High Relapse Rate of Hepatitis C for Patients with Minimally Detectable HCV RNA During Therapy

Abstract

Purpose: The reported treatment relapse rates with pegylated interferon and weight-based ribavirin are about 15-20% for HCV genotype-1 and 5-10% for genotype-2 or 3 patients. Many clinical laboratories apply the Cobas Taqman RT-PCR assay for serum HCV RNA quantification. It has a dynamic range between 43 and 69,000,000 IU/ml and its lowest limit of detection is 18 IU/ml. HCV RNA levels below 18 IU/ml are reported as “undetectable”. HCV RNA levels between 18-43 IU/ml are reported as “detectable but <43 IU/ml” which we referred to as “minimally detectable” in this abstract. The clinical significance of the minimally detectable versus undetectable viral levels during therapy is uncertain. The aim of the study is to evaluate the treatment relapse rates among those with minimally detectable HCV RNA level reported at least once during therapy. Methods: The molecular laboratory records of all patients who received combination therapy for chronic hepatitis C at our tertiary care liver clinics from 2009-2011 were reviewed. Baseline and serial HCV RNA levels during and 6-month after therapy were examined. Those with minimally detectable viral loads at any time points during therapy were identified for detailed medical record review. The treatment relapse rates were recorded. Results: Twenty-five (12 HCV genotype-1, 13 genotype-2 or 3) patients with minimally detectable HCV RNA levels during therapy were identified. 21 (84%) of the patients were Caucasians with average age of 51 years. Male accounted for 67% and 77% of the genotype-1 and genotype-2 or 3 patients. Treatment relapse rates were 75% (9 of 12) for genotype-1 and 46% (6 of 13) for genotype 2 or 3 patients. The baseline HCV RNA levels and fibrosis scores were not significantly different between those with or without relapse. Six of 9 (67%) genotype-1 patients with relapse had 2 or more minimally detectable viral loads reported either continuously or intermittently with undetectable levels during therapy. This trend was less clear for genotype 2 or 3 patients due to their shorter treatment duration. Conclusion: There is a significantly higher treatment relapse rate among patients with minimally detectable HCV RNA levels observed during therapy compared to the relapse rates cited in the literature. This could represent incomplete viral suppression on treatment. Further comparison of the response rate with those who maintained consistently undetectable HCV RNA levels on treatment in our patient cohort is being conducted.