Optimal Follow-up Time to Determine the Sustained Virological Response in Patients With Chronic Hepatitis C Receiving Pegylated-interferon and Ribavirin

Masashi Namikawa; Satoru Kakizaki; Yutaka Yata; Yuichi Yamazaki; Norio Horiguchi; Ken Sato; Hitoshi Takagi; Masatomo Mori

Disclosures

J Gastroenterol Hepatol. 2012;27(1):69-75. 

In This Article

Abstract and Introduction

Abstract

Background and Aim: This study evaluated whether the assessment of hepatitis C virus (HCV)-RNA at 12 weeks (FW+12) post-treatment follow-up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real-time polymerase chain reaction (PCR) HCV assay.
Methods and Results: Two hundred and twenty-two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg-IFN) and ribavirin were administered for 24–72 weeks based on the genotype and viral load. Serum HCV-RNA was measured using real-time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty-eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load.
Conclusion: The assessment of serum HCV-RNA FW+12, using the highly sensitive real-time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV-RNA FW+12 may be effective in most patients.

Introduction

The recommended therapy for chronic hepatitis C is a combination of pegylated interferon (Peg-IFN) and ribavirin, and the major purpose of therapy to reach the sustained virological response (SVR).[1–4] The current standard for the determination of SVR is undetectable serum hepatitis C virus (HCV)-RNA 24 weeks (FW+24) after the end of treatment[5] and the continued viral response after FW+24.[1–4] This standard is based on the results of many previous reports that late relapse is rarely observed after FW+24.[6,7] This criterion is based on investigations using qualitative HCV-RNA assays with the lowest limits of detection of 50–100 IU/mL, to establish undetectable serum HCV-RNA at the end of therapy and after treatment.[6,7]

A highly sensitive method to detect HCV-RNA was recently developed and applied in clinical settings.[8,9] The highly sensitive methods include transcription-mediated amplification (TMA) and a real-time polymerase chain reaction (PCR) HCV assay.[8–12] Martinot-Peignoux et al.[8] reported the efficacy of a new assay based on TMA to predict SVR at FW+12. The TMA assay has a lowest detection limit of 5–10 IU/mL.[8] Theoretically, this highly sensitive method could detect residual serum HCV-RNA in a proportion of patients, who had been classified as having a virological response with a less sensitive assay.[8] Therefore, the assessment of HCV-RNA FW+12, using the TMA assay, is considered to be as effective as FW+24 to predict SVR.[8]

The real-time PCR assay is also highly sensitive to detect HCV-RNA and a popular method to assess the HCV-RNA.[9–12] Bortoletto et al.[9] reported that TMA and the real-time PCR HCV assay have comparable sensitivity and specificity in identifying minimal residual HCV-RNA. The lower limit of quantitative detection of the real-time PCR assay is 15 IU/mL[10–12] in comparison to the lowest detection limit of 5–10 IU/mL of the TMA assay.[8] However, even HCV-RNA signals below the quantitative limit are detected by the real-time PCR assay. Therefore, it is difficult to determine whether the TMA or the real-time HCV assays are optimal for the detection of minimal residual viremia at the end of antiviral therapy with Peg-IFN and ribavirin and in predicting relapse after withdrawal of treatment.

This study evaluated whether the assessment of HCV-RNA FW+12 by the real-time PCR HCV assay was as effective as FW+24 to evaluate SVR.

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