|
1
|
Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
Collapse
Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
| |
Collapse
|
|
2
|
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.
Collapse
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
| |
Collapse
|
|
3
|
Garvey P, Murphy N, Flanagan P, Brennan A, Courtney G, Crosbie O, Crowe J, Hegarty J, Lee J, McIver M, McNulty C, Murray F, Nolan N, O'Farrelly C, Stewart S, Tait M, Norris S, Thornton L. Disease outcomes in a cohort of women in Ireland infected by hepatitis C-contaminated anti-D immunoglobulin during 1970s. J Hepatol 2017; 67:1140-1147. [PMID: 28843656 DOI: 10.1016/j.jhep.2017.07.034] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 06/21/2017] [Accepted: 07/15/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIM In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression. METHODS We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression. RESULTS Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n=374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR=4.9 [2.5-9.5]) and diabetes mellitus (aSHR=5.0 [2.9-8.8]). CONCLUSIONS Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history. LAY SUMMARY In the mid-1990s, a group of women were diagnosed with chronic hepatitis C virus (HCV) infection following receipt of contaminated anti-D immunoglobulin between 1977 and 1979 in Ireland. Seventy-two (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of high alcohol consumption.
Collapse
Affiliation(s)
- Patricia Garvey
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland; European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control, Stockholm, Sweden.
| | - Niamh Murphy
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | - Paula Flanagan
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | - Aline Brennan
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | | | | | - John Crowe
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - John Hegarty
- St Vincent's University Hospital, Dublin, Ireland
| | - John Lee
- University College Hospital, Galway, Ireland
| | - Margaret McIver
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| | | | | | - Niamh Nolan
- St Vincent's University Hospital, Dublin, Ireland
| | | | | | - Michele Tait
- Health Service Executive, Dr. Steevens Hospital, Dublin, Ireland
| | | | - Lelia Thornton
- Health Service Executive-Health Protection Surveillance Centre, Dublin, Ireland
| |
Collapse
|
|
4
|
Zignego AL, Ramos-Casals M, Ferri C, Saadoun D, Arcaini L, Roccatello D, Antonelli A, Desbois AC, Comarmond C, Gragnani L, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement. Autoimmun Rev 2017; 16:523-541. [PMID: 28286108 DOI: 10.1016/j.autrev.2017.03.004] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 02/26/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.
Collapse
Affiliation(s)
- Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - David Saadoun
- Sorbonne University, 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
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Dario Roccatello
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - Anne Claire Desbois
- Sorbonne University, 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
| | - Cloe Comarmond
- Sorbonne University, 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
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Klinik für Rheumatologie Oberarzt, Ratzeburger Allee 160 (Haus 40), 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room, 32 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, 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
| |
Collapse
|
|
5
|
Cacoub P, Comarmond C. New insights into HCV-related rheumatologic disorders: A review. J Adv Res 2016; 8:89-97. [PMID: 28149645 PMCID: PMC5272935 DOI: 10.1016/j.jare.2016.07.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 07/17/2016] [Accepted: 07/18/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infected patients are known to be exposed to major liver complications i.e. cirrhosis and hepatocellular carcinoma. In addition, many extrahepatic manifestations including rheumatologic disorders have been reported in up to two-third of HCV infected patients. These manifestations include frank auto-immune and rheumatic diseases (such as arthralgia, myalgia, arthritis, sicca syndrome and vasculitis) which may dominate the course of infection. Until recently, the standard of care of HCV has been the use of interferon-alpha based regimens, which not only had limited effectiveness in HCV cure but were poorly tolerated. In patients with rheumatic diseases interferon-based regimens may be problematic given their association with a wide variety of autoimmune toxicities. Recent therapeutic advances with new direct anti-HCV therapies (interferon-free) which are more effective and better tolerated, make screening for this comorbidity in patients with rheumatic disorders more important than ever. This review aimed to outline main HCV extrahepatic with a special focus on rheumatologic manifestations.
