Typically, Dr. Hendricks explains, when a patient presents with the possibility of hepatitis C, the physician conducts a battery of tests, including an antibody test that shows exposure to hepatitis C virus. Consensus guidelines also call for an HCV RNA test to indicate viral persistence, and thus, to confirm the diagnosis.
Refining that diagnosis to identify the specific genotype is extremely important.
"This is where molecular diagnostics also kicks in," explains Dr. Hendricks. Hepatitis C has six major genotypes, which can be divided further into subtypes. Genotype 1 and, sometimes, genotype 4, are treated differently from all the other genotypes.
"With Genotype 1, therapy lasts 48 weeks. For non-one genotypes, therapy lasts 24 weeks, as a rule of thumb," he says. Baseline testing, therefore, has two components genotyping and quantification of HCV genotype 1 virus.
Therapies have advanced dramatically in the past decade, as cure rates have climbed from 15%, with interferon for 12 months of treatment in 1992, to 55%, with a combination of pegylated interferon and ribavirin in 2002, reports Dr. Hendricks.
Consequently, "pegylated interferon and ribavirin are used most often in therapy," despite some nasty side effects.
Those side effects and the cost of treatment spurred the consensus committees to call for another quantification test at week 12. If there is less than a 2 log10 change in the viral load, stopping treatment is strongly recommended.
"Almost no one is cured past that point, even with the full course of therapy, without that drop in viral load," Dr. Hendricks explains. "To detect a 2 log10 change in viral load, quantitative HCV RNA assays must be linear and reproducible," and, ideally, have a wide dynamic range.
"At the end of the therapy, you run a more sensitive assay, a qualitative HCV RNA assay, which says a virus is or is not detected. Six months after completion of therapy, patients are tested again," to determine whether the clearance of virus is sustained.
If the virus is not detected, the patient is considered to be cured. Ultra-sensitive qualitative HCV RNA assays may provide additional value by detecting the virus during, or at the end of therapy, when HCV is missed by less sensitive assays. Trials are needed, he says, to determine whether such assays would provide real clinical benefit.
According to K.K. Jain, M.D., founder, Jain PharmaBiotech (Basel, Switzerland), some 500 companies are involved in molecular diagnostics, and account for a $6.5 billion global market this year. By 2010, that figure is expected to increase to $12 billion.
By $2015, he predicts a global market of $35 billion for molecular diagnostics.