How to Predict Hepatitis C Disease Progression

New procedure seeks to guide therapeutic decisions.

An experimental test that detects a drug resistant hepatitis C virus (HCV) mutation may also help predict how the disease progresses.

The quick and accurate method to detect the mutation was developed by researchers at Hiroshima University. The system is able to measure the presence of HCV Y93H drug resistant mutant strains while also determining the proportion of patients who carry the mutation prior to treatment.

Furthermore, the Y93H mutation was successfully detected in more than half of serum samples with low HCV titers. The new system may also offer caregivers vital pre-treatment information that guides therapeutic decisions and predicts disease progression in genotype 1b patients.

The Y93H mutation was previously found to be a key predictor of virologic failure.

The commonly used direct sequencing method to detect the mutation can only detect viral subpopulations with frequencies of at least 10% to 20%. Meanwhile, next generation sequencing offers a more sensitive method to evaluate viral mutations, but is complex to perform and too expensive for widespread clinical use.

The test combines nested PCR and the Invader assay with primers and probes that allow the Y93H mutation to be detected with a success rate of 98.9% among a total of 702 HCV genotype 1b patients. The proportion of patients with the Y93H mutation was estimated at 23.6%, which is comparable to the proportion assayed by real-time PCR and ranked between deep sequencing and direct sequencing.

The new system also achieved a high assay success rate and was more sensitive in detecting Y93H than direct sequencing.

"Our assay system also showed a much lower detection limit for Y93H than using direct sequencing, and Y93H frequencies obtained by this method correlated well with those of deep-sequencing analysis,” lead investigator Professor Kazuaki Chayama said.