|May 10, 2013 |
Please share this email with others interested in improving public health practice through evidence-based strategies. A library of "Did You Know?" information is available online.
Hepatitis C is a serious virus infection that over time can cause liver damage and even liver cancer. Early treatment can prevent this damage. Too many people with hepatitis C do not know they are infected, so they don't get the medical care they need.
3 MillionAbout 3 million adults in the US are infected with the hepatitis C virus, most are baby boomers.
3 in 4Up to 3 in 4 people who are infected don't know they have hepatitis C so they aren't getting the necessary medical care.
1945-1965Baby boomers, anyone born from 1945 through 1965, should get tested for hepatitis C.
Once infected with the hepatitis C virus, nearly 8 in 10 people remain infected for life. A simple blood test, called a hepatitis C antibody test, can tell if you have ever been infected, but cannot tell whether you are still infected. Only a different follow-up blood test can determine if you are still infected. CDC data show only half of people with a positive hepatitis C antibody test had the follow-up test reported to the health department. The other half did not have a follow-up test reported, although some of them may have been tested. Without the follow-up test, a person will not know if they still have hepatitis C and cannot get the medical care they need.
Baby boomers (people born from 1945 through 1965) can:
- Ask your doctor, nurse, or other health care provider for a hepatitis C blood test.
- Encourage family and friends born from 1945 through 1965 to get tested for hepatitis C.
- Test all baby boomers and people with other risks for hepatitis C.
- Make sure everyone who tests positive on the first test gets the follow-up test to find out if they are still infected.
Many baby boomers got infected before the dangers of hepatitis C were well known.Anyone can get hepatitis C, but adults born from 1945 through 1965 are 5 times more likely to have hepatitis C.
- Hepatitis C is mostly spread through contact with an infected person's blood.
- Some people could have gotten infected before widespread screening of blood began in 1992.
- People who have injected drugs, even if only once in the past, could have been infected with the virus from sharing a needle or drug equipment with someone who had hepatitis C.
- Many people do not know how or when they were infected.
- Most people with hepatitis C don't have any symptoms. If symptoms do appear, they can be a sign of serious liver damage.
- Hepatitis C can cause liver scarring and liver failure if left untreated.
- Hepatitis C is a leading cause of liver cancer.
- Successful treatment can get rid of hepatitis C from the body.
- A screening blood test, called an antibody test, shows if a person has ever been infected with the hepatitis C virus.
- If the antibody test is positive, a follow-up RNA blood test is needed to see if a person is still infected with the hepatitis C virus.
- A CDC study shows through health department reports that only 50% of adults who had a positive antibody test had a follow-up test reported. Without a follow-up test, people won't know if they are still infected with the hepatitis C virus.
SOURCE: CDC Recommendations 1998, 1999, and 2012
SOURCE: CDC updated guidance, 2013
US government is:
- Working together with many federal agencies to carry out the Strategic Action Plan for Viral Hepatitis [PDF - 672KB].
- Funding programs that support hepatitis C testing and getting people linked to care and treatment.
- Educating doctors, nurses, and other health care providers about hepatitis C, developing clinical tools and issuing updated guidance to help carry out recommended testing.
- Working with states and communities to improve reporting of hepatitis C test results in order to get people needed services.
- Increasing coverage under the Affordable Care Act so more people will have health insurance for testing and treatment.
State and local public health departments can:
- Let people know where they can get blood tests for hepatitis C.
- Follow-up with health care providers and laboratories for people who have a positive hepatitis C antibody test but have no record of a follow-up test.
- Monitor and report people with hepatitis C infection and promote best practices for testing and linking patients to care.
Doctors, nurses, and other health care providers can:
- Set up systems to make to make sure all patients born from 1945 through 1965 are tested for hepatitis C.
- Test patients with other risks for hepatitis C, including blood transfusions before 1992 or injection drug use.
