|
1
|
Tang X, Gan P, Huang S, Pan X, Wang R, Wang P, Xia H, Zeng X, Ren W, Shi L, Zhou X, Linghu E. The scientific progress and prospects of hepatitis C research from 2013 to 2022. Am J Transl Res 2022; 14:7806-7819. [PMID: 36505327 PMCID: PMC9730086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 10/27/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND OBJECTIVE Hepatitis C (HC) is a global health issue, with an estimated 350,000 people dying annually from this liver-related disease. This study determined the development trends and research hotspots regarding HC by investigating the related articles within the past ten years. METHODS Publications on HC were retrieved from the Web of Science Core Collection (WoSCC) on June 6, 2022. Bibliometric visualization was conducted through VOSviewer and CiteSpace. Original articles and reviews served as the foundation for this analytical research. RESULTS Of the total 17,773 records of HC research published from 2013 to 2022, the top 1,000 articles were retrieved and distributed among 78 countries and 270 journals. The US, where 7 of the top 10 institutions were located, mainly contributed to the study (51.9%). Johns Hopkins University distributed the most related articles (45 articles). Hepatology (IF 2021 = 17.298) ranked first, with 109 articles in the top 10 journals. Dore GJ was the most productive author (40 articles). The keywords of sustained virologic response, therapy, sofosbuvir, cirrhosis, ledipasvir, and hepatocellular carcinoma offered hints regarding research hotspots. The burst keywords regarding the virus, like HCV, HIV, and care and intervention showed as research frontiers. CONCLUSIONS Treatment has been a trending topic in HC research, and future research may focus more on HCV and HIV co-infection, treatment, and elimination of HC.
Collapse
Affiliation(s)
- Xiaowei Tang
- Department of Gastroenterology, The First Medical Center of Chinese PLA General HospitalBeijing, China,Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Peiling Gan
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Shu Huang
- Department of Gastroenterology, The People’s Hospital of LianshuiHuaian, Jiangsu, China
| | - Xiao Pan
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Ruiyu Wang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Ping Wang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Huifang Xia
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Xinyi Zeng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Wensen Ren
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Lei Shi
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Xian Zhou
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical UniversityLuzhou, Sichuan, China,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan ProvinceLuzhou, Sichuan, China
| | - Enqiang Linghu
- Department of Gastroenterology, The First Medical Center of Chinese PLA General HospitalBeijing, China
| |
Collapse
|
|
2
|
Peng X, Tian A, Li J, Mao Y, Jiang N, Li T, Mao X. Diagnostic Value of FibroTouch and Non-invasive Fibrosis Indexes in Hepatic Fibrosis with Different Aetiologies. Dig Dis Sci 2022; 67:2627-2636. [PMID: 34059990 DOI: 10.1007/s10620-021-07049-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 05/09/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Liver biopsy is the gold standard for staging liver fibrosis, but it has numerous drawbacks, mainly associated with bleeding and bile fistula risks. A number of non-invasive techniques have been investigated, but they all have their own disadvantages. To avoid the risks mentioned above and to improve the diagnostic value, we still need to search for a more accurate non-invasive method to evaluate the degree of liver fibrosis. AIM This study aimed to evaluate the diagnostic performance of FibroTouch versus other non-invasive fibrosis indexes in hepatic fibrosis of different aetiologies. METHODS This study retrospectively enrolled 227 patients with chronic hepatic liver disease admitted to the first hospital of Lanzhou University from 2017 to 2020. Liver biopsy was performed in all of the patients, and their biochemical indicators were all tested. Non-invasive indexes including the fibrosis index based on four factors (FIB-4), the aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio index (GPRI) were all calculated. Transient elastography was performed using FibroTouch. RESULTS The correlation between FibroTouch and the pathology of liver fibrosis was significantly higher than that between the non-invasive fibrosis indexes and the biopsy results (r = 0.771, p < 0.05). The area under the receiver operating curve (AUC) of FibroTouch was significantly higher than that of FIB-4, APRI, and GPRI for the diagnosis of significant fibrosis (≥ S2 fibrosis stage), advanced fibrosis (≥ S3 fibrosis stage), and cirrhosis (= S4 fibrosis stage) (p < 0.05). The patients were grouped according to different aetiologies. The diagnostic value of FibroTouch had much higher credibility in different fibrosis stages for different causes compared with other non-invasive indexes. The AUC of FibroTouch showed both higher specificity and higher sensitivity than FIB-4, APRI, and GPRI for different liver fibrosis stages with different aetiologies. CONCLUSIONS FibroTouch demonstrates the highest diagnostic value for liver fibrosis and cirrhosis among non-invasive methods, showing better results than FIB-4, APRI, and GPRI, and surpassed only by liver biopsy. FibroTouch is reliable in assessing liver fibrosis with different aetiologies.
