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1
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Country versus pharmaceutical company interests for hepatitis C treatment. Health Care Manag Sci 2022; 25:725-749. [PMID: 36001218 PMCID: PMC9399601 DOI: 10.1007/s10729-022-09607-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 07/06/2022] [Indexed: 11/04/2022]
Abstract
Hepatitis C virus (HCV) is one of the leading causes of liver disease and is responsible for massive health and economic burden worldwide. The disease is asymptomatic in its early stages, but it can progress over time to fatal end-stage liver disease. Thus, the majority of individuals infected with HCV are unaware of their chronic condition. Recent treatment options for HCV can completely cure the infection but are costly. We developed a game model between a pharmaceutical company (PC) and a country striving to maximize its citizens' utility. First, the PC determines the price of HCV treatment; then, the country responds with corresponding screening and treatment strategies. We employed an analytical framework to calculate the utility of the players for each selected strategy. Calibrated to detailed HCV data from Israel, we found that the PC will gain higher revenue by offering a quantity discount rather than using standard fixed pricing per treatment, by indirectly forcing the country to conduct more screening than it desired. By contrast, risk-sharing agreements, in which the country pays only for successful treatments are beneficial for the country. Our findings underscore that policy makers worldwide should prudently consider recent offers by PCs to increase screening either directly, via covering HCV screening, or indirectly, by providing discounts following a predetermined volume of sales. More broadly, our approach is applicable in other healthcare settings where screening is essential to determine treatment strategies.
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2
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The role of diffusion tensor imaging for the assessment of liver fibrosis and inflammation in chronic viral hepatitis: A preliminary study. MARMARA MEDICAL JOURNAL 2020. [DOI: 10.5472/marumj.741724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Collister M, Rempel J, Yang J, Kaita K, Raizman Z, Gong Y, Minuk G. Circulating and inducible IL-32α in chronic hepatitis C virus infection. CANADIAN LIVER JOURNAL 2019. [DOI: 10.3138/canlivj-2018-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Background: Interleukin 32 (IL-32) is a recently described pro-inflammatory cytokine implicated in chronic hepatitis C virus (HCV)-related inflammation and fibrosis. IL-32α is the most abundant IL-32 isoform. Methods: Circulating IL-32α levels were documented in patients with chronic HCV infections ( n = 31) and compared with individuals who spontaneously resolved HCV infection ( n = 14) and HCV-naive controls ( n = 20). In addition, peripheral blood mononuclear cells (PBMC) from the chronic HCV ( n = 12) and HCV-naive ( n = 9) cohorts were investigated for responses to HCV core and non-structural (NS)3 protein induced IL-32α production. Finally, correlations between IL-32α levels, hepatic fibrosis and subsequent responses to interferon-based therapy were documented in patients with chronic HCV. Results: Circulating IL-32α levels in patients with chronic HCV were similar to those of spontaneously resolved and HCV-naive controls. HCV protein induced IL-32α responses were similar in chronic HCV patients and HCV-naive controls. In patients with chronic HCV, serum IL-32α levels correlated with worsening METAVIR fibrosis (F) scores from F0 to F3 ( r = 0.596, P < 0.001) as did NS3 induced IL-32α responses ( r = 0.837, P < 0.05). However, these correlations were not sustained with the inclusion of IL-32α levels at F4 scores, suggesting events at F4 interfere with IL-32α synthesis or release. In chronic HCV patients who underwent treatment ( n = 28), baseline in vivo and in vitro induced IL-32α concentrations were not predictive of therapeutic outcomes. Conclusions: IL-32α activity is associated with worsening fibrosis scores in non-cirrhotic, chronic HCV patients.
