Q&A regarding updated CDC guidance published July 24, 2020

Testing and Clinical Management of Health Care Personnel Potentially Exposed to Hepatitis C Virus — CDC Guidance, United States, 2020 MMWR Recommend Rep 2020;69(No. RR-6):1–8.

1) What is the purpose of this guidance?

This guidance provides CDC recommendations for laboratory testing and follow-up of healthcare personnel (HCP) who have been potentially exposed to hepatitis C virus (HCV) through an exposure to blood or other infectious body fluid.  Although sharps injury prevention measures have led to overall decreases in exposures in recent decades, HCP blood and body fluid exposures and sharp object injuries continue to occur in healthcare settings such as hospitals, nursing homes, clinics, emergency departments, and during provision of in-home services.[1, 2]

This new guidance for post-exposure testing supersedes all previous guidance including the HCV testing algorithm formerly made available in 2016 on the CDC Division of Viral Hepatitis website, [3] as well as the algorithm published earlier in MMWR in 2001.[4]

2) What has been updated in this new guidance, and how does it differ from the HCV testing algorithm made available in 2016 on the CDC Division of Viral Hepatitis website, as well as guidance published earlier in MMWR in 2001?  Why?  

This new guidance includes three important updates: 1) This report updates the post-exposure laboratory testing algorithm for the exposed HCP with testing for antibodies to HCV four to six months after exposure which was not included in the 2016 algorithm, based on current understanding of early HCV infection viral dynamics. 2) This report also reflects updated guidance from professional organizations that recommends treatment of acute HCV infection[5] (www.hcvguidelines.orgexternal icon ). 3) Guidance for laboratory testing of the patient who is the source of the blood or body fluid is also updated in consideration of the increasing incidence of acute HCV infection among growing numbers of persons who inject drugs.[6]

3) Also new: What is the recommendation for HCP exposed to blood or body fluids from a source patient who tests HCV RNA negative but positive for hepatitis C antibody (anti-HCV)? 

Follow-up testing for HCP exposed to blood or body fluids from a source who tests anti-HCV positive but HCV RNA negative is not currently recommended, as source persons with that laboratory result profile are not considered infectious.  However if there are concerns regarding specimen integrity including handling and storage conditions that may have compromised test results[7], or if at any time clinical signs of HCV infection appear in the HCP, follow-up testing may be warranted. Note that if the HCV RNA levels are below the lower limit of quantitation of the assay, the results are reported as <xx IU/ml (e.g. <15 IU/ml if the lower limit of quantitation of the assay is 15 IU/ml). This means that HCV RNA was detected in the sample but is not quantifiable, and that the person from whom the sample was collected should be considered to have current HCV infection. [7]

To the best of our knowledge we are unaware of transmissions to HCP from a HCV RNA negative, HCV antibody (anti-HCV) positive source.  However, most published descriptions of HCV-exposed HCP focus on source anti-HCV test results rather than tests for HCV RNA (nucleic acid tests, or NAT) [8] and limited published data are available to confirm the lack of risk to HCP[9-12].  Chimpanzee challenge studies have suggested that there is an infectious titer (chimpanzee infective dose) required to transmit infection, and that this level of inoculum is different in other animal models (humanized liver–mouse models).[13] Data are available from one European case-control study of HCP who became anti-HCV positive after exposure to an anti-HCV positive source during 1991-2002, which demonstrated that among the small number for whom source HCV RNA status was known (n=37, 62% of HCP who became anti-HCV positive), all sources had been HCV RNA positive.[9]

4) Do HCP who were tested under the 2016 algorithm with a single HCV RNA test at 3 or more weeks after exposure need to be re-tested for HCV antibody (anti-HCV) now, since they did not have the currently recommended anti-HCV test at 4-6 months post-exposure?  

