RVR Rates Research Articles

Effect of season and sunlight on viral kinetics during hepatitis C virus therapy

Background and aimsRapid viral response (RVR) during antiviral treatment for hepatitis C virus (HCV) predicts sustained viral response (SVR). Recently, vitamin D levels have been associated with SVR. As sunlight...

Daclatasvir combined with peginterferon-α and ribavirin for the treatment of chronic hepatitis C: a meta-analysis.

Daclatasvir, a HCV NS5A inhibitor, is a new direct-acting antiviral drug for chronic hepatitis C (CHC). This study aimed to evaluate the efficacy and safety of daclatasvir combined with peginterferon-α (pegIFN-α) and ribavirin (RBV) for the treatment of CHC. The databases of PUBMED, EMBASE, COCHRANE, WANFANG, and CNKI were retrieved to identify eligible studies. Pooled risk ratio (RR) and 95 % confidence interval (CI) were calculated using random or fixed models. A total of six RCTs including 1100 adult patients with CHC met the inclusion criteria and the patients were infected with HCV genotype 1–4, with the genotype 1 infection accounting for 73.1 %. Meta-analysis showed daclatasvir-based combination therapy yielded a significantly higher probability of achieving the overall RVR (46.43 vs. 18.97 %) with pooled RR of 3.77 (95 % CI 1.95–7.28, p < 0.0001) and a slightly higher probability of achieving the overall SVR24 (65.08 vs. 47.77 %) with pooled RR of 1.41 (95 % CI 1.18–1.68, p < 0.0001), and did not show increased adverse events compared with the pegIFN-α/RBV regimen (control group). Subgroup analysis showed the rate of RVR and SVR24 in high-dose daclatasvir (60 mg/day) group were slightly higher than the overall results; the rate of RVR in low-dose daclatasvir (10 mg/day) group was also higher than the control group, but its SVR24 rate was similar between the two groups. Daclatasvir combined with pegIFN-α/RBV is effective and safe in treating adult patients with CHC, especially HCV genotype 1 infection, and daclatasvir (60 mg/day) is a better choice as compared with daclatasvir (10 mg/day).

Comparison of three quantitative HCV RNA assays in samples from HCV genotype 1- or 4-infected patients treated with the NS3/4A protease inhibitor simeprevir

BackgroundMonitoring HCV RNA levels during treatment is an important tool for managing protease-inhibitor-based regimens, and different assays used in clinical practice can impact treatment decisions. ObjectivesThe concordance of three HCV RNA assays was determined, and their impact on treatment decisions assessed using samples from HCV genotype (GT) 1- and GT4-infected patients treated with the NS3/4A inhibitor simeprevir in combination with pegylated interferon-α/ribavirin. Study designPlasma samples collected during the simeprevir Phase III studies QUEST-1 and QUEST-2 (GT1), and RESTORE (GT4) were analyzed with the Roche High-Pure-System COBAS® TaqMan® HCV v2.0 (HPS), the Roche AmpliPrep COBAS® TaqMan® HCV v2.0 (CAP), and the Abbott RealTime HCV (ART) assay. ResultsIn GT1, of the 440 samples, 81% were undetectable (rapid virological response; RVR) by HPS at Week 4, 76% by CAP and 44% by ART. In GT4 (103 samples), RVR rates were 67% by HPS and 24% by ART. HCV RNA <25IU/mL at Week 4 was observed for 95–96% and 92% GT1 samples and 86% and 74% GT4 samples by HPS/CAP and ART, respectively. At Week 12, assay concordance for undetectability was high in GT1 and GT4, (95–98% and 93%, respectively). ConclusionsWhile different HCV RNA assays can lead to substantially different RVR rates, a good concordance was observed with a cut-off of 25IU/mL. Sustained virologic response rates among GT1 patients achieving RVR or <25IU/mL at Week 4 were high and similar between assays used. At later time points, when viremia is low, assay concordance was high.