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Affiliation(s)
- Mark Collister
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada
| | - Julia Rempel
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada
| | - Jiaqi Yang
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada
| | - Kelly Kaita
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada
| | - Zach Raizman
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada
| | - Yuwen Gong
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada
| | - Gerald Minuk
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada
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4
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Collister M, Rempel J, Yang J, Kaita K, Raizman Z, Gong Y, Minuk G. Circulating and inducible IL-32α in chronic hepatitis C virus infection. CANADIAN LIVER JOURNAL 2019; 2:23-30. [DOI: 10.3138/canlivj.2018-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 05/30/2018] [Indexed: 12/09/2022]
Abstract
Background: Interleukin 32 (IL-32) is a recently described pro-inflammatory cytokine implicated in chronic hepatitis C virus (HCV)-related inflammation and fibrosis. IL-32α is the most abundant IL-32 isoform. Methods: Circulating IL-32α levels were documented in patients with chronic HCV infections ( n = 31) and compared with individuals who spontaneously resolved HCV infection ( n = 14) and HCV-naive controls ( n = 20). In addition, peripheral blood mononuclear cells (PBMC) from the chronic HCV ( n = 12) and HCV-naive ( n = 9) cohorts were investigated for responses to HCV core and non-structural (NS)3 protein induced IL-32α production. Finally, correlations between IL-32α levels, hepatic fibrosis and subsequent responses to interferon-based therapy were documented in patients with chronic HCV. Results: Circulating IL-32α levels in patients with chronic HCV were similar to those of spontaneously resolved and HCV-naive controls. HCV protein induced IL-32α responses were similar in chronic HCV patients and HCV-naive controls. In patients with chronic HCV, serum IL-32α levels correlated with worsening METAVIR fibrosis (F) scores from F0 to F3 ( r = 0.596, P < 0.001) as did NS3 induced IL-32α responses ( r = 0.837, P < 0.05). However, these correlations were not sustained with the inclusion of IL-32α levels at F4 scores, suggesting events at F4 interfere with IL-32α synthesis or release. In chronic HCV patients who underwent treatment ( n = 28), baseline in vivo and in vitro induced IL-32α concentrations were not predictive of therapeutic outcomes. Conclusions: IL-32α activity is associated with worsening fibrosis scores in non-cirrhotic, chronic HCV patients.
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Affiliation(s)
- Mark Collister
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba
| | - Julia Rempel
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba
| | - Jiaqi Yang
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba
| | - Kelly Kaita
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba
| | - Zach Raizman
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba
| | - Yuwen Gong
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba
| | - Gerald Minuk
- Section of Hepatology, University of Manitoba, College of Medicine, Winnipeg, Manitoba
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Boglione L, Cardellino CS, Cusato J, De Nicolò A, Cariti G, Di Perri G, D'Avolio A. Treatment with PEG-IFN and ribavirin in patients with chronic hepatitis C, low grade of hepatic fibrosis, genotype 1 and 4 and favorable IFNL3 genotype: A pharmacogenetic prospective study. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2017; 51:167-172. [PMID: 28315743 DOI: 10.1016/j.meegid.2017.03.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 03/08/2017] [Accepted: 03/14/2017] [Indexed: 12/12/2022]
Abstract
The new direct-acting antivirals agents (DAAs) rapidly changed the treatment approach in chronic hepatitis C (CHC); however, the interferon (IFN)-free therapies availability is currently different in some countries, due to higher costs of these drugs. Naïve treated patients, who are not eligible for IFN-free therapies, could be selected for standard dual treatment with pegylated (PEG)-IFN and ribavirin (RBV), through IFN lambda 3 gene polymorphisms and fibrosis stage evaluation. Inclusion criteria were: naïve treated CHC patients with GT1 or GT4, without major contraindication to PEG-IFN or RBV, with fibrosis stage F0-F2 and IFNL3 rs8099917/rs12979860 TT/CC genotypes. 65 patients were included in the study. Overall SVR was observed in 50 patients (76.9%); SVR rates among different genotypes were as follows: 15 with GT1a (71.4%), 27 with GT1b (79.4%) and 8 for GT4 (80%). The RBV cutoff at 2weeks of 1800ng/mL, predictor of RVR, was determined (p=0.003; sensibility=60.4%, specificity=88.2%, positive predictive value=88.9%, negative predictive value=100%). In multivariate analysis, factors significantly associated with treatment failure were living alone condition (OR=4.302; 95%IC=1.254-16.257; p=0.034) and RBV plasma level <1800ng/mL at 2weeks (OR=4.970; 95%IC=1.405-17.565; p=0.009). Considering a pharmacogenetic-guided approach, dual therapy with PEG-IFN and RBV can be considered a reliable option for patients ineligible for IFN-free treatments, who are motivated and well informed about all the aspects related to PEG-IFN administration.