Collapse
Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France
| | - Cloé Comarmond
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France
| |
Collapse
|
|
6
|
Brook G, Bhagani S, Kulasegaram R, Torkington A, Mutimer D, Hodges E, Hesketh L, Farnworth S, Sullivan V, Gore C, Devitt E, Sullivan AK. United Kingdom National Guideline on the Management of the viral hepatitides A, B and C 2015. Int J STD AIDS 2016; 27:501-25. [PMID: 26745988 DOI: 10.1177/0956462415624250] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 12/01/2015] [Indexed: 12/13/2022]
Affiliation(s)
- Gary Brook
- London North West Healthcare NHS Trust, London, UK
| | | | | | | | - David Mutimer
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Louise Hesketh
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Simon Farnworth
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | | | - Emma Devitt
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | - Ann K Sullivan
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | |
Collapse
|
|
7
|
Estimating the clinical and economic benefit associated with incremental improvements in sustained virologic response in chronic hepatitis C. PLoS One 2015; 10:e0117334. [PMID: 25635922 PMCID: PMC4311930 DOI: 10.1371/journal.pone.0117334] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 12/22/2014] [Indexed: 01/18/2023] Open
Abstract
Introduction Hepatitis C virus (HCV) infection is one of the principle causes of chronic liver disease. Successful treatment significantly decreases the risk of hepatic morbidity and mortality. Current standard of care achieves sustained virologic response (SVR) rates of 40–80%; however, the HCV therapy landscape is rapidly evolving. The objective of this study was to quantify the clinical and economic benefit associated with increasing levels of SVR. Methods A published Markov model (MONARCH) that simulates the natural history of hepatitis C over a lifetime horizon was used. Discounted and non-discounted life-years (LYs), quality-adjusted life-years (QALYs) and cost of complication management were estimated for various plausible SVR rates. To demonstrate the robustness of projections obtained, the model was validated to ten UK-specific HCV studies. Results QALY estimates ranged from 18.0 years for those treated successfully in fibrosis stage F0 to 7.5 years (discounted) for patients in fibrosis stage F4 who remain untreated. Predicted QALY gains per 10% improvement in SVR ranged from 0.23 (F0) to 0.64 (F4) and 0.58 (F0) to 1.35 (F4) in 40 year old patients (discounted and non-discounted results respectively). In those aged 40, projected discounted HCV-related costs are minimised with successful treatment in F0/F1 (at approximately £300), increasing to £49,300 in F4 patients who remain untreated. Validation of the model to published UK cost-effectiveness studies produce R2 goodness of fit statistics of 0.988, 0.978 and of 0.973 for total costs, QALYs and incremental cost effectiveness ratios, respectively. Conclusion Projecting the long-term clinical and economic consequences associated with chronic hepatitis C is a necessary requirement for the evaluation of new treatments. The principle analysis demonstrates the significant impact on expected costs, LYs and QALYs associated with increasing SVR. A validation analysis demonstrated the robustness of the results reported.
Collapse
|
|
8
|
Cacoub P, Gragnani L, Comarmond C, Zignego AL. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46 Suppl 5:S165-73. [PMID: 25458776 DOI: 10.1016/j.dld.2014.10.005] [Citation(s) in RCA: 190] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 10/03/2014] [Indexed: 02/09/2023]
Abstract
Hepatitis C virus (HCV) infected patients are known to be at risk of developing liver complications i.e. cirrhosis and liver cancer. However, the risks of morbidity and mortality are underestimated because they do not take into account non-liver consequences of chronic hepatitis C virus infection. Numerous extrahepatic manifestations have been reported in up to 74% of patients, from perceived to disabling conditions. The majority of data concern hepatitis C virus-related autoimmune and/or lymphoproliferative disorders, from mixed cryoglobulinaemia vasculitis to frank lymphomas. More recently, other hepatitis C virus-associated disorders have been reported including cardiovascular, renal, metabolic, and central nervous system diseases. This review aims to outline most of the extrahepatic manifestations that are currently being investigated, including some of autoimmune and/or lymphoproliferative nature, and others in which the role of immune mechanisms appears less clear. Beyond the liver, hepatitis C virus chronic infection should be analyzed as a multifaceted systemic disease leading to heavy direct and indirect costs. The accurate consideration of extrahepatic consequences of such a systemic infection significantly increases the weight of its pathological burden. The need for effective viral eradication measures is underlined.
Collapse
Affiliation(s)
- Patrice Cacoub
- Sorbonne University, 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.
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Cloe Comarmond
- Sorbonne University, 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
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| |
Collapse
|
|
9
|
Sebastiani G, Gkouvatsos K, Pantopoulos K. Chronic hepatitis C and liver fibrosis. World J Gastroenterol 2014; 20:11033-11053. [PMID: 25170193 PMCID: PMC4145747 DOI: 10.3748/wjg.v20.i32.11033] [Citation(s) in RCA: 159] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 04/14/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.