- Make sure everyone who has a positive hepatitis C antibody test gets the follow-up blood RNA test and is linked to lifesaving care and treatment if infected.
Baby boomers and all persons at risk can:
- Ask their doctor, nurse, or other health care provider about getting tested for hepatitis C.
- Make sure to get a follow-up test if the antibody test is positive to see if they are still infected with the hepatitis C virus.
- To learn more about hepatitis, visit:
People living with hepatitis C can:
- Eat a healthy diet, stay physically active, see a doctor on a regular basis and ask if you could benefit from new and better treatments.
- Talk to your doctor before taking over the counter medicines and avoid alcohol because they can cause liver damage.
- Reduce the risk of transmission to others by not donating blood or sharing personal items that might come into contact with blood.
Vital Signs: Evaluation of Hepatitis C Virus Infection Testing and Reporting — Eight U.S. Sites, 2005–2011
WeeklyMay 10, 2013 / 62(18);357-361
On May 7, 2013, this report was posted as an MMWR Early Release on the MMWR website (http://www.cdc.gov/mmwr).
AbstractBackground: Hepatitis C virus (HCV) infection is a serious public health problem. New infections continue to occur, and morbidity and mortality are increasing among an estimated 2.7–3.9 million persons in the United States living with HCV infection. Most persons are unaware of their infection status. Existing CDC guidelines for laboratory testing and reporting of antibody to HCV do not distinguish between past infection that has resolved and current infection that requires care and evaluation for treatment. To identify current infection, a test for HCV RNA is needed.
Methods: Surveillance data reported to CDC from eight U.S. sites during 2005–2011 were analyzed to determine the proportion of persons newly reported on the basis of a positive test result for HCV infection. Persons reported with a positive result from an HCV antibody test only were compared with persons reported with a positive result for HCV RNA and examined by birth cohort (1945–1965 compared with all other years), surveillance site, and number of reported deaths. Annual rates of persons newly reported with HCV infection in 2011 also were calculated for each site.
Results: Of 217,755 persons newly reported, 107,209 (49.2%) were HCV antibody positive only, and 110,546 (50.8%) were reported with a positive HCV RNA result that confirmed current HCV infection. In both groups, persons were most likely to have been born during 1945–1965 (58.5% of those who were HCV antibody positive only; 67.2% of those who were HCV RNA positive). Among all persons newly reported for whom death data were available, 6,734 (3.4%) were known to have died; deaths were most likely among persons aged 50–59 years. In 2011, across all sites, the annual rate of persons newly reported with HCV infection (positive HCV antibody only and HCV RNA positive) was 84.7 per 100,000 population.
Conclusions: Hepatitis C is a commonly reported disease predominantly affecting persons born during 1945–1965, with deaths more frequent among persons of relatively young age. The lack of an HCV RNA test for approximately one half of persons newly reported suggests that testing and reporting must improve to detect all persons with current infection.
Implications for Public Health: In an era of continued HCV transmission and expanding options for curative antiviral therapies, surveillance that identifies current HCV infection can help assess the need for services and link persons with infection to appropriate care and treatment.
In the United States, hepatitis C virus (HCV) infection is a common bloodborne infection. Based on data from national surveys, an estimated 3.2 (95% confidence interval [CI] = 2.7–3.9) million persons in the United States are living with hepatitis C (1). Once infected, approximately 80% of persons remain infected (i.e., chronically infected) and are at risk for substantial morbidity and mortality in later life (2). Although treatment can be curative, an estimated 45%–85% of infected persons are unaware of their HCV infection (3). HCV infection is a major cause of liver disease, including cirrhosis and liver cancer (4–7), and in the United States, is the leading indication for liver transplantation (8). Moreover, rates of liver cancer and deaths from HCV infection have increased over time; approximately 15,000 HCV-associated deaths were recorded in 2007 (4,9). In addition, considerable costs are associated with HCV infection, both in lost productivity and health-care expenditures (10–11).
