+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Hepatitis C Cascade of Care: Identifying Priorities to Improve Clinical Outcomes


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them.


          We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation.

          Main measures

          Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs).


          We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals.


          We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points.

          Related collections

          Most cited references49

          • Record: found
          • Abstract: found
          • Article: not found

          The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.

          Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype 1a, and 17.0 percent with genotype 1b). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection.
            • Record: found
            • Abstract: found
            • Article: not found

            Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options.

            Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.).
              • Record: found
              • Abstract: found
              • Article: not found

              Recommendations of the Panel on Cost-effectiveness in Health and Medicine.

              To develop consensus-based recommendations for the conduct of cost-effectiveness analysis (CEA). This article, the second in a 3-part series, describes the basis for recommendations constituting the reference case analysis, the set of practices developed to guide CEAs that inform societal resource allocation decisions, and the content of these recommendations. The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS). The panel reviewed the theoretical foundations of CEA, current practices, and alternative methods used in analyses. Recommendations were developed on the basis of theory where possible, but tempered by ethical and pragmatic considerations, as well as the needs of users. The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts prepared by panel working groups were solicited from federal government methodologists, health agency officials, and academic methodologists. The panel's methodological recommendations address (1) components belonging in the numerator and denominator of a cost-effectiveness (C/E) ratio; (2) measuring resource use in the numerator of a C/E ratio; (3) valuing health consequences in the denominator of a C/E ratio; (4) estimating effectiveness of interventions; (5) incorporating time preference and discounting; and (6) handling uncertainty. Recommendations are subject to the ¿rule of reason,¿ balancing the burden engendered by a practice with its importance to a study. If researchers follow a standard set of methods in CEA, the quality and comparability of studies, and their ultimate utility, can be much improved.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                19 May 2014
                : 9
                : 5
                [1 ]HIV Epidemiology and Outcomes Research Unit, Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts, United States of America
                [2 ]Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America
                [3 ]Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York, United States of America
                [4 ]Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts, United States of America
                [5 ]Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, United States of America
                [6 ]Massachusetts General Hospital Boston, Massachusetts, United States of America
                University of Sydney, Australia
                Author notes

                Competing Interests: Dr. Kim reports that he has served on the scientific advisory boards of Gilead Sciences and Abbvie Pharmaceuticals. Dr Kim’s institution has also received research support funds from Bristol-Meyers Squibb. These relationships do not alter the authors' adherence to PLOS ONE policies on sharing data and materials. No other authors have competing interests to declare.

                Conceived and designed the experiments: BL DB JL BS. Performed the experiments: BL DB JL BS. Analyzed the data: BL DB JL BS MW JS SA AYK. Contributed reagents/materials/analysis tools: JS MW. Wrote the paper: BP DB JL SA JS MW AYK BS.


                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 11
                This study was supported by the National Institutes on Drug Abuse (R01DA031059, R01DA027379) and National Institute of Allergy and Infectious Disease (K01AI73193). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Computer and Information Sciences
                Computerized Simulations
                Medicine and health sciences
                Health Care
                Health Care Policy
                Treatment Guidelines
                Health Care Quality
                Infectious Disease Epidemiology
                Gastroenterology and hepatology
                Liver diseases
                Infectious hepatitis
                Hepatitis C
                Infectious Diseases
                Viral Diseases



                Comment on this article