HCV Demands More Attention

Edition: September 2001 - Vol 9 Number 09
Article#: 1048
Author: Laura Thill

Since 1989, heightened awareness of the hepatitis C virus (HCV) has led physicians to accept it as a major cause of liver disease in the United States, according to David Bernstein, M.D. (''Diagnosis and Management of Hepatitis C,'' Gastroenterology Clinical Management Vol. 1, Feb 2, 2001). In addition to liver disease, HCV is linked to such disorders as renal, endocrine, dermatologic, hematologic (including lymphoma), and diabetes mellitus, among others.


About 3.9 million Americans will test positive for the HCV antibody and 2.7 million are actively infected, comprising one percent of the U.S. population, says Bernstein. Symptoms of the virus generally do not surface. If they do, however, they include fatigue, abdominal pain, appetite and weight loss and pruritus.


In spite of its name, HCV is not similar to Hepatitis A or B. Classified in the Flaviviridae family, it is in a league with those viruses causing yellow fever and dengue.


Spread of the Disease


HCV resides in the blood and is spread parenterally through contact with the blood of an infected individual. The biggest risk factor for this disease is intravenous drug use. Before blood donor screening programs and surrogate hepatitis tests were instituted in 1992, blood transfusions also presented a substantial risk for HCV. The following chart identifies low- and high-risk factors that contribute to the spread of HCV:


Potential Hepatitis C Risk Factors


Common


Intravenous drug use.


Blood transfusions prior to 1992.


Accidental needlestick injury.


Sexual transmission.


Perinatal transmission.


Kidney dialysis.


Transplants prior to 1992.


Hemophilia.


Uncommon


Intranasal cocaine.


Body piercing.


Tatoos.


Sharing household items.


Fistfights involving blood contact.


Source: Diagnosis and Management of Hepatitis C, David Bernstein, M.D., Gasteroentology Clinical Management Vol. 1, Feb 2, 2001.


There have also been cases suggesting the spread of HCV between patients exposed to a disinfected colonoscope or during cardiothoracic surgery. Needlestick injuries provide a lower risk for HCV than for hepatitis B, but a higher risk rate compared to that for HIV. When an infected patient cannot be tested to determine his or her hepatitis viral load, Bernstein suggests testing the needlestick recipient and initiating treatment if he or she is HCV-RNA-positive.


Sexual transmission accounts for a small percentage of HCV cases – probably less than five percent – as does perinatal transmission. Other risk groups include those who received clotting factor concentrates before 1987, hemodialysis patients, hemophiliacs, and organ or bone marrow transplant recipients before 1992, according to Bernstein.





Disease Progression


Certain factors affect how quickly HCV progresses to cirrhosis. Factors that have a negative impact on the disease include:


Alcohol use.


Age and sex. HCV progresses more rapidly in patients infected with the disease after age 40, and men have increased disease progression over women.


HIV and HBC coinfection.


Two tests available to detect the anti-hepatitis C antibody (anti-HCV Ab) are enzyme immunoassays (EIA) and recombinant immunoblot assays (RIBA).


EIA antibody testing, first developed in 1989, is easy to perform, according to Bernstein. It is reportedly less expensive than some other forms of testing and boasts a high level of sensitivity. However, a positive EIA-antibody test alone is not enough on which to base a diagnosis of HCV. False-positive EIA testing is known to occur in patients who are low-risk or have autoimmune diseases. A second positive assay is necessary to confirm the diagnosis.


RIBA testing is supplemental to EIA testing. The RIBA test is comprised of the same HCV antiagents as found in EIA testing. When two or more antigens are positive, diagnosis of HCV is probable. RIBA testing is useful in determining whether an EIA test is false positive or positive.


Therapy


Antiviral therapy used to treat HCV has two goals, according to Bernstein:


•To rid the body of the virus (antiviral therapy).


•To slow disease progression and improve patient's quality of life.


IFN Monotherapy


Interferol (IFN) monotherapy has provided standard treatment for HCV. However, patients who continue to retain levels of the HCV virus after 12 weeks of IFN therapy generally are taken off this therapy. Patients with no signs of cirrhosis or HCV genotype 2 and 3, and low levels of HCV-RNA, tend to have better results with IFN treatment. Side effects of this therapy include flu-like illness initially, followed by fatigue, headache, neuropsychiatric changes, and depression.


Combination Therapy


Trials have been conducted testing the effects of a combination therapy – IFN-alpha-2b plus ribavirin. Side effects of ribavirin generally include anemia, depression, fatigue, irritability, rash, cough, shortness of breath and insomnia. Patients treated with combination therapy tend to have a lower relapse rate after therapy is discontinued.


Relapse patients who are initially treated with IFN monotherapy may be treated with higher doses of IFN monotherapy, or with combination IFN and ribavirin. Physicians do not have firm knowledge for treating relapse patients who initially receive combination therapy.


Nearly 60 percent of patients treated with combination therapy do not respond to treatment, according to Bernstein, and there is little data to support that higher levels of IFN plus ribavirin will affect patients differently. More clinical testing is needed to explore treatment possibilities for relapse patients and nonresponders.





New HCV Tests Soon To Be Available


With a greater understanding of the hepatitis C virus and its implications for world health has come a surge of diagnostic products.


One such test, the HCV RNA Qualitative test (Bayer Diagnostics, Tarrytown, NY), is available as Analyte Specific Reagents for qualified U.S. labs to develop their own assay, according to Bayer Diagnostics. In other countries, the HCV RNA Qualitative Assay is only available for investigational use.


The HCV RNA test is designed to offer patients early detection of the hepatitis C virus, as well as helping monitor patient response to therapy. Features reportedly include:


• Detection of < 50 HCV copies/mL and < 5 HCV International Units/mL (WHO 96/790) for early detection of viral replication.


• 99.5 percent or greater specificity.


• Contamination prevention systems to enhance reliability.


Two other HCV tests recently introduced – both of them FDA-approved for research in the United States – are the Amplicor HCV test and the Cobas Amplicor HCV test (Roche Diagnostics, Basel, Switzerland). Both tests are based on RNA detection. The presence of RNA in serum indicates infection. The tests work via a technology called Polymerase Chain Reaction (PCR). They are commercially available in areas outside of the United States.