Collapse
Affiliation(s)
- Xuebin Peng
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Aiping Tian
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Junfeng Li
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Yongwu Mao
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Ni Jiang
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Ting Li
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Xiaorong Mao
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.
| |
Collapse
|
|
3
|
Carrier P, Debette-Gratien M, Jacques J, Loustaud-Ratti V. Cirrhotic patients and older people. World J Hepatol 2019; 11:663-677. [PMID: 31598192 PMCID: PMC6783402 DOI: 10.4254/wjh.v11.i9.663] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/18/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
The global population is aging, and so the number of older cirrhotic patients is increasing. Older patients are characterised by a risk of frailty and comorbidities, and age is a risk factor for mortality in cirrhotic patients. The incidence of non-alcoholic fatty liver disease as an aetiology of cirrhosis is increasing, while that of chronic viral hepatitis is decreasing. Also, cirrhosis is frequently idiopathic. The management of portal hypertension in older cirrhotic patients is similar to that in younger patients, despite the greater risk of treatment-related adverse events of the former. The prevalence of hepatocellular carcinoma increases with age, but its treatment is unaffected. Liver transplantation is generally recommended for patients < 70 years of age. Despite the increasing prevalence of cirrhosis in older people, little data are available and few recommendations have been proposed. This review suggests that comorbidities have a considerable impact on older cirrhotic patients.
Collapse
Affiliation(s)
- Paul Carrier
- Fédération d’Hépatologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
- Faculté de Médecine et de Pharmacie de Limoges, Rue Docteur Marcland, Limoges 87042, France
| | - Marilyne Debette-Gratien
- Fédération d’Hépatologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
- Faculté de Médecine et de Pharmacie de Limoges, Rue Docteur Marcland, Limoges 87042, France
| | - Jérémie Jacques
- Service de Gastroentérologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
| | - Véronique Loustaud-Ratti
- Fédération d’Hépatologie, Centre Hospitalier Universitaire Dupuytren de Limoges, Limoges 87042, France
- Faculté de Médecine et de Pharmacie de Limoges, Rue Docteur Marcland, Limoges 87042, France.
| |
Collapse
|
|
4
|
Younossi ZM, Chan HLY, Dan YY, Lee MH, Lim YS, Kruger E, Tan SC. Impact of ledipasvir/sofosbuvir on the work productivity of genotype 1 chronic hepatitis C patients in Asia. J Viral Hepat 2018; 25:228-235. [PMID: 29053909 DOI: 10.1111/jvh.12808] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 08/30/2017] [Indexed: 12/16/2022]
Abstract
Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor clinical prognosis and a detrimental impact on patients' lives, including on work productivity. To estimate the value of productivity losses due to genotype 1 (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to estimate the potential productivity gains associated with treating patients with ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a time horizon of 1 year. Hepatitis C virus patients entered the model at 12 weeks post-treatment, having achieved or not achieved sustained virological response (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of data from the ION 1-3 studies. These rates were converted into hours of lost productivity, multiplied by the average wage and applied to the total employed, adult GT1 population in each country. Results were compared assuming no treatment, and assuming all patients were treated with LDV/SOF. Total productivity losses due to untreated HCV were: $11.3 million, $17.1 m, $146.0 m and $349.1 m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment resulted in economic gains of $4.5 m, $6.8 m, $58.7 m and $138 m, respectively. These gains were due to reduced presenteeism. The results were sensitive to changes in the prevalence of HCV and the average wage. In conclusion, productivity losses due to untreated HCV infection represent a substantial economic burden. By instituting universal HCV treatment with LDV/SOF (or other therapies with high SVR rates), productivity gains can be achieved.
Collapse
Affiliation(s)
- Z M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.,Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Y Y Dan
- University Medicine Cluster, National University Hospital, Singapore City, Singapore
| | - M H Lee
- National Yang-Ming University, Taipei, Taiwan
| | - Y-S Lim
- Department of Gastroenterology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, South Korea
| | - E Kruger
- IMS Health, Singapore City, Singapore
| | - S C Tan
- IMS Health, Singapore City, Singapore
| |
Collapse
|
|
5
|
Adar T, Ilan Y, Elstein D, Zimran A. Liver involvement in Gaucher disease – Review and clinical approach. Blood Cells Mol Dis 2018; 68:66-73. [DOI: 10.1016/j.bcmd.2016.10.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 10/17/2016] [Indexed: 02/07/2023]
|
|
6
|
Snyder B, Goebel S, Koide F, Ptak R, Kalkeri R. Synergistic antiviral activity of Sofosbuvir and type-I interferons (α and β) against Zika virus. J Med Virol 2017; 90:8-12. [PMID: 28851097 DOI: 10.1002/jmv.24932] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 08/07/2017] [Indexed: 01/09/2023]
Abstract
Zika virus (ZIKV) is transmitted by mosquitoes and causes Dengue-like illness, neurological symptoms such as Guillain-Barré Syndrome and microcephaly in children born to infected pregnant mothers. Recently, the World Health Organization (WHO) declared ZIKV infection as a Global Health Emergency. However, there are no known prophylactic or therapeutic measures against this virus. As a proof of concept toward combination therapeutic strategy against ZIKV, combinations of host-targeted (Interferon-α and Interferon-β) and direct acting (Sofosbuvir) antivirals were evaluated in a hepatic cell line (Huh7) using a Cytoprotection (CP) assay. The combination of these antivirals resulted in synergistic inhibition of ZIKV infection in the in vitro CP assay. Additional testing in a ZIKV yield assay demonstrated that combination treatment of these antivirals conferred >2-log reduction in the release of viral RNA. Measurement of ZIKV proteins in the cells infected with multiple ZIKV strains isolated from different geographical regions (Americas, Asia, and Africa) using an immunofluorescence assay confirmed the effective antiviral activity of this combination against ZIKV. These results demonstrate the in vitro proof of concept (POC) for using a combination approach utilizing the strengths of both virus and host-targeted antivirals. These results suggest the effectiveness of the combination strategy in combating ZIKV, in the in vitro systems. Further evaluation of such combination therapies in vivo might provide an impetus for the development of effective ZIKV therapeutic strategies.
