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Bollerup S, Hallager S, Engsig F, Mocroft A, Krarup H, Madsen LG, Thielsen P, Balslev U, Mens H, Barfod TS, Clausen MR, Hobolth L, Laursen AL, Tarp B, Roege BT, Hansen JB, Mygind L, Christensen PB, Gerstoft J, Weis N. Mortality and cause of death in persons with chronic hepatitis B virus infection versus healthy persons from the general population in Denmark. J Viral Hepat 2022; 29:727-736. [PMID: 35633092 DOI: 10.1111/jvh.13713] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/15/2022] [Accepted: 05/10/2022] [Indexed: 01/04/2023]
Abstract
The study aimed to determine adjusted all-cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age- and sex-matched persons from the general population. We used nationwide registers to identify persons aged ≥18 years with chronic HBV infection in 2002-2017 in Denmark and included 10 age- and sex-matched controls for each. Follow-up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause-specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow-up of 7.7 years (range 0.0-15.5), 315 (5%) persons with-and 1525 (2%) without-chronic HBV infection died. The adjusted all-cause MRR was 1.5 (95% CI 1.2-2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6-17.7]), external causes (MRR 3.3 [2.5-4.7]), endocrine disease (MRR 3.2 [1.8-5.4]), genitourinary disease (MRR 3.2 [1.2-7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2-2.0]). In conclusion, this study showed an increased all-cause mortality in persons with chronic HBV infection in comparison with age- and sex-matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma).
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Affiliation(s)
- Signe Bollerup
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Sofie Hallager
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Frederik Engsig
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Amanda Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK.,Centre of Excellence for Health, Immunity and Infections (CHIP) and PERSIMUNE, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Henrik Krarup
- Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.,Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Lone G Madsen
- Department of Medical Gastroenterology, Zealand University Hospital, Koege, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Peter Thielsen
- Department of Gastroenterology, Herlev Hospital, Herlev, Denmark
| | - Ulla Balslev
- Department of Infectious Diseases, Herlev Hospital, Herlev, Denmark
| | - Helene Mens
- Department of Lung- and Infectious diseases, North Zealand Hospital, Hilleroed, Denmark
| | - Toke S Barfod
- Department of Internal Medicine and Infectious Diseases, Zealand University Hospital, Roskilde, Denmark
| | - Mette R Clausen
- Department of Medical Gastroenterology and Hepatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Lise Hobolth
- Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark
| | - Alex L Laursen
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | - Britta Tarp
- Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, Denmark
| | - Birgit T Roege
- Department of Internal Medicine, Kolding Hospital, Kolding, Denmark
| | - Jesper B Hansen
- Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Lone Mygind
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Peer B Christensen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.,Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Jan Gerstoft
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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One-step diagnosis strategy together with multidisciplinary telematics referral perform an effective approach for identifying and treating patients with active Hepatitis C infection. Ann Hepatol 2022; 27:100542. [PMID: 34571265 DOI: 10.1016/j.aohep.2021.100542] [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: 02/02/2021] [Revised: 04/04/2021] [Accepted: 04/05/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Implementation of a one-step strategy for diagnosis of active Hepatitis C virus (HCV) infection would encourage the early diagnosis and reduce the time to access antiviral treatments. The aim of this study was to evaluate the impact of a HCV one-step diagnosis compared to the traditional two-step protocol in terms of the time required for patients to be seen by specialists and the time taken to start antiviral treatment. MATERIAL AND METHODS A comparative study was carried out to assess two diagnostic algorithms (one-step and two-step) for active HCV infection. Serological markers were quantified using the same serum sample to determine both anti-HCV antibodies (HCV-Ab) and HCV core antigen (HCV-cAg) by Architect i2000 SR kit. In this period, a multidisciplinary procedure was started for telematics referral of viremic patients. RESULTS One-step approach reduced the time required for patient HCV diagnosis, referral to a specialist, access to treatment, and eliminated the loss of patients to follow-up. Significant differences were observed between one-step and two-step diagnosis methods in the time required for patients to be seen by a specialist (18 days [Interquartile range (IQR) = 14-42] versus 107 days [IQR = 62-148]) and for the initiation of treatment (54 days [IQR = 43-75] versus 200 days [IQR = 116-388]), mainly for patients with advanced fibrosis (35 days [IQR = 116-388] versus 126 days [IQR = 152-366]). CONCLUSIONS Use of HCV-cAg has proven to be a useful tool for screening patients with active hepatitis C. The development of a multidisciplinary protocol for the communication of results improved the efficiency of the care process.
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Cao M, Ding C, Xia C, Li H, Sun D, He S, Chen W. Attributable deaths of liver cancer in China. Chin J Cancer Res 2021; 33:480-489. [PMID: 34584373 PMCID: PMC8435823 DOI: 10.21147/j.issn.1000-9604.2021.04.05] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 08/13/2021] [Indexed: 12/12/2022] Open
Abstract
Objective There is little information about contributions of the well-known risk factors to the liver cancer burden. We conducted a comparative study to estimate the liver cancer burden attributable to major risk factors. Methods Liver cancer deaths for adults were estimated from 978 county-level surveillance points in China in 2014. Risk factors were identified from the International Agency for Research on Cancer and the World Cancer Research Fund International. Population attributable fraction (PAF) by age, sex, and province was calculated using multiple formulas. Results In total, 72.4% of liver cancer deaths could be attributable to the studied risk factors. Hepatitis B virus (HBV) was responsible for the largest fraction of liver cancer burden in both genders (PAF=55.6% in males, PAF=46.5% in females). PAFs for liver cancer burden attributable to smoking (15.7% vs. 4.8%), and alcohol drinking (10.3% vs. 1.6%) were significantly higher in males than in females. The burden of HBV-attributable deaths was the highest in Qinghai province.