Understanding the effect of the HCV polymerase inhibitor mericitabine on early viral kinetics in the phase 2 JUMP‐C and PROPEL studies

The aim was to evaluate early viral kinetics in patients receiving mericitabine [hepatitis C virus (HCV) nucleoside polymerase inhibitor] with peginterferon alfa-2a (40KD) and ribavirin in two clinical trials (PROPEL and JUMP-C). We examined rapid virological responses (RVRs; week 4 HCV RNA <15 IU ml(-1) ) and complete early virological responses (cEVR; week 12 HCV RNA <15 IU ml(-1) ) in HCV genotype 1/4-infected patients receiving mericitabine (500 or 1000 mg) or placebo twice daily plus peginterferon alfa-2a and ribavirin. Among IL28B rs12979860 CC genotype patients receiving 500 or 1000 mg mericitabine or placebo, respectively, RVR rates were 64.3% (95% confidence interval: 38.8-83.7%), 95.1% (83.9-98.7%) and 33.3% (20.2-49.7%), and cEVR rates were 100% (78.5-100%), 100% (91.4-100%) and 80.6% (65.0-90.3%). Among non-CC genotype patients, RVR rates were 26.5% (14.6-43.1%), 52.3% (43.0-61.3%) and 5.7% (2.2-13.8%), and cEVR rates were 76.5% (60.0-87.6%), 84.6% (76.6-90.1%) and 28.6% (19.3-40.1%), respectively. In multiple regression analysis, IL28B genotype (P < 0.0001), mericitabine dose (P < 0.0001) and bodyweight (P = 0.0009) were associated with first-phase (α) slope (change in log10 HCV RNA from baseline to week 1). Mericitabine-containing triple therapy reduces the impact of IL28B genotype on RVR and cEVR compared with peginterferon alfa-2a and ribavirin dual therapy. The IL28B genotype, mericitabine dose and bodyweight are the most important factors associated with the α slope, and there is no evidence of a pharmacokinetic drug-drug interaction between mericitabine and ribavirin.

Treatment efficacy of pegylated interferon plus ribavirin therapy in chronic hepatitis C patients with mixed genotype 1/2 infection

The treatment efficacy of patients with mixed hepatitis C virus (HCV) genotype 1/genotype 2 (HCV-1/2) remains unknown. We aimed to elucidate the sustained virological response (SVR) rate in patients with HCV-1/2 infection. One hundred and ten HCV-1/2 patients treated with response-guided peginterferon/ribavirin therapy (24 weeks for patients with a rapid virological response [RVR] and low viral loads; 48 weeks for patients without a RVR or high viral loads) were allocated. Two hundred HCV-1 patients were selected as a historical control. Interleukin-28B (IL-28B) rs8099917 genotype was tested for the association with an SVR. The rates of RVR, sustained virologic response (SVR), and relapse rate were 71.8%, 87.3%, and 11.1%, respectively. The SVR rate was significantly higher in patients with an abbreviated regimen as compared with those with 48-week regimen (95.5% vs 75.0%, P = 0.002), and both were similar to the HCV-1 historical control. Stepwise logistic regression analysis revealed that lower baseline viral loads were the single factor predictive of an RVR (odds ratio/95% confidence intervals [OR/CI] of 41.62/9.72-178.19, P < 0.001). The achievement of an RVR was the single best factor predictive of an SVR (OR/CI: 7.5/1.33-42.27, P = 0.02). Nevertheless, an abbreviated regimen became the single factor associated with an SVR if treatment regimen was taken into consideration (OR/CI: 11.0/1.25-96.79, P = 0.03). The SVR rate did not differ between patients with rs8099917 TT and TG/GG genotype (91.7% vs 87.5%, P = 0.63). The treatment efficacy of patients with HCV-1/2 was satisfactory. The role of IL-28B genetic variants in the population with response-guided therapy was limited.

Are statins a viable option for the treatment of infections with the hepatitis C virus?

