Semin Liver Dis 2020; 40(04): 392-402
DOI: 10.1055/s-0040-1713657
Review Article

Simplification of Care for Chronic Hepatitis C Virus Infection

Jean-Michel Pawlotsky
1   Department of Virology, National Reference Center for Viral Hepatitis B, C and D, Henri Mondor Hospital, University of Paris-Est—INSERM U955, Créteil, France
Christian B. Ramers
2   Division of Infectious Diseases, Department of Medicine, UC San Diego School of Medicine, La Jolla, California
John F. Dillon
3   Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom
Jordan J. Feld
4   Toronto Centre for Liver Disease, University Health Network, Sandra Rotman Centre for Global Health, Toronto, ON, Canada
Jeffrey V. Lazarus
5   Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain
› Author Affiliations
Funding This study was funded by AbbVie.


In 2016, the World Health Organization (WHO) set a target for eliminating viral hepatitis as a major public health threat by 2030. However, while today's highly effective and well-tolerated pangenotypic direct-acting antiviral regimens have maximized simplification of hepatitis C virus (HCV) treatment, there remain a plethora of barriers to HCV screening, diagnosis, and linkage to care. As of 2017, only 19% of the estimated 71 million individuals living with chronic HCV worldwide were diagnosed and in 2015 to 2016, only 21% of diagnosed individuals had accessed treatment. Simplification and decentralization of the HCV care cascade would bolster patient engagement and support the considerable scale-up needed to achieve WHO targets. Recent developments in HCV screening and diagnosis, together with reduced pretreatment assessment and on-treatment monitoring requirements, can further streamline the care continuum, ensuring patients are linked to care quickly and earlier in the disease course, and minimize clinic visits.

Publication History

Article published online:
28 July 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

  • References

  • 1 Cooke GS, Andrieux-Meyer I, Applegate TL. et al; Lancet Gastroenterology & Hepatology Commissioners. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol 2019; 4 (02) 135-184
  • 2 World Health Organization (WHO). Global health sector strategy on viral hepatitis, 2016–2021: towards ending viral hepatitis. Available at:;jsessionid=3353B8BE60FB5081680122276F404913?sequence=1 . Accessed April 2020
  • 3 World Health Organization (WHO). Hepatitis C: key facts. Available at: . Accessed April 2020
  • 4 Lazarus JV, Pericàs JM, Picchio C. et al. We know DAAs work, so now what? Simplifying models of care to enhance the hepatitis C cascade. J Intern Med 2019; 286 (05) 503-525
  • 5 American Association for the Study of Liver Diseases (AASLD) IDSA. HCV guidance: Recommendations for testing, managing, and treating hepatitis C. Available at: . Accessed April 2020
  • 6 European Association for the Study of the Liver. Electronic address:; European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol 2018; 69 (02) 461-511
  • 7 World Health Organization (WHO). Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. Available at: . Accessed April 2020
  • 8 US Preventive Services Task Force. Hepatitis C virus infection in adolescents and adults: screening. Available at: . Accessed April 2020
  • 9 Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. Centers for Disease Control. CDC recommendations for hepatitis C screening among adults - United States, 2020. MMWR Recomm Rep 2020; 69 (02) 1-17
  • 10 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55 (02) 245-264
  • 11 Mishra P, Murray J, Birnkrant D. Direct-acting antiviral drug approvals for treatment of chronic hepatitis C virus infection: scientific and regulatory approaches to clinical trial designs. Hepatology 2015; 62 (04) 1298-1303