CDC guidelines for HCV laboratory testing and reporting, published in 2003, do not focus on identifying persons with current infection (12); therefore, depending on the HCV test used, reports to surveillance programs can include persons with a test result indicating past HCV infection that has resolved and also persons with a test result that identifies current HCV infection. Analysis of state and local surveillance data can be used to assess the proportion of persons who might need additional testing to discriminate previous resolved infection from current infection. Analysis of such data also can estimate the number of persons with current HCV infection requiring clinical assessment for treatment, as well as guide prevention strategies. In addition, these surveillance data can serve as a baseline for indirectly evaluating use of the recent HCV testing recommendations to identify HCV infection among persons born during 1945–1965, a group that demonstrates the highest prevalence of infection, compared with those born in other years (3). Finally, examining mortality patterns among persons reported with current HCV infection can improve understanding of the natural history of the disease.
In 2011, CDC supported surveillance for HCV infection at eight U.S. sites (Colorado, Connecticut, Minnesota, New Mexico, New York City, New York state, Oregon, and San Francisco). CDC began receiving data in 2005 from four sites (Colorado, Minnesota, New York state and Oregon), one site in 2006 (New Mexico), two sites in 2008 (New York City and San Francisco), and one site in 2009 (Connecticut). For all sites, clinical laboratories reported only positive test results of HCV infection (i.e., from HCV antibody testing or from HCV RNA testing); health departments did not require reporting of negative results. Reports were reviewed and de-duplicated to ensure that persons with newly reported positive HCV test results were included only once in the surveillance database.
For this analysis, persons reported to CDC during 2005–2011 were categorized as 1) reported with only a positive test result for HCV antibody (HCV antibody positive only) or 2) reported with a positive HCV RNA result from HCV nucleic acid testing or HCV genotyping (HCV RNA positive). Persons who tested HCV antibody positive only were considered as having had a past HCV infection that had resolved, a false-positive test result, or current HCV infection. Persons who tested HCV RNA positive were considered currently HCV infected. Although no laboratory test exists to distinguish acute from chronic HCV infection, for the purpose of this study all persons determined to be currently infected were considered to have chronic infection.
Each group (HCV antibody positive only and HCV RNA positive) was examined by birth cohort (1945–1965 compared with all other birth years) and surveillance site. Annual rates of all persons newly reported per 100,000 population in 2011 also were calculated for each site using denominators available from U.S. Census population estimates (available at http://www.census.gov/compendia/statab). In addition, seven of the sites reported the frequency of known deaths from any cause among persons newly reported with HCV infection. Sites matched their hepatitis C databases with vital records at the person level. Death status was examined by sex, age group, birth cohort, and type of test result (HCV antibody positive only or HCV RNA positive).
During 2005–2011, among the eight sites, a total of 217,755 persons were newly reported with a positive test result for HCV infection. Of these, 107,209 (49.2%) were HCV antibody positive only and 110,546 (50.8%) were HCV RNA positive. In both groups, persons were more likely born during 1945–1965. Persons born during these years accounted for 58.5% of those who were HCV antibody positive only and 67.2% of those who were HCV RNA positive (Table 1). The distribution of persons reported on the basis of positive HCV antibody only varied by site, ranging from 76% in New Mexico to 23% in Minnesota (Figure). Among sites reporting deaths, 6,734 (3.4%) of 197,844 persons newly reported with HCV infection were known to have died. The highest percentage of these deaths occurred among persons aged 50–59 years (44.8%), and most deaths (71.5%) were among those born during 1945–1965, compared with other years. The percentage of deaths among persons reported with HCV antibody positive only (4.6%) was significantly higher than among those reported as HCV RNA positive (2.4%; p<0 .01="" 100="" 2011="" 239.2="" 36.0="" 84.7="" across="" all="" and="" annual="" antibody="" class="callout-pink" francisco="" hcv="" in="" infection="" minnesota="" newly="" of="" only="" per="" persons="" population="" positive="" range:="" rate="" reported="" rna="" san="" sites="" span="" the="" to="" was="" with="">Table 20>
). Conclusions and Comment
These data show that approximately one half of persons newly reported with HCV infection to state or local authorities at eight surveillance sites did not have a report of a positive HCV RNA test; thus, it was not possible to determine whether the reports indicated past resolved HCV infection or current HCV infection. Previous studies have shown similar results. A separate analysis of surveillance data reported for 2006–2007 found that 47.3% of persons reported with positive HCV antibody did not have HCV RNA test results (13). A multisite cohort study of patients in care for chronic viral hepatitis revealed that 37.7% of 9,086 patients with a positive HCV antibody test during 2006–2008 had no documented follow-up testing for HCV RNA (14). A retrospective study of HCV antibody testing in selected U.S. primary-care settings among persons born during 1945–1965 found that, among patients who were antibody positive, 32% received no follow-up HCV RNA testing (15). In New York City, 33% of persons reported through routine surveillance did not have HCV RNA testing (16).
