Table of Contents
Overview and Statistics
What is the case definition for acute Hepatitis C?
Because the clinical characteristics are similar for all types of acute viral hepatitis, the specific viral cause of illness cannot be determined solely on the basis of signs, symptoms, history, or current risk factors, but must be verified by specific serologic testing. For specific serologic tests required to meet the case definition, see the following link:
What is the case definition for chronic Hepatitis C?
Laboratory testing is required for confirmation of the etiologic cause of viral hepatitis. For specific serologic tests, see the following link:
Is additional guidance on viral hepatitis case determination and surveillance available?
Yes. See the Guidelines for Viral Hepatitis Surveillance and Case Management, available at /hepatitis/SurveillanceGuidlines.htm.
What is the incidence of HCV infection in the United States?
The number of acute cases of hepatitis C reported in the US increased from, 1,778 in 2012 to 2,138 in 2013. The CDC estimates approximately 29,718 cases occurred in 2013, after adjusting for asymptomatic infection and underreporting.
What is the prevalence of chronic HCV infection in the United States?
Approximately 2.7 million persons in the United States have chronic HCV infection. Infection is most prevalent among those born during 1945-1965, the majority of whom were likely infected during the 1970s and 1980s when rates were highest.
Who is at risk for HCV infection?
The following persons are at known to be at increased risk for HCV infection:
- Current or former injection drug users, including those who injected only once many years ago
- Recipients of clotting factor concentrates made before 1987, when more advanced methods for manufacturing those products were developed
- Recipients of blood transfusions or solid organ transplants before July 1992, when better testing of blood donors became available
- Chronic hemodialysis patients
- Persons with known exposures to HCV, such as
- health care workers after needlesticks involving HCV-positive blood
- recipients of blood or organs from a donor who tested HCV-positive
- Persons with HIV infection
- Children born to HCV-positive mothers
Is it possible for someone to become infected with HCV and then spontaneously clear the infection?
Yes. Approximately 15%-25% of persons clear the virus from their bodies without treatment and do not develop chronic infection; the reasons for this are not well known.
How likely is HCV infection to become chronic?
HCV infection becomes chronic in approximately 75%-85% of cases.
Why do most persons remain chronically infected with HCV?
A person infected with HCV mounts an immune response to the virus, but replication of the virus during infection can result in changes that evade the immune response. This may explain how the virus establishes and maintains chronic infection.
What are the chances of someone developing chronic HCV infection, chronic liver disease, cirrhosis, or liver cancer or dying as a result of Hepatitis C?
Of every 100 persons infected with HCV, approximately
- 75-85 will go on to develop chronic infection
- 60-70 will go on to develop chronic liver disease
- 5-20 will go on to develop cirrhosis over a period of 20-30 years
- 1-5 will die from the consequences of chronic infection (liver cancer or cirrhosis)
Can persons become infected with a different strain of HCV after they have cleared the initial infection?
Yes. Prior infection with HCV does not protect against later infection with the same or different genotypes of the virus. This is because persons infected with HCV typically have an ineffective immune response due to changes in the virus during infection. For the same reason, no effective pre- or postexposure prophylaxis (i.e., immune globulin) is available.
Is Hepatitis C a common cause for liver transplantation?
Yes. Chronic HCV infection is the leading indication for liver transplants in the United States.
How many deaths can be attributed to chronic HCV infection?
A recent CDC analysis of death certificate data found that HCV-attributable deaths increased significantly between 1999 and 2007. CDC estimates that there were 15,106 deaths caused by HCV in 2007. The citation can be found at "The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007." Ly, K., et al. Annals Of Internal Medicine, 2012. 156(4): p. 271-278
Is there a Hepatitis C vaccine?
No vaccine for Hepatitis C is available. Research into the development of a vaccine is under way.
Transmission and Symptoms
How is HCV transmitted?