  • 12 Mulligan K, Sullivan J, Yoon L, Chou J, Van Nuys K. Evaluating HCV screening, linkage to care, and treatment across insurers. Am J Manag Care 2018; 24 (08) e257-e264
  • 13 Smith BD, Morgan RL, Beckett GA. et al; Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep 2012; 61 (RR-4): 1-32
  • 14 Jemal A, Fedewa SA. Recent hepatitis C virus testing patterns among baby boomers. Am J Prev Med 2017; 53 (01) e31-e33
  • 15 Konerman MA, Thomson M, Gray K. et al. Impact of an electronic health record alert in primary care on increasing hepatitis c screening and curative treatment for baby boomers. Hepatology 2017; 66 (06) 1805-1813
  • 16 Grebely J, Larney S, Peacock A. et al. Global, regional, and country-level estimates of hepatitis C infection among people who have recently injected drugs. Addiction 2019; 114 (01) 150-166
  • 17 Trickey A, Fraser H, Lim AG. et al. The contribution of injection drug use to hepatitis C virus transmission globally, regionally, and at country level: a modelling study. Lancet Gastroenterol Hepatol 2019; 4 (06) 435-444
  • 18 Iversen J, Grebely J, Topp L, Wand H, Dore G, Maher L. Uptake of hepatitis C treatment among people who inject drugs attending Needle and Syringe Programs in Australia, 1999-2011. J Viral Hepat 2014; 21 (03) 198-207
  • 19 Delile JM, de Ledinghen V, Jauffret-Roustide M. et al. Hepatitis C virus prevention and care for drug injectors: the French approach. Hepatol Med Policy 2018; 3: 7
  • 20 Scherz N, Bruggmann P, Brunner N. Direct-acting antiviral therapy for hepatitis C infection among people receiving opioid agonist treatment or heroin assisted treatment. Int J Drug Policy 2018; 62: 74-77
  • 21 Akiyama MJ, Norton BL, Arnsten JH, Agyemang L, Heo M, Litwin AH. Intensive models of hepatitis C care for people who inject drugs receiving opioid agonist therapy: a randomized controlled trial. Ann Intern Med 2019; 170 (09) 594-603
  • 22 McLeod A, Weir A, Aitken C. et al. Rise in testing and diagnosis associated with Scotland's Action Plan on Hepatitis C and introduction of dried blood spot testing. J Epidemiol Community Health 2014; 68 (12) 1182-1188
  • 23 Esmat G, El-Sayed MH, Hassany M, Doss W, Waked I. National Committee for the Control of Viral Hepatitis. One step closer to elimination of hepatitis C in Egypt. Lancet Gastroenterol Hepatol 2018; 3 (10) 665
  • 24 Eckman MH, Ward JW, Sherman KE. Cost effectiveness of universal screening for hepatitis C virus infection in the era of direct-acting, pangenotypic treatment regimens. Clin Gastroenterol Hepatol 2019; 17 (05) 930-939.e9
  • 25 Deuffic-Burban S, Huneau A, Verleene A. et al. Assessing the cost-effectiveness of hepatitis C screening strategies in France. J Hepatol 2018; 69 (04) 785-792
  • 26 Koneru A, Nelson N, Hariri S. et al. Increased hepatitis C virus (HCV) detection in women of childbearing age and potential risk for vertical transmission—United States and Kentucky, 2011–2014. MMWR Morb Mortal Wkly Rep 2016; 65 (28) 705-710
  • 27 Dibba P, Cholankeril R, Li AA. et al. Hepatitis C in pregnancy. Diseases 2018; 6 (02) 31
  • 28 Indolfi G, Easterbrook P, Dusheiko G. et al. Hepatitis C virus infection in children and adolescents. Lancet Gastroenterol Hepatol 2019; 4 (06) 477-487
  • 29 Saab S, Kullar R, Gounder P. The urgent need for hepatitis C screening in pregnant women: a call to action. Obstet Gynecol 2020; 135 (04) 773-777
  • 30 Modin L, Arshad A, Wilkes B. et al. Epidemiology and natural history of hepatitis C virus infection among children and young people. J Hepatol 2019; 70 (03) 371-378
  • 31 Andreone P, Di Marco V, Gaeta GB, Fagiuoli S, Vukotic R, Craxì A. Current and forthcoming perspectives in linkage to care of hepatitis C virus infection: assessment of an Italian focus group. Dig Liver Dis 2019; 51 (07) 915-921