Given these findings and recent developments in both HCV testing technologies and clinical care for persons with HCV infection, CDC is amending the guidelines for HCV laboratory testing and result reporting that have been in use since 2003 (12). In guidance accompanying this Vital Signs report, CDC recommends following a positive HCV antibody test with HCV RNA testing (17). This guidance is also consistent with that provided in the 2012 HCV testing recommendations for persons born during 1945–1965 (3). The new guidelines will help identify persons with current HCV infection and provide the data necessary to link those who are infected to care, including preventive services, medical management, and evaluation for antiviral treatment.
An unexpected result was the finding of a significantly greater percentage of deaths among persons who were HCV antibody positive only compared with those who were HCV RNA positive. Because persons in the latter group have demonstrated current infection, they would be expected to fare less well than those who were HCV antibody positive only and might or might not be currently infected. The difference between the groups in the percentage of deaths might be explained by health-care access. HCV RNA testing might not be available in sites providing HCV antibody testing and RNA testing requires successful referral to a health-care provider. Thus, this finding could suggest that persons reported on the basis of a positive HCV antibody test only might have had less opportunity to access health care or might have accessed health care less often than those with current infection.
This study also revealed a high rate of reported HCV infection at these U.S. sites, especially among persons born during 1945–1965. These findings reinforce recent CDC recommendations for HCV antibody testing of persons born during 1945–1965, and linkage to care for those with a follow-up positive result after HCV RNA testing (3). These data further showed that deaths were more likely among persons aged 50–59 years and among persons born during 1945–1965 compared with those born in other years, illustrating the important impact of HCV infection on years of life lost.
The findings in this report are subject to at least five limitations. First, state and local health departments only report positive HCV test results to CDC. Thus, it was not known whether persons who were reported HCV antibody positive only might actually have been tested for HCV RNA with a negative result. Another possibility is that HCV RNA testing was performed with a positive result, but was not reported. Second, some positive HCV antibody test results might have been false-positives. However, the high specificity of 3rd generation HCV antibody assays used during the period of study would have minimized the number of false positives (18). Third, among sites, there was variation in reporting by health-care providers, laboratories, and health departments, which might affect the consistency of the information reported. For example, the Connecticut hepatitis C surveillance system did not enter HCV RNA results for persons reported with a positive antibody test that previously had been confirmed to be positive for antibody to HCV by another laboratory test. Fourth, some sites began reporting surveillance data to CDC in 2006 or 2008, and in one case, 2009, thereby underestimating the number of cases reported during the entire 2005–2011 study period. In contrast, the number of deaths reported was from all-cause mortality, and therefore was likely an overestimation of HCV-attributable mortality. Finally, HCV surveillance data might not be representative of all persons with HCV infection, and the findings from these eight sites might not be representative of other U.S. cities and states.