HCV is transmitted primarily through large or repeated percutaneous (i.e., passage through the skin) exposures to infectious blood, such as
- Injection drug use (currently the most common means of HCV transmission in the United States)
- Receipt of donated blood, blood products, and organs (once a common means of transmission but now rare in the United States since blood screening became available in 1992)
- Needlestick injuries in health care settings
- Birth to an HCV-infected mother
HCV can also be spread infrequently through
- Sex with an HCV-infected person (an inefficient means of transmission)
- Sharing personal items contaminated with infectious blood, such as razors or toothbrushes (also inefficient vectors of transmission)
- Other health care procedures that involve invasive procedures, such as injections (usually recognized in the context of outbreaks)
What is the prevalence of HCV infection among injection drug users (IDUs)?
The most recent surveys of active IDUs indicate that approximately one third of young (aged 18-30 years) IDUs are HCV-infected. Older and former IDUs typically have a much higher prevalence (approximately 70%-90%) of HCV infection, reflecting the increased risk of continued injection drug use. The high HCV prevalence among former IDUs is largely attributable to needle sharing during the 1970s and 1980s, before the risks of bloodborne viruses were widely known and before educational initiatives were implemented.
Is cocaine use associated with HCV transmission?
There are very limited epidemiologic data to suggest an additional risk from non-injection (snorted or smoked) cocaine use, but this risk is difficult to differentiate from associated injection drug use and sex with HCV-infected partners.
What is the risk of acquiring HCV infection from transfused blood or blood products in the United States?
Now that more advanced screening tests for HCV are used in blood banks, the risk is considered to be less than 1 chance per 2 million units transfused. Before 1992, when blood screening for HCV became available, blood transfusion was a leading means of HCV transmission.
Can HCV be spread during medical or dental procedures?
As long as Standard Precautions and other infection control practices are used consistently, medical and dental procedures performed in the United States generally do not pose a risk for the spread of HCV. However, HCV has been spread in health care settings when injection equipment, such as syringes, was shared between patients or when injectable medications or intravenous solutions were mishandled and became contaminated with blood. Health care personnel should understand and adhere to Standard Precautions, which includes safe injection practices and other guidance aimed at reducing bloodborne pathogen risks for patients and health care personnel. If health care-associated HCV infection is suspected, this should be reported to state and local public health authorities.
Can HCV be spread within a household?
Yes, but this does not occur very often. If HCV is spread within a household, it is most likely a result of direct, through-the-skin exposure to the blood of an infected household member.
What are the signs and symptoms of acute HCV infection?
Persons with newly acquired HCV infection usually are asymptomatic or have mild symptoms that are unlikely to prompt a visit to a health care professional. When symptoms occur, they can include
- Dark urine
- Clay-colored stool
- Abdominal pain
- Loss of appetite
- Joint pain
What percentage of persons infected with HCV develop symptoms of acute illness?
Approximately 20%-30% of those newly infected with HCV experience fatigue, abdominal pain, poor appetite, or jaundice.
How soon after exposure to HCV do symptoms appear?
In those persons who do develop symptoms, the average time period from exposure to symptom onset is 4-12 weeks (range: 2-24 weeks).
What are the signs and symptoms of chronic HCV infection?
Most persons with chronic HCV infection are asymptomatic. However, many have chronic liver disease, which can range from mild to severe, including cirrhosis and liver cancer. Chronic liver disease in HCV-infected persons is usually insidious, progressing slowly without any signs or symptoms for several decades. In fact, HCV infection is often not recognized until asymptomatic persons are identified as HCV-positive when screened for blood donation or when elevated alanine aminotransferase (ALT, a liver enzyme) levels are detected during routine examinations.
Testing and Diagnosis
Who should be tested for HCV infection?
HCV testing is recommended for anyone at increased risk for HCV infection, including:
- Persons born from 1945 through 1965
- Persons who have ever injected illegal drugs, including those who injected only once many years ago
- Recipients of clotting factor concentrates made before 1987
- Recipients of blood transfusions or solid organ transplants before July 1992
- Patients who have ever received long-term hemodialysis treatment
- Persons with known exposures to HCV, such as
- health care workers after needlesticks involving HCV-positive blood
- recipients of blood or organs from a donor who later tested HCV-positive
- All persons with HIV infection
- Patients with signs or symptoms of liver disease (e.g., abnormal liver enzyme tests)
- Children born to HCV-positive mothers (to avoid detecting maternal antibody, these children should not be tested before age 18 months)
What blood tests are used to detect HCV infection?