  • 32 Chevaliez S, Pawlotsky JM. New virological tools for screening, diagnosis and monitoring of hepatitis B and C in resource-limited settings. J Hepatol 2018; 69 (04) 916-926
  • 33 World Health Organization (WHO). WHO prequalification of in vitro diagnostics public reports: hepatitis C assays. Available at: . Accessed April 2020
  • 34 Tang W, Chen W, Amini A. et al. Diagnostic accuracy of tests to detect hepatitis C antibody: a meta-analysis and review of the literature. BMC Infect Dis 2017; 17 (Suppl. 01) 695
  • 35 Bregenzer A, Conen A, Knuchel J. et al. Management of hepatitis C in decentralised versus centralised drug substitution programmes and minimally invasive point-of-care tests to close gaps in the HCV cascade. Swiss Med Wkly 2017; 147: w14544
  • 36 Anderson ES, Galbraith JW, Deering LJ. et al. Continuum of care for hepatitis C virus among patients diagnosed in the emergency department setting. Clin Infect Dis 2017; 64 (11) 1540-1546
  • 37 Parisi MR, Tecco S, Gastaldi G. et al. Point-of-care testing for hepatitis C virus infection at alternative and high-risk sites: an Italian pilot study in a dental clinic. New Microbiol 2017; 40 (04) 242-245
  • 38 Chiong F, Post J. Opportunistic assessment and treatment of people with hepatitis C virus infection admitted to hospital for other reasons: a prospective cohort study. Int J Drug Policy 2019; 65: 50-55
  • 39 Hughes BL, Page CM, Kuller JA. Society for Maternal-Fetal Medicine (SMFM). Electronic address: Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol 2017; 217 (05) B2-B12
  • 40 Morano JP, Zelenev A, Lombard A, Marcus R, Gibson BA, Altice FL. Strategies for hepatitis C testing and linkage to care for vulnerable populations: point-of-care and standard HCV testing in a mobile medical clinic. J Community Health 2014; 39 (05) 922-934
  • 41 Calderon Y, Cowan E, Schramm C. et al. HCV and HBV testing acceptability and knowledge among urban emergency department patients and pharmacy clients. Prev Med 2014; 61: 29-33
  • 42 Lazarus JV, Picchio C, Dillon JF, Rockstroh JK, Weis N, Buti M. Too many people with viral hepatitis are diagnosed late—with dire consequences. Nat Rev Gastroenterol Hepatol 2019; 16 (08) 451-452
  • 43 Vázquez-Morón S, Ardizone Jiménez B, Jiménez-Sousa MA, Bellón JM, Ryan P, Resino S. Evaluation of the diagnostic accuracy of laboratory-based screening for hepatitis C in dried blood spot samples: a systematic review and meta-analysis. Sci Rep 2019; 9 (01) 7316
  • 44 Rege S, Sanchez Y, Marx S. et al. PS-066-Patient flow across physician specialties over the course of the hepatitis C care cascade: a real-world analysis from the United States. J Hepatol 2019; 70: e40
  • 45 Centre for Disease Analysis. Web Annex C. Estimates of the coverage of diagnosis and treatment for hepatitis B and C virus infection, by WHO region and income group, 2015. In: Global Hepatitis Report 2017. Geneva: World Health Organization; 2018 (WHO/CDS/HIV/18.47). Available at: . Accessed April 2020
  • 46 European Union HCV Collaborators. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study. Lancet Gastroenterol Hepatol 2017; 2 (05) 325-336
  • 47 Hajarizadeh B, Grebely J, McManus H. et al. Chronic hepatitis C burden and care cascade in Australia in the era of interferon-based treatment. J Gastroenterol Hepatol 2017; 32 (01) 229-236
  • 48 Veterans Health Administration. Review of hepatitis C virus care within the Veterans Health Administration. Available at: . Accessed April 2020
  • 49 Falade-Nwulia O, McAdams-Mahmoud A, Irvin R. et al. Primary care providers knowledge, attitude and practices related to hepatitis C screening and treatment in the oral direct acting antiviral agents era. J Community Med Health Educ 2016; 6 (05) 6
  • 50 American Association for the Study of Liver Diseases (AASLD) IDSA. Simplified HCV treatment algorithm for treatment-naive adults without cirrhosis. Available at: . Accessed April 2020