Monitoring current HCV infection in states and localities can help gauge what interventions and services are needed to identify persons with HCV infection and effectively link them to appropriate care and treatment. This is of particular importance now in an era of continued HCV transmission and rapidly improving therapeutic options for persons living with HCV infection. To help identify persons with current HCV infection, public health and clinical care providers can offer HCV antibody testing to persons born during 1945–1965, in addition to those with other HCV risk factors, and test for HCV RNA those persons who test positive for HCV antibody. Laboratories can ensure that test results are reported to state and local health authorities, and health departments can develop strategies to monitor and increase the use of HCV RNA testing of persons who are HCV antibody positive.
Reported byKatherine Bornschlegel, MPH, New York City Dept of Health and Mental Hygiene, New York, New York. Deborah Holtzman, PhD, R. Monina Klevens, DDS, John W. Ward, MD, Div of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC. Corresponding contributor: Deborah Holtzman, firstname.lastname@example.org, 404-718-8555.
AcknowledgmentsTerry Bryant, New Mexico Department of Health; Kashif Iqbal, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Emily McGibbon, New York City Department of Health and Mental Hygiene; Elena M. Rizzo, New York State Department of Health; Melissa Sanchez, San Francisco Department of Public Health; Suzanne Speers, Connecticut Department of Public Health; Kristin Sweet, Minnesota Department of Health; Ann Thomas, Oregon Public Health Division; Candace Vonderwahl, Colorado Department of Public Health and Environment.
- Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WI, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144:705–14.
- Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009;49:1335–74.
- CDC. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR 2012;61(No. RR-4).
- Kanwal F, Hoang T, Kramer JR, et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology 2011;140:1182–8.
- Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: liver, biliary tract, and pancreas. Gastroenterology 2009;136:1134–44.
- Yang JD, Kim WR, Coelho R, et al. Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma. Clin Gastroenterol Hepatol 2011;9:64–70.
- Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin 2012;62:128.
- Kim WR, Terrault NA, Pedersen RA, et al. Trends in waiting list registration for liver transplantation for viral hepatitis in the United States. Gastroenterology 2009;137:1680–6.
- Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156:271–8.
- Su J, Brook RA, Kleinman NL, Corey-Lisle P. The impact of hepatitis C virus infection on work absence, productivity, and healthcare benefit costs. Hepatology 2010;52:436–42.
- Davis KL, Mitra D, Medjedovic J, et al. Direct economic burden of chronic hepatitis C virus in a United States managed care population. J Clin Gastroenterol 2011;45:17–24.
- CDC. Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. MMWR 2003;52(No. RR–3).
- Klevens RM, Miller J, Vonderwahl C et al. Population-based surveillance for hepatitis C virus, United States, 2006–2007. Emerg Infect Dis 2009;15:1499–502.
- Moorman AC, Gordon SC, Rupp LB, et al. Baseline characteristics and mortality among people in care for chronic viral hepatitis: The Chronic Hepatitis Cohort Study. Clin Infect Dis 2013;56:40–50.
- Rein DB, Wagner D, Brown K, et al. Hepatitis C antibody testing and follow-up in primary care settings: a retrospective study of four large, primary care service centers. Programs and abstracts of the National Summit on HIV and Viral Hepatitis Diagnosis, Prevention and Access to Care, November 26–28, 2012, Washington, DC.
- McGibbon E, Bornschlegel K, Balter S. Half a diagnosis: gap in confirming infection among hepatitis C antibody-positive patients. Am J Med. In press 2013.
- CDC. Testing for HCV infection: An update of guidance for clinicians and laboratorians. MMWR 2013;62(18).
- Stramer SL, Dodd RY, Brodsky JP. The value of screening signal-to-cutoff ratios for hepatitis C virus antibody confirmation. Transfusion. November 26, 2012. Epub ahead of print.
Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians
Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians
WeeklyMay 10, 2013 / 62(18);362-365
On May 7, 2013, this report was posted as an MMWR Early Release on the MMWR website (http://www.cdc.gov/mmwr).
