Recently, combination treatment for HCV has been able to eradicate the virus in approximately half of all cases, greatly expanding the need for laboratory tests for HCV infection. Because different tests are needed for different purposes, new tests have become available to assist clinicians in diagnosing the presence (or absence) of the infection, and to monitor treatment efficacy.
One of the nation’s leading investigators will provide an update on the status of HCV testing. D. Robert Dufour, MD, Chief of Pathology and Laboratory Medicine at the Veteran’s Affairs Medical Center in Washington, DC and Professor of Pathology at the George Washington University Medical Center, also in Washington, DC will make his remarks during the 54th Annual Meeting of the American Association of Clinical Chemistry (AACC). The meeting, which expects some 11,000 attendees, is being held in Orlando, FL July 28-August 1, 2002.
Background
The Hepatitis C virus is a single stranded RNA virus. To date, it has not been possible to grow the virus in a culture. It is the most common chronic infectious disease in Europe and North America and affects an estimated 170 million people worldwide. There are six different strains or “genotypes” of the virus, although only three of these are commonly seen in the U.S.
Testing for HCV Exposure
The most widely used test is designed to detect antibodies to one or more HCV proteins. Most laboratories report results as either positive or negative; positive results indicate that the person has been exposed to HCV. The Centers for Disease Control and Prevention recently developed new guidelines for laboratories that will require them to separate “low positives” from “strong positive” tests and do follow up testing before reporting results to a physician. The guidelines are expected to be released this fall.
Testing for HCV Infection
However, in most instances of patient testing, the clinical question is not whether the person has been exposed to HCV, but whether the individual is currently infected, which requires testing of another sort: HCV RNA. There are two major types of HCV RNA testing, one qualitative (which simply tells whether the virus is present or not) and one quantitative (which tells how much of the virus is present). Most qualitative HCV RNA tests are used for initial analysis to identify positive individuals. Recently, a test to detect a protein produced by HCV (core antigen) has become available, and seems to provide similar information to HCV RNA tests, but at a lower cost.
HCV Genotype Testing
But because antibody and HCV RNA tests do not indicate which strain of HCV an individual is infected, tests to determine the genotype have been developed. Most rely on detecting sequences in the RNA that correspond to those of the six known strains of HCV. The simplest technique, termed the Line Probe assay (LiPA), involves immobilized HCV RNA sequences that are allowed to hybridize to RNA in the sample, with visual detection of hybrids by an enzyme reaction. The pattern of bands allows determination of genotype in most cases. By contrast, direct sequencing of a segment of the HCV genome, and comparison to libraries of known HCV genotypes, allows detection of infection by more than one strain of the virus.
Treating Chronic HCV Infection: Cutting Treatment Time in Half for Some
There are three potential treatments for individuals positive for HCV RNA: interferon monotherapy, standard interferon plus ribavirin, and pegylated interferon plus ribavirin. Combination treatments are more effective than interferon monotherapy, but some patients cannot take ribavirin. With combination therapy, it has been shown that individuals who are genotype 2 or 3 will respond just as well to 24 weeks of treatment as to 48 weeks of treatment.
Monitoring Treatment
Treatment for HCV with interferon is both expensive and has many side effects. Therefore, it is important to determine whether the treatment is effective in eliminating HCV RNA from the blood. Treatment is usually monitored by using very sensitive assays for HCV RNA and the criteria for determining treatment “response” can vary, based on the type of treatment used. The goal of treatment is to eradicate HCV RNA from the body, which correlates with the absence of HCV RNA in the blood after treatment has been stopped for six months. Proposed consensus guidelines from the National Institutes of Health (NIH) are considering whether to recommend testing at 12 weeks of treatment to see if the patient is responding, rather than waiting 24 weeks. The testing being considered would check quantitative HCV RNA, also called viral load (i.e., how much of the virus is in the system) before treatment begins, and whether it has fallen a certain amount after three months of treatment. (Refer to: www.guidelines@nih.gov).
Risk Factors for HCV
Dr. Dufour says that the following are the most common risk factors for HCV infection:
- Illegal drug use, especially injectable drugs
- Blood transfusion(s) before 1992
- Ten or more sex partners
- Dialysis
Should You Be Tested for HCV?
Dr. Dufour recommends that anyone who believes they have the above risk factors be tested for HCV. A screening test costs between $25.00-$30.00 and the ability to diagnose and eventually monitor the effectiveness of treatment has never been better than it is today.
Editor’s Note: To interview Dr. Dufour, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.
Or contact the AACC Newsroom at: 407.685.4215.