Focus on the Predictive Role of HCV RNA Monitoring

Pegylated interferon-alpha (Peg-IFN) plus ribavirin is the current standard of care of chronic hepatitis C (CHC). For patients infected with HCV genotype 1 (HCV-1), the recommended treatment duration is 48 weeks, whereas for patients infected with HCV-2/3, the recommended treatment duration is 24 weeks. Professor Ming-Lung Yu, from Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, presented a report on the role of HCV RNA monitoring. He said that recent studies on viral kinetics showed that on-treatment virological responses assessed by HCV RNA monitoring during therapy had been the most important predictors associated with the response to Peg-IFN/ribavirin. A rapid virological response at week 4 (RVR), defined as PCR-negative of serum HCV RNA at 4 weeks of treatment, is the single best positive predictor of a sustained virological response (SVR) to Peg-IFN-ribavirin for both HCV-1 and HCV-2/3 patients with a high degree of accuracy of prediction. In contrast, early virological response (EVR), defined as PCR-seronegative of HCV RNA or decrease of HCV RNA by 2 logs from baseline values after 12 weeks of therapy, is an even more robust negative predictor. The likelihood of an SVR is approximately 0% to 2% in cases without an EVR for HCV-1 patients. Thus it is recommended that HCV-1 patients who do not achieve an EVR should stop the treatment. More recently, EVR has been suggested to be subdivided into RVR, complete EVR (no RVR, but HCV RNA < 50 IU/ml at week 12) and partial EVR (HCV RNA > 2 log drop in HCV RNA but still detectable [> 50 IU/ml] at week 12) to further improve the prediction of patients who are likely to achieve an SVR and may allow for tailoring of treatment duration.

Professor Yu stated that individualized therapy has become a major consideration for clinicians. It is desirable to expose CHC patients to the lowest doses and shortest durations of treatment possible to reduce the likelihood of adverse events and to minimize costs, without compromising treatment efficacy for the rapid responders. On the other hand, some difficult-to-treat patients have to receive longer and/or higher dose therapy to achieve responses. Recently, several studies have demonstrated that shorter 24-week regimens for HCV-1 patients with lower viral loads and a RVR at week 4 were as effective as the current recommendations 48-week treatment. Studies investigating shorter treatment durations for HCV-2/3 patients with a RVR, however, did not observe consistent results because the shorter therapy arm and the dose of ribavirin varied across different studies. Nevertheless, a recent meta-analysis demonstrated only optimal shorter therapy (16 weeks with weight-based, standard dose of ribavirin), but not suboptimal shorter therapy (12-14 weeks or low dose ribavirin, 800 mg/d) could provide efficacy equal to a standard 24-week treatment in HCV-2/3 patients with a RVR. Meanwhile, an extended 72-week regimen with weight-based, standard dose of ribavirin could improve the treatment efficacy for slow responders (pEVR) of HCV-1 patients, but not in cEVR patients. HCV genotype and HCV RNA monitoring during therapy could provide information for individualized therapy decision making for CHC patients to maximize the efficacy with optimal regimen.