Hepatitis C Surveillance
A healthy human liver (top) contrasted with a liver from an individual that died from hepatitis C (bottom). Note the extensive damage and scarring from chronic liver disease.
I What is Hepatitis C?
Five different viruses (termed A,B,C,D, and E) cause viral hepatitis. Four other viruses that are believed to cause hepatitis have been identified, but not much is known about them. Hepatitis C virus (HCV) accounts for the great majority of what was referred to as non-A, non-B hepatitis. The hepatitis C virus was identified in 1989, and in 1990 a hepatitis C antibody test (anti-HCV) became available to identify individuals exposed to HCV.
In general, individuals infected with HCV are often identified because they are found to have elevated liver enzymes on a routine blood test or because a hepatitis C antibody is found to be positive at the time of blood donation. In 1992, a more specific test for anti-HCV became available and eliminated some of the false positive reactions that were previously troublesome. In general, elevated liver enzymes and a positive antibody test for HCV (anti-HCV) means that an individual has chronic hepatitis C. The anti-HCV test will remain positive for several years after recovery from acute hepatitis C. A small percentage of patients still may have false positive hepatitis C antibody reactions. In these two cases, liver enzymes are typically normal. A small percentage of patients (less than 10%) may recover from acute hepatitis C, but their anti-HCV test will remain positive.
It appears that the formation of antibodies in response to the virus (associated with immunity in other forms of viral infections) does not apply with hepatitis C. Researchers believe this is because the virus changes to new forms of the original virus which caused the body to produce antibodies. It is estimated that up to 85% of the people infected with the hepatitis C virus each year will develop chronic infection.
Specific information regarding the natural history of hepatitis C is not yet available. In general, however, chronic hepatitis C appears to be a slowly progressive disease that may gradually advance over 10-40 years. There is some evidence that the disease may progress faster when acquired in middle age or older. In one study, chronic hepatitis confirmed by liver biopsy was identified on the average of ten years following blood transfusions and cirrhosis on an average of 20 years. It also appears that HCV, like the hepatitis B virus, is associated with an increased chance of developing hepatocellular carcinoma, a type of primary liver cancer. Almost all HCV-related liver cancer occurs with cirrhosis (scarring) of the liver. The exact magnitude of this risk is unknown but appears to be a late risk factor occurring on the average of 30 years after the time of infection. This is more prevalent in the Far East than in the U. S.
II How is Hepatitis C Transmitted?
HCV can be transmitted through blood transfusions. However, all blood is now tested for the presence of this virus by the antibody test. It is estimated that the risk of post-transfusion hepatitis C has been reduced from the 8-10% frequency of infection several years ago (before 1990) to less than 0.5% (after 1990). Other individuals who may come in contact with infected blood, instruments, or needles, such as I.V. drug users, health care workers or laboratory technicians are also at risk of acquiring hepatitis C, as are those who undergo tattooing or body piercing. Currently, there is no vaccine available to immunize individuals against this virus.
The risk for transmitting hepatitis C sexually is unknown. There have been occasional documented cases of people with chronic hepatitis C transmitting the virus to their only, long-term sexual partner. The U.S. Public Health Service says that because of the lack of sufficient information those with only one, long-term sexual partner need not change their sexual practices. Many physicians who counsel patients with hepatitis C recommend the same thing to those in a monogamous relationship. Spouses or long-term sexual partners of newly diagnosed patients are advised to be tested for hepatitis C. The Centers for Disease Control and Prevention (CDC) say there is a slight increased risk of becoming infected with hepatitis C if you have multiple sex partners. Whether the use of latex condoms is 100% effective in preventing someone from infecting their sexual partner or becoming infected is uncertain.
III Signs and Symptoms
Most people infected with chronic hepatitis C virus (HCV) have few symptoms or physical signs of the virus in the first two decades after infection. However, about 20 percent of those with HCV develop vague symptoms, including mild intermittent fatigue and malaise. Fatigue, which may lead to a significant decrease in quality of life, may be the first and only sign that the liver is being affected by the virus.
Much of the fatigue a person with HCV experiences is due to an activated immune system attempting to eliminate the virus. Despite the effective creation of antibodies against the hepatitis C virus can undergo frequent mutation, allowing it to avoid being eliminated from the body in 85 percent of those who contract it. In an ongoing effort to rid the body of the virus, the immune system continues to create weapons against the virus including antibodies, interleukins, and white blood cells. At times, the immune response leads to the production of immune complexes, collections of antibodies that course through the body. Immune complexes may deposit in the joints, the blood vessels in the skin, or in the kidney, leading to arthritis, rashes or glomerulonephritis (a form of kidney disease). These conditions are referred to as "extra-hepatic manifestations" of hepatitis.