Conclusions HBV still contributes to the majority of liver cancer burden than any other risk factors. Targeted preventive measures should be implemented based on the degree of contributions of risk factors to liver cancer deaths.
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Affiliation(s)
- Maomao Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - Chao Ding
- Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Changfa Xia
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - He Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - Dianqin Sun
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - Siyi He
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Beijing 100021, China
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Palladino C, Ezeonwumelu IJ, Mate-Cano I, Borrego P, Martínez-Román P, Arca-Lafuente S, Resino S, Taveira N, Briz V. Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain. Sci Rep 2020; 10:13024. [PMID: 32747734 PMCID: PMC7398927 DOI: 10.1038/s41598-020-69692-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 07/07/2020] [Indexed: 11/29/2022] Open
Abstract
Hepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5–15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.
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Affiliation(s)
- Claudia Palladino
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
| | - Ifeanyi Jude Ezeonwumelu
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal
| | - Irene Mate-Cano
- Laboratory of Viral Hepatitis, National Center for Microbiology, Institute of Health Carlos III, Carretera Majadahonda-Pozuelo km 2.2, Majadahonda, 28220, Madrid, Spain
| | - Pedro Borrego
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal
| | - Paula Martínez-Román
- Laboratory of Viral Hepatitis, National Center for Microbiology, Institute of Health Carlos III, Carretera Majadahonda-Pozuelo km 2.2, Majadahonda, 28220, Madrid, Spain
| | - Sonia Arca-Lafuente
- Laboratory of Viral Hepatitis, National Center for Microbiology, Institute of Health Carlos III, Carretera Majadahonda-Pozuelo km 2.2, Majadahonda, 28220, Madrid, Spain
| | - Salvador Resino
- Laboratory of Viral Hepatitis, National Center for Microbiology, Institute of Health Carlos III, Carretera Majadahonda-Pozuelo km 2.2, Majadahonda, 28220, Madrid, Spain
| | - Nuno Taveira
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.,Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Caparica, Portugal
| | - Verónica Briz
- Laboratory of Viral Hepatitis, National Center for Microbiology, Institute of Health Carlos III, Carretera Majadahonda-Pozuelo km 2.2, Majadahonda, 28220, Madrid, Spain.
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Patients with suboptimal hepatitis B virus diagnostic characterization are at risk of liver fibrosis progression. Eur J Gastroenterol Hepatol 2020; 32:426-432. [PMID: 31490418 DOI: 10.1097/meg.0000000000001527] [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
BACKGROUND Many patients with chronic hepatitis B virus infection remain infradiagnosed and untreated. In a national health system with unrestricted access to treatment, our aims were to assess the level of compliance with clinical guidelines and the characteristics and risk of fibrosis progression in patients with suboptimal diagnosis. METHODS In a cohort of patients with positive hepatitis B surface antigen from January 2011 to December 2013, data were registered to assess characteristics and compliance with guidelines. For assessing the risk of liver fibrosis, positive hepatitis B surface antigen patients from January 2008 to December 2013 were grouped depending on DNA request. Liver fibrosis was estimated by serological scores. RESULTS Of 41 158 subjects with hepatitis B surface antigen request, 351 (0.9%) tested positive, and DNA was not available from 110 patients (66.4% male, mean 42.4 ± 14.5 years) after a median of 25.6 months (range 12.0-43.5). Most of these patients (76%) were assessed by primary care. Half of the patients (47.2%) showed hypertransaminasemia, at least significant fibrosis, or both conditions. After long follow-up (mean 90.1 ± 45.2 months), these patients had a higher risk of achieving at least significant fibrosis during follow-up (log-rank 8.73; P = 0.003). CONCLUSION In more than one-third of patients with positive hepatitis B surface antigen, DNA was not requested despite showing hypertransaminasemia and significant fibrosis. Patients without DNA request are at high risk of liver fibrosis progression. Thus, educational measures and other strategies are necessary, especially targeting primary care, to improve access to treatment.
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García F, Domínguez-Hernández R, Casado M, Macías J, Téllez F, Pascasio JM, Casado MÁ, Alados JC. The simplification of the diagnosis process of chronic hepatitis C is cost-effective strategy. Enferm Infecc Microbiol Clin 2019; 37:634-641. [PMID: 30982677 DOI: 10.1016/j.eimc.2019.03.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/22/2019] [Accepted: 03/01/2019] [Indexed: 01/29/2023]
Abstract
BACKGROUND The cascade of care of the hepatitisC are complex. The diagnosis of active infection in the same serum sample would simplify the process establishing a rapid access for patients to treatment. Our objective was to estimate the impact on healthcare and economic outcomes of the diagnosis of chronic infection in one-step diagnosis compared to standard diagnosis in Andalusia (8.39 million people). METHODS A decision tree was developed to estimate the referral of patients with chronic infection, loss of follow-up, access to treatment and costs of the diagnosis of the infection, for both processes. The unit costs (€, 2018) of the health resources (medical visits, antibodies, viral load and genotype), without considering the pharmacological cost, were obtained form public sources in Andalusia. RESULTS Of the total estimated population (269,526 patients), 1,389 patients would be referred to the specialised care in the one-step diagnosis and 1,063 in de standard diagnosis, being treated 1,320 and 1,009, respectively. In one-step diagnosis, no negative viral loud patient would be referred to specialist versus 540 with standard diagnosis. One-step diagnosis would generate a cost saving of €184,928 versus standard diagnosis (€15,671,493 vs €15,856,421). When compared one-step diagnosis to standard diagnosis, the savings per patient with positive viral load referred to specialist would be €3,634 (€11,279 vs €14,923). CONCLUSION The one-step diagnosis will achieve an increase in diagnosed patients, will increase the access of chronic patient to treatment and will generate cost savings, demonstrating its efficiency in the system in Andalusia.
