Most hepatitis C infections cause no symptoms until liver damage is advanced, so nearly one in three people with the infection do not know they have it. Diagnosis therefore depends on testing people who may have been exposed rather than on waiting for symptoms.
Who to test
Testing combines broad screening with testing of specific risk groups. The Centers for Disease Control and Prevention recommends testing every adult at least once and every pregnant patient during each pregnancy.
The World Health Organization recommends testing people at increased risk, including blood donors, people who inject drugs, people in prisons and other closed settings, men who have sex with men, migrants from high-prevalence regions, health-care workers exposed to blood, and people with HIV or tuberculosis. Where antibody prevalence in the general population exceeds 2%, it also recommends general-population testing of adolescents and adults.
The two-step test
Diagnosis uses two blood tests in sequence, and the distinction between them is the key idea.
The first is an anti-HCV antibody test, usually an enzyme immunoassay. A reactive result shows that the person has been exposed to the virus at some point, but not that they are still infected, because about 30% of infected people clear the virus spontaneously and yet keep the antibody for life.
The reactive antibody test is therefore followed by a nucleic acid test (NAT) for HCV RNA, which detects virus that is currently present and confirms chronic infection. A detectable RNA result means current infection and prompts an offer of treatment.
Timing matters when exposure is recent. Antibodies usually take 8-11 weeks to become detectable, whereas HCV RNA appears within 1-2 weeks, so a suspected recent exposure is tested with an RNA test even if the antibody is still negative.
Once chronic infection is confirmed, the degree of liver damage is assessed, by biopsy or by non-invasive blood tests and imaging, because fibrosis and cirrhosis guide how the patient is followed up.