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Hepatitis C and transfusion: A 'lookback' primer

Joy L Fridey, MD
Section Editor
Arthur J Silvergleid, MD
Deputy Editor
Jennifer S Tirnauer, MD


In 2000, primary care physicians, surgeons, and other medical specialists began receiving notification from hospital blood banks that a patient they had previously treated or were currently treating may have been exposed to hepatitis C virus (HCV) as a result of blood transfusion. This United States Public Health Service (USPHS)-mandated notification, developed in conjunction with the US Food and Drug Administration (FDA), may have come as a surprise to community physicians who were faced with the task of locating patients, informing them about the possible exposure, providing appropriate testing and counseling, and possibly evaluating or treating those who were found to be HCV positive, in a process referred to as "lookback."

Strictly speaking, lookback is the process through which patients who may have received pathogen-infected blood are identified by tracing a suspect donor's previous donations to those recipients for the purpose of testing, evaluation, and providing treatment as indicated. Transfusion recipients who are the focus of HCV lookback are those who have been transfused with blood from a now HCV-confirmed positive donor who either had not been previously tested for HCV or who was negative for HCV at the time of previous donations; or from a donor who is now HCV test reactive, but results cannot be confirmed, or further testing cannot performed using an assay that meets FDA specifications. Lookback is required for other pathogens such as HIV, but hepatitis C was unique because of the United States federal government's prescriptive requirements for patient notification that involve the physician of record.

Recognizing that involvement in an HCV lookback process is an infrequent and possibly new experience for many practitioners, the purpose of this discussion is to review the rationale for HCV lookback, define lookback, outline regulatory expectations, and provide physicians in the United States with resources that can make the patient notification process less onerous. Similar programs exist in other countries.

Recommendations for screening and diagnosis of HCV infection in the general population is presented separately. (See "Screening for chronic hepatitis C virus infection".)


It is estimated that up to four million Americans are infected with HCV [1]. The majority of these individuals have been exposed to the virus through the sharing of needles used in injection drug use, and a smaller percentage through sexual contact, perinatally, or occupationally. Approximately one-third of infected people do not identifiably fall into these risk categories, but have a history of behavior, such as multiple sex partners, that places them at higher risk [2,3]. (See "Epidemiology and transmission of hepatitis C virus infection".)