  • 51 American Association for the Study of Liver Diseases (AASLD) IDSA. Simplified HCV treatment algorithm for treatment-naive adults with compensated cirrhosis. Available at: . Accessed April 2020
  • 52 Wade AJ, Doyle JS, Gane E. et al. Outcomes of treatment for hepatitis C in primary care, compared to hospital-based care: a randomized, controlled trial in people who inject drugs. Clin Infect Dis 2020; 70 (09) 1900-1906
  • 53 Beste LA, Glorioso TJ, Ho PM. et al. Telemedicine specialty support promotes hepatitis C treatment by primary care providers in the Department of Veterans Affairs. Am J Med 2017; 130 (04) 432.e3-438.e3
  • 54 Arora S, Thornton K, Murata G. et al. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med 2011; 364 (23) 2199-2207
  • 55 Kattakuzhy S, Gross C, Emmanuel B. et al; and the ASCEND Providers. Expansion of treatment for hepatitis C virus infection by task shifting to community-based nonspecialist providers: a nonrandomized clinical trial. Ann Intern Med 2017; 167 (05) 311-318
  • 56 Lee A, Hanson J, Fox P, Spice G, Russell D, Boyd P. A decentralised, multidisciplinary model of care facilitates treatment of hepatitis C in regional Australia. J Virus Erad 2018; 4 (03) 160-164
  • 57 Nasir IA, Yakubu S, Mustapha JO. Epidemiology and synergistic hepatopathology of malaria and hepatitis C virus coinfection. Virology (Auckl) 2017; 8: X17724411
  • 58 Popping S, Bade D, Boucher C. et al. The global campaign to eliminate HBV and HCV infection: International Viral Hepatitis Elimination Meeting and core indicators for development towards the 2030 elimination goals. J Virus Erad 2019; 5 (01) 60-66
  • 59 Rhea S, Seña AC, Hilton A, Hurt CB, Wohl D, Fleischauer A. Integrated hepatitis C testing and linkage to care at a local health department sexually transmitted disease clinic: determining essential resources and evaluating outcomes. Sex Transm Dis 2018; 45 (04) 229-232
  • 60 Cachay ER, Hill L, Ballard C. et al. Increasing hepatitis C treatment uptake among HIV-infected patients using an HIV primary care model. AIDS Res Ther 2013; 10 (01) 9
  • 61 Bischoff J, Boesecke C, Ingiliz P. et al; GECCO study group. Has increased rollout of direct acting antiviral therapy decreased the burden of late presentation and advanced liver disease in patients starting hepatitis C virus therapy in Germany?. J Clin Gastroenterol 2020; 54 (02) 192-199
  • 62 Chirikov VV, Marx SE, Manthena SR, Strezewski JP, Saab S. Development of a comprehensive dataset of hepatitis C patients and examination of disease epidemiology in the United States, 2013–2016. Adv Ther 2018; 35 (07) 1087-1102
  • 63 Trivedi HD, Patwardhan VR, Malik R. Chronic hepatitis C infection—noninvasive assessment of liver fibrosis in the era of direct acting antivirals. Dig Liver Dis 2019; 51 (02) 183-189
  • 64 Norton BL, Akiyama MJ, Zamor PJ, Litwin AH. Treatment of chronic hepatitis C in patients receiving opioid agonist therapy: a review of best practice. Infect Dis Clin North Am 2018; 32 (02) 347-370
  • 65 Bruggmann P, Litwin AH. Models of care for the management of hepatitis C virus among people who inject drugs: one size does not fit all. Clin Infect Dis 2013; 57 (Suppl. 02) S56-S61
  • 66 Fontana RJ, Lens S, McPherson S. et al. Efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve adults with HCV genotype 1–6 and aspartate aminotransferase to platelet ratio index (APRI) ≤1. Hepatology 2018; 68: 388A-389A
  • 67 Gupta N, Kateera F, Desalegn H, Ocama P, Njouom R, Lacombe K. Is resistance to direct-acting antivirals in sub-Saharan Africa a threat to HCV elimination? Recommendations for action. J Hepatol 2020; 72 (03) 583-584