CDC now recommends the 4-6 month post-exposure anti-HCV test out of an abundance of caution because of the potential for periods of intermittent aviremia during acute infection described in several earlier publications, primarily when older HCV RNA testing methodologies were used. [14-29]  Relevance to use of newer highly sensitive RNA testing is unclear. To the best of our knowledge we are not aware of infections missed by the abbreviated HCV RNA-based testing schedule made available in 2016, which was prompted by marked improvements in HCV RNA testing methodologies which have greater test sensitivity.[30] Our assessment based upon sparse data is that the risk to persons tested under the 2016 guidance is minimal, but not zero.  While testing during a period of intermittent aviremia is a theoretical possibility, we do not recommend notification and re-testing of persons tested under this past algorithm.  However, for any person who has signs or symptoms of viral hepatitis, or for those who wish absolute certain confirmation that transmission did not occur from the past exposure, a test for anti-HCV with reflex to RNA could be considered.

5)  Why is baseline testing of the source for HCV viral RNA (rather than only testing the source for hepatitis C antibody, anti-HCV) recommended?

This updated guidance provides two options for initial source testing: preferred option A, to test the source for HCV RNA; or option B, to test for anti-HCV then if positive test for HCV RNA.  HCV RNA is the more reliable test to determine current HCV infection, particularly in cases when a source is known or suspected to have recent risks for HCV (for example, injection drug use within the past four months), or if risk cannot be reliably assessed.[3]  Persons with very recently acquired acute infection typically have detectable HCV RNA levels as early as one to two weeks after exposure.[7, 14-24] Anti-HCV does not become positive until on average 8-11 weeks after exposure,[4, 7] although this may be delayed among persons with immunosuppression, such as that which occurs with HIV infection.[31, 32] 

The incidence of acute HCV infection is increasing in the United States, primarily related to injection drug use, with a 3.7-fold rise in cases reported to CDC between 2010 and 2017.[6]  Early infections that tested anti-HCV negative but HCV RNA positive were identified among 5.3% of HCV RNA-positive deceased organ donors who had recent behavioral risk factors for viral hepatitis during 2014-2017.[33] These data suggest the possibility that in some healthcare settings HCP may be exposed to source patients with early HCV infection prior to development of detectable HCV antibody.

6) If the source is known to have had a recent negative anti-HCV or HCV RNA test prior to the exposure, is a repeat test of the source at baseline still recommended?   

Previous negative tests do not necessarily reflect the HCV status at the time of exposure.  Therefore, only an HCV RNA test or anti-HCV test at or after the time of the HCP exposure can be considered negative for source testing.  Source baseline testing per Option A or Option B is recommended.

7) If the source is found to have negative HCV tests (Option A or Option B) at baseline, is baseline HCV testing of the HCP still recommended?   

If the source tests negative for HCV following Option A or Option B, then no baseline HCV testing is clinically indicated for the HCP on the basis of the exposure. However, baseline testing may be indicated for other bloodborne pathogens.  In addition, HCP testing for HCV infection may be considered for other purposes, including medicolegal concerns, per institutional protocols, or obtaining HCV RNA testing when the source tested negative for anti-HCV under Option B but has ongoing exposures. Note that screening for HCV infection is recommended at least once in a lifetime for all adults aged ≥18 years (except in settings where the prevalence of HCV infection is <0.1%; currently prevalence among US adults is estimated to be 1.0%). [34]

8) Is there currently recommended post-exposure prophylaxis (PEP) for HCP potentially exposed to HCV, to prevent infection?  

Postexposure prophylaxis (PEP) of hepatitis C is not recommended for HCP who have occupational exposure to blood and other body fluids.[3-5, 35-37] Recent estimates indicate that about 0.2% of HCP exposures to HCV antibody positive blood or body fluids through a break in the skin (also known as percutaneous exposures) resulted in transmission, with even lower incidence for non-percutaneous exposures.[8]  Thus routine PEP use for all occupational percutaneous exposures would treat approximately 1000 HCV-exposed individuals for every two who might become infected. The effectiveness and duration of treatment that would be required for HCV PEP has not been established.[36, 37] A pilot trial of a two-week DAA PEP regimen was initiated in 2019 [38]  for HCP who experience hollow-bore needle exposure to an HCV RNA positive source, factors that may be associated with increased transmission risk, but was ended in early 2020 with no enrollment.[8]  In contrast with the other bloodborne pathogens (hepatitis B virus and HIV) for which PEP is recommended, if HCV transmission does occur, currently available direct acting antiviral therapy is highly effective in eradicating both acute and chronic HCV infections.[5, 36, 37, 39-41]