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Affiliation(s)
- Federico García
- Unidad de Gestión Clínica de Microbiología Clínica, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada (Ibs.GRANADA), Granada, España.
| | | | - Marta Casado
- Departamento de Gastroenterología, Complejo Hospitalario Torrecárdenas, Almería, España
| | - Juan Macías
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, España
| | - Francisco Téllez
- Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Puerto Real, Puerto Real, Cádiz, España
| | - Juan Manuel Pascasio
- Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Universitario Virgen del Rocío, IBIS, CIBERehd, Sevilla, España
| | | | - Juan Carlos Alados
- Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Jerez, Jerez de la Frontera, Cádiz, España
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Wu CC, Chen YS, Cao L, Chen XW, Lu MJ. Hepatitis B virus infection: Defective surface antigen expression and pathogenesis. World J Gastroenterol 2018; 24:3488-3499. [PMID: 30131655 PMCID: PMC6102499 DOI: 10.3748/wjg.v24.i31.3488] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 06/01/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed.
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MESH Headings
- DNA, Viral/genetics
- DNA, Viral/isolation & purification
- Disease Progression
- Genome, Viral/genetics
- Hepatitis B Surface Antigens/genetics
- Hepatitis B Surface Antigens/immunology
- Hepatitis B Surface Antigens/metabolism
- Hepatitis B virus/genetics
- Hepatitis B virus/immunology
- Hepatitis B, Chronic/immunology
- Hepatitis B, Chronic/pathology
- Hepatitis B, Chronic/prevention & control
- Hepatitis B, Chronic/virology
- Humans
- Liver/immunology
- Liver/pathology
- Liver/virology
- Liver Failure, Acute/immunology
- Liver Failure, Acute/pathology
- Liver Failure, Acute/prevention & control
- Liver Failure, Acute/virology
- Mutation
- Virus Replication/genetics
- Virus Replication/immunology
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Affiliation(s)
- Chun-Chen Wu
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Ying-Shan Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Liang Cao
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
- Department of Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, United States
| | - Xin-Wen Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Meng-Ji Lu
- Institute of Virology, University Hospital of Essen, Essen 45122, Germany
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Turnes J, Domínguez-Hernández R, Casado MÁ. Value and innovation of direct-acting antivirals: long-term health outcomes of the strategic plan for the management of hepatitis C in Spain. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 109:809-817. [PMID: 29152988 DOI: 10.17235/reed.2017.5063/2017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To assess the long-term healthcare costs and health outcomes in association with the access to new direct-acting antivirals (DAAs), during the first year of the National Strategic Plan for Chronic Hepatitis C (SPCHC) in patients with chronic hepatitis C (CHC) in Spain. METHODS A decision tree and a lifetime Markov model were developed to simulate the natural history, morbidity, and mortality of a cohort of 51,900 patients with CHC before (pre-DAA strategy) and after (post-DAA strategy) access to DAAs, following SPCHC approval. The percentage of patients treated, transition probabilities, disease management costs, health state utility values, sustained virologic response rates and treatment costs were obtained from the literature and published data from Spain. The results were expressed in terms of costs (€, 2016), quality-adjusted life years (QALYs) and prevention of clinical events, with an annual discount rate of 3%. RESULTS The post-DAA strategy would prevent 8,667 cases of decompensated cirrhosis, 5,471 cases of hepatocellular carcinoma, 1,137 liver transplants and 9,608 liver-related deaths. The cohort of 51,900 patients would require investments of 1,606 and 1,230 million euros with the post-DAA and pre-DAA strategies, respectively. This would produce 819,674 and 665,703 QALYs. CONCLUSIONS The use of new DAA-based treatments in CHC patients during the first year after the implementation of the SPCHC significantly reduced long-term morbidity and mortality and increased quality of life; demonstrating that this plan is an efficient use of public health resources.
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Affiliation(s)
- Juan Turnes
- Department of Gastroenterology and Hepatology, Complejo Hospitalario Universitario de Pontevedra
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do Amaral AE, Cisilotto J, Creczynski-Pasa TB, de Lucca Schiavon L. Circulating miRNAs in nontumoral liver diseases. Pharmacol Res 2017; 128:274-287. [PMID: 29037479 DOI: 10.1016/j.phrs.2017.10.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 10/11/2017] [Accepted: 10/12/2017] [Indexed: 12/23/2022]
Abstract
In recent years, there has been increasing interest in finding new biomarkers for diagnosis and prognostication of liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules involved in the regulation of gene expression and have been studied in relation to several conditions, including liver disease. Mature miRNAs can reach the bloodstream by passive release or by incorporation into lipoprotein complexes or microvesicles, and have stable and reproducible concentrations among individuals. In this review, we summarize studies involving circulating miRNAs sourced from the serum or plasma of patients with nontumoral liver diseases in attempt to bring insights in the use of miRNAs as biomarkers for diagnosis, as well as for prognosis of such diseases. In addition, we present pre-analytical aspects involving miRNA analysis and strategies for normalization of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data related to the studies evaluated.
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Affiliation(s)
- Alex Evangelista do Amaral
- Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Delfino Conti Street, 88040-370 Florianopolis, SC, Brazil.
| | - Júlia Cisilotto
- Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Delfino Conti Street, 88040-370 Florianopolis, SC, Brazil.
| | - Tânia Beatriz Creczynski-Pasa
- Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Delfino Conti Street, 88040-370 Florianopolis, SC, Brazil.
| | - Leonardo de Lucca Schiavon
- Department of Internal Medicine, Division of Gastroenterology, Federal University of Santa Catarina, Maria Flora Pausewang Street, 88036-800 Florianopolis, SC, Brazil.
