Hepatitis C (HCV)
Serum (note: dedicated tube for hepatitis C PCR)
Anti HCV (total antibody to HCV)
HCV- RNA quantitative (viral load)
Hepatitis C is an RNA virus that was the major cause of transfusion-associated hepatitis until blood screening assays were introduced. Six major genotypes of HCV have been defined and there are more than 50 subtypes.
Mode of transmission
The main groups at risk of infection are:
- Recipients of blood products before testing of donor samples began 1992
- Injecting drug users through shared needles
- Renal failure patients on haemodialysis
- Organ transplant recipients
- Tattooing with shared contaminated needles or needle-like devices, for example, in prisons, is a mode of HCV transmission
- Perinatal transmission
In certain immigrant populations, poor infection control practices during procedures have been responsible for many infections, for example, among Egyptians receiving chemoprophylaxis for schistosomiasis.
The role of sexual transmission is controversial. If sexual transmission does occur, it is at a very low level that makes it inappropriate to routinely recommend safe sex among long-term monogamous couples. Sexual transmission is likely to be more efficient where there is HIV co-infection and high HCV viral load.
The risk of transmission from an HCV-infected mother to her newborn is about 5%, if she is HIV negative. This increases to about 19%, if the woman is co-infected with HIV. Breastfeeding does not increase the risk of HCV transmission and need not be avoided, except if the mother is also infected with HIV. Breastfeeding should be suspended if the nipples are cracked or if the baby has broken mucosa or skin cuts in or near the mouth.
|Incubation period||Symptom onset average 6–8 weeks|
|Appearance of anti-HCV||Averages 8–9 weeks|
|Appearance of HCV RNA||Averages 1–2 weeks|
Acute infection: Most acutely infected patients are asymptomatic or have a mild illness. Jaundice occurs in fewer than 25% and 10–20% have only non-specific symptoms, such as anorexia, malaise, abdominal pain. In patients who experience acute symptoms, the illness typically lasts for 2–12 weeks. Severe acute hepatitis C is rare.
Chronic infection is common after primary infection with HCV. Only 15–25% clear HCV infection spontaneously within the first year. Symptoms are often absent, minimal, intermittent or nonspecific. Fatigue is commonly reported. Other symptoms include anorexia, nausea, abdominal discomfort and intolerance to alcohol and fatty foods. Up to one third of patients have a normal serum ALT and there is little correlation between the ALT level and the presence of symptoms. Extrahepatic manifestations can occur, for example, porphyria cutanea tarda (qv), lichen planus and vasculitic rashes associated with cryoglobulinaemia (qv).
The major consequence of HCV infection is progression to cirrhosis and its complications, for example, ascites, hepatocellular carcinoma. Progression to cirrhosis occurs in approximately 15–20% of those with chronic HCV infection after 15–40 years. The progression of chronic hepatitis C is accelerated by alcohol consumption and by co-infection with HIV and/or chronic HBV.
Laboratory diagnosis: who should be tested?
Several organisations have provided guidelines for who should be tested for HCV.
The US Center for Disease Control and Prevention (CDC) recommends that testing for HCV should be routine in patients at increased risk for infection, including those who:
- Ever injected illegal drugs
- Received blood, blood products or organs before 1992
- Were ever on chronic haemodialysis
- Have evidence of liver disease, including persistently abnormal ALT level
Testing should also be performed, based upon the need for exposure management including:
- Healthcare workers after a blood and body fluid exposure to HCV-positive blood
- Children born to HCV-positive women
In addition, the American Association for the Study of Liver Diseases recommends testing the following groups:
- Those with HIV infection
- Those with unexplained abnormal aminotransferase levels
- Current sexual partners of HCV-infected persons
Routine testing is not recommended (unless an additional risk factor is identified) in:
- Healthcare workers (except where they have sustained blood or body fluid exposure)
- Household (non-sexual) contacts of HCV-positive persons
- The general population
Laboratory diagnosis: available tests
1. Antibody test (anti-HCV)
An enzyme immunoassay (EIA) that detects antibodies against several HCV antigens is the first test used when screening patients suspected of having chronic HCV infection. In acute HCV infection, anti-HCV antibodies are detected in 50–70% of patients by the time symptoms develop and are usually present in the rest after a further 3–6 weeks. Immunosuppressed patients may not develop detectable anti-HCV antibodies. HCV antibodies are not protective, for example, against other strains of HCV. False-positive low-level reactivity may occur in the EIA test.
Patients with a hepatitis C antibody, detected on the initial screening EIA, have a second EIA assay performed which has a different set of antigens. If the initial screen is detected and the confirmatory assay is not detected, then the patient is said to have an ‘equivocal’ hepatitis C antibody result.
For patients with reactive EIA tests, a follow-up repeat serology test and a nucleic acid amplification test, to directly detect HCV RNA, are indicated.
2. Direct identification of virus (HCV RNA)
Detection of HCV RNA by PCR confirms current infection with HCV. HCV RNA testing should be performed:
- In those with reactive anti-HCV results
- In those with unexplained liver disease whose anti-HCV test is negative and who are immunocompromised or suspected of having acute HCV infection.
- Infants born to HCV-infected mothers can be tested for HCV RNA between two and six months of age (or else have an anti-HCV antibody test after 15 months of age).
HCV RNA testing may be qualitative or quantitative. The initial test is usually a hepatitis C qualitative PCR test. If this is detected, then a hepatitis C quantitative test (viral load) is usually indicted. The viral load does not correlate with the extent of hepatitis, fibrosis or risk of disease progression. However, it does provide some prognostic value with regard to response to antiviral therapy.
Explanations for the four possible patterns of results
Anti-HCV non-reactive/HCV RNA not detected:
- No evidence of acute or chronic HCV infection
Anti-HCV reactive/HCV RNA not detected:
- Previous HCV infection, viraemia not detectable. HCV infection has cleared either spontaneously or during treatment. For untreated patients with normal liver enzymes, HCV RNA and liver enzymes should be repeated in six months and, if there is no change in results, no further follow-up is necessary.
- Detection of maternal anti-HCV antibodies in babies. Maternally-acquired antibodies are no longer present by 12 months of age in 95% of infants.
- False-positive anti-HCV result
Anti-HCV non-reactive/HCV RNA detected:
- Acute HCV infection – HCV RNA is detectable before the appearance of anti-HCV antibodies
- Immunosuppressed patients – conditions associated with diminished antibody production include HIV infection, transplant recipients, chronic hemodialysis
- False-positive HCV RNA test
Anti-HCV reactive/HCV RNA detected:
- Current HCV infection with circulating virus, either acute or chronic
Antiviral therapy is now recommended for all individuals with persistent infection, as indicated by the detection of HCV RNA in the blood. Several antiviral agents are available and have the potential to eliminate HCV in the vast majority of cases. It is still recommended that the infecting HCV genotype be established prior to treatment but is not essential due to the availability of pan-genotypic antivirals.
Hepatitis A and B vaccination should be offered to all susceptible patients with chronic hepatitis C.
For further information on epidemiology and treatment of hepatitis C, refer to:
- 35 Hepatitis C [Internet]. Australian Government Department of Health, 2020. [Accessed Nov 2021] <www.health.gov.au> (Keywords hepatitis c)
- Viral Hepatitis - Hepatitis C Information [Internet]. Centers for Disease Control and Prevention (CDC), 2020. [Accessed Nov 2021] <www.cdc.gov/hepatitis/hcv/index.htm>
- eTG complete [Internet] . Therapeutic Guidelines, 2021. [Accessed Nov 2021] <www.tg.org.au> (Keywords hepatitis c)