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Indiana State Department of Health

Epidemiology Resource Center Home > Surveillance and Investigation > Surveillance and Investigation Division > Newsletters > Indiana Epidemiology Archived Newsletters > Epi_Newsletter_May_2007-Page2 Interpretation of Hepatitis C Lab Reports

Indiana Epidemiology Newsletter
May 2007

Michael Wilkinson, BS
Hepatitis C Epidemiologist

The U.S. Food and Drug Administration (FDA) first licensed tests to detect antibody to hepatitis C virus (anti-HCV) in 1990. Since that time, new versions of these and other FDA-approved anti-HCV tests have been used widely for clinical diagnosis and screening of asymptomatic persons. This article will describe some of these commonly used tests and methods of interpreting results.

Serology

Serologic testing for the presence of HCV antibody (anti-HCV) is recommended for initially identifying or screening persons with hepatitis C since serologic screening is less expensive than other tests. However, serologic testing cannot determine acute, chronic, or resolved infection, only that the patient has been exposed to HCV. Enzyme linked immunosorbent assay (ELISA or EIA) is one of the more commonly used initial screening tests. Positive EIA tests are then confirmed using polymerase chain reaction (PCR) or recombinant immune assay (RIBA) testing. RIBA is most often used to ensure the initial antibody test was not a false positive. PCR testing is the most sensitive detection test for determining active infection (see Table 1).

According to the Centers for Disease Control and Prevention (CDC), a person is considered to have serologic evidence of HCV infection if a RIBA or PCR test is positive for HCV. However, many laboratories report a positive result based on a positive screening test result only and do not verify these results with more specific serologic or nucleic acid testing unless ordered by the requesting physician. Reasons include the lack of an established laboratory standard for confirmatory testing, lack of understanding regarding the performance and interpretation of the screening and supplemental HCV tests, and the high cost of the supplemental HCV tests.

Unfortunately, understanding the interpretation of anti-HCV screening test results, knowing when more specific testing should be performed, and understanding which tests should be used for confirmation can be confusing. Recently, the CDC issued recommendations for using signal-to-cutoff ratios (s/co) in lieu of supplemental testing. The use of s/co ratios minimizes the amount of supplemental testing needed, while improving the reliability of reported test results and reducing costs of supplemental testing (MMWR, February 7, 2003, Vol. 52, http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5203a1.htm). A specific s/co ratio can be identified for each test that would predict a true antibody-positive result (as defined by the results of supplemental testing) ≥95% of the time, regardless of the anti-HCV prevalence or characteristics of the population being tested. Most laboratory tests use 3.8 as the reference value most often used with the signal to cut-off ratio test.
For more information on serologic testing, please visit the CDC Web site at http://www.cdc.gov/ncidod/diseases/hepatitis/serology/index.htm

Viral Load Testing

Viral loads are confirmatory blood tests that measure the amount of HCV ribonucleic acid (RNA) in the blood and confirm whether an individual is actively infected with HCV. There are two categories of viral load tests—qualitative and quantitative. The presence of viral RNA indicates that the virus is actively replicating (reproducing and infecting new cells). Usually, a viral load test is done after a person has tested positive for exposure to HCV based on an initial antibody test.

Qualitative viral load tests – These tests determine the overall presence of HCV RNA in the blood. This type of test is usually used to confirm chronic HCV infection. If viral RNA is detected, a positive result is reported; if viral RNA is not detected, the test result is negative.

Quantitative viral load tests – These tests measure the amount of virus in one milliliter of blood. They are often used to assess whether or not treatment with interferon or interferon plus ribavirin is likely to be successful and, later, if treatment is working.

Viral load test results were previously measured in number of copies but are now typically reported in terms of international units per milliliter (IU/mL). However, more than one PCR test may need to be performed, since low-level viremia may be present and not detected by the test. Viremia can fluctuate for no apparent reason; therefore, it is possible to have a negative PCR test (when viral load is below the threshold value) and the person can actually be positive for HCV (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5203a1.htm).

Interpreting viral load test results – HCV viral load is often reported as low or high with the value expressed as the number of RNA copies per milliliter of blood or as international units (IU) per milliliter (ml) of blood. The reference range depends on the exact test being used, but in general, the reference ranges are:
• Low – less than 2 million copies/ml or less than 800,000 IU/ml
• High – more than 2 million copies/ml or more than 800,000 IU/ml

Changes in viral load are sometimes expressed in terms of logs. A log change is a 10-fold increase or decrease. An easy way to determine a log drop in viral load is to decrease the value by one zero. For instance, a one-log drop in a viral load of 1,000,000 international units is 100,000 international units; a two-log drop in a viral load of 1,000,000 international units is 10,000 international units. (Hepatitis C Support Project, VERSION 2.1, November 2006; Alan Franciscus, November 2006)

Liver Function Tests (LFT)

LFTs are the most common tests to determine liver problems. These tests measure the level of chemicals detected in the blood that are produced when the liver is not functioning properly. Other LFTs may indicate when the liver is inflamed and not functioning properly. Bilirubin (responsible for jaundice color) increases and albumin decreases.
Alanine aminotransferase (ALT or SGPT) – ALT/SGPT levels vary by age and laboratory testing, but normal range is generally between 7-56 units/liter (u/l). This is a protein, specifically an enzyme, that leaks out of liver cells when liver cells are damaged. An increase in ALT above normal range can mean ongoing liver damage, although the damage may not be the result of HCV. Patients with chronic hepatitis C may have ALT levels that fluctuate between 20-40 points between blood tests. In some patients with HCV, ALT levels can remain normal. It is important that ALT tests be repeated over time to get best indications of the level of liver damage. ALT is probably the best test to indicate liver damage.

Aspartate aminotransferase (AST or SGOT) – AST/SGOT levels vary by age and laboratory testing, but normal range is generally between 5-35 u/L. This is an enzyme produced by liver cells and is similar to ALT. AST is also produced in muscle, heart, kidney, and brain tissue. Often, ALT and AST will be elevated at the same time.

Case Definitions

No HCV test can distinguish acute and chronic hepatitis C infection. This is why it is critical to know the case definitions of acute and chronic hepatitis C. The case definition includes laboratory and ALT markers, so understanding these is important. To be classified as acute, a case must meet three distinct criteria: 1.) Discrete onset of hepatitis symptoms; 2.) ALT levels that are at least 7 times the upper limit of the reference range; 3.) Test positive for HCV antibody and negative for hepatitis A and hepatitis B. If a case meets all three of these characteristics, the case is classified as acute. If a case tests positive for HCV antibody and does not meet the other criteria, the case is considered chronic.

Acute Hepatitis C Case Definition

  • Discrete onset of symptoms: dark urine, pale stool, fatigue, jaundice

  • ALT must be 7 times upper limit of reference range

  • HCV antibody positive

    • HCV antibody positive by EIA with signal to cut-off ratio >= to 3.8 OR

    • Anti-HCV by RIBA alone is confirmatory OR

    • HCV RNA positive

  • Patient must also be hepatitis A and hepatitis B negative

>80% of acute hepatitis C cases will become chronic and not clear the virus within 6 months.

Chronic Hepatitis C Case Definition

  • HCV positive 6 months or longer:

    • HCV antibody positive by EIA with signal to cut-off ratio >= to 3.8 OR

    • Anti-HCV by RIBA alone is confirmatory OR

    • HCV RNA positive

>most are asymptomatic
>liver enzymes may be normal
>antibody and perhaps RNA will be positive