Collapse
|
|
10
|
Innes H, Goldberg D, Dusheiko G, Hayes P, Mills PR, Dillon JF, Aspinall E, Barclay ST, Hutchinson SJ. Patient-important benefits of clearing the hepatitis C virus through treatment: a simulation model. J Hepatol 2014; 60:1118-26. [PMID: 24509410 DOI: 10.1016/j.jhep.2014.01.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 01/20/2014] [Accepted: 01/27/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Given an appreciable risk of adverse-effects, current therapies for chronic hepatitis C virus (HCV) infection pose a dilemma to patients. We explored, via simulation modelling, patient-important benefits of attaining a sustained viral response (SVR). METHODS We created the HCV Individualised Treatment-decision model (the HIT-model) to simulate, on a per patient basis, the lifetime course of HCV-related liver disease according to two distinct scenarios: (i) SVR attained, and (ii) SVR not attained. Then, for each model subject, the course of liver disease under these alternative scenarios was compared. The benefit of SVR was considered in terms of two patient-important outcomes: (1) the percent-probability that SVR confers additional life-years, and (2) the percent-probability that SVR confers additional healthy life-years, where "healthy" refers to years spent in compensated disease states (i.e., the avoidance of liver failure). RESULTS The benefit of SVR varied strikingly. It was lowest for patients aged 60 years with initially mild fibrosis; 1.6% (95% CI: 0.8-2.7) and 2.9% (95% CI: 1.5-4.7) probability of gaining life-years and healthy life-years, respectively. Whereas it was highest for patients with initially compensated cirrhosis aged 30 years; 57.9% (95% CI: 46.0-69.0) and 67.1% (95% CI: 54.1-78.2) probability of gaining life-years and healthy life-years, respectively. CONCLUSIONS For older patients with less advanced liver fibrosis, SVR is less likely to confer benefit when measured in terms of averting liver failure and premature death. These data have important implications. Foremost, it may inform the contemporary patient dilemma of immediate treatment with existing therapies (that have poor adverse effect profiles) vs. awaiting future regimens that promise better tolerability.
Collapse
Affiliation(s)
- Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
| | - David Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK
| | - Geoffrey Dusheiko
- UCL Institute of Liver and Digestive Disease, Royal Free Hospital, London, UK
| | | | | | | | - Esther Aspinall
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK
| | | | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK
| |
Collapse
|
|
11
|
Younossi ZM, Kanwal F, Saab S, Brown KA, El-Serag HB, Kim WR, Ahmed A, Kugelmas M, Gordon SC. The impact of hepatitis C burden: an evidence-based approach. Aliment Pharmacol Ther 2014; 39:518-31. [PMID: 24461160 DOI: 10.1111/apt.12625] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Revised: 10/11/2013] [Accepted: 12/30/2013] [Indexed: 12/08/2022]
Abstract
BACKGROUND Infection with the hepatitis C virus (HCV) has been considered a major cause of mortality, morbidity and resource utilisation in the US. In addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent developments in the diagnosis and treatment of HCV, including new recommendations pertaining to screening for HCV by the Centers for Disease Control and Prevention and newer treatment regimens with high efficacy, short duration and the potential for interferon-free therapies, have energised the health care practitioners regarding HCV management. AIM To assess the full impact of HCV burden on clinical, economic and patient-reported outcomes. METHODS An expert panel was convened to assess the full impact of HCV burden on a number of important outcomes using an evidence-based approach predicated on Grading of Recommendations Assessment, Development and Evaluation methodology. The literature was summarised, graded using an evidence-based approach and presented during the workshop. Workshop presentations were intended to review recent, relevant evidence-based literature and provide graded summary statements pertaining to HCV burden on topics including the relationships between HCV and the development of important outcomes. RESULTS The associations of HCV with cirrhosis, HCC, liver-related mortality, type 2 diabetes mellitus, rheumatological diseases and quality of life impairments are supported by strong evidence. Also, there is strong evidence that sustained viral eradication of HCV can improve important outcomes such as mortality and quality of life. CONCLUSIONS The current evidence suggests that HCV has been associated with tremendous clinical, economic and quality of life burden.