In the United States, an estimated 4.1 million persons have been infected with hepatitis C virus (HCV), of whom an estimated 3.2 (95% confidence interval [CI] = 2.7–3.9) million are living with the infection (1). New infections continue to be reported particularly among persons who inject drugs and persons exposed to HCV-contaminated blood in health-care settings with inadequate infection control (2).
Since 1998, CDC has recommended HCV testing for persons with risks for HCV infection (3). In 2003, CDC published guidelines for the laboratory testing and result reporting of antibody to HCV (4). In 2012, CDC amended testing recommendations to include one-time HCV testing for all persons born during 1945–1965 regardless of other risk factors (1).
CDC is issuing this update in guidance because of 1) changes in the availability of certain commercial HCV antibody tests, 2) evidence that many persons who are identified as reactive by an HCV antibody test might not subsequently be evaluated to determine if they have current HCV infection (5), and 3) significant advances in the development of antiviral agents with improved efficacy against HCV (6). Although previous guidance has focused on strategies to detect and confirm HCV antibody (3,4), reactive results from HCV antibody testing cannot distinguish between persons whose past HCV infection has resolved and those who are currently HCV infected. Persons with current infection who are not identified as currently infected will not receive appropriate preventive services, clinical evaluation, and medical treatment. Testing strategies must ensure the identification of those persons with current HCV infection.
This guidance was written by a workgroup convened by CDC and the Association of Public Health Laboratories (APHL), comprising experts from CDC, APHL, state and local public health departments, and academic and independent diagnostic testing laboratories, in consultation with experts from the Veterans Health Administration and the Food and Drug Administration (FDA). The workgroup reviewed laboratory capacities and practices relating to HCV testing, data presented at the CDC 2011 symposium on identification, screening and surveillance of HCV infection (7), and data from published scientific literature on HCV testing. Unpublished data from the American Red Cross on validation of HCV antibody testing also were reviewed.
Changes in HCV Testing Technologies
Since the 2003 guidance was published (4), there have been two developments with important implications for HCV testing:
- Availability of a rapid test for HCV antibody. The OraQuick HCV Rapid Antibody Test (OraSure Technologies) is a rapid assay for the presumptive detection of HCV antibody in fingerstick capillary blood and venipuncture whole blood. Its sensitivity and specificity are similar to those of FDA–approved, laboratory-conducted HCV antibody assays (8). In 2011, a Clinical Laboratory Improvements Amendments waiver was granted to the test by FDA. The waiver provides wider testing access to persons at risk for HCV infection, permitting use of the assay in nontraditional settings such as physician offices, hospital emergency departments, health department clinics, and other freestanding counseling and testing sites.
- Discontinuation of RIBA HCV. The Chiron RIBA HCV 3.0 Strip Immunoblot Assay (Novartis Vaccines and Diagnostics) that was recommended (4) for supplemental testing of blood samples after initial HCV antibody testing is no longer available. As a result, the only other FDA-approved supplemental tests for HCV infection are those that detect HCV viremia.
In 2011, FDA approved boceprevir (Victrelis, Merck & Co.) and telaprevir (Incivek, Vertex Pharmaceuticals) for treatment of chronic hepatitis C genotype 1 infection, in combination with pegylated interferon and ribavirin, in adult patients with compensated liver disease. Boceprevir and telaprevir interfere directly with HCV replication. Persons who complete treatment using either of these drugs combined with pegylated interferon and ribavirin are more likely to clear virus (i.e., have virologic cure), compared to those given standard therapy based on pegylated interferon and ribavirin (9). Viral clearance, when sustained, stops further spread of HCV and is associated with reduced risk for hepatocellular carcinoma (10) and all-cause mortality (11). Other compounds under study in clinical trials hold promise for even more effective therapies (6).
