Diagnosis and further investigation

• hepatitis C antibody testing
  • hepatitis C antibody results should be interpreted with caution because the presence of antibodies does not distinguish between current and spontaneously resolved infection
    • note that it may take up to 3 months following infection for antibodies to hepatitis C to become detectable, a negative test result during this period can be misleading
  • a second blood test should always be done to confirm an initial positive result or if the patient tests negative within 3 months of any possible exposure to the virus
  • if the repeat test is also positive, the patient should be offered referral to a specialist unit (e.g. the local hepatology, gastroenterology or infectious diseases unit) for further management
    • if a patient has had two positive hepatitis C antibody tests then a genome detection assay, such as the polymerase chain reaction (PCR) assay, is used to confirm the presence of hepatitis C RNA and, therefore, active viral replication
      • patients with both positive antibody and HCV RNA tests need further assessment and should be referred to specialists like hepatologist, gastroenterologist or infectious disease physician (although some investigations can be carried out in the primary care) (2)
      • in a positive antibody test and a negative hepatitis C RNA test, patients should undergo a second HCV test after 6 months and if still negative discuss about preventing re infection, alcohol intake, injecting behaviour etc. (2)
      • a positive antibody test and negative hepatitis C RNA test could indicate:
        • spontaneous clearance of the virus - this occurs in about 15% of cases;
        • a false-positive antibody test;
        • the patient has a level of hepatitis C RNA below the limit of detection of the assay;
        • or a successful response to antiviral therapy
    • liver biopsy
      • provides useful information about the stage and severity of liver disease
      • is the most accurate investigation method of assessing liver damage in patients with chronic hepatitis C virus (3)
      • it has been suggested that liver biopsy should be routinely done only in patients with 'hard to treat' genotypes (1 and 4), if there is strong clinical evidence of co-existent liver disease (such as alcohol-related damage), or in patients with genotype 2 or 3 infection who fail to respond to therapy (1)

Notes:

• if a patient is being considered for treatment then further blood tests will be required to determine viral load and the hepatitis C genotype since response to therapy is largely determined by these factors
  • six major genotypes of hepatitis C; in the UK, genotypes 1, 2 and 3 are prevalent
    • hepatitis C infection with genotype 1 or 4 is more difficult to treat than with genotype 2 or 3
• it is advisable to also test for hepatitis B infection; also many specialist units also test for HIV infection, after appropriate counselling, because this condition worsens the outcome in hepatitis C

Reference:

• (1) Drug and Therapeutics Bulletin 2005; 43(3):17-24
• (2) Royal College of General Practitioners (RCGP) 2007. Guidance for the prevention, testing, treatment and management of hepatitis C in primary care
• (3) Department of health (DH) 2004. Hepatitis C: Essential information for professionals and guidance on testing