Collapse
Affiliation(s)
- Z M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA; Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA, USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
12
|
Szpakowski JL, Tucker LY. Causes of death in patients with hepatitis B: a natural history cohort study in the United States. Hepatology 2013; 58:21-30. [PMID: 23080403 DOI: 10.1002/hep.26110] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2012] [Revised: 09/20/2012] [Accepted: 10/09/2012] [Indexed: 02/02/2023]
Abstract
UNLABELLED The natural history of hepatitis B virus (HBV) infection in a U.S. population has not been well described. We identified the causes of death in 6,689 health plan members infected with HBV who were followed between March 1, 1996 and December 31, 2005. Causes of death were grouped into HBV-related (subdivided into decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]), cancer, cardiovascular, and other/unknown. The study cohort included 3,244 females and 3,445 males; 68.3% were of Asian-Pacific Islander (API) descent, 11.8% were white (non-Hispanic), and 19.9% were of other or unknown race. Exposure to HBV antivirals and preexisting comorbidities were uncommon. Males had higher overall 10-year death rates than females, both for total deaths (8.9% versus 4.1%) and for HBV-related deaths (4.8% versus 1.2%). The death rate rose markedly with increasing age, and approximately 40% of all deaths in subjects over the age of 40 were HBV related. The death rate from HCC was twice that of DCC. HCC deaths represented 70% of cancer deaths in males and 37% in females. On multivariable analysis, when subjects with antecedent HCC and DCC were excluded, the only significant predictor of HBV mortality in both sexes was age. CONCLUSION HBV was the cause of death in over 40% of those who died during the study, and the mortality increased markedly with increasing age over 40 in males and over 50 in females. HBV-related mortality was four times more common in males than in females and was as common in non-Asians as in those of API origin. HBV-related deaths were twice as common from HCC as from DCC.
Collapse
|
|
13
|
Boulhosa RSSB, Oliveira LPM, Jesus RP, Cavalcante LN, Lemaire DC, Vinhas L, Lyra LGC, Lyra AC. The impact of nutritional supplementation on quality of life in patients infected with hepatitis C virus. J Hum Nutr Diet 2013; 26 Suppl 1:7-15. [DOI: 10.1111/jhn.12087] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- R. S. S. B. Boulhosa
- Medicine and Health Post-Graduation Program; Federal University of Bahia; Salvador Brazil
| | - L. P. M. Oliveira
- Medicine and Health Post-Graduation Program; Federal University of Bahia; Salvador Brazil
- Nutrition Science Department; Federal University of Bahia; Salvador Brazil
| | - R. P. Jesus
- Nutrition Science Department; Federal University of Bahia; Salvador Brazil
| | - L. N. Cavalcante
- Medicine and Health Post-Graduation Program; Federal University of Bahia; Salvador Brazil
- Gastro-Hepatology Unit; Hospital São Rafael; Salvador Brazil
| | - D. C. Lemaire
- Laboratory of Immunology; Health Science Institute; Federal University of Bahia; Salvador Brazil
| | - L. Vinhas
- Center for Treatment and Surgery of Obesity; Salvador Brazil
| | - L. G. C. Lyra
- Gastro-Hepatology Unit; Hospital São Rafael; Salvador Brazil
| | - A. C. Lyra
- Medicine and Health Post-Graduation Program; Federal University of Bahia; Salvador Brazil
- Gastro-Hepatology Unit; Hospital São Rafael; Salvador Brazil
| |
Collapse
|
|
14
|
Kielland KB, Skaug K, Amundsen EJ, Dalgard O. All-cause and liver-related mortality in hepatitis C infected drug users followed for 33 years: a controlled study. J Hepatol 2013; 58:31-7. [PMID: 22960427 DOI: 10.1016/j.jhep.2012.08.024] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Revised: 08/22/2012] [Accepted: 08/27/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The course of chronic hepatitis C virus (HCV) in injecting drug users (IDUs) has not been well described. The aim of this study was to compare long-term all-cause and liver-related mortality among anti-HCV positive IDUs with and without persisting HCV infection. METHODS A retrospective-prospective controlled cohort design was applied. All IDUs admitted to resident drug treatment (1970-1984) and with available stored sera were screened for anti-HCV antibody. Anti-HCV positive individuals were further tested for the presence of HCV RNA. All-cause and liver-related mortality was compared between HCV RNA positive (n=328) and HCV RNA negative individuals (n=195). The observation was accomplished through register linkage to national registers. Mean observation time was 33 years. RESULTS All-cause mortality rate was 1.85 (95% CI 1.62-2.11) per 100 person-years, male 2.11 (95% CI 1.84-2.46), female 1.39 (95% CI 1.07-1.79). Mortality rates were not influenced by persisting HCV infection. Main causes of death were intoxications (45.0%), suicide (9.1%), and accidents (8.2%). Liver disease was the cause of death in 7.5% of deaths among HCV RNA positive subjects. Five of 13 deaths among male IDUs with persisting HCV infection occurring after the age of 50 years were caused by liver disease. CONCLUSIONS The all-cause mortality in IDUs is high and with no difference between HCV RNA positive and HCV RNA negative individuals, the first three decades after HCV transmission. However, among IDUs with chronic HCV infection who have survived until 50years of age, HCV infection emerges as the main cause of death.