Because antiviral treatment is intended for persons with current HCV infection, these persons need to be distinguished from persons whose infection has resolved. HCV RNA in blood, by nucleic acid testing (NAT), is a marker for HCV viremia and is detected only in persons who are currently infected. Persons with reactive results after HCV antibody testing should be evaluated for the presence of HCV RNA in their blood.
Benefits of Testing for Current HCV Infection
Accurate testing to identify current infection is important to 1) help clinicians and other providers correctly identify persons infected with HCV, so that preventive services, care and treatment can be offered; 2) notify tested persons of their infection status, enabling them to make informed decisions about medical care and options for HCV treatment, take measures to limit HCV-associated disease progression (e.g., avoidance or reduction of alcohol intake, and vaccination against hepatitis A and B), and minimize risk for transmitting HCV to others; and 3) inform persons who are not currently infected of their status and the fact that they are not infectious.
Recommended Testing Sequence
The testing sequence in this guidance is intended for use by primary care and public health providers seeking to implement CDC recommendations for HCV testing (1,3,4). In most cases, persons identified with HCV viremia have chronic HCV infection. This testing sequence is not intended for diagnosis of acute hepatitis C or clinical evaluation of persons receiving specialist medical care, for which specific guidance is available (12).
Testing for HCV infection begins with either a rapid or a laboratory-conducted assay for HCV antibody in blood (Figure). A nonreactive HCV antibody result indicates no HCV antibody detected. A reactive result indicates one of the following: 1) current HCV infection, 2) past HCV infection that has resolved, or 3) false positivity. A reactive result should be followed by NAT for HCV RNA. If HCV RNA is detected, that indicates current HCV infection. If HCV RNA is not detected, that indicates either past, resolved HCV infection, or false HCV antibody positivity.
Initial Testing for HCV Antibody. An FDA-approved test for HCV antibody should be used. If the OraQuick HCV Rapid Antibody Test is used, the outcome is reported as reactive or nonreactive. If a laboratory-based assay is used, the outcome is reported as reactive or nonreactive without necessarily specifying signal-to-cutoff ratios.
Testing for HCV RNA. An FDA-approved NAT assay intended for detection of HCV RNA in serum or plasma from blood of at-risk patients who test reactive for HCV antibody should be used. There are several possible operational steps toward NAT after initial testing for HCV antibody:
- Blood from a subsequent venipuncture is submitted for HCV NAT if the blood sample collected is reactive for HCV antibody during initial testing.
- From a single venipuncture, two specimens are collected in separate tubes: one tube for initial HCV antibody testing; and a second tube for HCV NAT if the HCV antibody test is reactive.
- The same sample of venipuncture blood used for initial HCV antibody testing, if reactive, is reflexed to HCV NAT without another blood draw for NAT (13).
- A separate venipuncture blood sample is submitted for HCV NAT if the OraQuick HCV Rapid Antibody Test for initial testing of HCV antibody has used fingerstick blood.
If testing is desired to distinguish between true positivity and biologic false positivity for HCV antibody, then, testing may be done with a second HCV antibody assay approved by FDA for diagnosis of HCV infection that is different from the assay used for initial antibody testing. HCV antibody assays vary according to their antigens, test platforms, and performance characteristics, so biologic false positivity is unlikely to be exhibited by more than one test when multiple tests are used on a single specimen (14).
Test Interpretation and Further Action
"Acute hepatitis C" and "hepatitis C (past or present)" are nationally notifiable conditions, and are subject to mandated reporting to health departments by clinicians and laboratorians, as determined by local, state or territorial law and regulation. Surveillance case definitions are developed by the Council of State and Territorial Epidemiologists in collaboration with CDC (15). In all but a few jurisdictions, positive results from HCV antibody and HCV RNA testing that are indicative of acute, or past or present HCV infection, are reportable. Specific policies for laboratory reporting are found at health department websites (16).