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Boix R, Cano R, Gallego P, Vallejo F, Fernández-Cuenca R, Noguer I, Larrauri A. Hepatitis C hospitalizations in Spain, 2004-2013: a retrospective epidemiological study. BMC Health Serv Res 2017; 17:461. [PMID: 28679375 PMCID: PMC5498875 DOI: 10.1186/s12913-017-2410-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 06/27/2017] [Indexed: 01/29/2023] Open
Abstract
Background Hepatitis C is an important public health problem about which there is currently scarce epidemiological information. The objective of this study is to describe and analyse the demographic and epidemiological characteristics of hospitalized cases of hepatitis C in the Spanish population between 2004 and 2013. Methods The study uses the Hospital Discharge Records Database of the Spanish National Health System. It is a retrospective descriptive epidemiological study. The variables analysed were year of infection, age, sex, diagnostic category, days admitted and co-morbidity. Results There have been a total of 351,996 hospitalizations; 225,138 men (64%) and 126,858 women (36%). They are divided between acute hepatitis 8161 (2.3%); chronic hepatitis 325,185 (92.4%) and unspecified hepatitis 18,650 (5.3%). The mean age for men is 53.7 (+/−15.2) and for women 62.3 (+/−17.3). 22.8% also present with an Human immunodeficiency virus (HIV) disease coinfection, and 14.7% with opioid dependencies. The trend is for a gradual increase in cases without statistical significance. Conclusions The Hepatitis C cases hospitalized had high levels of chronicity, which entails two distinct patterns of illness in men and women – who are affected in different age ranges.
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Affiliation(s)
- R Boix
- National Centre of Epidemiology, Institute of Health Carlos III, C/Monforte de Lemos, 5, 28029, Madrid, Spain.
| | - R Cano
- National Centre of Epidemiology, Institute of Health Carlos III, C/Monforte de Lemos, 5, 28029, Madrid, Spain.,CIBER Epidemiología y Salud Pública (CIBERESP), C/ Monforte de Lemos, 3-5, 28029, Madrid, Spain
| | - P Gallego
- National Centre of Epidemiology, Institute of Health Carlos III, C/Monforte de Lemos, 5, 28029, Madrid, Spain
| | - F Vallejo
- National Centre of Epidemiology, Institute of Health Carlos III, C/Monforte de Lemos, 5, 28029, Madrid, Spain.,CIBER Epidemiología y Salud Pública (CIBERESP), C/ Monforte de Lemos, 3-5, 28029, Madrid, Spain
| | - R Fernández-Cuenca
- National Centre of Epidemiology, Institute of Health Carlos III, C/Monforte de Lemos, 5, 28029, Madrid, Spain.,CIBER Epidemiología y Salud Pública (CIBERESP), C/ Monforte de Lemos, 3-5, 28029, Madrid, Spain
| | - I Noguer
- National Centre of Epidemiology, Institute of Health Carlos III, C/Monforte de Lemos, 5, 28029, Madrid, Spain
| | - A Larrauri
- National Centre of Epidemiology, Institute of Health Carlos III, C/Monforte de Lemos, 5, 28029, Madrid, Spain.,CIBER Epidemiología y Salud Pública (CIBERESP), C/ Monforte de Lemos, 3-5, 28029, Madrid, Spain
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11
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Chang MS, Nguyen MH. Epidemiology of hepatitis B and the role of vaccination. Best Pract Res Clin Gastroenterol 2017; 31:239-247. [PMID: 28774405 DOI: 10.1016/j.bpg.2017.05.008] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 05/16/2017] [Accepted: 05/31/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) is a major cause of morbidity and mortality with a disproportionate impact on Asia and Africa. Current guidelines recommend screening at-risk populations for chronic HBV infection so that diagnosed individuals can be linked to appropriate hepatitis care. The vast majority of infected individuals are undiagnosed and untreated, and are at risk of developing cirrhosis, liver failure, and hepatocellular carcinoma. In individuals who are not yet infected, the HBV vaccine is safe and highly effective at preventing disease transmission. Countries with successful vaccination programs have been able to dramatically reduce their HBV prevalence. A concerted effort to screen, treat, and vaccinate at-risk individuals has the potential to eliminate HBV as a public health threat by 2030.
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Affiliation(s)
- Matthew S Chang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, 300 Pasteur Drive, Palo Alto, CA 94304, USA.
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, 300 Pasteur Drive, Palo Alto, CA 94304, USA.
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12
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Buti M, Calleja JL, García-Samaniego J, Serra MÁ, Crespo J, Romero M, Simón MÁ, Turnes J, Blasco AJ, Lázaro P, Robbins S, Razavi H. Elimination of hepatitis C in Spain: Adaptation of a mathematical model based on the public health strategic plan for addressing hepatitis C in the National Health System. ACTA ACUST UNITED AC 2017. [DOI: 10.1016/j.medcle.2017.03.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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13
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Elimination of hepatitis C in Spain: Adaptation of a mathematical model based on the public health strategic plan for addressing hepatitis C in the National Health System. Med Clin (Barc) 2017; 148:277-282. [PMID: 28159349 DOI: 10.1016/j.medcli.2016.12.018] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 12/22/2016] [Accepted: 12/27/2016] [Indexed: 11/22/2022]
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14
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Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22:8720-8734. [PMID: 27818588 PMCID: PMC5075547 DOI: 10.3748/wjg.v22.i39.8720] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/13/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.