Collapse
Affiliation(s)
- Knut Boe Kielland
- Innlandet Hospital Trust, Centre for Addiction Issues, PO Box 104, N-2381 Brumunddal, Norway.
| | | | | | | |
Collapse
|
|
15
|
Increased mortality in chronic HCV infection. Ann Hepatol 2012. [DOI: 10.1016/s1665-2681(19)31429-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
|
|
16
|
Roed T, Lebech AM, Kjaer A, Weis N. Hepatitis C virus infection and risk of coronary artery disease: a systematic review of the literature. Clin Physiol Funct Imaging 2012; 32:421-30. [PMID: 23031062 DOI: 10.1111/j.1475-097x.2012.01152.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2012] [Accepted: 06/25/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several chronic infections have been associated with cardiovascular diseases, including Chlamydia pneumoniae, human immunodeficiency virus and viral hepatitis. This review evaluates the literature on the association between chronic hepatitis C virus (HCV) infection and the risk of coronary artery disease (CAD). METHODS Studies were identified using several databases. Only studies on CAD in patients with HCV infection were included. A set of criteria for evaluating potential biases was made, based on known confounders and biases in observational research. Data were not synthesized because of the large heterogeneity in the included studies. RESULTS Twelve eligible references were identified. Nine did not comply with our criteria of minimizing bias, and six studies were evaluated as potentially heavily biased. The studies of the highest quality showed a trend towards association of HCV with CAD. Five studies showed this association (three studies significantly), while one showed that HCV was a protective factor against CAD. CONCLUSION Our findings suggest an increased risk of CAD in HCV-infected individuals. Further studies are needed to confirm this and to evaluate the magnitude of the association. Clinicians should be aware of this and strive to reduce CAD risk factors in patients with chronic HCV infection.
Collapse
Affiliation(s)
- Torsten Roed
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
| | | | | | | |
Collapse
|
|
17
|
Nelson KE. The Impact of Chronic Hepatitis C Virus Infection on Mortality. J Infect Dis 2012; 206:461-3. [DOI: 10.1093/infdis/jis394] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
|
|
18
|
Just SA, Grau K, Georgsen J, Weis N, Cowan S, Groenbaek K, Krarup H, Christensen PB. Long-term follow-up among Danish transfusion recipients identified in the national hepatitis C lookback. Transfusion 2011; 52:582-8. [DOI: 10.1111/j.1537-2995.2011.03309.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
19
|
Grebely J, Raffa JD, Lai C, Kerr T, Fischer B, Krajden M, Dore GJ, Tyndall MW. Impact of hepatitis C virus infection on all-cause and liver-related mortality in a large community-based cohort of inner city residents. J Viral Hepat 2011; 18:32-41. [PMID: 20196806 DOI: 10.1111/j.1365-2893.2010.01279.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to measure the impact of hepatitis C virus (HCV) infection on mortality in a cohort of inner city residents. The Community Health and Safety Evaluation is a community-based study of inner city residents followed retrospectively and prospectively through linkages with provincial virology and mortality databases. We identified participants having received HCV antibody testing, evaluated cause-specific mortality rates and factors associated with all-cause and liver-related mortality using Cox Proportional Hazards models. Overall, 2332 participants received HCV antibody testing (recent non-injection drug use - 81%). The prevalence of HCV and HIV was 64% (1495 of 2332) and 21% (485 of 2332), respectively. Between January 2003 and December 2007, there were 180 deaths (192 per 10.000 person-years; 95% CI: 165, 222), with 21% HIV-related, 20% drug-related and 7% liver-related. Mortality was associated with age >50 [adjusted hazard ratio (AHR) 2.80 vs < 40 years (referent group); 95% CI 1.93, 4.07, P < 0.001] and HIV infection (AHR 3.81; 95% CI 2.72, 5.34, P < 0.001), but not positive HCV antibody status (AHR 1.19; 95% CI 0.83, 1.72, P = 0.35). Liver-related mortality was associated with age >50 [AHR 18.49 vs < 40 years (referent group); 95% CI 2.27, 150.41, P < 0.001] and positive HCV antibody status (AHR 7.69; 95% CI 0.99, 59.98, P = 0.052). This study demonstrates a high rate of mortality in this population, particularly those with HIV. HCV-infected inner city residents >50 years of age were at significant risk of liver-related mortality. Continued surveillance of this population infected with HCV in the 1970s and 1980s is important.