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Affiliation(s)
- Lucio Boglione
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
| | - Chiara Simona Cardellino
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Jessica Cusato
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Amedeo De Nicolò
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Giuseppe Cariti
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Antonio D'Avolio
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
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Potentials of the elevated circulating miR-185 level as a biomarker for early diagnosis of HBV-related liver fibrosis. Sci Rep 2016; 6:34157. [PMID: 27677421 PMCID: PMC5039723 DOI: 10.1038/srep34157] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 09/08/2016] [Indexed: 12/19/2022] Open
Abstract
Early diagnosis of liver fibrosis is critical for early intervention and prognosis of various chronic liver diseases. Conventional repeated histological assessment is impractical due to the associated invasiveness. In the current study, we evaluated circulating miR-185 as a potential biomarker to predict initiation and progression of liver fibrosis. We found that miR-185 was significantly up-regulated in blood specimens from patients with HBV-liver fibrosis and rats with liver fibrosis, the miR-185 levels were correlated with liver fibrosis progression, but not with the different viral loads in HBV-infected patients. miR-185 was observed in collagen deposition regions during advanced liver fibrosis. We found that differences in miR-185 levels facilitated the discrimination between early-staged or advanced-staged liver fibrosis and the healthy controls with high specificity, sensitivity, and likelihood ratio using receiver-operator characteristic analysis. miR-185 targeted SREBF1, and increased expression of COL1A1 and a-SMA genes that are hallmarks of liver fibrosis. Our data supported that circulating miR-185 levels could be used as potential biomarkers for the early diagnosis of liver fibrosis.
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Tama M, Naylor P, Patel S, Altawil J, Gulati D, Antaki F, Mutchnick MG, Ehrinpreis M. Overestimate of Fibrosis by FIBROSpect® II in African Americans Complicates the Management of their Chronic Hepatitis C. J Clin Transl Hepatol 2016; 4:12-9. [PMID: 27047767 PMCID: PMC4807138 DOI: 10.14218/jcth.2015.00053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Revised: 02/02/2016] [Accepted: 02/04/2016] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA). AIMS This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays. METHODS All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records. RESULTS When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis. CONCLUSIONS The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.
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Affiliation(s)
- Maher Tama
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Paul Naylor
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
- Correspondence to: Paul Naylor, Gastroenterology, 603 Hudson Bldg, Harper University Hospital, 3990 John R, Detroit, MI 48201, USA. Tel: +1-313-745-8601, Fax: +1-313-745-8843, E-mail:
| | - Suhag Patel
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Johnny Altawil
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Dhiraj Gulati
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Fadi Antaki
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Milton G. Mutchnick
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
| | - Murray Ehrinpreis
- Wayne State University School of Medicine, Department of Internal Medicine, Division of Gastroenterology, Detroit, MI, USA
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Attar BM, Van Thiel DH. Hepatitis C virus: A time for decisions. Who should be treated and when? World J Gastrointest Pharmacol Ther 2016; 7:33-40. [PMID: 26855810 PMCID: PMC4734952 DOI: 10.4292/wjgpt.v7.i1.33] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 09/09/2015] [Accepted: 11/17/2015] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) regardless of the etiology of cirrhosis. Compared to individuals who are anti-hepatitis C virus (HCV) seronegative, anti-HCV seropositive individuals have a greater mortality from both hepatic as well as nonhepatic disease processes. The aim of this paper is do describe the burden of HCV infection and consider treatment strategies to reduce HCV-related morbidity and mortality. The newly developed direct acting antiviral (DAA) therapies are associated with greater rates of drug compliance, fewer adverse effects, and appear not to be limited by the presence of a variety of factors that adversely affect the outcome of interferon-based therapies. Because of the cost of the current DAA, their use has been severely rationed by insurers as well as state and federal agencies to those with advanced fibrotic liver disease (Metavir fibrosis stage F3-F4). The rationale for such rationing is that many of those recognized as having the disease progress slowly over many years and will not develop advanced liver disease manifested as chronic hepatitis C, cirrhosis, and experience any of the multiple complications of liver disease to include HCC. This mitigation has a short sided view of the cost of treatment of hepatitis C related disease processes and ignores the long-term expenses of hepatitis C treatment consisting of the cost of treatment of hepatitis C, the management of cirrhosis with or without decompensation as well as the cost of treatment of HCC and liver transplantation. We believe that treatment should include all HCV infected patients including those with stage F0-F2 fibrosis with or without evidence of coexisting liver disease. Specifically, interferon (IFN)-free regimens with the current effective DAAs without liver staging requirements and including those without evidence of hepatic diseases but having recognized extrahepatic manifestations of HCV infection is projected to be the most cost-effective approach for treating HCV in all of its varied presentations. Early rather than later therapy of HCV infected individuals would be even more efficacious than waiting particularly if it includes all cases from F0-F4 hepatic disease. Timely therapy will reduce the number of individuals developing advanced liver disease, reduce the cost of treating these cases and more importantly, reduce the lifetime cost of treatment of those with any form of HCV related disease as well as HCV associated all - cause mortality. Importantly, HCV treatment regimens without any restrictions would result in a substantial reduction in health care expenditure and simultaneously reduce the number of infected individuals who are infecting others.