Several blood tests are performed to test for HCV infection, including:
- Screening tests for antibody to HCV (anti-HCV)
- enzyme immunoassay (EIA)
- enhanced chemiluminescence immunoassay (CIA)
- Qualitative tests to detect presence or absence of virus (HCV RNA polymerase chain reaction [PCR])
- Quantitative tests to detect amount (titer) of virus (HCV RNA PCR)
How do I interpret the different tests for HCV infection?
A table on the interpretation of results of tests for Hepatitis C Virus (HCV) infection and further actions is available at www.cdc.gov/hepatitis/HCV/PDFs/hcv_graph.pdf [PDF - 1 page].
Is an algorithm for HCV diagnosis available?
A flow chart that outlines the serologic testing process beginning with anti HCV testing is available at www.cdc.gov/hepatitis/HCV/PDFs/hcv_flow.pdf [PDF - 1 page].
How soon after exposure to HCV can anti-HCV be detected?
HCV infection can be detected by anti-HCV screening tests (enzyme immunoassay) 4-10 weeks after infection. Anti-HCV can be detected in >97% of persons by 6 months after exposure.
How soon after exposure to HCV can HCV RNA be detected by PCR?
HCV RNA appears in blood and can be detected as early as 2-3 weeks after infection.
Under what circumstances is a false-positive anti-HCV test result likely?
False-positive anti-HCV tests appear more often when persons at low risk for HCV infection (e.g., blood donors) are tested. Therefore, it is important to follow-up all positive anti-HCV tests with a RNA test to establish current infection.
Under what circumstances might a false-negative anti-HCV test result occur?
Persons with early HCV infection might not yet have developed antibody levels high enough that the test can measure. In addition, some persons might lack the (immune) response necessary for the test to work well. In these persons, further testing such as PCR for HCV RNA may be considered.
Can a patient have a normal liver enzyme (e.g., ALT) level and still have chronic Hepatitis C?
Yes. It is common for patients with chronic Hepatitis C to have liver enzyme levels that go up and down, with periodic returns to normal or near normal levels. Liver enzyme levels can remain normal for over a year despite chronic liver disease.
Management and Treatment
What should be done for a patient with confirmed HCV infection?
HCV-positive persons should be evaluated (by referral or consultation, if appropriate) for presence of chronic liver disease, including assessment of liver function tests, evaluation for severity of liver disease and possible treatment, and determination of the need for Hepatitis A and Hepatitis B vaccination.
When might a specialist be consulted in the management of HCV-infected persons?
Any physician who manages a person with Hepatitis C should be knowledgeable and current on all aspects of the care of a person with Hepatitis C; this can include some internal medicine and family practice physicians as well as specialists such as infectious disease physicians, gastroenterologists, or hepatologists.
What is the treatment for acute hepatitis C?
Treatment for acute hepatitis C is similar to treatment for chronic hepatitis C. This issue was addressed in the 2009 AASLD Practice Guidance, the response rate to treatment is higher among persons with acute than with chronic HCV infection. However, the optimal treatment regimen and when it should be initiated remains uncertain.
What is the treatment for chronic Hepatitis C?
Until recently, the mainstay of treatment for chronic hepatitis C virus (HCV) infection has been pegylated interferon and ribavirin, with possible addition of boceprevir (Victrelis™) and telaprevir (Incivek™) (both protease inhibitors) for HCV genotype 1 infection. After given for 24-48 weeks, this treatment resulted in a sustained virologic response (a marker for cure), defined as undetectable HCV RNA in the patient's blood 24 weeks after the end of treatment in 50%-80% of patients (with higher SVR among persons with HCV genotypes 2 or 3 infections versus infections with HCV genotype 1, the most common genotype found in the United States).