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that are widely used for the treatment of hypercholesterolemia. Besides their cholesterol-lowering effect, statins have been reported to have antiviral activity against a variety of viruses, including hepatitis C virus (HCV). Several statins inhibit the in vitro replication of subgenomic HCV replicons and also suppress in vitro RNA replication of infectious HCV. The precise mechanism of the anti-HCV activity of statins has not yet been defined. Recent studies suggest that the antiviral effect may result from the inhibition of geranylgeranylation of cellular proteins, rather than the inhibition of cholesterol synthesis. Despite the antiviral effect observed in vitro, statin monotherapy seems to be insufficient for the treatment of chronic HCV infection. However, several prospective and retrospective studies have demonstrated that the addition of statins to IFN-α and ribavirin therapy increases SVR, RVR, and EVR rates without the occurrence of additional adverse events. These clinical data, together with the excellent safety profile and low cost, suggest that statins may play a role in HCV therapy until more potent and safe direct-acting antivirals become available. This article forms part of a symposium in Antiviral Research on “Hepatitis C: next steps toward global eradication.”

Efficacy of standard antiviral therapy retreatment following interferon treatment failure in chronic hepatitis C patients

To investigate the therapeutic efficacy of standard antiviral therapy applied after interferon (IFN) treatment failure in patients with chronic hepatitis C (CHC). CHC patients who completed a 48-week course of IFN therapy (pegylated (Peg)-IFNa-2a at 180 mug, qw, ih with or without ribavirin (RBV) at 15 mg/kg/w) in our hospital between January 2009 and June 2012 but who showed no response (at week 48) or who relapsed (at week 72) were enrolled in the study. Prior to initiating the 48-week course of retreatment therapy (Peg-IFNa-2a plus RBV as above), the hepatitis C virus (HCV) genotype was detected and the viral load measured (baseline) by PCR of HCV RNA. Each patient's response to therapy was classified as follows: baseline vs. week 4 (rapid virological response, RVR), vs. weeks 12 and 24 (early virological response, EVR), vs. week 48 (end of treatment virological response, ETVR) and vs. week 72 (sustained virological response, SVR). Of the total 235 cases administered retreatment therapy, 60.0% (n = 140) achieved RVR, 77.4% (n = 182) achieved EVR, 83.8% (n = 197) achieved ETVR, 68.0% (n = 68%) achieved SVR, and 15.7% (n = 37) relapsed. Stratification analysis of recurrence (n = 158) and non-responsive (n = 77) sub-groups showed that the recurrence group experienced significantly higher rates of RVR, EVR, ETVR and SVR, but a significantly lower rate of relapse. Stratification analysis of genotype 1b carrier (n = 206) and non-1b carrier (n = 29) sub-groups showed that the 1b carriers had significantly lower rates of RVR, EVR, ETVR and SVR, but a significantly higher rate of relapse. Finally, the patients who achieved RVR (vs. non RVR, n = 95) and EVR (vs. non-EVR, n = 53) showed higher rates of SVR and ETVR. CHC patients who fail to respond to the initial course of standard IFN-based therapy may achieve SVR upon retreatment, especially those infected with the HCV genotype 1b.

Nitazoxanide plus pegylated interferon and ribavirin in the treatment of genotype 4 chronic hepatitis C, a randomized controlled trial

Nitazoxanide has been proposed as a novel therapeutic agent for chronic hepatitis C virus (HCV) potentiating the effect of interferon and improving sustained virological response rates to up to 80% in genotype 4. This is an independent randomized trial to confirm the efficacy of nitazoxanide in the treatment of chronic hepatitis C genotype 4. This was an open-label trial. Treatment-naive genotype 4 HCV patients were recruited: Group 1 received weekly subcutaneous pegylated interferon 160 μg in addition to weight-based ribavirin (1200 mg if ≥ 75 kg and 1000 mg if <75 kg) for 48 weeks, Group 2 received 4 weeks lead-in therapy by nitazoxanide alone (500 mg bid) followed by triple therapy including nitazoxanide, pegylated interferon and ribavirin for a further 48 weeks. Fifty patients were recruited in each group. Baseline characteristics were similar except for a higher BMI in group 1 (28.5 vs. 26.5, P = 0.01). SVR rates were similar (24/50 (48%) vs. 25/50 (50%) in groups 1 and 2 respectively, P: 0.84). RVR, cEVR and ETR rates were also similar (61% vs. 53% - P:0.4, 70% vs. 72% - P:0.8 and 62% vs. 58% - P:0.6 in groups 1 and 2 respectively). Biochemical response at week 12 was also similar (57% vs. 46% in groups 1 and 2 respectively, P:0.26). Complications were similar except for a higher rate of dyspepsia in the group receiving nitazoxanide (32% vs. 14%, P:0.03). The addition of nitazoxanide to pegylated interferon and ribavirin does not improve the virological or biochemical response rates in chronic HCV genotype 4.

