HCV Testing

A comprehensive health evaluation should include a history for the risk of HCV infection.

HCV infection is seldom diagnosed during the acute phase:

A diagnosis of chronic hepatitis C is often made following a work up for complaints of:

"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."

American Association for the Study of Liver Diseases and the Infectious Diseases Society of America 2014 recommended testing protocol:

The first evidence os HCV infection may come from elevated liver functions test and the presence of anti-HCV. Tests to detect antibodies to HCV anti-HCV tests were first licensed by the Food and Drug Administration (FDA) in 1990. The CDC recommends that a person be considered positive for HCV infection only after an initial anti-HCV screening test has been verified by a more specific serologic or nucleic acid test (NAT). The verifying test ensures that the original test was not a false positive. If the individuals being tested present with evidence of liver disease, then false positives are very unlikely. However, in symptom-free individuals who are among populations with a low prevalence of HCV, false positives are a matter for concern.

Liver enzyme tests are often used to monitor treatment in conjunction with HCV-RNA tests to determine viral load. Baseline serum viral load levels and infecting genotype help to predict the outcome of therapy and influence the choice of the therapeutic regimen. HCV RNA can be detected in serum or plasma within 1 to 2 weeks after exposure to the virus.

Instant Feedback:
Baseline viral load levels and infecting genotype help to predict the outcome of therapy and influence the choice of the therapeutic regimen.

Liver enzyme tests
Normal range/ males
Normal range/ females
ALT (alanine aminotransferase)
also known as
SGPT (serum glutamate pyruvate transaminase)
10-32 U/L
9-24 U/L
AST (aspartate aminotransferase)
Also known as
(serum glutamic oxaloacetic transaminase)
8-20 U/L
8-20 U/L

According to the CDC, 15% of people with abnormal ALT levels are infected with HCV. Historically, an elevated ALT was used by blood centers as a surrogate marker for HCV from 1986 to 1995. In 1995 a National Institute of Health panel voted to eliminate the ALT screen due to the specificity of HCV tests used since 1992. These new tests have eliminated 85% of post-transfusion hepatitis C infections.

Liver enzymes can fluctuate and they can be influenced by a number of variables, so these tests are not definitive for HCV. However, if both ALT and AST are elevated, a hepatocellular disorder is indicated. These tests may be the first indication that there is a disorder involving the liver.

Antibody detection tests

These tests are easy to do and relatively inexpensive, but they are less sensitive in early stages of the disease. False negative results frequently occur in the acute phase of the infection. It can take 8 weeks to produce enough antibody to be detectable. Immunosuppressed patients and those on long-term dialysis may also return false negatives. False positives can occur in persons that have cleared the infection. As many as 25% of acute HCV infections clear spontaneously, these person will continue to produce HCV antibodies.

HCV RNA detection tests

Hepatitis C virus is an RNA virus, and the genetic code is unique to this virus. Several types of amplification tests (assays) are available to measure the amount of hepatitis C virus RNA in a person's serum. These tests are referred to as molecular tests because they recognize the viral RNA at the molecular level. If a person is infected with HCV, the average number of copies of the virus is in the 100,000s to several million, compared to those with HAV and HBV, who have 100s of millions or billions of copies of the viruses. The significance of the absolute values of HCV viral load has not yet been fully determined, so clinical decisions are usually made on the basis of "high" or "low" viral load, rather than exact levels.

Nucleic acid tests (NAT) detect HCV RNA and may be used to diagnosis acute and chronic HCV infection and to evaluate the management of patients with chronic HCV. NATs have the advantage of detecting active HCV infection by verifying the presence of antigens. There are 2 types of NATs:

Quantitative HCV RNA tests detect the presence of the virus itself and measure the amount in the plasma; the viral load. These are very sensitive tests with some able to detect as few as 5 copies /ml. HCV RNA tests are usually done at intervals to measure the effect of anti-viral therapy:

Qualitative HCV RNA tests are used to simply detect virus in the blood. They are highly sensitive to the presence of HCV RNA but do not calculate the viral load. The results are expressed as positive or negative and are FDA approved to diagnose infection

It is possible to get a negative test result for HCV RNA during the acute phase of HCV infection when the antigen level is low. Qualitative tests can detect the presence of HCV RNA, usually within 1-2 weeks of infection. While possible, false negative result are unlikely.

Instant Feedback:
Which type of test can detect the number of viral RNA molecules in a sample of plasma?

HCV genotyping
Genotyping is done to determine the type of HCV that is present. Genotyping is necessary prior to antiviral therapy, because some genotypes respond better to specific treatment than others. Knowing the genotype helps to plan therapy and to attain SVR.

Instant Feedback:
Liver enzyme tests are sufficient to diagnose HCV.