Collapse
Affiliation(s)
- Beth Snyder
- Department of Infectious Diseases Research, Drug Development, Southern Research, Frederick, Maryland
| | - Scott Goebel
- Department of Infectious Diseases Research, Drug Development, Southern Research, Frederick, Maryland
| | - Fusataka Koide
- Department of Infectious Diseases Research, Drug Development, Southern Research, Frederick, Maryland
| | - Roger Ptak
- Department of Infectious Diseases Research, Drug Development, Southern Research, Frederick, Maryland
| | - Raj Kalkeri
- Department of Infectious Diseases Research, Drug Development, Southern Research, Frederick, Maryland
| |
Collapse
|
|
7
|
Abstract
It is critical to recognize that hepatitis C virus (HCV) infection is, in fact, a multifaceted systemic disease with both hepatic and extrahepatic complications. It is also important to recognize that the comprehensive burden of HCV should include not only its clinical burden but also its burden on the economic and patient-reported outcomes. It is only through this comprehensive approach to HCV infection that we can fully appreciate its true burden and understand the full benefit of curing HCV for the patient and the society.
Collapse
Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA; Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
| |
Collapse
|
|
8
|
Abstract
The economic burden of chronic hepatitis C might exceed $10 billion annually in the United States alone. This disease has a worldwide prevalence of up to 3%, making the global burden of the disease comparably tremendous. The cost of the disease includes direct medical expenses for its hepatic and extrahepatic manifestations, and also indirect costs incurred from impaired quality of life and the loss of work productivity. Recent emergence of treatment options that are not only highly effective and safe but also costly has emphasized the need to study the disease from the economic point of view.
Collapse
Affiliation(s)
- Maria Stepanova
- Center for Outcomes Research in Liver Diseases, 2411 I Street NW, Washington, DC 20037, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA
| | - Zobair M Younossi
- Center for Outcomes Research in Liver Diseases, 2411 I Street NW, Washington, DC 20037, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
| |
Collapse
|
|
9
|
TURRI JAO, DECIMONI TC, FERREIRA LA, DINIZ MA, HADDAD LBDP, CAMPOLINA AG. Higher MELD score increases the overall cost on the waiting list for liver transplantation: a micro-costing analysis based study. ARQUIVOS DE GASTROENTEROLOGIA 2017; 54:238-245. [DOI: 10.1590/s0004-2803.201700000-35] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 04/10/2017] [Indexed: 12/18/2022]
Abstract
ABSTRACT BACKGROUND: The pre-transplant period is complex and includes lots of procedures. The severity of liver disease predisposes to a high number of hospitalizations and high costs procedures. Economic evaluation studies are important tools to handle costs on the waiting list for liver transplantation. OBJECTIVE: The objective of the present study was to evaluate the total cost of the patient on the waiting list for liver transplantation and the main resources related to higher costs. METHODS: A cost study in a cohort of 482 patients registered on waiting list for liver transplantation was carried out. In 24 months follow-up, we evaluated all costs of materials, medicines, consultations, procedures, hospital admissions, laboratorial tests and image exams, hemocomponents replacements, and nutrition. The total amount of each resource or component used was aggregated and multiplied by the unitary cost, and thus individual cost for each patient was obtained. RESULTS: The total expenditure of the 482 patients was US$ 6,064,986.51. Outpatient and impatient costs correspond to 32.4% of total cost (US$ 1,965,045.52) and 67.6% (US$ 4,099,940.99) respectively. Main cost drivers in outpatient were: medicines (44.31%), laboratorial tests and image exams (31.68%). Main cost drivers regarding hospitalizations were: medicines (35.20%), bed use in ward and ICU (26.38%) and laboratorial tests (13.72%). Patients with MELD score between 25-30 were the most expensive on the waiting list (US$ 16,686.74 ± 16,105.02) and the less expensive were those with MELD below 17 (US$ 5,703.22 ± 9,318.68). CONCLUSION: Total costs on the waiting list for liver transplantation increased according to the patient’s severity. Individually, hospitalizations, hemocomponents reposition and hepatocellular carcinoma treatment were the main cost drivers to the patient on the waiting list. The longer the waiting time, the higher the total cost on list, causing greater impact on health systems.
