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Hepatitis C Page 2
You can find out if you have hepatitis C by getting a blood test. The test for hepatitis C is based on the detection of antibodies to the virus, not the virus itself. Antibodies are produced by the body to fight viruses and they are found in your blood. The tests currently used to detect hepatitis C antibodies are the ELISA test, followed by the RIBA test. Positive tests indicate that you have been infected at some time in your life. You are then said to be hepatitis C positive.
Tests and Procedures
Enzyme Immunoassay
Anti-HCV is detected by enzyme immunoassay (EIA). The third-generation test (EIA-3) used today is more sensitive and specific than previous ones. However, as with all enzyme immunoassays, false-positive results are occasionally a problem with the EIA-3. Additional or confirmatory testing is often helpful.
The best approach to confirm the diagnosis of hepatitis C is to test for HCV RNA using a sensitive polymerase chain reaction (PCR) assay. The presence of HCV RNA in serum indicates an active infection. Testing for HCV RNA is also helpful in patients in whom EIA tests for anti-HCV are unreliable. For instance, immuno-compromised patients may test negative for anti-HCV despite having HCV infection because they may not produce enough antibodies for detection with EIA. Likewise, patients with acute hepatitis may test negative for anti-HCV when the physician first tests. Antibody is present in almost all patients by 1 month after onset of acute illness; thus, patients with acute hepatitis who initially test negative may need follow up testing. In these situations, HCV RNA is usually present and confirms the diagnosis.
Recombinant Immuno-blot Assay
Immuno-blot assays are used to confirm anti-HCV reactivity, too. These tests are also called "Western blots"; serum is incubated on nitrocellulose strips on which four recombinant viral proteins are blotted. Color changes indicate that antibodies are adhering to the proteins. An immuno-blot is considered positive if two or more proteins react and is considered indeterminate if only one positive band is detected. In some clinical situations, confirmatory testing by immuno-blotting is helpful, such as for the person with anti-HCV detected by EIA who tests negative for HCV RNA. The EIA anti-HCV reactivity could represent a false-positive reaction, recovery from hepatitis C, or continued virus infection with levels of virus too low to be detected (the last occurs only rarely when sensitive PCR assays are used). If the immuno-blot test for anti-HCV is positive, the patient has most likely recovered from hepatitis C and has persistent antibody virus.If the immuno-blot test is negative, the EIA result was probably a false positive.
Immunoblot tests are routine in blood banks when an anti-HCV-positive sample is found by EIA. Immuno-blot assays are highly specific and valuable in verifying anti-HCV reactivity. Indeterminate tests require further follow up testing, including attempts to confirm the specificity by repeat testing for HCV RNA.
PCR Amplification
PCR amplification can detect low levels of HCV RNA in serum. Testing for HCV RNA is a reliable way of demonstrating that hepatitis C infection is present and is the most specific test for infection. Testing for HCV RNA by PCR is particularly useful when aminotransferases are normal or only slightly elevated, when anti-HCV is not present, or when several causes of liver disease are possible. This method also helps diagnose hepatitis C in people who are immuno-suppressed, have recently had an organ transplant, or have chronic renal failure. A PCR assay has now been approved by the Food and Drug Administration for general use. This assay will detect HCV RNA in serum down to a lower limit of 50 to 100 copies per milliliter which is equivalent to 25 to 50 international units. Almost all patients with chronic hepatitis C will test positive by this assay.
Quantification of HCV RNA in Serum
Several methods are available for measuring the titer or level of virus in serum, which is an indirect assessment of viral load. These methods include a quantitative PCR and a branched DNA (bDNA) test. Unfortunately, these assays are not well standardized, and different methods from different laboratories can provide different results on the same specimen. In addition, serum levels of HCV RNA can vary spontaneously by 3- to 10-fold over time. Nevertheless, when performed carefully, quantitative assays provide important insights into the nature of hepatitis C. Most patients with chronic hepatitis C have levels of HCV RNA (viral load) between 100,000 (105) and 10,000,000 (107) copies per milliliter. Expressed as international units (IU), these averages are 50,000 to 5 million IU.
