Chronic Hepatitis C: Role of Rapid Virological Response
Chronic Hepatitis C: Role of Rapid Virological Response
Background For patients with chronic hepatitis C, attaining rapid virological response (RVR) is highly predictive of attaining SVR.
Aim To consider the predictive value of RVR in terms of SVR and relapse.
Methods Data were collected from published clinical trials to define the predictive value of RVR for SVR and evaluate the proposed continuum linking RVR to relapse.
Results These data support a 24-week regimen among genotype (G)1 patients who attain RVR with positive predictive values (PPVs) of 77.8% and 85.7% in patients with G1 infection treated for 24 and 48 weeks. Conversely, failure to attain RVR among G1 patients should not be viewed as a criterion for extending treatment duration beyond 48 weeks: negative predictive values (NPVs) were 60.9% and 52.7% in G1 patients without RVR treated for 48 and 72 weeks. Among G2/3 patients, RVR has a high PPV; however, the NPV varied with treatment duration indicating that a 24-week treatment regimen is warranted in G2/3 patients who fail to attain RVR.
Conclusions The present analysis confirms RVR as a strong predictor of SVR that can be used to tailor treatment duration, but which also should be appreciated in the context of treatment duration and regimen.
Sustained virological response (SVR), the goal of therapy for patients with chronic hepatitis C, is attained by 54–56% of patients who receive pegylated interferon (PEG-IFN) alfa plus ribavirin. Unfortunately, patients with chronic hepatitis C do not represent a homogeneous population with uniform responses to therapy. Therefore, developing an optimized therapeutic regimen suited to all patients has proved difficult. To optimize treatment outcomes and health care resources, research efforts have focused on an individualized approach to treatment in which therapeutic regimens are developed to suit the particular host and viral characteristics of each patient.
The essence of individualized treatment is to apply the minimum possible therapeutic burden on each patient without compromising the likelihood of attaining SVR. Thus, the individualized approach allows shorter treatment durations and lower dose regimens in patients who respond quickly to therapy, longer treatment durations and higher dose regimens in patients who respond slowly and early discontinuation of treatment in patients who do not respond at all. In principle, this approach is straightforward. However, identifying patients who fall into each category with a high degree of accuracy is important for its success.
Host and viral factors such as hepatitis C virus (HCV) genotype, baseline viral load, fibrosis, body weight and age influence response to therapy and can help predict treatment outcomes. Once treatment is initiated, on-treatment markers of response can further aid in predicting treatment outcomes. These markers include rapid virological response (RVR, undetectable HCV RNA at week 4 of therapy), partial early virological response (pEVR, ≤2 log10 decline in HCV RNA from baseline at week 12 of therapy) and complete EVR (cEVR, undetectable HCV RNA at week 12 of therapy).
Among patients who attain an end-of-treatment (EOT) response, two different clinical outcomes – SVR and relapse – are possible. Factors influencing attainment of SVR or relapse are becoming better defined. For example, the on-treatment period of undetectable HCV RNA is one of the most important factors influencing the ratio of SVR to relapse. In turn, two elements of the treatment regimen are critical: the time during treatment at which the patient first attains undetectable HCV RNA and the overall duration of treatment. For example, the standard duration of therapy for a patient infected with HCV genotype 1 (G1) is 48 weeks. Thus, G1 patients who attain RVR will experience 44 weeks of undetectable HCV RNA while on treatment; the ratio of SVR to relapse in these patients favours SVR. In contrast, G1 patients who do not attain undetectable HCV RNA until week 24 of therapy will experience only 24 weeks of undetectable HCV RNA while on treatment; the ratio of SVR to relapse in this case shifts dramatically to favour relapse.
Rapid virological response is the earliest on-treatment predictor of treatment response investigated to date. Theoretically, a continuum should connect RVR, treatment duration and the ratio of SVR to relapse. The objective of this review was to consider the predictive value of RVR in terms of SVR and relapse.