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Padam P, Clark S, Irving W, Gellissen R, Thomson E, Main J, Cooke GS. Reduced healthcare utilization following successful hepatitis C virus treatment in HIV-co-infected patients with mild liver disease. J Viral Hepat 2016; 23:123-9. [PMID: 26511293 PMCID: PMC4924594 DOI: 10.1111/jvh.12484] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 08/31/2015] [Indexed: 12/27/2022]
Abstract
New direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult-to-treat, including those HIV/HCV co-infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co-infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV-co-infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty-three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5,000 per-patient) compared to (£10 775 per-patient) non-SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co-infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease.
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Affiliation(s)
- P Padam
- Division of Infectious Diseases, Imperial College London, London, UK
| | - S Clark
- Division of Infectious Diseases, Imperial College London, London, UK
| | - W Irving
- NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, UK
| | - R Gellissen
- Department of Hepatology, Imperial College NHS Trust, London, UK
| | - E Thomson
- MRC Centre for Virus Research, University of Glasgow, Glasgow, UK
| | - J Main
- Department of Medicine, Imperial College London, London, UK
| | - G S Cooke
- Division of Infectious Diseases, Imperial College London, London, UK
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10
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Lo Re V, Kallan MJ, Tate JP, Lim JK, Goetz MB, Klein MB, Rimland D, Rodriguez-Barradas MC, Butt AA, Gibert CL, Brown ST, Park LS, Dubrow R, Reddy KR, Kostman JR, Justice AC, Localio AR. Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients. Open Forum Infect Dis 2015; 2:ofv109. [PMID: 26284259 PMCID: PMC4536329 DOI: 10.1093/ofid/ofv109] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 07/05/2015] [Indexed: 12/15/2022] Open
Abstract
Background. End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.
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Affiliation(s)
- Vincent Lo Re
- Departments ofMedicine
- Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
- Medical Service, Philadelphia VA Medical Center, Pennsylvania
| | - Michael J. Kallan
- Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Janet P. Tate
- VA Connecticut Healthcare System, West Haven
- Yale University School of Medicine, New Haven, Connecticut
| | - Joseph K. Lim
- VA Connecticut Healthcare System, West Haven
- Yale University School of Medicine, New Haven, Connecticut
| | - Matthew Bidwell Goetz
- VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, California
| | - Marina B. Klein
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada
| | - David Rimland
- Atlanta VA Medical Center and Emory University School of Medicine, Georgia
| | - Maria C. Rodriguez-Barradas
- Infectious Diseases Section, Michael E. DeBakey VA Medical Center and Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Adeel A. Butt
- VA Pittsburgh Healthcare System, Pennsylvania
- Hamad Healthcare Quality Institute, Doha, Qatar
- Hamad Medical Corporation, Doha, Qatar
| | - Cynthia L. Gibert
- Washington DC VA Medical Center, George Washington University Medical Center, Washington, District of Columbia
| | - Sheldon T. Brown
- James J. Peters VA Medical Center and Mt. Sinai School of Medicine, New York, New York
| | - Lesley S. Park
- Yale University School of Medicine, New Haven, Connecticut
- Yale School of Public Health, New Haven, Connecticut
| | - Robert Dubrow
- Yale University School of Medicine, New Haven, Connecticut
- Yale School of Public Health, New Haven, Connecticut
| | | | | | - Amy C. Justice
- VA Connecticut Healthcare System, West Haven
- Yale University School of Medicine, New Haven, Connecticut
| | - A. Russell Localio
- Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
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11
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Boglione L, Cusato J, Cariti G, Di Perri G, D'Avolio A. Treatment optimization of naïve HCV-1 patients using IL28B, RVR and fibrosis stage. Antiviral Res 2015; 116:45-7. [PMID: 25660111 DOI: 10.1016/j.antiviral.2015.01.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 01/26/2015] [Accepted: 01/29/2015] [Indexed: 01/30/2023]
