Diagnosis of Hepatitis C

Several tests for diagnosing hepatitis C infection are available, but since the levels of virus and the liver enzymes fluctuate, one single test may not give all the answers.

Liver Function Tests

ALT is a more specific indicator of hepato-biliary dysfunction than AST as ALT is primarily localized to the liver cells. Although the enzyme levels may reflect the extent of liver necrosis, they do not correlate with the outcome. Declining levels can indicate either recovery or poor prognosis. ALT levels are significantly higher than AST levels in uncomplicated acute or chronic viral hepatitis, unless severe necrosis occurs or there is underlying cirrhosis. ALT levels more than ten times the upper limit of normal is often observed in acute viral hepatitis.

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Antibody Based Methods / Immunoassays for HCV Detection.  

The antibody based methods e.g. the Hepatitis Panel are used as primary screens for HCV antibodies (anti-HCV) and are reproducible and inexpensive. They detect anti-HCV in 97% of infected individuals and have contributed to the significant decrease in the transmission of HCV through transfusions, etc. These are: 

EIA-Enzyme immunoassays

ELISA-Enzyme linked immunosorbant assays

RIBA-recombinant immunoblot assay which is a supplemental test to confirm samples that are repeatedly reactive by primary screen (EIA or ELISA)

The EIA and ELISA cannot distinguish active from past exposures and may not detect antibody for as long as six months after exposure. Both EIA and ELISA can produce false positive tests and this is most likely to happen while screening persons at low risk for HCV e.g. blood donors.

Use of supplemental anti-body testing i.e. RIBA, for all positive anti-HCV results by EIA is preferred. It confirms the presence of anti-HCV and can be performed on the same serum sample collected for the initial antibody testing.

According to the NIH Consensus Panel recommendations, a person is at low risk for HCV, if:

EIA is negative – it alone rules out HCV infection.

EIA is positive – needs the supplemental RIBA test (RIBA should be done if the anti-HCV is positive but the RNA is negative). If the: 

RIBA Negative – means anti-HCV was false positive.

RIBA Positive – this means that the person either has or previously had HCV infection and needs RNA PCR to differentiate between the two.

RIBA Indeterminate – seen in up to 10% of the patients, HCV infection needs to be confirmed with testing for HCV RNA by PCR or by testing for anti-HCV again in two or three months.

If the RIBA is positive but liver enzymes are normal then there are two possibilities:  

Either the individual has recovered from acute Hepatitis C sometime in the past and is now left simply with a positive anti-HCV test, or

The individual has active disease, but in chronic hepatitis C infection the liver enzymes can be normal for a variable period of time. This can be determined by either of the following:

Measure the virus i.e. RNA PCR, to determine presence of active infection.

Follow the patient for a few months using sequential repeated ALT levels to identify whether the ALT is persistently normal or in fact fluctuates and has transient elevations.

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Hepatitis Panel 

The hepatitis panel can easily diagnose and differentiate between infection with hepatitis A, B or C and includes:

Anti-HAV (Ig M specific): current HAV infection.

HbsAg: HBV infection, either acute or chronic.

Anti-HBc (IgM specific): presumptive evidence of acute or current HBV infection.

Anti-HCV (not anti-HBc): current or previous HCV infection.

If markers for acute hepatitis A and B are absent then the presence of anti-HCV indicates acute hepatitis C infection, assuming that other possible etiology of acute hepatitis in this age group is excluded e.g. Wilson’s Disease and Infectious Mononucleosis.

Additional tests permit a more detailed assessment of viral hepatitis and can help distinguish persons who are immune from those who are susceptible and in whom hepatitis A or B vaccination might be recommended. These include testing for both the antibodies, the IgG, which signifies previous infection and the IgM antibody, which is seen in recent infection. These tests are:

Total anti-HAV - In the absence of IgM antibodies it indicates the presence of IgG.

HBe Antigen - HBV infected person who is most likely to transmit the disease.

Total anti-HDV - might be considered only if the patient is currently infected with HBV

Anti-HBc assay.

Anti-HBs assay.

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Nucleic Acid Based Methods:  These are currently the most sensitive tests available and detect the level of viremia in the patient’s blood. These assays can detect the virus within 1-2 weeks of infection, which is weeks before the serological tests or the serum ALT (alanine aminotransferase) elevations. Some HCV infected individuals may be only intermittently HCV RNA positive, particularly those with acute hepatitis C or those with end-stage liver disease caused by HCV. These assays are of two types: 

PCR – Polymerase Chain Reaction – positive in >95% of infected individuals, and 

b-DNA – Branched DNA

These tests are also used for:

Differential diagnosis of elevated ALT levels.

Early diagnosis in high risk individuals.

Diagnosis in immuno-compromised individuals.

Confirmation of serologic tests and indicates current infection.

Distinguishing between active and resolved infections when anti-HCV is positive but ALT levels are normal.

Monitoring the efficacy of therapy.

In clinical settings, use of RT-PCR to detect HCV RNA might be appropriate to confirm the diagnosis of HCV infection.

Absence of HCV RNA in a person with an anti-HCV–positive result based on EIA testing alone i.e. without supplemental anti-HCV testing cannot differentiate between resolved infection and a false-positive anti-HCV test result. In addition, because some persons with HCV infection might experience intermittent viremia, the meaning of a single negative HCV RNA result is difficult to interpret, particularly in the absence of additional clinical information.

If the HCV RNA result is negative, supplemental anti-HCV testing should be performed so that the anti-HCV EIA result can be interpreted before the result is reported to the patient.

Histo-pathologic evaluation of the liver biopsy.

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HCV Genotypes

These help in determining the HCV type and the relationship to pathogenesis and response to therapy. For example, patients with genotypes 1a, 2, 3 or 5 respond better to interferon therapy than patients with 1b or 4 genotypes.

Is the viral load a factor in predicting the ease with which this virus can be transmitted?

We don’t have any data whether or not the virus titers are related to sexual transmission but there have been a couple of studies that showed that virus titers was related to transmission from mothers to infants.  It showed that mothers with higher titers were more likely to transmit than those with lower titers but there is no indication what that level might be, so it is really impossible to make any recommendations based on the viral loads of HCV RNA.

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