Viral levels as measured by HCV RNA do not correlate with the severity of the hepatitis or with a poor prognosis (as in HIV infection); but viral load does correlate with the likelihood of a response to antiviral therapy. Rates of response to a course of alpha interferon and ribavirin are higher in patients with low levels of HCV RNA. There are several definitions of a "low level" of HCV RNA, but the usual definition is below 1 million international units (2 million copies) per milliliter (mL).
In addition, monitoring HCV RNA levels during the early phases of treatment may provide early information on the likelihood of a response. Yet because of the shortcomings of the current assays for HCV RNA level, these tests are not always reliable guides to therapy.
Genotyping and Serotyping of HCV
There are 6 known genotypes and more than 50 subtypes of hepatitis C. The genotype of infection is helpful in defining the epidemiology of hepatitis C. Knowing the genotype orserotype (genotype-specific antibodies) of HCV is helpful in making recommendations and counseling regarding therapy. Patients with genotypes 2 and 3 are almost three times more likely to respond to therapy with alpha interferon or the combination of alpha interferon and ribavirin. Furthermore, when using combination therapy, the recommended duration of treatment depends on the genotype. For patients with genotypes 2 and 3, a 24-week course of combination treatment is adequate, whereas for patients with genotype 1, a 48-week course is recommended. For these reasons, testing for HCV genotype is often clinically helpful. Once the genotype is identified,it need not be tested again; genotypes do not change during the course of infection.
Liver Biopsy
Liver biopsy is not necessary for diagnosis but is helpful for grading the severity of disease and staging the degree of fibrosis and permanent architectural damage. Hematoxylin and eosin stains and Masson's trichrome stain are used to grade the amount of necrosis and inflammation and to stage the degree of fibrosis. Specific immuno-histochemical stains for HCV have not been developed for routine use. Liver biopsy is also helpful in ruling out other causes of liver disease, such as alcoholic liver injury or iron overload.
HCV causes the following changes in liver tissue:
Necrosis and inflammation around the portal areas, so-called "piecemeal necrosis" or "interface hepatitis."
Necrosis of hepatocytes and focal inflammation in the liver parenchyma.
Inflammatory cells in the portal areas ("portal inflammation").
Fibrosis, with early stages being confined to the portal tracts, intermediate stages being expansion of the portal tracts and bridging between portal areas or to the central area, and late stages being frank cirrhosis characterized by architectural disruption of the liver with fibrosis and regeneration.
Grading and staging of hepatitis by assigning scores for severity are helpful in managing patients with chronic hepatitis. The degree of inflammation and necrosis can be assessed as none, minimal, mild, moderate, or severe. The degree of fibrosis can be similarly assessed.
Scoring systems are particularly helpful in clinical studies on chronic hepatitis.
You need to be tested to detect, treat and prevent the spread of hepatitis C infection.
Testing means that you will be able to:
In the short term;
prevent the spread of the virus,
assess damage to the liver, and
make lifestyle changes.
In the long term;
monitor the progression of the infection,
detect liver problems early, and
receive medical treatment.
People who had blood transfusions and blood products.
Needle drug users.
Individuals with multiple sexual partners.
People exposed to needle stick injuries (e.g., health care workers)
Organ transplant recipients
Children of hepatitis C positive mothers.
At present, there are no standards for getting counselling before and after you are tested for hepatitis C. This means that people being tested across the country may not be well informed about the testing procedures and results.
Before being tested,
Ask your doctor to explain the tests being done.
If you test positive,
Ask for an explanation of what being positive means, e.g. symptoms, outcomes.
Make sure that your family can access information they need.
If you test negative,
Be aware that sometimes false negative results occur.
If you have hemophilia or another blood related disorder, be tested regularly because you will still receive blood products.
Be retested. Mistakes happen, so a second test can confirm the results.
Be monitored by your doctor.
Learn more about hepatitis C and how it may affect you.
Take steps to prevent the spread of infection.