Abstract
The treatment of patients with HCV genotype 1 is quickly changing. The clinician could optimize the selection of patients who may benefit from standard therapy with pegylated-interferon and ribavirin instead of more expensive new combinations with the directly acting antivirals. We retrospectively examined in our cohort of 232 patients with genotype 1 infection the role of interleukin 28B (both rs8099917 and rs12979860), fibrosis stage and rapid virological response. Global SVR in TT/CC patients was 88.3% (98% in F0-F1, 80% in F2-F3); in TT/TC was 68.2 (85% in F0-F1, 71.4% in F2-F3). Rapid virological response was related to rs12979860 CC genotype but is not useful to predict the virological response in TG/GG patients at rs8099917. The standard dual therapy may be successfully administered in all TT/CC and TT/TC patients without F4 fibrosis score. Conversely, patients with TG/CC or GG/CC genotypes should be treated with other therapeutic options.
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Affiliation(s)
- Lucio Boglione
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
| | - Jessica Cusato
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Giuseppe Cariti
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Antonio D'Avolio
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
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12
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Batxelli-Molina I, Calvayrac-Pawlowski S, Moulin V, Lapalus M, Hem S, Laune D, Asselah T, Jardin-Watelet B. Novel α-2-macroglobulin cleaved fragments as biomarkers of early liver fibrosis in patients with chronic hepatitis C. Future Virol 2015. [DOI: 10.2217/fvl.14.98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
ABSTRACT Aim: Liver biopsy is considered the gold standard for the diagnosis and staging of hepatic fibrosis in patients with chronic hepatitis C and is now progressively replaced by noninvasive procedures. We aimed at improving α-2-macroglobulin diagnostic value for liver fibrosis by identifying new isoforms that may be specifically related to early stages of the pathology. Materials & methods: α-2-Macroglobulin isoforms were characterized in serum samples from patients with chronic hepatitis C and mild (F1) to moderate (F2) fibrosis by proteomic methods. Results: New biological 40 kDa C-terminal α-2-macroglobulin fragments were identified as potential biomarkers of early fibrosis (fold change = 1.55; p < 0.01). Conclusion: The serum concentration of α-2-macroglobulin fragments allows a better differentiation of F1 and F2 fibrosis stages than total α-2-macroglobulin isoforms.
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Affiliation(s)
- Isabelle Batxelli-Molina
- SysDiag – UMR 3145 CNRS/Bio-Rad, Complex System Modeling and Engineering for Diagnosis, Cedex, France
| | | | - Véronique Moulin
- SysDiag – UMR 3145 CNRS/Bio-Rad, Complex System Modeling and Engineering for Diagnosis, Cedex, France
| | - Martine Lapalus
- Service d’Hépatologie and INSERM U773, CRB3, Université Paris Diderot, Hôpital Beaujon, Clichy, France
| | - Sonia Hem
- INRA UR1199, Laboratoire de Protéomique Fonctionnelle, Montpellier, France
| | - Daniel Laune
- SysDiag – UMR 3145 CNRS/Bio-Rad, Complex System Modeling and Engineering for Diagnosis, Cedex, France
| | - Tarik Asselah
- Service d’Hépatologie and INSERM U773, CRB3, Université Paris Diderot, Hôpital Beaujon, Clichy, France
| | - Bénédicte Jardin-Watelet
- SysDiag – UMR 3145 CNRS/Bio-Rad, Complex System Modeling and Engineering for Diagnosis, Cedex, France
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13
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Cheng R, Tu T, Shackel N, McCaughan GW. Advances in and the future of treatments for hepatitis C. Expert Rev Gastroenterol Hepatol 2014; 8:633-47. [PMID: 24846594 DOI: 10.1586/17474124.2014.909725] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Enormous progress has been made in the understanding of the hepatitis C virus and the development of novel therapeutic agents since the identification of the virus 25 years ago. From initial interferon monotherapy providing only 6% viral clearance rate in the 1980s, pharmacotherapeutics has now entered an exciting new era with direct-acting antiviral agents demonstrating viral clearance rates of more than 70%. We are now at the beginning of an era where combinations of direct-acting antiviral agents may pave the way for interferon-free regimens, even improving the viral clearance rate to near 100%.