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15
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Ferrarese A, Zanetto A, Gambato M, Bortoluzzi I, Nadal E, Germani G, Senzolo M, Burra P, Russo FP. Liver transplantation for viral hepatitis in 2015. World J Gastroenterol 2016; 22:1570-1581. [PMID: 26819523 PMCID: PMC4721989 DOI: 10.3748/wjg.v22.i4.1570] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 09/20/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
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16
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Montuclard C, Hamza S, Rollot F, Evrard P, Faivre J, Hillon P, Di Martino V, Minello A. Causes of death in people with chronic HBV infection: A population-based cohort study. J Hepatol 2015; 62:1265-1271. [PMID: 25625233 DOI: 10.1016/j.jhep.2015.01.020] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 01/05/2015] [Accepted: 01/15/2015] [Indexed: 01/30/2023]
Abstract
BACKGROUND & AIMS Mortality related to hepatitis B virus (HBV) is not well known in developed countries. The aim of this study was to investigate in a population-based cohort the excess risk of death in HBV patients compared with mortality in the general population and to identify risk factors related to all-cause mortality and HBV-related mortality. METHODS A specialized population-based registry has recorded data from patients with chronic HBV infection in a population of one million inhabitants in France since 1994. Standardized mortality rates for all-cause death and HBV-related death were calculated. Cumulative mortality rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed using a Cox model. RESULTS Between 1994 and 2009, 1117 people were diagnosed with chronic HBV infection. Of these 136 (12.2%) died. All-cause mortality was significantly higher in HBV-infected people (standardized mortality ratio (SMR) 1.7 [1.4-2.0]). There was substantial excess mortality due to hepatocellular carcinoma (SMR 15.9 [10-24.1]), non-Hodgkin lymphoma (SMR 8.6 [3.1-18.6]) and liver disease (SMR 10.2 [5.8-16.6]). The cumulative rates for all-cause mortality were 8.6% at 5 years, 12.6% at 10 years and 18.5% at 15 years. The corresponding values for HBV-related mortality were 3.5%, 4.2%, and 5.8%. The multivariate analysis for all-cause mortality and for HBV-related mortality showed that male sex, age over 45 at diagnosis, current alcoholism and nosocomial risk factors were predictors of increased mortality. CONCLUSION This study shows increased all-cause mortality in HBsAg-positive patients, with considerable excess mortality due to chronic liver disease, hepatocellular carcinoma and non-Hodgkin lymphoma.
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Affiliation(s)
- Celine Montuclard
- Department of Hepatogastroenterology, Dijon University Hospital, BP 87900, 21079 Dijon, France.
| | - Samia Hamza
- Burgundy University, France; Department of Hepatogastroenterology, Dijon University Hospital, BP 87900, 21079 Dijon, France
| | - Fabien Rollot
- Viral Hepatitis Registry, INSERM U866, France; Burgundy University, France
| | | | - Jean Faivre
- Burgundy University, France; Department of Hepatogastroenterology, Dijon University Hospital, BP 87900, 21079 Dijon, France
| | - Patrick Hillon
- Viral Hepatitis Registry, INSERM U866, France; Burgundy University, France; Department of Hepatogastroenterology, Dijon University Hospital, BP 87900, 21079 Dijon, France
| | - Vincent Di Martino
- Intensive Care and Hepatology Unit, University Hospital of Besançon, 25000, France
| | - Anne Minello
- Viral Hepatitis Registry, INSERM U866, France; Burgundy University, France; Department of Hepatogastroenterology, Dijon University Hospital, BP 87900, 21079 Dijon, France
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17
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Oliva-Moreno J, Peña-Longobardo LM, Alonso S, Fernández-Bolaños A, Gutiérrez ML, Hidalgo-Vega Á, de la Fuente E, Fernández-Rodríguez CM. Labour productivity losses caused by premature death associated with hepatitis C in Spain. Eur J Gastroenterol Hepatol 2015; 27:631-637. [PMID: 25853930 PMCID: PMC4415959 DOI: 10.1097/meg.0000000000000336] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Accepted: 02/10/2015] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV) infection places a huge burden on healthcare systems. There is no study assessing the impact of HCV infection on premature deaths in Spain. The aim of this study was to estimate productivity losses because of premature deaths attributable to hepatitis C occurring in Spain during 2007-2011. MATERIALS AND METHODS We use data from several sources (Registry of Deaths, Labour Force Survey and Wage Structure Survey) to develop a simulation model based on the human capital approach and to estimate the flows in labour productivity losses in the period considered. The attributable fraction method was used to estimate the numbers of deaths associated with HCV infection. Two sensitivity analyses were developed to test the robustness of the results. RESULTS Our model shows total productivity losses attributable to HCV infection of 1054.7 million euros over the period analysed. The trend in productivity losses is decreasing over the period. This result is because of improvements in health outcomes, reflected in the reduction of the number of years of potential productive life lost. Of the total estimated losses, 18.6% were because of hepatitis C, 24.6% because of hepatocellular carcinoma, 30.1% because of cirrhosis, 15.9% because of other liver diseases and 10.7% because of HIV-HCV coinfection. CONCLUSION The results show that premature mortality attributable to hepatitis C involves significant productivity losses. This highlights the need to extend the analysis to consider other social costs and obtain a more complete picture of the actual economic impact of hepatitis C infection.