An immune system activated to fight a virus like HCV might also begin developing antibodies against other tissues in the body, including the thyroid. The resulting autoimmune illness, such as autoimmune thyroiditis,can result in still more symptoms of fatigue.
The drugs interferon alpha-2b and interferon alpha-2a have been approved for the treatment of chronic hepatitis C.
Approximately 35 - 40% of patients treated for six months with interferon will respond, showing normalization of liver tests
and reduced inflammation on liver biopsy. However, of those who respond to treatment, approximately 60% will suffer a
relapse during several months after interferon treatment is discontinued. Thus, only 10-15% of patients treated with interferon
have a sustained, long-lasting response. Patients can be treated a second time and 85% of patients will enter a second
remission; however, the duration of treatment and dosage required for long-term remission in this group of patients has yet to
be determined.The hope is that improvement or normalization of liver tests and reduced inflammation in the liver will slow or
interrupt the development of progressive liver disease. However, the true impact of interferon treatment on the long-term
course of chronic hepatitis C and survival is unknown.
Side effects caused by interferon therapy can include "flu-like" symptoms, depression, headache, and decreased appetite. The
"flu-like" symptoms can be minimized by taking acetaminophen (e.g. Tylenol). In addition, interferon may depress the bone
marrow leading to reduced levels of white blood cells and platelets. Frequent blood tests are needed to monitor white blood
cells, platelets and liver enzymes. A liver biopsy is typically done prior to treatment to determine the severity of liver damage
and provide confirmation of the underlying disease.
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, immunocompromised 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.
Immunoblot 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 immunoblot 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 immunoblotting 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 immunoblot test for anti-HCV is positive, the patient has most likely recovered from hepatitis C and has persistent antibody without virus. If the immunoblot test is negative, the EIA result was probably afalse positive.
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 immunosuppressed, have recently had an organ transplant, or have chronic renal failure. At present, however, there are no PCR assays approved by the Food and Drug Administration for general use, although commercial test systems are available. Many commercial laboratories offer their own PCR assays, which are not subject to strict independent quality controls. Thus, the reliability and specificity of the PCR technique are not standardized. In addition, it is expensive and prone to technical or laboratory error. When ordering HCV RNA testing by PCR, the physician should use a high-quality laboratory willing to document standardization of the test.
The drugs interferon alpha-2b and interferon alpha-2a have been approved for the treatment of chronic hepatitis C. Approximately 35 - 40% of patients treated for six months with interferon will respond, showing normalization of liver tests and reduced inflammation on liver biopsy. However, of those who respond to treatment, approximately 60% will suffer a relapse during several months after interferon treatment is discontinued. Thus, only 10-15% of patients treated with interferon have a sustained, long-lasting response. Patients can be treated a second time and 85% of patients will enter a second remission; however, the duration of treatment and dosage required for long-term remission in this group of patients has yet to be determined.The hope is that improvement or normalization of liver tests and reduced inflammation in the liver will slow or interrupt the development of progressive liver disease. However, the true impact of interferon treatment on the long-term course of chronic hepatitis C and survival is unknown.
Side effects caused by interferon therapy can include "flu-like" symptoms, depression, headache, and decreased appetite. The "flu-like" symptoms can be minimized by taking acetaminophen (e.g. Tylenol). In addition, interferon may depress the bone marrow leading to reduced levels of white blood cells and platelets. Frequent blood tests are needed to monitor white blood cells, platelets and liver enzymes. A liver biopsy is typically done prior to treatment to determine the severity of liver damage and provide confirmation of the underlying disease.
VI Prevention and Control
At present, the only means of preventing new cases of hepatitis C are to screen the
blood supply, encourage health professionals to take precautions when handling
blood and body fluids, and inform people about high-risk behaviors. Programs to
promote needle exchange offer some hope of decreasing the spread of hepatitis C among
injection drug users. Vaccines and immunoglobulin products do not exist for hepatitis C, and
development seems unlikely in the near future because these products would require
antibodies to all the genotypes and variants of hepatitis C.
Nevertheless, advances in immunology and innovative approaches to immunization
make it likely that some form of vaccine for hepatitis C will
eventually be developed.
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School of Public Health
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