  • 68 World Health Organization W. Progress report on access to hepatitis C treatment: Focus on overcoming barriers in low- and middle-income countries. Available at: . Accessed April 2020
  • 69 Marshall AD, Pawlotsky JM, Lazarus JV, Aghemo A, Dore GJ, Grebely J. The removal of DAA restrictions in Europe—One step closer to eliminating HCV as a major public health threat. J Hepatol 2018; 69 (05) 1188-1196
  • 70 National Viral Hepatitis Roundtable. Hepatitis C: the state of Medicaid access: 2017 National Summary Report, October 23, 2017. Available at: . Accessed April 2020
  • 71 Cunningham EB, Amin J, Feld JJ. et al; SIMPLIFY study group. Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use: The SIMPLIFY study. Int J Drug Policy 2018; 62: 14-23
  • 72 Kattakuzhy S, Mathur P, Gross C. et al. High SVR in PWID with HCV despite imperfect medication adherence: data from the Anchor study. Hepatology 2018; 68: 12A (abstract18)
  • 73 The National Academies of Sciences, Engineering, and Medicine. A national strategy for the elimination of hepatitis B and C: phase two report, Available at: . Accessed April 2020
  • 74 AbbVie. Mavyret (glecaprevir/pibrentasvir) US prescribing information (September 2019). Available at: . Accessed April 2020
  • 75 Gilead. Epclusa (sofosbuvir/velpatasvir) US prescribing information. Available at: . Accessed April 2020
  • 76 Republic of Rwanda Ministry of Health. Rwanda's fight in the elimination of hepatitis C virus. Available at: . Accessed April 2020
  • 77 Iyengar S, Tay-Teo K, Vogler S. et al. Prices, costs, and affordability of new medicines for hepatitis C in 30 countries: an economic analysis. PLoS Med 2016; 13 (05) e1002032-e1002032
  • 78 Perazzo H, Castro R, Luz PM. et al. Effectiveness of generic direct-acting agents for the treatment of hepatitis C: systematic review and meta-analysis. Bull World Health Organ 2020; 98 (03) 188-197K
  • 79 VanOpdorp JR, Ferrentino N, Strader DB, Lidofsky SD. Utility of laboratory monitoring during hepatitis C treatment with ribavirin-free direct-acting antiviral regimens. J Viral Hepat 2019; 26 (06) 778-781
  • 80 D'Ambrosio R, Pasulo L, Puoti M. et al; NAVIGATORE-Lombardia Study Group. Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C. J Hepatol 2019; 70 (03) 379-387
  • 81 Maasoumy B, Buggisch P, Mauss S. et al. Clinical significance of detectable and quantifiable HCV RNA at the end of treatment with ledipasvir/sofosbuvir in GT1 patients. Liver Int 2018; 38 (11) 1906-1910
  • 82 Cuadrado A, Llerena S, Cobo C. et al. Microenvironment eradication of hepatitis C: a novel treatment paradigm. Am J Gastroenterol 2018; 113 (11) 1639-1648
  • 83 Dore G, Feld J, Thompson A. et al. PS-178-Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir: the SMART-C study. J Hepatol 2019; 70: e110
  • 84 Mutasa-Apollo T, Ford N, Wiens M. et al. Effect of frequency of clinic visits and medication pick-up on antiretroviral treatment outcomes: a systematic literature review and meta-analysis. J Int AIDS Soc 2017; 20 (Suppl. 04) 21647
  • 85 Welzel TM, Yang M, Sajeev G. et al. Assessing patient preferences for treatment decisions for new direct acting antiviral (DAA) therapies for chronic hepatitis C virus infections. Adv Ther 2019; 36 (09) 2475-2486
  • 86 Aspinall EJ, Corson S, Doyle JS. et al. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis 2013; 57 (Suppl. 02) S80-S89
  • 87 Heffernan A, Cooke GS, Nayagam S, Thursz M, Hallett TB. Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model. Lancet 2019; 393 (10178): 1319-1329
  • 88 Loustaud-Ratti V, Debette-Gratien M, Carrier P. European Association for the Study of the Liver and French hepatitis C recent guidelines: the paradigm shift. World J Hepatol 2018; 10 (10) 639-644
  • 89 Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of hepatitis C infection: a consensus statement. Available at: . Accessed April 2020