  1. Mitchell AH, Parker GB, Kanamori H, et al. Comparing non-safety with safety device sharps injury incidence data from two different occupational surveillance systems. J Hosp Infect 2017; 96: 195-198.
  2. International Safety Center. EPINet Sharps Injury and Blood and Body Fluid Data Reports. [cited 2019 July]  https://internationalsafetycenter.org/exposure-reports/external icon
  3. Centers for Disease Control and Prevention (CDC). Information for Healthcare Personnel Potentially Exposed to Hepatitis C Virus (HCV), Recommended Testing and Follow-up. Posted in 2016 [cited 2019 January] Formerly available at: https://www.cdc.gov/hepatitis/pdfs/testing-followup-exposed-hc-personnel-3d.pdfpdf icon
  4. Centers for Disease Control and Prevention (CDC). Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Morb Mortal Wkly Rep 2001; 50: 1-42.
  5. American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA). HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. [cited 2019 November]  Available at: https://www.hcvguidelines.org/external icon
  6. Centers for Disease Control and Prevention (CDC). Surveillance for Viral Hepatitis—United States, 2017. Figure 4.1. Reported number of acute hepatitis C cases- United States, 2001-2017.  [cited 2019 September]  Available at: https://www.cdc.gov/hepatitis/statistics/2017surveillance/TablesFigures-HepC.htm
  7. Association of Public Health Laboratories (APHL). Infectious Diseases, January 2019. Interpretation of Hepatitis C Virus Test Results: Guidance for Laboratories. [cited 2019 June]  Available at:  https://www.aphl.org/aboutAPHL/publications/Documents/ID-2019Jan-HCV-Test-Result-Interpretation-Guide.pdfpdf iconexternal icon
  8. Egro FM, Nwaiwu CA, Smith S, et al. Seroconversion rates among health care workers exposed to hepatitis C virus-contaminated body fluids: The University of Pittsburgh 13-year experience. Am J Infect Control 2017; 45: 1001-1005.
  9. Yazdanpanah Y, De Carli G, Migueres B, et al. Risk factors for hepatitis C virus transmission to health care workers after occupational exposure: a European case-control study. Clin Infect Dis 2005; 41: 1423-30.
  10. Saffo S CR, Kamili S, Wiese N, Hayden T, Jain D, Taddei T, Abstract 1548. Occult HCV infection in patients treated with direct-acting antiviral agents: does this phenomenon exist and is it the driving force for tumorigenesis? , in The 68th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2017. October 20-24, 2017: Washington, DC.
  11. El Ekiaby M, Moftah F, Goubran H, et al. Viremia levels in hepatitis C infection among Egyptian blood donors and implications for transmission risk with different screening scenarios. Transfusion 2015; 55: 1186-94.
  12. Frias M, Rivero-Juarez A, Tellez F, et al. Evaluation of hepatitis C viral RNA persistence in HIV-infected patients with long-term sustained virological response by droplet digital PCR. Sci Rep 2019; 9: 12507.
  13. Bukh J, Meuleman P, Tellier R, et al. Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models. J Infect Dis 2010; 201: 1381-9.
  14. Busch M and Kleinman S. Nucleic acid amplification testing of blood donors for transfusion-transmitted infectious diseases. Transfusion 2000; 40: 143-159.
  15. Glynn SA, Wright DJ, Kleinman SH, et al. Dynamics of viremia in early hepatitis C virus infection. Transfusion 2005; 45: 994-1002.
  16. Hajarizadeh B, Grebely J, Applegate T, et al. Dynamics of HCV RNA levels during acute hepatitis C virus infection. J Med Virol 2014; 86: 1722-9.
  17. Lavillette D, Morice Y, Germanidis G, et al. Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection. J Virol 2005; 79: 6023-34.
  18. Mosley JW, Operskalski EA, Tobler LH, et al. The course of hepatitis C viraemia in transfusion recipients prior to availability of antiviral therapy. J Viral Hepat 2008; 15: 120-8.
  19. Nubling CM, Unger G, Chudy M, et al. Sensitivity of HCV core antigen and HCV RNA detection in the early infection phase. Transfusion 2002; 42: 1037-45.