Collapse
Affiliation(s)
- J Grebely
- National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, NSW, Australia.
| | | | | | | | | | | | | | | |
Collapse
|
|
20
|
Hospitalization rates associated with hepatitis B and HIV co-infection, age and sex in a population-based cohort of people diagnosed with hepatitis C. Epidemiol Infect 2010; 139:1151-8. [DOI: 10.1017/s095026881000258x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
SUMMARYTo determine the extent age, sex and co-infection affect morbidity in people infected with hepatitis C virus (HCV), we performed a population-based study linking HCV notifications in New South Wales, Australia with their hospital (July 2000 to June 2006), hepatitis B virus (HBV) and HIV notification, and death records. Poisson models were used to calculate hospitalization rate ratios (RRs) for all-cause, illicit drug and liver-related admissions. Co-infection RRs were used to estimate attributable risk (AR). The 86 501 people notified with HCV contributed 422 761 person-years of observation; 0·8% had HIV, 3·7% HBV, and 0·04% had both. RRs for males were equal to or lower than for females in younger ages, but higher in older ages (Pfor interaction ⩽0·013). HBV/HIV co-infection resulted in ARs of over 70% for liver disease and 30–60% otherwise. However, at the cohort level the impact was minimal (population ARs 1·3–8·7%). Our findings highlight the importance and success of public health measures, such as needle and syringe exchange programmes, which have helped to minimize the prevalence of co-infection in Australia. The findings also suggest that the age of study participants needs to be considered whenever the burden of HCV-related morbidity is reported by sex. The results are likely to be representative of patterns in hospital-related morbidity for the entire HCV-infected population in Australia and the ARs generalizable to other developed countries.
Collapse
|
|
21
|
Abstract
In the late 1960's, only types A and B hepatitis were believed to exist, distinguished by circumstances of exposure and incubation periods. In the early 1970's, studies of transfusion recipients were begun with the belief that hepatitis B would be responsible should transfusion-associated hepatitis develop. After discovery of the viruses of hepatitis A and B, neither agent was found responsible, hence non-A, non-B (NANB) hepatitis. Initial follow-up of these cases showed that approximately 50% developed chronic hepatitis based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after the hepatitis C virus had been identified as the cause for NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in over 80% of infected adults but in only about 50% of infected children or young women. Follow-up over 2 to 4 decades indicated that many infected persons developed progressive hepatic fibrosis, sometimes culminating in cirrhosis and/or liver cancer. Long-term natural history studies have proved to be challenging because disease onset is often silent and progression extremely slow. Differing strategies have been used to determine the natural history, the descriptions and results of which are presented in this review.
