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What is the most efficient testing algorithm for diagnosing hepatitis C virus? | |||||||||||||||||||||||||||||||||||||||||||||
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Hepatitis C Virus Infection
The Hepatitis C Virus was discovered in 1989. Recent studies show that 2% of the U.S. population is infected, but about 90% of those infected are unaware. Approximately 10-15% of infections spontaneously resolve. Ten percent develop chronic liver failure, and HCV is a leading cause of liver transplants in the United States. Current treatment is partially effective depending on, among other factors, viral load and HCV genotype and subtype. New drugs look promising. Tests The tests available for the diagnosis of HCV are as follows: Hepatitis C Antibody (anti-HCV by EIA) Diagnosis of HCV Infection HCV infection is usually not suspected until the patient donates blood and has a positive anti-HCV, or the patient has chemistry testing performed for the flu or other mild illness and is found to have a high Alanine Aminotransferase (ALT) test and then additional testing shows a positive anti-HCV. Thus, in-spite of the 2% incidence, almost all patients who need a diagnostic workup will have a positive anti-HCV test. Confirmation The confirmation assays ultimately identify: 1) patients who are currently infected; 2) those who were infected but have recovered; and 3) those who were never infected (i.e. false-positive anti-HCV by EIA). The anti-HCV by EIA has a specificity of 99.9% and therefore a false-positive rate of 0.1%. With a spontaneous recovery rate of 10%, those who are currently infected will make up 90% of the true positive results. Accordingly, for a population of 100,000 with an incidence of 2%, at least 2,100 will test positive for Hepatitis C Antibody. This number would then break down as follows:
The Issue: For patient care, the challenge is to identify a test ordering algorithm that will identify those currently infected with HCV in the shortest possible time. For cost-effectiveness, the goal is to develop a pattern that will eliminate the largest number of candidates from progressing to each successive round of testing. Common Algorithm for Diagnosing HCV
The common algorithm for diagnosing HCV fails the challenges for optimal turn-around time and cost effectiveness. The anti-HCV by RIBA test is performed at least 4 times weekly. Results are reported the next day. HCV RNA by PCR is performed daily and results are reported within 5 days. Thus, with this ordering pattern, those currently infected are not identified for at least six days and perhaps much more depending on when the RIBA test is performed and whether an additional sample must be drawn. Also, confirming first with the anti-HCV RIBA assay will only eliminate the EIA false-positives. Using our example above, for 2,100 RIBA tests performed, 100 false-positives will be eliminated and 2,000 HCV RNA by PCR tests will subsequently need to be performed.
Recommended Algorithm for Diagnosing HCV
The recommended algorithm better suits the issues of patient care and cost. By confirming with HCV RNA by PCR first, those currently infected with HCV are identified in no more than 5 days. Also, this pattern will eliminate the largest group first. Referring to our example, for 2,100 PCR tests performed, 1,800 current infections will be confirmed, and only 300 samples will subsequently need to have anti-HCV by RIBA tests performed.
Comparison of Algorithms Contrasting the test ordering patterns reveals that the recommended algorithm provides a decrease in time to identify current infection, and a substantial reduction in cost by approximately 37%. The following is based on a population of 100,000 with 2% prevalence: (Smaller populations will yield proportional savings). Common Diagnostic Algorithm
Recommended Diagnostic Algorithm
Comparative savings: $209,500 or 36.6%
Analysis To gauge the degree of compliance with the recommended test ordering pattern for HCV diagnosis, examine the ratio of anti-HCV by RIBA to HCV RNA by PCR. While assessing the ratio, it is important to acknowledge that the HCV RNA by PCR, quant. test is also commonly used for monitoring viral load over time for chronically infected patients. It is generally recognized that the test should be administered three times annually. Therefore, with the common algorithm, depending on whether the PCR test is being used for monitoring, the RIBA to PCR ratio will be between 1:0.95 and 1:3.5. With the recommended algorithm, the ratio is at least 1:7 and may be as high as 1:25 or more. Ratios between 1:3.5 and 1:7 are considered transitional.
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