: 29653647 DOI: 10.1016/j.ahj.2017.10.024] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 10/29/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND The objective was to examine the role of a sustained virological response (SVR) on major adverse cardiovascular events (MACEs) in patients with compensated hepatitis C virus (HCV) cirrhosis. METHODS Patients with the following criteria were enrolled in 35 French centers: (1) biopsy-proven HCV cirrhosis; (2) Child-Pugh A; (3) positive viremia; and (4) no prior liver complication, and then prospectively followed. All patients received HCV treatment after inclusion. MACEs included stroke, myocardial infarction, ischemic heart disease, heart failure, peripheral arterial disease, cardiac arrest, and cardiovascular death. SVR, defined as negative viremia 12 weeks posttreatment, was considered as a time-dependent covariate, and its effect on MACE occurrence was assessed. The median follow up was 57.5 months, ending in December 2015. RESULTS Sixty-two of 878 (7.1%) patients presented a total of 79 MACEs. The main predictive baseline factors of MACEs were Asian ethnic origin, history of MACEs, arterial hypertension, diabetes mellitus, current smoking, low serum albumin level, high total bilirubin level, and low platelet count. In multivariate analysis, SVR was associated with a decreased risk of MACEs (hazard ratio=0.35, 95% CI 0.09-0.97, P=.044), whereas Asian ethnic origin, arterial hypertension, smoking, and low serum albumin level remained predictive of MACE occurrence. The 5-year survival rate was 60.1% versus 87.5% in patients who did versus those who did not present a MACE (P<.001). CONCLUSIONS In patients with compensated HCV-related cirrhosis, Asian ethnic origin, arterial hypertension, smoking, and low serum albumin are independent predictive factors of cardiovascular events, whereas an SVR is associated with a decreased rate of cardiovascular events.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
| | - Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris
| | - Richard Layese
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
| | | | - Anne Claire Desbois
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | | | - Carole Cagnot
- Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENCH)
| | | | | | - Stanislas Pol
- Université Paris Descartes, APHP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1223 et USM20, Institut Pasteur, Paris, France
| | | | | | - Denis Ouzan
- Institut Arnaud Tzanck, Service d'Hépatologie, St Laurent du Var
| | | | | | - Albert Tran
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, "Hepatic Complications in Obesity", Nice, France and University Hospital of Nice, Digestive Centre, Nice, France
| | | | | | - Ghassan Riachi
- Hôpital Charles-Nicolle, Service d'Hépato-gastro-entérologie, Rouen
| | - Paul Calès
- CHU d'Angers, Service d'Hépatologie, Angers
| | | | - Laurent Alric
- Service de Médecine Interne-Pôle Digestif CHU Toulouse, UMR 152, IRD, Toulouse 3 University
| | | | | | | | - Armand Abergel
- Hôpital Hôtel Dieu, Service d'Hépatologie, Clermont-Ferrand
| | | | - Ariane Mallat
- AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil
| | | | - Pierre Attali
- AP-HP, Hôpital Paul Brousse, Service d'Hépatologie, Villejuif
| | - Yannick Bacq
- Hôpital Trousseau, Unité d'Hépatologie, CHRU de Tours
| | - Claire Wartelle
- Hôpital d'Aix-En-Provence, Service d'Hépatologie, Aix-En-Provence
| | - Thông Dao
- Hôpital de la Côte de Nacre, Service d'Hépatologie, Caen
| | - Dominique Thabut
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris
| | | | | | | | | | | | | | | | - Corinne Isnard Bagnis
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Nephrology, Paris, France
| | - Marianne Ziol
- Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris; AP-HP, Hôpital Jean Verdier, Service d'Anatomopathologie, Bondy; CRB (liver disease biobank) Groupe Hospitalier Paris Seine-Saint-Denis BB-0033-00027
| | - Angela Sutton
- CRB (liver disease biobank) Groupe Hospitalier Paris Seine-Saint-Denis BB-0033-00027; AP-HP, Hôpital Jean Verdier, Service de Biochimie, Bondy
| | - Eric Letouze
- Inserm, UMR-1162, "Génomique fonctionnelle des tumeur solides", Paris
| | - Françoise Roudot-Thoraval
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
| | - Etienne Audureau
- AP-HP, Hôpital Henri Mondor, Unité de Recherche Clinique (URC-Mondor), and Université Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, UPEC, Créteil
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45
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Innes H, McAuley A, Goldberg D, Hutchinson SJ. Reply. Hepatology 2018; 67:1173. [PMID: 29266353 DOI: 10.1002/hep.29749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 12/18/2017] [Indexed: 12/07/2022]
Affiliation(s)
- Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow, United Kingdom
| | - Andrew McAuley
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow, United Kingdom
| | - David Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow, United Kingdom
| | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow, United Kingdom
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46
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Younossi ZM. The efficacy of new antiviral regimens for hepatitis C infection: Evidence from a systematic review. Hepatology 2018; 67:1160-1162. [PMID: 29023922 DOI: 10.1002/hep.29580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 09/12/2017] [Accepted: 10/03/2017] [Indexed: 12/12/2022]
Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital.,Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
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47
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Petta S, Craxi A. Can we prevent and modify cardiometabolic disorders by controlling HCV infection? Gut 2018; 67:403-404. [PMID: 28706079 DOI: 10.1136/gutjnl-2017-314505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 06/15/2017] [Indexed: 12/08/2022]
Affiliation(s)
- Salvatore Petta
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Antonio Craxi
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
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48
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Roche B, Coilly A, Duclos-Vallee JC, Samuel D. The impact of treatment of hepatitis C with DAAs on the occurrence of HCC. Liver Int 2018; 38 Suppl 1:139-145. [PMID: 29427487 DOI: 10.1111/liv.13659] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 11/23/2017] [Indexed: 12/13/2022]
Abstract
Hepatitis C virus infection is a major cause of chronic hepatitis resulting in cirrhosis and hepatocellular carcinoma (HCC). The recent introduction of direct acting antivirals (DAA), results in sustained virological response (SVR) rates of >90% in treated patients whatever the stage of liver fibrosis with an excellent safety profile. This major advancement has allowed treatment of a larger number of patients, some with more advanced liver dysfunction and a higher risk of HCC. An SVR is associated with a reduced risk of hepatic decompensation, the need for liver transplantation and both liver-related and overall mortality. This high rate of SVR has raised hopes that there would be a significant reduction in the incidence of HCC. However, the impact of DAA-based regimens on the occurrence of HCC in patients with cirrhosis, and in particular the recurrence of HCC following successful curative treatment is controversial. Published studies suggest that DAA does not increase the risk of de novo HCC following SVR. A more controversial topic is the effect of a DAA-based SVR on the recurrence of HCC following curative treatment of early HCC. Well-designed studies with robust comparisons are needed to determine the effect of DAA on the recurrence of HCC. At present, patients with HCV cirrhosis who have undergone resection or ablation for HCC should not be dissuaded from receiving DAA therapy to prevent the progression of liver disease. Monitoring for HCC with liver imaging and AFP should be performed twice a year indefinitely post-SVR in patients with HCV cirrhosis.