Collapse
Affiliation(s)
- Leonard B. Seeff
- National Institute of Diabetes and Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| |
Collapse
|
|
22
|
McDonald SA, Hutchinson SJ, Bird SM, Mills PR, Dillon J, Bloor M, Robertson C, Donaghy M, Hayes P, Graham L. A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland. Stat Methods Med Res 2008; 18:271-83. [DOI: 10.1177/0962280208094690] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Infection with the hepatitis C virus (HCV) is known to increase the risk of death from severe liver disease and, because HCV status is strongly associated with a history of injecting drug use, the effect of a key disease progression cofactor, infection with human immunodeficiency virus (HIV), is of interest . We examined all-cause, liver-related and drug-related mortality and excess risk of death from these causes in a large cohort of HCV-monoinfected and HIV-coinfected persons in Scotland. The study population consisted of 20,163 persons confirmed to be infected with hepatitis C through laboratory testing in Scotland between 1991 and 2005. Records with sufficient identifiers were linked to the General Register Office for Scotland death register to retrieve associated mortality data, and were further linked to a national database of HIV-positive individuals to determine coinfection status. A total of 1715 HCV monoinfected and 305 HIV coinfected persons died of any cause during the follow-up period (mean of 5.4 and 6.4 years, respectively). Significant excess mortality was observed in both HCV monoinfected and HIV coinfected populations from liver-related underlying causes (standardised mortality ratios of 25, 95% CI = 23—27; and 37, 95% CI = 26—52 for the two groups, respectively) and drug-related causes (25, 95% CI = 23—27; 39, 95% CI = 28—53. The risk of death from hepatocellular carcinoma, alcoholic or non-alcoholic liver disease, or from a drug-related cause, was greatly increased compared with the general Scottish population, with the highest standardised mortality ratio observed for hepatocellular carcinoma in the monoinfected group (70, 95% CI = 57—85). This study has revealed considerable excess mortality from liver- and drug-related causes in the Scottish HCV-diagnosed population; these data are crucial to inform on the clinical management, and projected future public health burden, of HCV infection.
Collapse
Affiliation(s)
| | - Sharon J Hutchinson
- Health Protection Scotland, Glasgow, United Kingdom, and Department of Statistics and Modelling Science, University of Strathclyde, Glasgow, United Kingdom
| | - Sheila M Bird
- MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom
| | | | - John Dillon
- Ninewells Hospital and Medical School, Dundee, United Kingdom
| | - Mick Bloor
- Centre for Drugs Misuse Research, University of Glasgow, Glasgow, United Kingdom
| | - Chris Robertson
- Health Protection Scotland, Glasgow, United Kingdom, Department of Statistics and Modelling Science, University of Strathclyde, Glasgow, United Kingdom
| | | | - Peter Hayes
- Edinburgh Royal Infirmary, Edinburgh, United Kingdom
| | - Lesley Graham
- Information Services Division, National Services Scotland, Edinburgh, United Kingdom
| |
Collapse
|
|
23
|
Guiltinan AM, Kaidarova Z, Custer B, Orland J, Strollo A, Cyrus S, Busch MP, Murphy EL. Increased all-cause, liver, and cardiac mortality among hepatitis C virus-seropositive blood donors. Am J Epidemiol 2008; 167:743-50. [PMID: 18203734 DOI: 10.1093/aje/kwm370] [Citation(s) in RCA: 106] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hospital-based studies suggest that hepatitis C virus (HCV) infection causes frequent cirrhosis, hepatocellular carcinoma, and mortality, but epidemiologic studies have shown less morbidity and mortality. The authors performed a retrospective cohort study of 10,259 recombinant immunoblot assay-confirmed, HCV antibody-positive (HCV+), allogeneic blood donors from 1991 to 2002 and 10,259 HCV antibody-negative (HCV-) donors matched for year of donation, age, gender, and Zone Improvement Plan Code (ZIP Code). Vital status through 2003 was obtained from the US National Death Index, and hazard ratios with 95% confidence intervals were calculated by survival analysis. After a mean follow-up of 7.7 years, there were 601 (2.92%) deaths: 453 HCV+ and 148 HCV- (hazard ratio (HR) = 3.13, 95% confidence interval (CI): 2.60, 3.76). Excess mortality in the HCV+ group was greatest in liver-related (HR = 45.99, 95% CI: 11.32, 186.74), drug- or alcohol-related (HR = 10.81, 95% CI: 4.68, 24.96), and trauma/suicide (HR = 2.99, 95% CI: 2.05, 4.36) causes. There was also an unexpected increase in cardiovascular mortality among the HCV+ donors (HR = 2.21, 95% CI: 1.41, 3.46). HCV infection is associated with a significant, threefold increase in overall mortality among former blood donors, including significantly increased mortality from liver and cardiovascular causes. High rates of mortality from drug/alcohol and trauma/suicide causes are likely due to lifestyle factors and may be at least partially preventable.
Collapse
|
|
24
|
Tacke F, Trautwein C. Causes of death in hepatitis B and/or C virus infected-people - lessons for clinical practice. Hepatology 2007; 45:1076-7. [PMID: 17393502 DOI: 10.1002/hep.21621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Frank Tacke
- Department of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany
| | | |
Collapse
|