Collapse
|
|
10
|
Sayiner M, Wymer M, Golabi P, Ford J, Srishord I, Younossi ZM. Presence of hepatitis C (HCV) infection in Baby Boomers with Medicare is independently associated with mortality and resource utilisation. Aliment Pharmacol Ther 2016; 43:1060-8. [PMID: 26991652 DOI: 10.1111/apt.13592] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 11/09/2015] [Accepted: 03/02/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatitis C virus is common among Baby Boomers (BB). As this cohort ages, they will increasingly become Medicare eligible. AIM To evaluate resource utilisation and mortality of BB-Medicare recipients with HCV. METHODS We used in-patient and out-patient Medicare databases (2005-2010). HCV was identified using ICD-9 codes. Outcomes included resource utilisation [payment/case and in-patient length of stay (LOS)] and short-term mortality. RESULTS Of 1 153 862 BB Medicare recipients (2005-2010), 3.2% (N = 37 365) had HCV. During this period, in-patient Medicare-BB (39 793-55 235) and their claims (78 924-106 232) increased. Furthermore, their overall mortality increased from 8.94% to 10.25% (P < 0.0001). In multivariate analysis, HCV [OR = 1.23 (1.16-1.29)], older age [OR = 1.98 (1.82-2.14)], male gender [OR = 1.25 (1.22-1.29)], ESRD [OR = 1.31 (1.26-1.36)], Charlson score [OR = 1.41 (1.40-1.42)] and LOS [OR = 1.02 (1.02-1.02)] predicted mortality. LOS decreased from 12.98 to 11.74 days (P < 0.0001), whereas total payments increased from $22 157 to $23 185 (P < .0001). During the study, the number of out-patient Medicare BB patients (123 097-192 110) and claims (863 978-1 340 260) also increased. Furthermore, overall mortality increased from 3.15% to 3.31% (P = 0.0131). Again, HCV [OR = 1.23 (1.16-1.30)], older age [OR = 2.03 (1.89-2.17)], ESRD [OR = 3.40 (3.28-3.51)], disabled status [OR = 1.49 (1.40-1.58)] and Charlson score [OR = 1.39 (1.38-1.40)] predicted mortality. Annual total out-patient payments increased from $3781 to $4001 (P < 0.0001). HCV [36.04% [34.28-37.82%)], 45-49 age [4.21% (3.14-5.28%)], ESRD [966.31% (954.86-977.88%)], disabled status [43.22% (41.67-44.80%)], Charlson score [46.78% (46.31-47.26%)] and study year [2.72% (2.58-2.85%)] independently predicted increases in payments. CONCLUSIONS In Baby Boomer Medicare recipients, diagnosis of HCV is independently associated with higher mortality and resource utilisation.
Collapse
Affiliation(s)
- M Sayiner
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - M Wymer
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - P Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - J Ford
- Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA, USA
| | - I Srishord
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - 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
|
|
11
|
Belfrage AK, Abdurakhmanov E, Kerblom E, Brandt P, Oshalim A, Gising J, Skogh A, Neyts J, Danielson UH, Sandström A. Discovery of pyrazinone based compounds that potently inhibit the drug-resistant enzyme variant R155K of the hepatitis C virus NS3 protease. Bioorg Med Chem 2016; 24:2603-20. [PMID: 27160057 DOI: 10.1016/j.bmc.2016.03.066] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 03/17/2016] [Accepted: 03/21/2016] [Indexed: 01/15/2023]
Abstract
Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors with variations in the C-terminus. Biochemical evaluation was performed using genotype 1a, both the wild-type and the drug resistant enzyme variant, R155K. Surprisingly, compounds without an acidic sulfonamide retained good inhibition, challenging our previous molecular docking model. Moreover, selected compounds in this series showed nanomolar potency against R155K NS3 protease; which generally confer resistance to all HCV NS3 protease inhibitors approved or in clinical trials. These results further strengthen the potential of this novel substance class, being very different to the approved drugs and clinical candidates, in the development of inhibitors less sensitive to drug resistance.
Collapse
Affiliation(s)
- Anna Karin Belfrage
- Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-75123 Uppsala, Sweden
| | - Eldar Abdurakhmanov
- Department of Chemistry-BMC, Uppsala University, Box 576, SE-75123 Uppsala, Sweden
| | - Eva Kerblom
- Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-75123 Uppsala, Sweden
| | - Peter Brandt
- Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-75123 Uppsala, Sweden
| | - Anna Oshalim
- Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-75123 Uppsala, Sweden
| | - Johan Gising
- Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-75123 Uppsala, Sweden
| | - Anna Skogh
- Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-75123 Uppsala, Sweden
| | - Johan Neyts
- Rega Institute, Department of Microbiology and Immunology, University of Leuven, B-3000 Leuven, Belgium
| | - U Helena Danielson
- Department of Chemistry-BMC, Uppsala University, Box 576, SE-75123 Uppsala, Sweden
| | - Anja Sandström
- Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-75123 Uppsala, Sweden.
| |
Collapse
|
|
12
|
Bernal-Soriano MC, Gimeno A, Sánchez-Paya J, Portilla J. [Influence of sample conservation on quantification of Hepatitis C Virus RNA]. Enferm Infecc Microbiol Clin 2016; 34:689-690. [PMID: 26847857 DOI: 10.1016/j.eimc.2015.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2015] [Accepted: 12/26/2015] [Indexed: 10/22/2022]
Affiliation(s)
| | - Adelina Gimeno
- Servicio de Microbiología, Hospital General Universitario de Alicante, Alicante, España
| | - Jose Sánchez-Paya
- Servicio de Medicina Preventiva, Hospital General Universitario de Alicante, Alicante, España; Universidad Miguel Hernández, Elche, Alicante, España
| | - Joaquín Portilla
- Universidad Miguel Hernández, Elche, Alicante, España; Servicio de Enfermedades Infecciosas, Hospital General Universitario de Alicante, Alicante, España
| |
Collapse
|
|
13
|
Golabi P, Otgonsuren M, Suen W, Koenig AB, Noor B, Younossi ZM. Predictors of Inpatient Mortality and Resource Utilization for the Elderly Patients With Chronic Hepatitis C (CH-C) in the United States. Medicine (Baltimore) 2016; 95:e2482. [PMID: 26817883 PMCID: PMC4998257 DOI: 10.1097/md.0000000000002482] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
New incidents of chronic hepatitis C (CH-C) have stabilized yet the full impact of CH-C is not realized.Assess inpatient mortality and resource utilization for CH-C patients hospitalized in the United States.Adult CH-C patients were identified from The National Inpatient Sample (NIS) 2005 to 2009 database using the International Classification of Disease, Ninth Revision (ICD-9) diagnosis codes (070.51, 070.54, 070.70, 070.71, 070.41, and 070.44) also used to identify comorbidities.324,823 hospitalized CH-C patients were identified. Of these, 13.63% (N = 44,288) were older than 65. The rate of hospitalization for the elderly cohort steadily increased over the study period with Medicare as the payer for the majority (86%). This cohort had higher inpatient charges, approximately a half day longer hospital stay (P < 0.001) and more moderate or severe illness. During the index hospitalization, older CH-C patients were twice more likely to die than the younger age-group (5% versus 2%, P < 0.001). In the adjusted model, older age (OR: 1.02 [95% CI, 1.02-1.03]), severity of illness (OR: 12.06 [95% CI, 10.68-13.62]), and number of diagnoses (OR: 1.10 [95% CI, 1.09-1.11]) were associated with higher in-hospital mortality; severity of illness and having private insurance were significantly associated with charge per hospital stay (P < 0.001).The number of CH-C patients 65 and older increased due to the aging of the baby boomer population. Early treatment of CH-C patients with highly effective, well-tolerated, new anti-HCV regimens may prevent this significant societal burden.