  20. Page K, Osburn W, Evans J, et al. Frequent longitudinal sampling of hepatitis C virus infection in injection drug users reveals intermittently detectable viremia and reinfection. Clin Infect Dis 2013; 56: 405-13.
  21. Thimme R, Oldach D, Chang KM, et al. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 2001; 194: 1395-406.
  22. Villano SA., Vlahov D, Nelson KE, et al. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 1999; 29: 908-914.
  23. Wang CC, Krantz E, Klarquist J, et al. Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing viral clearance. J Infect Dis 2007; 196: 1474-82.
  24. Gruener NH, Heeg M, Obermeier M, et al. Late appearance of hepatitis C virus RNA after needlestick injury: necessity for a more intensive follow-up. Infect Control Hosp Epidemiol 2009; 30: 299-300.
  25. Weseslindtner L, Neumann-Haefelin C, Viazov S, et al. Acute infection with a single hepatitis C virus strain in dialysis patients: Analysis of adaptive immune response and viral variability. J Hepatol 2009; 50: 693-704.
  26. Morin T, Pariente A, Lahmek P, et al. Favorable outcome of acute occupational hepatitis C in healthcare workers: a multicenter French study on 23 cases. Eur J Gastroenterol Hepatol 2011; 23: 515-20.
  27. Bunchorntavakul C, Jones LM, Kikuchi M, et al. Distinct features in natural history and outcomes of acute hepatitis C. J Clin Gastroenterol 2015; 49: e31-e40.
  28. Sacks-Davis R, Grebely J, Dore GJ, et al. Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection–the InC3 Study. J Infect Dis 2015; 212: 1407-19.
  29. Larghi A, Zuin M, Crosignani A, et al. Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studies. Hepatology 2002; 36: 993-1000.
  30. Kamili S, Drobeniuc J, Araujo AC, et al. Laboratory diagnostics for hepatitis C virus infection. Clin Infect Dis 2012; 55 Suppl 1: S43-8.
  31. Thomson EC, Nastouli E, Main J, et al. Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV. AIDS 2009; 23: 89-93.
  32. Vanhommerig JW, Thomas XV, van der Meer JT, et al. Hepatitis C virus (HCV) antibody dynamics following acute HCV infection and reinfection among HIV-infected men who have sex with men. Clin Infect Dis 2014; 59: 1678-85.
  33. Abara W, Collier M, Moorman A, et al. Characteristics of deceased solid organ donors and screening results for hepatitis B, C, and human immunodeficiency viruses—United States, 2010-2017. MMWR Morb Mortal Wkly Rep 2019; 68.
  34. Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson A B. CDC recommendations for hepatitis C screening among adults– United States, 220. MMWR Rec Rep 2020; 69: 1-17.
  35. University of California at San Francisco Clinician Consultation Center. PEP Quick Guide for Occupational Exposures. Exposures to HCV. [cited 2019 July]  Available at: http://nccc.ucsf.edu/clinical-resources/pep-resources/pep-quick-guide/#_edn1external icon
  36. Naggie S, Holland DP, Sulkowski MS, et al. Hepatitis C Virus postexposure prophylaxis in the healthcare worker: why direct-acting antivirals don’t change a thing. Clin Infect Dis 2017; 64: 92-99.
  37. ughes HY and Henderson DK. Postexposure prophylaxis after hepatitis C occupational exposure in the interferon-free era. Curr Opin Infect Dis 2016; 29: 373-80.
  38. Clinical Trial NCT03313414: HCV Post-Exposure Prophylaxis for Health Care Workers, initiated August 2019 https://clinicaltrials.gov/ct2/show/NCT03313414?id=NCT03313414&rank=1&load=cartexternal icon
  39. Naggie S, Fierer DS, Hughes MD, et al. Ledipasvir/Sofosbuvir for 8 weeks to treat acute hepatitis C virus infections in men with Human Immunodeficiency Virus infections: Sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals. e-pub ahead of print, Clin Infect Dis 2019.
  40. Boerekamps A, De Weggheleire A, van den Berk GE, et al. Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial. Lancet Gastroenterol Hepatol 2019; 4: 269-277.
  41. Deterding K, Spinner CD, Schott E, et al. Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study. The Lancet Infectious Diseases 2017; 17: 215-222.