In late 2013, The Food and Drug Administration approved two new direct acting antiviral drugs, Sofosbuvir (Sovaldi™) and Simeprevir (Olysio™) to treat chronic HCV infection. Both medications have proven efficacy when used as a component of a combination antiviral regimen to treat HCV-infected adults with compensated liver disease, cirrhosis, HIV co-infection, and hepatocellular carcinoma awaiting liver transplant. Clinical trials have shown that these new medications achieve SVR in 80%-95% of patients after 12-24 weeks of treatment.
Sofosbuvir (Sovaldi™) is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) NS5B polymerase enzyme, which plays an important role in HCV replication. It is taken orally once a day at a 400-mg dose. The drug is approved for two chronic hepatitis C indications: In combination with pegylated interferon and ribavirin for treatment-naïve adults with HCV genotype 1 and 4 infections, and in combination with ribavirin for adults with HCV genotypes 2 and 3 infection. The second indication is the first approval of an interferon-free regimen for the treatment of chronic HCV infection. For more information, see prescribing information [PDF - 34 pages].
Simeprevir (Olysio™) is a protease inhibitor that blocks a specific protein needed by the hepatitis C virus to replicate. It is to be used as a component of a combination antiviral treatment regimen of peginterferon-alfa and ribavirin for genotype 1 infections only. It is taken orally once a day at a 150-mg dose. The treatment duration is 24-48 weeks depending on prior treatment history and response to treatment. Because the efficacy of simeprevir is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism, screening for this mutation is strongly recommended by the manufacturer before treatment initiation. For more information, see prescribing information [PDF - 44 pages].
For current information on approved treatments for Hepatitis C, please visit the Food and Drug Administration (FDA).
How many different genotypes of HCV exist?
At least six distinct HCV genotypes (genotypes 1-6) and more than 50 subtypes have been identified. Genotype 1 is the most common HCV genotype in the United States.
Is it necessary to do viral genotyping when managing a person with chronic Hepatitis C?
Yes. Because there are at least six known genotypes and more than 50 subtypes of HCV, genotype information is helpful in defining the epidemiology of Hepatitis C and in making recommendations regarding treatment. Knowing the genotype can help predict the likelihood of treatment response and, in many cases, determine the duration of treatment.
- Patients with genotypes 2 and 3 are almost three times more likely than patients with genotype 1 to respond to therapy with alpha interferon or the combination of alpha interferon and ribavirin
- When using combination therapy, the recommended duration of treatment depends on the genotype. For patients with genotypes 2 and 3, a 24-week course of combination treatment is adequate, whereas for patients with genotype 1, a 48-week course is recommended.
Once the genotype is identified, it need not be tested again; genotypes do not change during the course of infection.
Can superinfection with more than one genotype of HCV occur?
Superinfection is possible if risk behaviors (e.g., injection drug use) for HCV infection continue, but it is believed to be very uncommon.
Does chronic Hepatitis C affect only the liver?
A small percentage of persons with chronic HCV infection develop medical conditions due to Hepatitis C that are not limited to the liver. These conditions are thought to be attributable to the body's immune response to HCV infection. Such conditions can include
- Diabetes mellitus, which occurs three times more frequently in HCV-infected persons
- Glomerulonephritis, a type of kidney disease caused by inflammation of the kidney
- Essential mixed cryoglobulinemia, a condition involving the presence of abnormal proteins in the blood
- Porphyria cutanea tarda, an abnormality in heme production that causes skin fragility and blistering
- Non-Hodgkins lymphoma, which might occur somewhat more frequently in HCV-infected persons
What topics should be discussed with patients who have HCV infection?
- Patients should be informed about the low but present risk for transmission with sex partners.
- Sharing personal items that might have blood on them, such as toothbrushes or razors, can pose a risk to others.
- Cuts and sores on the skin should be covered to keep from spreading infectious blood or secretions.
- Donating blood, organs, tissue, or semen can spread HCV to others.