Collapse
Affiliation(s)
- Pegah Golabi
- From the Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA (PG, MO, WS, ABK, BN, ZMY); and Center for Liver Diseases, Department of Medicine, Inova Fair Falls Church, VA (WS, ZMY)
| | | | | | | | | | | |
Collapse
|
|
14
|
Shiffman ML. Universal screening for chronic hepatitis C virus. Liver Int 2016; 36 Suppl 1:62-6. [PMID: 26725899 DOI: 10.1111/liv.13012] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 10/27/2015] [Indexed: 02/13/2023]
Abstract
Chronic hepatitis C virus (HCV) infection affects an estimated 123 million persons worldwide and is the leading cause of cirrhosis and hepatocellular carcinoma in most countries. Approximately 75% of persons with chronic HCV were born between the years 1945-1965 and screening of patients in this birth cohort is now advocated. Unfortunately, these recommendations are not readily applied and a sizable population of infected persons who could benefit from treatment fall outside the birth cohort. Universal screening for HCV would be optimal. However, the primary limitation once patients are identified is accessing treatment which remains restricted in most countries.
Collapse
Affiliation(s)
- Mitchell L Shiffman
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA, USA
| |
Collapse
|
|
15
|
Ma GX, Zhang GY, Jung MY, Ma XS, Zhai S, Zhao M, Ma X, Lee S. HCV Screening Behaviors and Infection Status among Vietnamese Americans. Am J Health Behav 2015; 39:640-51. [PMID: 26248174 PMCID: PMC6632077 DOI: 10.5993/ajhb.39.5.6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES The aim of this study was to identify socio-economic and acculturation factors associated with hepatitis C (HCV) screening and infection among US Vietnamese Americans. METHODS Participants were recruited from 7 Vietnamese community-based organizations in Pennsylvania and New Jersey. The analysis ultimately included 309 participants who participated in a HCV education intervention program. RESULTS Overall, 82.5% (255 of 309) intervention participants completed HCV screening over the 6 months prior to the post-intervention assessment. In multivariate-adjusted analysis, participants who lived in Vietnam for 40 years versus 20 years were more likely to receive HCV screening; unemployed individuals were less likely to receive HCV screening than employed people. Among screened participants, 7.5% had HCV infection. CONCLUSIONS These findings will guide future culturally and linguistically appropriate interventions to reduce HCV infection and HCV-related liver cancer.
Collapse
Affiliation(s)
- Grace X Ma
- Department of Public Health and Center for Asian Health, College of Public Health, Temple University, Philadelphia, PA, USA
| | - Guo Yolanda Zhang
- Center for Asian Health, College of Public Health, Temple University, Philadelphia, PA, USA
| | - Mary Y Jung
- Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park, MD, USA
| | - Xiang S Ma
- Center for Asian Health, College of Public Health, Temple University, Philadelphia, PA, USA
| | - Shumenghui Zhai
- Center for Asian Health, College of Public Health, Temple University, Philadelphia, PA, USA
| | - Mei Zhao
- Center for Asian Health, College of Public Health, Temple University, Philadelphia, PA, USA
| | - Xiaoli Ma
- College of Medicine, Drexel University, Philadelphia, PA, USA.
| | - Sunmin Lee
- Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park, MD, USA
| |
Collapse
|
|
16
|
King LY, Canasto-Chibuque C, Johnson KB, Yip S, Chen X, Kojima K, Deshmukh M, Venkatesh A, Tan PS, Sun X, Villanueva A, Sangiovanni A, Nair V, Mahajan M, Kobayashi M, Kumada H, Iavarone M, Colombo M, Fiel MI, Friedman SL, Llovet JM, Chung RT, Hoshida Y. A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration. Gut 2015; 64:1296-302. [PMID: 25143343 PMCID: PMC4336233 DOI: 10.1136/gutjnl-2014-307862] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 07/29/2014] [Indexed: 12/08/2022]
Abstract
OBJECTIVE The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression. DESIGN We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100,000/mm(3)), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years). RESULTS In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001). CONCLUSIONS A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions.