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Affiliation(s)
- Robert Cheng
- Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia
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14
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Shiffman ML, Long AG, James A, Alexander P. My treatment approach to chronic hepatitis C virus. Mayo Clin Proc 2014; 89:934-42. [PMID: 24867397 DOI: 10.1016/j.mayocp.2014.04.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Revised: 04/19/2014] [Accepted: 04/22/2014] [Indexed: 12/31/2022]
Abstract
The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014, the standard of care and new backbone of HCV treatment is the polymerase inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype 1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV). In patients with cirrhosis or extrahepatic manifestations of HCV who cannot tolerate PEGINF, we use 12 weeks of SOF and simeprevir. The latter is less costly and more effective than SOF and RBV for 24 weeks. Our treatment approach in all patients with genotype 2 is SOF and RBV for 12 weeks. Hepatitis C virus genotype 3 is now the most costly and difficult to cure. Our approach to treatment-naive patients with genotype 3 is SOF and RBV for 24 weeks. In patients who have previously undergone PEGINF and RBV treatment, we use PEGINF, SOF, and RBV for 12 weeks, which is equally if not more effective and less costly than SOF and RBV for 24 weeks. Patients with cirrhosis who cannot tolerate PEGINF should be treated for 24 weeks with SOF and RBV, although the sustained virologic response is suboptimal.
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Affiliation(s)
- Mitchell L Shiffman
- Liver Institute of Virginia, Bon Secours Health System, Richmond, and Newport News, VA.
| | - April G Long
- Liver Institute of Virginia, Bon Secours Health System, Richmond, and Newport News, VA
| | - Amy James
- Liver Institute of Virginia, Bon Secours Health System, Richmond, and Newport News, VA
| | - Phillip Alexander
- Liver Institute of Virginia, Bon Secours Health System, Richmond, and Newport News, VA
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15
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Abstract
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The May 2014 monograph topics are droxidopa, elosulfase alfa, vorapaxar, ramucirumab, and pimavanserin. The DUE/MUE is on droxidopa.
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Affiliation(s)
- Dennis J Cada
- Founder and Contributing Editor, The Formulary ; Washington State University , Spokane, Washington
| | - Jasen Cong
- Drug Information Resident, Drug Information Center, Washington State University , Spokane, Washington
| | - Danial E Baker
- Director, Drug Information Center, and Professor of Pharmacy Practice, College of Pharmacy, Washington State University Spokane, PO Box 1495 , Spokane, Washington 99210-1495 . The authors indicate no relationships that could be perceived as a conflict of interest
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16
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Tovo CV, Mattos AAD, Almeida PRLD. Chronic hepatitis C genotype 1 virus: who should wait for treatment? World J Gastroenterol 2014; 20:2867-2875. [PMID: 24659878 PMCID: PMC3961974 DOI: 10.3748/wjg.v20.i11.2867] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 11/21/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Elucidation of the natural history of chronic hepatitis C (CHC) and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment (triple therapy) in favour of waiting for new drug availability for patients who are at low risk of progression to significant liver disease. Newer generation drugs are currently under development, and are expected to feature improved efficacy and safety profiles, as well as less complex and shorter duration delivery regimens, compared to the current standards of care. In addition, patients with cirrhosis and prior null responders have a low rate (around 15%) of achieving sustained virological response (SVR) with triple therapy, and physicians must also consider the decision to wait for new treatments in the future for these patients as well. Naïve patients are the most likely to achieve a close to 100% SVR rate; therefore, it may be advisable to recommend that patients with mild to moderate CHC should wait for the newer therapy options. In contrast, patients with advanced fibrosis and cirrhosis will be those with the greatest need for expedited therapeutic intervention. There remains a need, however, for establishing definitive clinical management guidelines to maximize the benefit of waiting for new drugs and minimize risk of side effects and non-response to the current triple therapy.