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Affiliation(s)
- Juan Oliva-Moreno
- University of Castille-La Mancha, Seminar of Research on Economy and Health
| | | | - Sonia Alonso
- Service of Gastroenterology, Fundacion Alcorcon University Hospital, University Rey Juan Carlos, Madrid, Spain
| | | | - María Luisa Gutiérrez
- Service of Gastroenterology, Fundacion Alcorcon University Hospital, University Rey Juan Carlos, Madrid, Spain
| | | | - Elsa de la Fuente
- Service of Gastroenterology, Fundacion Alcorcon University Hospital, University Rey Juan Carlos, Madrid, Spain
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18
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García Comas L, Ordobás Gavín M, Sanz Moreno JC, Ramos Blázquez B, Gutiérrez Rodríguez A, Astray Mochales J, Moreno Guillén S. Prevalence of hepatitis C antibodies in the population aged 16-80 years in the Community of Madrid 2008-2009. J Med Virol 2015; 87:1697-701. [PMID: 25989026 DOI: 10.1002/jmv.24219] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/23/2015] [Indexed: 12/18/2022]
Abstract
Together with AIDS, the burden of hepatitis C virus (HCV) in Spain heads the list of communicable diseases in terms of impact on public health. The aim of this study was to estimate the prevalence of HCV antibodies in the Community of Madrid, assess changes in recent years and analyse associated risk factors. Descriptive cross-sectional study of a target population consisting of Community of Madrid residents aged 16-80 years old. Two-stage cluster sampling was performed, with stratification by socioeconomic status and percentage immigrant population. The sampling frame consisted of public blood extraction centers attached to the Madrid Health Service. Seroprevalence of HCV antibodies, prevalence ratios by age groups in comparison with 1999 survey data and prevalence association with risk factors were assessed using a logistic regression model. Prevalence of HCV antibodies for the age group 16-80 years was 1.8% (95% CI: 1.3-2.5). The age group with the highest prevalence was 41-60 years. In comparison with the 1999 survey, prevalence fell for the age groups 21-30 and 31-40 years and increased for the age group 41-60. Statistically significant associations were found for age, education, history of hepatitis C and consultation regarding liver problems. Seroprevalence of HCV antibodies in the Community of Madrid is similar to that shown in other regions of Spain. It is increasing in older age groups as the population at risk ages. Incidence of hepatitis C may be decreasing considering the decrease in the seroprevalence in the population younger than 40 related to the previous serosurvey.
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Affiliation(s)
- Luis García Comas
- Subdirectorate of Health Promotion and Prevention, Health Department of the Community of Madrid (institution at which the work was performed), Madrid, Spain
| | - María Ordobás Gavín
- Subdirectorate of Health Promotion and Prevention, Health Department of the Community of Madrid (institution at which the work was performed), Madrid, Spain
| | - Juan Carlos Sanz Moreno
- Health Department of the Community of Madrid, Regional Public Health Laboratory, Madrid, Spain
| | - Belén Ramos Blázquez
- Health Department of the Community of Madrid, Regional Public Health Laboratory, Madrid, Spain
| | - Angeles Gutiérrez Rodríguez
- Subdirectorate of Health Promotion and Prevention, Health Department of the Community of Madrid (institution at which the work was performed), Madrid, Spain
| | - Jenaro Astray Mochales
- Subdirectorate of Health Promotion and Prevention, Health Department of the Community of Madrid (institution at which the work was performed), Madrid, Spain
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19
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Niederau C. Chronic hepatitis B in 2014: great therapeutic progress, large diagnostic deficit. World J Gastroenterol 2014; 20:11595-617. [PMID: 25206267 PMCID: PMC4155353 DOI: 10.3748/wjg.v20.i33.11595] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Revised: 01/03/2014] [Accepted: 04/27/2014] [Indexed: 02/06/2023] Open
Abstract
This review analyzes progress and limitations of diagnosis, screening, and therapy of patients with chronic hepatitis B infection. A literature review was carried out by framing the study questions. Vaccination in early childhood has been introduced in most countries and reduces the infection rate. Treatment of chronic hepatitis B can control viral replication in most patients today. It reduces risks for progression and may reverse liver fibrosis. The treatment effect on development of hepatocellular carcinoma is less pronounced when cirrhosis is already present. Despite the success of vaccination and therapy chronic hepatitis B remains a problem since many infected patients do not know of their disease. Although all guidelines recommend screening in high risk groups such as migrants, these suggestions have not been implemented. In addition, the performance of hepatocellular cancer surveillance under real-life conditions is poor. The majority of people with chronic hepatitis B live in resource-constrained settings where effective drugs are not available. Despite the success of vaccination and therapy chronic hepatitis B infection remains a major problem since many patients do not know of their disease. The problems in diagnosis and screening may be overcome by raising awareness, promoting partnerships, and mobilizing resources.
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20
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Bruggmann P, Berg T, Øvrehus ALH, Moreno C, Brandão Mello CE, Roudot-Thoraval F, Marinho RT, Sherman M, Ryder SD, Sperl J, Akarca U, Balık I, Bihl F, Bilodeau M, Blasco AJ, Buti M, Calinas F, Calleja JL, Cheinquer H, Christensen PB, Clausen M, Coelho HSM, Cornberg M, Cramp ME, Dore GJ, Doss W, Duberg AS, El-Sayed MH, Ergör G, Esmat G, Estes C, Falconer K, Félix J, Ferraz MLG, Ferreira PR, Frankova S, García-Samaniego J, Gerstoft J, Giria JA, Gonçales FL, Gower E, Gschwantler M, Guimarães Pessôa M, Hézode C, Hofer H, Husa P, Idilman R, Kåberg M, Kaita KDE, Kautz A, Kaymakoglu S, Krajden M, Krarup H, Laleman W, Lavanchy D, Lázaro P, Marotta P, Mauss S, Mendes Correa MC, Müllhaupt B, Myers RP, Negro F, Nemecek V, Örmeci N, Parkes J, Peltekian KM, Ramji A, Razavi H, Reis N, Roberts SK, Rosenberg WM, Sarmento-Castro R, Sarrazin C, Semela D, Shiha GE, Sievert W, Stärkel P, Stauber RE, Thompson AJ, Urbanek P, van Thiel I, Van Vlierberghe H, Vandijck D, Vogel W, Waked I, Wedemeyer H, Weis N, Wiegand J, Yosry A, Zekry A, Van Damme P, Aleman S, Hindman SJ. Historical epidemiology of hepatitis C virus (HCV) in selected countries. J Viral Hepat 2014; 21 Suppl 1:5-33. [PMID: 24713004 DOI: 10.1111/jvh.12247] [Citation(s) in RCA: 182] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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Affiliation(s)
- P Bruggmann
- Arud Centres for Addiction Medicine, Zurich, Switzerland
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Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol 2013; 58:593-608. [PMID: 23419824 DOI: 10.1016/j.jhep.2012.12.005] [Citation(s) in RCA: 903] [Impact Index Per Article: 75.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Accepted: 12/05/2012] [Indexed: 12/14/2022]
Abstract
To survey the burden of liver disease in Europe and its causes 260 epidemiological studies published in the last five years were reviewed. The incidence and prevalence of cirrhosis and primary liver cancer are key to understand the burden of liver disease. They represent the end-stage of liver pathology and thus are indicative of the associated mortality. About 0.1% of Hungarian males will die of cirrhosis every year compared with 0.001% of Greek females. WHO estimate that liver cancer is responsible for around 47,000 deaths per year in the EU. Harmful alcohol consumption, viral hepatitis B and C and metabolic syndromes related to overweight and obesity are the leading causes of cirrhosis and primary liver cancer in Europe. Chronic hepatitis B affects 0.5-0.7% of the European population. In the last decade the prevalence of chronic hepatitis C was 0.13-3.26%. It is of great concern that about 90% of people in Europe infected by viral hepatitis are unaware of their status. Available data suggest the prevalence rate of NAFLD is 2-44% in the general European population (including obese children) and 42.6-69.5% in people with type 2 diabetes. Each of these four major causes of liver disease is amenable to prevention and treatment, reducing the burden of liver disease in Europe and saving lives. Further surveys are urgently needed to implement cost-effective prevention programmes and novel treatments to tackle this problem.