Collapse
Affiliation(s)
- Lindsay Y. King
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, U.S
| | - Claudia Canasto-Chibuque
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | - Kara B. Johnson
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, U.S
| | - Shun Yip
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | - Xintong Chen
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | - Kensuke Kojima
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | - Manjeet Deshmukh
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | - Anu Venkatesh
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | - Poh Seng Tan
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S,Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore
| | - Xiaochen Sun
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | | | - Angelo Sangiovanni
- M. & A. Migliavacca Center for Liver Disease and 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Venugopalan Nair
- Department of Neurology, Icahn School of Medicine at Mount Sinai, U.S
| | - Milind Mahajan
- Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, U.S
| | | | | | - Massimo Iavarone
- M. & A. Migliavacca Center for Liver Disease and 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Massimo Colombo
- M. & A. Migliavacca Center for Liver Disease and 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Maria Isabel Fiel
- Department of Pathology, Icahn School of Medicine at Mount Sinai, U.S
| | - Scott L. Friedman
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| | - Josep M. Llovet
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S,HCC Translational Research Laboratory, Barcelona Clinic Liver Cancer Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer Centro de Investigaciones en Red de Enfermedades Hepáticas y Digestivas, Hosptial Clínic Barcelona, Catalonia, Spain,Institució Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Catalonia, Spain
| | - Raymond T. Chung
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, U.S
| | - Yujin Hoshida
- Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, U.S
| |
Collapse
|
|
17
|
Younossi ZM, Stepanova M, Marcellin P, Afdhal N, Kowdley KV, Zeuzem S, Hunt SL. Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the ION-1, -2, and -3 clinical trials. Hepatology 2015; 61:1798-808. [PMID: 25627448 DOI: 10.1002/hep.27724] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 01/22/2015] [Indexed: 12/15/2022]
Abstract
UNLABELLED Treatment with interferon (IFN) and ribavirin (RBV) significantly impairs quality of life and other patient-reported outcomes (PROs). Patient experience with IFN- and RBV-free anti-HCV (hepatitis C virus) regimens has not been reported. We assessed PROs in patients treated with ledipasvir and sofosbuvir (LDV/SOF) with and without RBV. Four different PRO questionnaires were administered at baseline, during, and post-treatment in HCV genotype 1 patients treated with LDV/SOF±RBV (ION-1, -2, and -3). A total of 1,952 patients were enrolled to be treated for 8 (N = 431), 12 (N = 867), or 24 weeks (N = 654) with LDV/SOF (N = 1,080) or LDV/SOF+RBV (N = 872). Baseline demographics and psychiatric disorders were similar between treatment groups (all P > 0.05). Patients receiving LDV/SOF regimens showed significant improvement of PRO scores during treatment (up to +7.4%, +7.0%, and +6.7% on a normalized 0%-100% scale in the 8-, 12-, and 24-week-long treatment groups, respectively (all P < 0.0001). These PRO improvements coincided with early viral suppression after 2 weeks of treatment and maximized by the end of treatment. On the other hand, during treatment with LDV/SOF+RBV, PRO scores declined (up to -5.5% regardless of treatment duration; P < 0.0001). Receiving RBV was an independent predictor of PRO impairment in multivariate analysis (beta up to -5.9%; P < 0.0001). Patients who achieved sustained virological response at 12 weeks showed significant improvement of their PROs post-treatment (up to +8.3%; P < 0.0001). CONCLUSION IFN- and RBV-free regimens with LDV/SOF result in early HCV suppression with simultaneous improvement in PROs that continued throughout the duration of treatment and post-treatment.
Collapse
Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
| | - Maria Stepanova
- CLDQ LLC, Washington, DC
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
| | | | - Nezam Afdhal
- Hepatology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Kris V Kowdley
- Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, WA
| | - Stefan Zeuzem
- Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany
| | - Sharon L Hunt
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
| |
Collapse
|
|
18
|
Raedler LA. Viekira Pak (Ombitasvir, Paritaprevir, and Ritonavir Tablets; Dasabuvir Tablets): All-Oral Fixed Combination Approved for Genotype 1 Chronic Hepatitis C Infection. AMERICAN HEALTH & DRUG BENEFITS 2015; 8:142-7. [PMID: 26629280 PMCID: PMC4665049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
|
|
19
|
Raedler LA. Once-a-Day Harvoni (Ledipasvir plus Sofosbuvir), a New Oral Combination for the Treament of Patients with Genotype 1 Chronic Hepatitis C Infection. AMERICAN HEALTH & DRUG BENEFITS 2015; 8:54-58. [PMID: 26629267 PMCID: PMC4665066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
|
|
20
|
Younossi Z, Henry L. The impact of the new antiviral regimens on patient reported outcomes and health economics of patients with chronic hepatitis C. Dig Liver Dis 2014; 46 Suppl 5:S186-96. [PMID: 25458773 DOI: 10.1016/j.dld.2014.09.025] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 09/29/2014] [Indexed: 12/11/2022]
Abstract
Hepatitis C is an important cause of chronic liver disease worldwide with an estimated 170 million people infected. Hepatitis C virus (HCV)-infected patients are physically and mentally impacted by fatigue, depression and anxiety causing an impairment of health related quality of life (HRQOL), lower worker productivity and other patient reported outcomes (PROs). Although anti-HCV regimens containing first generation direct acting antiviral agents (DAAs) were associated with significant side effects, the second generation DAAs, sofosbuvir (SOF) and simeprevir (SMV), are associated with fewer side effects, better tolerability and high cure rates. Despite these advantages, key stakeholders are currently trying to find ways to best integrate these new therapeutic regimens into the management of patients with chronic hepatitis C for the benefit of all. The purpose of this article is to offer insight into the other key and equally important outcomes (PRO's, HRQOL and cost) which should be considered when assessing the applicability of these new regimens for the care of patients infected with HCV. Our review provides evidence that the new treatment regimens for HCV not only have high efficacy rates but are also associated with better patient reported outcomes and cost per case of HCV cured. Additionally, compared to other medical interventions, these new regimens are cost-effective from a societal perspective.
