The CDC currently recommends "One-time screening is recommended for persons born between 1945 and 1965, without ascertainment of HCV risk."

Persons outside the recommended age range should be assessed for risk. At risk patients should be tested for HCV

• Recipients of blood transfusions or solid organ transplants before July 1992
• Persons born from 1945 through 1965
• Persons who have ever injected recreational drugs, including those who injected only once many years ago
• Intranasal drug use
• Recipients of clotting factor concentrates made before 1987
• 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)

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

• HCV antibody (anti-HCV) tests should be employed when a patient is suspected of acute or chronic HCV infection. 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.
• HCV RNA tests should be used to confirm HCV when:
  • Anti-HCV test is positive
  • HCV antiviral treatment is considered
  • HCV infection is suspected in immunocompromised patients if anti-HCV tests are negative.
• HCV positive patients should be counseled in techniques to avoid transmission of HCV.

HCV infection is seldom diagnosed during the acute phase:

• CDC estimates the number of acute cases to be 13.4 times greater than reported cases. Many persons spontaneously clear the acute viremia with no lasting liver damage.
• Up to 85% of those with untreated acute hepatitis C progress to chronic infection.
• ≈20% of chronically infected will develop cirrhosis over a period of 20–30 years.
• 1%–5% chronically infected will die from chronic liver disease or hepatocellular carcinoma. 2010 reported deaths due to HCV equaled 16,627 but the CDC believes this is just a fraction of the actual deaths.
• Acute HCV symptoms are experienced by about 20%–30% of newly infected persons. The average time period from HCV exposure to symptom onset is 4–12 weeks. Some of the more common acute phase symptoms include:
  • Fever
  • Fatigue
  • Joint pain
  • Loss of appetite
  • Nausea
  • Vomiting
  • Abdominal pain
  • Jaundice
  • Clay-colored stool
  • Dark urine

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

• RUQ discomfort,
• fatigue or
• poor appetite

"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:

• HCV testing is recommended at least once for persons born between 1945 and 1965.
• An anti-HCV test is recommended for HCV screening, and if the result is positive, current infection should be confirmed by a sensitive RNA test.
• Among persons with a negative anti-HCV test who are suspected of having liver disease, testing for HCV RNA or follow-up testing for anti-HCV is recommended if exposure to HCV occurred within the past 6 months; testing for HCV RNA can also be considered in persons who are immunocompromised.
• Among persons suspected of re-infection after previous spontaneous or treatment-related viral clearance, initial HCV-RNA testing is recommended because an anti-HCV test is expected to be positive.
• Quantitative HCV RNA testing is recommended prior to the initiation of antiviral therapy to document the baseline level of viremia (ie, baseline viral load).
• Testing for HCV genotype is recommended to guide selection of the most appropriate antiviral regimen.
• If found to have positive results for anti-HCV test and negative results for HCV RNA by PCR, persons should be informed that they do not have evidence of current (active) HCV infection.

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.

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:

• 12 weeks
• 24 weeks
• End of treatment
• 6 months after treatment completed

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.

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.