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Affiliation(s)
- Martin Blachier
- Department of Public Health, Hôpital Henri Mondor, Université Paris-Est Créteil, France
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22
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Vietri J, Prajapati G, El Khoury AC. The burden of hepatitis C in Europe from the patients' perspective: a survey in 5 countries. BMC Gastroenterol 2013; 13:16. [PMID: 23324473 PMCID: PMC3551635 DOI: 10.1186/1471-230x-13-16] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Accepted: 01/09/2013] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Few studies have examined the impact of Hepatitis C virus (HCV) infection on patient reported outcomes in Europe. This study was conducted to assess the burden of HCV infection in terms of work productivity loss, activity impairment, health-related quality of life, healthcare resource utilization, and associated costs. METHODS The 2010 European National Health and Wellness Survey (n = 57,805) provided data. Patients reporting HCV infection in France, Germany, the UK, Italy, and Spain were matched to respondents without HCV using propensity scores. Outcome measures included the Work Productivity and Activity Impairment (WPAI) questionnaire and the Medical Outcomes Study Short Form-12 (SF-12v2) questionnaire. Subgroup analyses focused on treatment-naïve patients. RESULTS HCV Patients (n = 286) had more work impairment (30% vs. 18%, p < .001), more impairment in non-work activities (34% vs. 28%, p < .05), and more annual physician visits per patient (19.8 vs. 13.3, p < .001). Estimated indirect and direct costs were €2,956 (p < .01) and €495 (p < .001) higher than in matched controls, respectively. Health-related quality of life was also lower among HCV patients. Treatment-naïve HCV patients (n = 139) also reported higher work impairment (29% vs. 15%, p < .01), as well as more frequent physician visits (19.5 vs. 12.1, p < .01) than matched controls. Each treatment-naïve HCV infected patient incurred €934 in direct costs vs. €508 (p < .01 in matched controls. Employed treatment-naïve patients reported higher productivity loss per year compared to matched controls (€6,414 vs. €3,642, p < .05). CONCLUSION HCV infection in Europe is associated with considerable economic and humanistic burden. This is also true of diagnosed patients who have never been treated for HCV.
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Affiliation(s)
- Jeffrey Vietri
- Health Outcomes Practice, Kantar Health, Princeton, NJ, USA.
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Tauil MDC, Amorim TRD, Pereira GFM, Araújo WND. [Hepatitis B mortality in Brazil, 2000-2009]. CAD SAUDE PUBLICA 2012; 28:472-8. [PMID: 22415179 DOI: 10.1590/s0102-311x2012000300007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Accepted: 11/21/2011] [Indexed: 11/21/2022] Open
Abstract
This descriptive study focused on the mortality profile associated with hepatitis B virus (HBV) in Brazil as a whole and by region, based on data from the Mortality Information System (MIS). The study sample consisted of deaths from HBV recorded in the MIS from January 1, 2000, to December 31, 2009. The crude mortality rate remained constant in the country; the proportion of hepatocellular carcinoma with HBV as the associated cause was no greater than 7%. The standardized mortality rate was highest in the North of Brazil, and the proportional mortality rate was higher in males. In 2009, the potential years of life lost (PYLL) were highest in males in the 50-59-year age bracket and in females in the 40-49-year bracket. The largest increase in PYLL occurred in males 60 to 69 years of age. The study emphasizes the importance of scaling up preventive measures against HBV, in addition to expanding access to early diagnosis in order to reduce HBV mortality in the coming decades.
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Affiliation(s)
- Márcia de Cantuária Tauil
- Programa de Treinamento em Epidemiologia Aplicada aos Serviços do SUS, Ministério da Saúde, Brasília, Brazil.