Collapse
Affiliation(s)
- Zobair Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.
| | - Linda Henry
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
| |
Collapse
|
|
21
|
Sharma S, Khalili K, Nguyen GC. Non-invasive diagnosis of advanced fibrosis and cirrhosis. World J Gastroenterol 2014; 20:16820-16830. [PMID: 25492996 PMCID: PMC4258552 DOI: 10.3748/wjg.v20.i45.16820] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 08/23/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis is a common and growing public health problem globally. The diagnosis of cirrhosis portends an increased risk of morbidity and mortality. Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis. However, despite its universal use, liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks. In order to overcome the limitations of liver biopsy, a number of non-invasive techniques have been investigated for the assessment of cirrhosis. This review will focus on currently available non-invasive markers of cirrhosis. The evidence behind the use of these markers will be highlighted, along with an assessment of diagnostic accuracy and performance characteristics of each test. Non-invasive markers of cirrhosis can be radiologic or serum-based. Radiologic techniques based on ultrasound, magnetic resonance imaging and elastography have been used to assess liver fibrosis. Serum-based biomarkers of cirrhosis have also been developed. These are broadly classified into indirect and direct markers. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, reflect extracellular matrix turnover, and include molecules involved in hepatic fibrogenesis. On the whole, radiologic and serum markers of fibrosis correlate well with biopsy scores, especially when excluding cirrhosis or excluding fibrosis. This feature is certainly clinically useful, and avoids liver biopsy in many cases.
Collapse
|
|
22
|
Niu B, Forde KA, Goldberg DS. Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data. Pharmacoepidemiol Drug Saf 2014; 24:107-11. [PMID: 25335773 DOI: 10.1002/pds.3721] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 09/06/2014] [Accepted: 09/09/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Despite the use of administrative data to perform epidemiological and cost-effectiveness research on patients with hepatitis B or C virus (HBV, HCV), there are no data outside of the Veterans Health Administration validating whether International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes can accurately identify cirrhotic patients with HBV or HCV. The validation of such algorithms is necessary for future epidemiological studies. METHODS We evaluated the positive predictive value (PPV) of ICD-9-CM codes for identifying chronic HBV or HCV among cirrhotic patients within the University of Pennsylvania Health System, a large network that includes a tertiary care referral center, a community-based hospital, and multiple outpatient practices across southeastern Pennsylvania and southern New Jersey. We reviewed a random sample of 200 cirrhotic patients with ICD-9-CM codes for HCV and 150 cirrhotic patients with ICD-9-CM codes for HBV. RESULTS The PPV of 1 inpatient or 2 outpatient HCV codes was 88.0% (168/191, 95% CI: 82.5-92.2%), while the PPV of 1 inpatient or 2 outpatient HBV codes was 81.3% (113/139, 95% CI: 73.8-87.4%). Several variations of the primary coding algorithm were evaluated to determine if different combinations of inpatient and/or outpatient ICD-9-CM codes could increase the PPV of the coding algorithm. CONCLUSIONS ICD-9-CM codes can identify chronic HBV or HCV in cirrhotic patients with a high PPV and can be used in future epidemiologic studies to examine disease burden and the proper allocation of resources.
Collapse
Affiliation(s)
- Bolin Niu
- Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | | | | |
Collapse
|
|
23
|
Schanzer DL, Paquette D, Lix LM. Historical trends and projected hospital admissions for chronic hepatitis C infection in Canada: a birth cohort analysis. CMAJ Open 2014; 2:E139-44. [PMID: 25295233 PMCID: PMC4183164 DOI: 10.9778/cmajo.20130087] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Much of the recent increase in hospital admission rates and mortality associated with hepatitis C in Canada is believed to be because of a higher prevalence of hepatitis C virus infection among those born between 1945 and 1965 (the baby boomer generation). We explored the effects of birth cohort on the rates of and projected trends in hospital admissions associated with hepatitis C. METHODS The hospital records of 17 344 inpatients with a diagnosis of chronic hepatitis C and liver disease, including liver cancer, were extracted from the Canadian Discharge Abstract Database for April 2004 to March 2011. For each 5-year birth cohort from 1915 to 1984, regression analysis was used to estimate the temporal trends associated with the average age of the cohort during the study period. Future hospital admissions were predicted based on the assumption that past trends would continue. RESULTS Hospital admissions associated with hepatitis C and liver disease increased an average of 6.0% (95% confidence interval [CI] 4.4%-7.7%) a year over the study period. As of 2010, hospital admission rates were highest for the 1950-1954 and 1955-1959 birth cohorts, at 17.6 (95% CI 13.2-23.5) and 13.7 (95% CI 10.3-18.2) times the rate for the 1970-1974 birth cohort. The corresponding same-age rate ratios predicted under a status quo scenario were 3.6 (95% CI 2.3-4.9) and 3.4 (95% CI 2.1-4.7). Same-age rate ratios were significantly higher for the four 5-year birth cohorts between 1950 and 1969 compared with other birth cohorts. INTERPRETATION Hospital admissions associated with chronic hepatitis C and liver disease were significantly higher for the 1950-1954 and 1955-1959 birth cohorts than for most other birth cohorts. Without further interventions, the disease burden associated with hepatitis C will continue to increase for most birth cohorts, likely peaking after age 70 years. The substantial disease burden emerging in younger birth cohorts should be monitored.