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Literature review current through: Nov 2017. | This topic last updated: Feb 27, 2017.
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  1. www.cdc.gov/hepatitis/HCV/index.htm (Accessed on March 24, 2010).
  2. Alter MJ. Epidemiology of hepatitis C. Hepatology 1997; 26:62S.
  3. Alter MJ, Hadler SC, Judson FN, et al. Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA 1990; 264:2231.
  4. Zou S, Stramer SL, Dodd RY. Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogeneic donations. Transfus Med Rev 2012; 26:119.
  5. Zou S, Dorsey KA, Notari EP, et al. Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion 2010; 50:1495.
  6. Alter MJ. Public Health Service, Centers for Disease Control and Prevention. August 22, 1997 Memorandum.
  7. Guidance for Industry. Current Good Manufacturing Practice of Blood and Blood Components: (1) Quarantine and Disposition of Units from Prior Collections from Donors with Repeatedly Reactive Screening Tests for Antibody to Hepatitis C Virus (Anti-HCV); (2) Supplemental Testing, and the Notification of Consignees and Blood Recipients of Donor Test Results for Anti-HCV. US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research Center, September, 1998.
  8. Current Good Manufacturing Practice for Blood and Blood Components; Notification of Consignees and Transfusion Recipients Receiving Blood and Blood Products at Increased Risk of Transmitting Hepatitis C Infection; Final Rule. Federal Register, 72(160), August 24, 2007.
  9. Requirements for Blood and Blood Components Intended for Transfusion or for Further Manufacturing Use; Final Rule. Federal Register: May 22, 2015 (Volume 80, Number 99), Page 29842, US Department of Health and Human Services, Food and Drug Administration. Available online at https://www.gpo.gov/fdsys/pkg/FR-2015-05-22/html/2015-12228.htm
  10. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999; 341:556.
  11. Wall A, Lau W, Lewis J, et al. Hepatitis C virus (HCV) targeted lookback program. Transfusion 1997; 37:98S.
  12. Christensen PB, Groenbaek K, Krarup HB. Transfusion-acquired hepatitis C: the Danish lookback experience. The Danish HCV [hepatitis C virus] Lookback Group. Transfusion 1999; 39:188.
  13. Vrielink H, van der Poel CL, Reesink HW, et al. Look-back study of infectivity of anti-HCV ELISA-positive blood components. Lancet 1995; 345:95.
  14. Lau W, Bischochio M, Poon A. Hepatitis C targeted lookback in pediatric patients. Transfusion 1997; 37:99S.
  15. Goldman M, Juodvalkis S, Gill P, Spurll G. Hepatitis C lookback. Transfus Med Rev 1998; 12:84.
  16. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332:1463.
  17. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997; 349:825.
  18. Gumber SC, Chopra S. Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. Ann Intern Med 1995; 123:615.
  19. Koff RS, Dienstag JL. Extrahepatic manifestations of hepatitis C and the association with alcoholic liver disease. Semin Liver Dis 1995; 15:101.
  20. Seeff LB, Buskell-Bales Z, Wright EC, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med 1992; 327:1906.
  21. Di Bisceglie AM, Order SE, Klein JL, et al. The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Am J Gastroenterol 1991; 86:335.
  22. Di Bisceglie AM, Goodman ZD, Ishak KG, et al. Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis. Hepatology 1991; 14:969.
  23. Everhart JE, Di Bisceglie AM, Murray LM, et al. Risk for non-A, non-B (type C) hepatitis through sexual or household contact with chronic carriers. Ann Intern Med 1990; 112:544.
  24. Dienstag JL. Sexual and perinatal transmission of hepatitis C. Hepatology 1997; 26:66S.
  25. Alter MJ, Coleman PJ, Alexander WJ, et al. Importance of heterosexual activity in the transmission of hepatitis B and non-A, non-B hepatitis. JAMA 1989; 262:1201.
  26. Ohto H, Terazawa S, Sasaki N, et al. Transmission of hepatitis C virus from mothers to infants. The Vertical Transmission of Hepatitis C Virus Collaborative Study Group. N Engl J Med 1994; 330:744.
  27. Resti M, Azzari C, Mannelli F, et al. Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1. Tuscany Study Group on Hepatitis C Virus Infection. BMJ 1998; 317:437.
  28. Wiley TE, McCarthy M, Breidi L, et al. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology 1998; 28:805.
  29. Menozzi D, Udulutch T, Llosa AE, Galel SA. HCV lookback in the United States: effectiveness of an extended lookback program. Transfusion 2000; 40:1393.
  30. Bowker SL, Smith LJ, Rosychuk RJ, Preiksaitis JK. A review of general hepatitis C virus lookbacks in Canada. Vox Sang 2004; 86:21.
  31. Goldman M, Patterson L, Long A. Recent Canadian experience with targeted hepatitis C virus lookback. Transfusion 2006; 46:690.
  32. Williams JL, Cagle HH, Christensen CJ, et al. Results of a hepatitis C general transfusion lookback program for patients who received blood products before July 1992. Transfusion 2005; 45:1020.
  33. Luban NL, Colvin CA, Mohan P, Alter HJ. The epidemiology of transfusion-associated hepatitis C in a children's hospital. Transfusion 2007; 47:615.
  34. Whitlock M, Lord S, Buxton JA, et al. Evaluating the impact of public health notification of suspected transfusion-transmissible hepatitis C virus infection and effectiveness of lookback and traceback investigations by Canadian Blood Services in British Columbia, Canada, August 2002 through February 2005. Transfusion 2007; 47:1534.