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Differences in the causes of death of HIV-positive patients in a cohort study by data sources and coding algorithms. AIDS 2012; 26:1829-34. [PMID: 22410685 DOI: 10.1097/qad.0b013e328352ada4] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To compare causes of death (CoDs) from two independent sources: National Basic Death File (NBDF) and deaths reported to the Spanish HIV Research cohort [Cohort de adultos con infección por VIH de la Red de Investigación en SIDA CoRIS)] and compare the two coding algorithms: International Classification of Diseases, 10th revision (ICD-10) and revised version of Coding Causes of Death in HIV (revised CoDe). METHODS Between 2004 and 2008, CoDs were obtained from the cohort records (free text, multiple causes) and also from NBDF (ICD-10). CoDs from CoRIS were coded according to ICD-10 and revised CoDe by a panel. Deaths were compared by 13 disease groups: HIV/AIDS, liver diseases, malignancies, infections, cardiovascular, blood disorders, pulmonary, central nervous system, drug use, external, suicide, other causes and ill defined. RESULTS There were 160 deaths. Concordance for the 13 groups was observed in 111 (69%) cases for the two sources and in 115 (72%) cases for the two coding algorithms. According to revised CoDe, the commonest CoDs were HIV/AIDS (53%), non-AIDS malignancies (11%) and liver related (9%), these percentages were similar, 57, 10 and 8%, respectively, for NBDF (coded as ICD-10). When using ICD-10 to code deaths in CoRIS, wherein HIV infection was known in everyone, the proportion of non-AIDS malignancies was 13%, liver-related accounted for 3%, while HIV/AIDS reached 70% due to liver-related, infections and ill-defined causes being coded as HIV/AIDS. CONCLUSION There is substantial variation in CoDs in HIV-infected persons according to sources and algorithms. ICD-10 in patients known to be HIV-positive overestimates HIV/AIDS-related deaths at the expense of underestimating liver-related diseases, infections and ill defined causes. CoDe seems as the best option for cohort studies.
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Abstract
OBJECTIVE Hepatitis C virus (HCV) affects 170 million patients worldwide and is the leading cause of liver cirrhosis and hepatocellular carcinoma. The aim of the current study is to examine the burden of HCV in the European Union (EU) from a patient perspective. METHODS Using data from the 2010 EU National Health and Wellness Survey, patients who reported a diagnosis of HCV (n=332) were compared with a propensity-score-matched non-HCV control group (n=332) on measures of quality of life (using the SF-12v2), work productivity, and healthcare resource utilization in the past 6 months. All analyses applied sampling weights to project to the respective country populations. RESULTS Projected prevalence estimates of HCV were 0.59% in France, 0.44% in Germany, 1.42% in Italy, 0.82% in Spain, and 0.35% in the UK. HCV patients reported significantly lower levels of emotional role limitations (means=66.4 vs. 70.6, P=0.040), physical functioning (means=63.8 vs. 71.9, P=0.001), general health (means=48.3 vs. 54.4, P=0.004), bodily pain (means=64.3 vs. 70.8, P=0.002), and physical component summary scores (means=42.9 vs. 45.3, P=0.002) than the matched controls. Patients with HCV also reported significantly higher levels of presenteeism (means=27.1 vs. 21.0%, P=0.044) and a greater number of physician visits in the past 6 months (means=9.9 vs. 6.7, P<0.001). CONCLUSION Using a population-based survey methodology and a propensity-score matching analysis, these results add to the literature by documenting the significant effect that HCV has on a variety of both humanistic and economic outcomes in the EU.
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García-Fulgueiras A, García-Pina R, Morant C, de Larrea-Baz NF, Alvarez E. Burden of disease related to hepatitis C and hepatitis B in Spain: a methodological challenge of an unfolding health problem. J Viral Hepat 2011; 18:e453-60. [PMID: 21914063 DOI: 10.1111/j.1365-2893.2011.01467.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Most previous studies of burden of disease (BoD) in the area of transmissible diseases have assessed the burden of hepatitis C and B without including the end stages of the disease and using an incident approach. We aimed to assess the disability-adjusted life years (DALYs) related to hepatitis C and B in Spain in 2006 taking into account related cirrhosis and liver cancer. A prevalence approach was used to estimate current years lived with disability (YLD) because of viral hepatitis contracted years/decades before. We added years of life lost (YLL) to obtain DALYs. Around 76,000 DALYs were attributed to hepatitis C virus (HCV) and 15,323 to hepatitis B virus (HBV) when calculated without applying social values. Applying the discount rate and age-weighting used in the Global Burden Disease study, the BoD nearly halved. In any case, the burden related to hepatitis C including long-term outputs becomes the leading cause of DALYs among transmissible diseases in Spain. The mortality component (YLL) represents more than 90% of the BoD in both HCV and HBV. The findings emphasize the need to provide good surveillance systems not only concerning acute viral hepatitis, but also chronic and end-stage consequences to allow a reliable assessment of the prevention and public health control policies.
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Trends of acute hepatitis B hospitalizations, comorbidities, fatality rate, and costs associated with the hospitalization in Spain (2001-2006). Eur J Gastroenterol Hepatol 2010; 22:961-6. [PMID: 20168236 DOI: 10.1097/meg.0b013e32833783b4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
INTRODUCTION The objective of this study is to analyze data related to hospitalization, comorbidities, fatality rate, average stays, and costs associated with hospitalized cases of acute hepatitis B in Spain, during 2001-2006. METHODS A retrospective study to analyze the characteristics of acute hepatitis B patients admitted to Spanish hospitals was performed using the minimum basic data set. Costs were calculated using the diagnosis-related groups for the disease. RESULTS The total number of hospitalized patients diagnosed with acute hepatitis B was 2160, of which 73.8% were diagnosed in men. The highest rate corresponds to the group aged 20-39 years (2.33/100 000 inhabitants). Ninety deaths (4.2%) were reported out of the total hospitalized patients. The average hospital stay was 10 days. The trends in the rate of hospitalized acute hepatitis B cases were not statistically significant. There were no differences found in the average length of stay or in the cost during the study period. The estimated total cost was 7 451 098 euros. CONCLUSION The rate of hospitalized acute hepatitis B patients in Spain did not change during the 2001-2006 period. Having an adequate surveillance system and continuing with the universal immunization and risk group programs, and health education, remain a high priority.
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