Collapse
Affiliation(s)
- Dena L Schanzer
- Infectious Disease Prevention and Control Branch, Public Health Agency of Canada, Ottawa, Ont
| | - Dana Paquette
- Infectious Disease Prevention and Control Branch, Public Health Agency of Canada, Ottawa, Ont
| | - Lisa M Lix
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Man
| |
Collapse
|
|
24
|
Wong RJ, Chou C, Bonham CA, Concepcion W, Esquivel CO, Ahmed A. Improved survival outcomes in patients with non-alcoholic steatohepatitis and alcoholic liver disease following liver transplantation: an analysis of 2002-2012 United Network for Organ Sharing data. Clin Transplant 2014; 28:713-21. [PMID: 24654688 DOI: 10.1111/ctr.12364] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2014] [Indexed: 12/15/2022]
Abstract
There is an increasing trend of patients with hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease undergoing liver transplantation in the US. Our study utilized data from the 2002 to 2012 United Network for Organ Sharing registry to evaluate model for end-stage liver disease era trends in US liver transplantations focused on patients with non-alcoholic steatohepatitis (NASH), hepatitis C (HCV), alcoholic liver disease (ALD), and HCC. Survival outcomes were stratified by liver disease etiology and compared across time periods using Kaplan-Meier and Cox proportional hazards models. Patients with NASH were more likely to be women, had higher body mass index (BMI), and had higher prevalence of diabetes and cardiac disease. However, overall long-term survival was significantly higher in patients with NASH and ALD (p < 0.001). Compared to HCV, patients with NASH had significantly higher post-transplantation survival (HR 0.69, 95% CI 0.63-0.77), and lower risk of graft failure (HR 0.76, 95% CI 0.69-0.83). Despite having higher BMI and higher prevalence of diabetes and cardiac disease, patients with NASH had better post-liver transplantation survival compared to patients with HCV or HCC. Patients with ALD also had superior survival outcomes. However, these survival differences were limited to patients without HCC that underwent liver transplantation.
Collapse
Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | | | | | | | | | | |
Collapse
|
|
25
|
Abstract
The
progress in HCV therapy in the last three years is similar
to the progress that took HIV therapy ∼14 years. We are at
the brink of approval for an all-oral drug combination that is dosed
once daily as a single pill, has >95% efficacy, and is well tolerated.
This article summarizes the path to this success and the challenges
still ahead.
Collapse
Affiliation(s)
- Ann D. Kwong
- InnovaTID, Inc., 125 Cambridge Park Drive, Cambridge, Massachusetts 02140, United States
| |
Collapse
|
|
26
|
Abstract
Hepatitis C (HCV) coinfection is the leading cause of liver-related morbidity and is a leading cause of mortality in human immunodeficiency virus (HIV)-infected individuals in the antiretroviral therapy era. Direct-acting antiviral (DAA) therapies are transforming how HCV is treated with significant improvements in efficacy and tolerability. In this article, DAA agents expected to be available in 2014 are reviewed, including telaprevir, boceprevir, sofosbuvir, simeprevir, faldaprevir, and daclatasvir. Available data regarding clinical efficacy, adverse effects, and drug interactions in HIV-HCV coinfection are discussed. The management of adverse effects of HCV therapy and treatment considerations in patients with cirrhosis are also reviewed.
Collapse
Affiliation(s)
- Cody A Chastain
- Division of Infectious Diseases, Vanderbilt University Medical Center, A-2200 MCN, 1161 21st Avenue, Nashville, TN, 37232-2582, USA,
| | | |
Collapse
|
|
27
|
Kondo Y, Shimosegawa T. Direct effects of hepatitis C virus on the lymphoid cells. World J Gastroenterol 2013; 19:7889-7895. [PMID: 24307783 PMCID: PMC3848137 DOI: 10.3748/wjg.v19.i44.7889] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Revised: 10/01/2013] [Accepted: 11/12/2013] [Indexed: 02/06/2023] Open
Abstract
It has been reported that the direct binding of hepatitis C virus (HCV) and/or the replication of HCV in the extrahepatic organs and, especially, lymphoid cells, might affect the pathogenesis of extrahepatic diseases with HCV infection. More than one decade ago, several reports described the existence of HCV-RNA in peripheral blood mononuclear cells. Moreover, many reports describing the existence of HCV in B lymphocytes and B cell lymphoma have been published. In addition to B lymphocytes, it was reported that HCV replication could be detected in T lymphocytes and T cell lines. Among the extrahepatic diseases with HCV infection, mixed cryoglobulinemia-related diseases and autoimmune-related diseases are important for understanding the immunopathogensis of HCV persistent infection. Moreover, HCV persistent infection can cause malignant lymphoma. The biological significance of lymphotropic HCV has not yet become clear. However, several candidates have been considered for a long time. One is that lymphotropic HCV is an HCV reservoir that might contribute to the recurrence of HCV infection and difficult-to-treat disease status. The other important issue is the carcinogenesis of the lymphoid cells and disturbances of the immune responses. Therefore, the extrahepatic diseases might be induced by direct interaction between HCV and lymphoid cells. In this article, we summarize various studies showing the direct effect of HCV on lymphoid cells and discuss the biological significance of lymphotropic HCV.
Collapse
|