Research, development, validation, and cost-effectiveness studies are ongoing to inform the best practices for detecting HCV viremia and for distinguishing between resolved HCV infection and biologic false positivity for HCV antibody in persons in whom HCV RNA is not detected. Outcomes of these studies will provide comprehensive guidance on testing, reporting, and clinical management, and will improve case definitions for disease notification and surveillance.
Reported byJane P. Getchell, DrPH, Kelly E. Wroblewski, MPH, Assn of Public Health Laboratories. Alfred DeMaria Jr, MD, Massachusetts Dept of Public Health. Christine L. Bean, PhD, New Hampshire Dept of Health. Monica M. Parker, PhD, New York State Dept of Health. Mark Pandori, PhD, San Francisco Dept of Public Health. D. Robert Dufour, MD, VA Medical Center, Washington, DC. Michael P. Busch, MD, PhD, Blood Systems Inc. Mark E. Brecher, MD, LabCorp. William A. Meyer, PhD, Rick L. Pesano, MD, PhD, Quest Diagnostics. Chong-Gee Teo, MD, PhD, Geoffrey A. Beckett, MPH, Aufra C. Araujo, PhD, Bernard M. Branson, MD, Jan Drobeniuc, MD, PhD, Rikita Hatia, MPH, Scott D. Holmberg, MD, MPH, Saleem Kamili, PhD, John W. Ward, MD, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC. Corresponding contributor: Chong-Gee Teo, email@example.com, 404-639-2378.
- CDC. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR 2012;61(No. RR-4).
- CDC. Viral hepatitis surveillance, United States, 2009–2011. Atlanta, GA: US Department of Health and Human Services, CDC; 2012. Available at http://www.cdc.gov/hepatitis/statistics/2010surveillance/index.htm.
- CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No. RR–19).
- CDC. Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. MMWR 2003;52(No. RR–3).
- CDC. Vital signs: evaluation of hepatitis C virus infection testing and reporting—eight U.S. sites, 2005–2011. MMWR 2013;62(18).
- Poordad F, Dieterich D. Treating hepatitis C: current standard of care and emerging direct-acting antiviral agents. J Viral Hepat 2012;19:449–64.
- CDC. Viral Hepatitis Resource Center: 2011 HCV Symposium. Atlanta, GA: US Department of Health and Human Services, CDC; 2011. Available at http://www.cdc.gov/hepatitis/resources/mtgsconf/hcvsymposium2011.htm.
- Shivkumar S, Peeling R, Jafari Y, Joseph L, Pant Pai N. Accuracy of rapid and point-of-care screening tests for hepatitis C: a systematic review and meta-analysis. Ann Intern Med 2012;157:558–66.
- Cooper C, Lester R, Thorlund K, et al. Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a multiple treatment comparison meta-analysis. QJM 2013;106:153–63.
- Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma. A meta-analysis of observational studies. Ann Intern Med 2013;158:329–37.
- Backus LI, Boothroyd DB, Phillips BR, Belperio P, Halloran J, Mole LA. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol 2011;9:509–16.
- Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009;49:1335–74.
- Gale HB, Dufour DR, Qazi NN, Kan VL. Comparison of serial hepatitis C virus detection in samples submitted through serology for reflex confirmation versus samples directly submitted for quantitation. J Clin Microbiol 2011;49:3036–9.
- Vermeersch P, Van Ranst M, Lagrou K. Validation of a strategy for HCV antibody testing with two enzyme immunoassays in a routine clinical laboratory. J Clin Virol 2008;42:394–8.
- CDC. MMWR: Public health resources—state health departments. Atlanta, GA: US Department of Health and Human Services, CDC; 2011. Available at: http://www.cdc.gov/mmwr/international/relres.html.
- CDC. 2013 National notifiable infectious conditions. Atlanta, GA: US Department of Health and Human Services, CDC; 2012. Available at http://wwwn.cdc.gov/nndss/script/conditionlist.aspx?type=0&yr=2013.
CDC DVH - Know More Hepatitis