Abstract and Introduction
Abstract
Background For patients with chronic hepatitis C, attaining rapid virological response (RVR) is highly predictive of attaining SVR.
Aim To consider the predictive value of RVR in terms of SVR and relapse.
Methods Data were collected from published clinical trials to define the predictive value of RVR for SVR and evaluate the proposed continuum linking RVR to relapse.
Results These data support a 24-week regimen among genotype (G)1 patients who attain RVR with positive predictive values (PPVs) of 77.8% and 85.7% in patients with G1 infection treated for 24 and 48 weeks. Conversely, failure to attain RVR among G1 patients should not be viewed as a criterion for extending treatment duration beyond 48 weeks: negative predictive values (NPVs) were 60.9% and 52.7% in G1 patients without RVR treated for 48 and 72 weeks. Among G2/3 patients, RVR has a high PPV; however, the NPV varied with treatment duration indicating that a 24-week treatment regimen is warranted in G2/3 patients who fail to attain RVR.
Conclusions The present analysis confirms RVR as a strong predictor of SVR that can be used to tailor treatment duration, but which also should be appreciated in the context of treatment duration and regimen.
Introduction
Sustained virological response (SVR), the goal of therapy for patients with chronic hepatitis C, is attained by 54–56% of patients who receive pegylated interferon (PEG-IFN) alfa plus ribavirin. Unfortunately, patients with chronic hepatitis C do not represent a homogeneous population with uniform responses to therapy. Therefore, developing an optimized therapeutic regimen suited to all patients has proved difficult. To optimize treatment outcomes and health care resources, research efforts have focused on an individualized approach to treatment in which therapeutic regimens are developed to suit the particular host and viral characteristics of each patient.
The essence of individualized treatment is to apply the minimum possible therapeutic burden on each patient without compromising the likelihood of attaining SVR. Thus, the individualized approach allows shorter treatment durations and lower dose regimens in patients who respond quickly to therapy, longer treatment durations and higher dose regimens in patients who respond slowly and early discontinuation of treatment in patients who do not respond at all. In principle, this approach is straightforward. However, identifying patients who fall into each category with a high degree of accuracy is important for its success.
Host and viral factors such as hepatitis C virus (HCV) genotype, baseline viral load, fibrosis, body weight and age influence response to therapy and can help predict treatment outcomes. Once treatment is initiated, on-treatment markers of response can further aid in predicting treatment outcomes. These markers include rapid virological response (RVR, undetectable HCV RNA at week 4 of therapy), partial early virological response (pEVR, ≤2 log10 decline in HCV RNA from baseline at week 12 of therapy) and complete EVR (cEVR, undetectable HCV RNA at week 12 of therapy).
Among patients who attain an end-of-treatment (EOT) response, two different clinical outcomes – SVR and relapse – are possible. Factors influencing attainment of SVR or relapse are becoming better defined. For example, the on-treatment period of undetectable HCV RNA is one of the most important factors influencing the ratio of SVR to relapse. In turn, two elements of the treatment regimen are critical: the time during treatment at which the patient first attains undetectable HCV RNA and the overall duration of treatment. For example, the standard duration of therapy for a patient infected with HCV genotype 1 (G1) is 48 weeks. Thus, G1 patients who attain RVR will experience 44 weeks of undetectable HCV RNA while on treatment; the ratio of SVR to relapse in these patients favours SVR. In contrast, G1 patients who do not attain undetectable HCV RNA until week 24 of therapy will experience only 24 weeks of undetectable HCV RNA while on treatment; the ratio of SVR to relapse in this case shifts dramatically to favour relapse.
Rapid virological response is the earliest on-treatment predictor of treatment response investigated to date. Theoretically, a continuum should connect RVR, treatment duration and the ratio of SVR to relapse. The objective of this review was to consider the predictive value of RVR in terms of SVR and relapse.
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