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Affiliation(s)
- Bruno Roche
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France.,Inserm, Unité 1193, Université Paris-Saclay, Villejuif, France.,Hepatinov, Villejuif, France
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France.,Inserm, Unité 1193, Université Paris-Saclay, Villejuif, France.,Hepatinov, Villejuif, France
| | - Jean Charles Duclos-Vallee
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France.,Inserm, Unité 1193, Université Paris-Saclay, Villejuif, France.,Hepatinov, Villejuif, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, France.,Inserm, Unité 1193, Université Paris-Saclay, Villejuif, France.,Hepatinov, Villejuif, France
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Vassalle C, Petta S, Pepe A, Craxi A, Bondin M, Cacoub P. Expert opinion on managing chronic HCV in patients with cardiovascular disease. Antivir Ther 2018; 23:35-46. [PMID: 30451152 DOI: 10.3851/imp3248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment of HCV, there remains a need for increased awareness among specialists so that patients are more likely to obtain the treatment required to mitigate disease progression.
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Affiliation(s)
- Cristina Vassalle
- Laboratory Medicine Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Alessia Pepe
- MRI Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Antonio Craxi
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | | | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
- INSERM, UMR_S 959, Paris, France
- CNRS, FRE3632, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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50
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Innes H, McAuley A, Alavi M, Valerio H, Goldberg D, Hutchinson SJ. The contribution of health risk behaviors to excess mortality in American adults with chronic hepatitis C: A population cohort-study. Hepatology 2018; 67:97-107. [PMID: 28777874 DOI: 10.1002/hep.29419] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 07/06/2017] [Accepted: 08/01/2017] [Indexed: 01/01/2023]
Abstract
UNLABELLED In resource-rich countries, chronic hepatitis C (CHC) infection is associated with a sizeable excess mortality risk. The extent to which this is due to (1) the biological sequelae of CHC infection versus (2) a high concomitant burden of health risk behaviors (HRBs) is unclear. We used data from the 1999-2010 U.S. National Health and Nutritional Examination Surveys (NHANES), which include detailed information on HRBs and CHC infection status. We calculated the prevalence of the five major HRBs-alcohol use; cigarette smoking, physical inactivity, unhealthy diet, and illicit drug use-according to CHC after adjusting for sociodemographic differences. Mortality status after survey interview was ascertained by linkage to the U.S. National Death Index. To assess the contribution of HRBs to the excess mortality risk, we determined the all-cause mortality rate ratio (MRR) for individuals with CHC relative to individuals without, and then calculated the attenuation in this MRR following adjustment for HRBs. This analysis included 27,468 adult participants of NHANES of which 363 tested positive for CHC. All HRBs were markedly more prevalent among individuals with CHC versus individuals without. CHC was associated with a 2.4-fold higher mortality rate after adjustment for sociodemographic factors (MRR, 2.36; 95% CI, 1.60-3.49). Subsequent adjustment for all five HRBs attenuated this ratio by 50.7% to MRR 1.67 (95% CI, 1.14-2.44). Higher levels of attenuation (69.1%) were observed among individuals aged 45-70 years, who form the target demographic for U.S. birth cohort screening. CONCLUSION At least half the excess mortality risk for individuals with CHC in the United States may be attributed to HRBs rather than CHC. The remedial response to hepatitis C must not neglect action on HRBs if it is to fully resolve the high mortality problem in this population. (Hepatology 2018;67:97-107).
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Affiliation(s)
- Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow Caledonian University, Glasgow, United Kingdom
| | - Andrew McAuley
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow Caledonian University, Glasgow, United Kingdom
| | - Maryam Alavi
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia
| | - Heather Valerio
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow Caledonian University, Glasgow, United Kingdom
| | - David Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow Caledonian University, Glasgow, United Kingdom
| | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.,Health Protection Scotland, Glasgow Caledonian University, Glasgow, United Kingdom
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