- HCV is not spread by sneezing, hugging, holding hands, coughing, sharing eating utensils or drinking glasses, or through food or water.
- Patients may benefit from a joining support group.
What should HCV-infected persons be advised to do to protect their livers from further harm?
- HCV-positive persons should be advised to avoid alcohol because it can accelerate cirrhosis and end-stage liver disease.
- Viral hepatitis patients should also check with a health professional before taking any new prescription pills, over-the counter drugs (such as non-aspirin pain relievers), or supplements, as these can potentially damage the liver.
Should HCV-infected persons be restricted from working in certain occupations or settings?
CDC's recommendations for prevention and control of HCV infection specify that persons should not be excluded from work, school, play, child care, or other settings on the basis of their HCV infection status. There is no evidence of HCV transmission from food handlers, teachers, or other service providers in the absence of blood-to-blood contact.
Hepatitis C and Health Care Personnel
What is the risk for HCV infection from a needlestick exposure to HCV-contaminated blood?
After a needlestick or sharps exposure to HCV-positive blood, the risk of HCV infection is approximately 1.8% (range: 0%-10%).
Other than needlesticks, do other exposures, such as splashes to the eye, pose a risk to health care personnel for HCV transmission?
Although a few cases of HCV transmission via blood splash to the eye have been reported, the risk for such transmission is expected to be very low. Avoiding occupational exposure to blood is the primary way to prevent transmission of bloodborne illnesses among health care personnel. All health care personnel should adhere to Standard Precautions . Depending on the medical procedure involved, Standard Precautions may include the appropriate use of personal protective equipment (e.g., gloves, masks, and protective eyewear).
What follow-up testing is recommended for health care personnel exposed to HCV-positive blood?
- For the source, perform baseline testing for anti-HCV.
- For the person exposed to an HCV-positive source, perform baseline and follow-up testing, including
- baseline testing for anti-HCV and ALT activity AND
- follow-up testing for anti-HCV (e.g., at 4-6 months) and ALT activity. If earlier diagnosis of HCV infection is desired, testing for HCV RNA may be performed at 4-6 weeks.
- Confirmation by supplemental anti-HCV testing of all anti-HCV results reported as positive by enzyme immunoassay.
Should HCV-infected health care personnel be restricted in their work?
There are no CDC recommendations to restrict a health care worker who is infected with HCV. The risk of transmission from an infected health care worker to a patient appears to be very low. All health care personnel, including those who are HCV positive, should follow strict aseptic technique and Standard Precautions, including appropriate hand hygiene, use of protective barriers, and safe injection practices.
Pregnancy and HCV Infection
Should pregnant women be routinely tested for anti-HCV?
No. Since pregnant women have no greater risk of being infected with HCV than non-pregnant women and interventions to prevent mother-to-child transmission are lacking, routine anti-HCV testing of pregnant women is not recommended. Pregnant women should be tested for anti-HCV only if they have risk factors for HCV infection.
What is the risk that an HCV-infected mother will spread HCV to her infant during birth?
Approximately 6 of every 100 infants born to HCV-infected mothers become infected with the virus. Transmission occurs at the time of birth, and no prophylaxis is available to prevent it. The risk is increased by the presence of maternal HCV viremia at delivery and also is 2-3 times greater if the woman is coinfected with HIV. Most infants infected with HCV at birth have no symptoms and do well during childhood. More research is needed to find out the long-term effects of perinatal HCV infection.
Should a woman with HCV infection be advised against breastfeeding?
No. There is no evidence that breastfeeding spreads HCV. However, HCV-positive mothers should consider abstaining from breastfeeding if their nipples are cracked or bleeding.
When should children born to HCV-infected mothers be tested to see if they were infected at birth?
Children should be tested for anti-HCV no sooner than age 18 months because anti-HCV from the mother might last until this age. If diagnosis is desired before the child turns 18 months, testing for HCV RNA could be performed at or after the infant's first well-child visit at age 1-2 months. HCV RNA testing should then be repeated at a subsequent visit, independent of the initial HCV RNA test result.