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Abstract
The treatment of chronic HCV is evolving rapidly. In 2014, three new oral antiviral agents, simeprevir, faldeprevir and sofosbuvir will become available for patients with HCV genotype 1. These agents have far less side effects than the first generation protease inhibitors telaprevir and boceprevir. Treatment will therefore be easier for patients to tolerate but still require peginterferon and ribavirin (PEGINF/RBV). The first IFN free therapy, sofosbuvir (SOF) and ribavirin (RBV), will also become available in 2014. This treatment is highly effective for patients with HCV genotype 2. However, SVR rates with SOF/RBV appear to be similar to that achieved with PEGINF/RBV in patients with HCV genotype 3. The first IFN-free all oral antiviral therapy combination for patients with HCV genotype 1 may be available late in 2014 or early 2015. The factors which should be considered when deciding whether to treat a patient with HCV now or to delay treatment until IFN free therapies are available is discussed.
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Affiliation(s)
- Mitchell L Shiffman
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, Richmond, VA, USA; Sercive d'Hépatologie, Hôpital Pitié Salpêtrière, Paris, France
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18
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Labarga P, Fernández-Montero JV, López M, Barreiro P, de Mendoza C, Sierra-Enguita R, Treviño A, Soriano V. Progression to advanced liver fibrosis in HIV/HCV-coinfected patients and prioritization of new hepatitis C therapies. Antivir Ther 2014; 19:799-803. [DOI: 10.3851/imp2816] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2014] [Indexed: 10/25/2022]
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Kittner JM, Weiss NM, Wiltink J, Schattenberg JM, Grambihler A, Thieringer F, Weinmann A, Zimmermann T, Koch S, Schuchmann M, Galle PR. Defer or treat? Reasons for treatment decisions in patients with chronic hepatitis C genotype 1 in the early era of directly acting antiviral agents. Dig Liver Dis 2014; 46:67-71. [PMID: 24125691 DOI: 10.1016/j.dld.2013.08.139] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 07/31/2013] [Accepted: 08/20/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND In chronic genotype 1 hepatitis C, telaprevir or boceprevir plus peginterferon and ribavirin have become the new standard of care. Aim of this study was to identify factors contributing to the decision whether to defer or treat with the current triple regimens. METHODS Prospective assessment of eight parameters on 0-4-point scales by the attending physician at a German tertiary referral centre between 1st September 2011 and 31st December 2012. RESULTS 307 patients were evaluated at least once by one of the 11 hepatologists involved; 267 patients were considered, but only 163 were recommended to receive triple therapy. Multivariate regression analysis revealed that a higher degree of fibrosis was most strongly associated with a recommendation for treatment (OR 2.69), followed by the patients' demand (OR 2.27), presumed efficacy (OR 1.62), and tolerability (OR 1.58). A high risk of decompensation was associated with the decision to defer (OR 0.39). Speed of progression, compliance, extrahepatic manifestation, gender and age were not significantly related to the recommendation. Treatment was finally started in 101 patients (32.9%). CONCLUSION In chronic genotype 1 hepatitis C, advanced fibrosis and patients' preference are the main rationales to choose treatment rather than deferral in a real-life setting.
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Affiliation(s)
- Jens M Kittner
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany.
| | - Nora M Weiss
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jörg Wiltink
- Clinic of Psychosomatic Medicine and Psychotherapy, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jörg M Schattenberg
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Annette Grambihler
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Florian Thieringer
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Arndt Weinmann
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Tim Zimmermann
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Sandra Koch
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Marcus Schuchmann
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Peter R Galle
- 1st Medical Department, Internal Medicine Department, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
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Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay. Bioorg Med Chem Lett 2013; 23:6879-85. [DOI: 10.1016/j.bmcl.2013.09.102] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Revised: 09/27/2013] [Accepted: 09/30/2013] [Indexed: 01/09/2023]
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