Natural Killer KIR3DS1 Is Closely Associated with HCV Viral Clearance and Sustained Virological Response in HIV/HCV Patients

AimTo evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patientsMethodsHIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed.ResultsSixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week1: p = 0.01; week2: p = 0.038; week 4: p = 0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week1: p<0.001; week2: p = 0.01; week 4: p = 0.02), RVR (p = 0.015) and SVR (p = 0.029) than those not carrying KIR3DS1.ConclusionOur results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.

Virological responses in chronic hepatitis C patients undergoing prolonged therapy with low-dose Peg-IFNα-2a.

Standard dose therapy with pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin is not suitable for all patients because of the side effects. This study aims to evaluate the virological responses of low-dose but long-course Peg-IFNα-2a therapy compared with standard therapy. Ninety patients with chronic hepatitis C were divided into three groups according to their tolerance to Peg-IFNα-2a. The courses of treatment were 96 or 48 weeks respectively in patients with HCV genotypes 1b or 2a in the 67.5 μg and 90 μg groups, and were 48 or 24 weeks in the 180 μg groups. Serum HCV RNA was quantified to determine RVR, EVR, SVR and ETR. There were no statistical differences in HCV RNA load, HCV genotype at the baseline of the three groups (p>0.05). The rates of RVR, EVR, SVR and ETR (no significant differences in each group), were 63.04%, 82.61%, 71.74% and 85.87% in all 92 patients. Genotype 1b (95% CI=11.97-82.89; p=0.0075) and RVR (95% CI=0.12-0.53; p<0.001) were important predictors of SVR. Patients with low-dose but long-course Peg-IFNα-2a therapy had similar virological responses compared to those with standard therapy. HCV genotype and RVR were independent predictors of SVR.

1093 POPULATION PHARMACOKINETIC (PK) ANALYSIS OF RIBAVIRIN (COPEGUS) IN CHRONIC HEPATITIS C (CHC) PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) LEADS TO CHANGES IN RECOMMENDED DOSING

Methods: A total number of 74 treatment-naive patients with HCV1 was included and randomly assigned to either the bezafibrate group (A, N= −38) or a placebo group (B, N = −36). Group A was pre-treated with 400mg bezafibrate daily for 16 weeks followed by 48 weeks of PR and 400mg bezafibrate per day. Group B was given 400mg of placebo daily for 16 weeks and was then treated with PR and 400mg placebo for 48 weeks. Follow-up was done until 24 weeks after end of treatment. Clinical, hematological, biochemical and virological data were recorded in the pre-treatment, the treatment and the follow-up period. Results: Viral load in the pre-treatment phase did not differ significantly between both groups. Viral kinetic modeling showed that there were no significant differences in interferon treatment efficacy between both groups (p > 0.2). Although the fitted curves of viral kinetics were highly similar, the bezafibrate group had lower HCV-RNA at begin of antiviral treatment. RVR rates were 18.4% (bezafibrate group) and 11.1% (placebo group). cEVR rate in the bezafibrate group was 55.3%, whereas in the placebo group, 41.7% of patients reached cEVR. Additionally, there was a significant negative correlation between screening GGT levels and treatment efficacy (r = −0.28, p = 0.023). Conclusions: Pre-treatment GGT values seem to have an impact on antiviral treatment efficacy and the application of bezafibrate prior to antiviral therapy led to a significant reduction in GGT levels and also some reduction in viral load.

1204 PHARMACOKINETICS OF MIRAVIRSEN, A MIR-122 INHIBITOR, PREDICT THE PROLONGED VIRAL LOAD REDUCTION IN TREATMENT NAIVE GENOTYPE 1 HCV INFECTED PATIENTS

(6/6), respectively in arm C and 88% (7/8), 94%, (15/16) and 83% (5/6), respectively, in arm D. Conclusions: There was an association between IL28B genotype and undetectable HCVRNA at Week 2 in arms C and D, however this association disappears by Week 4 due to high RVR rates across all IL28B genotypes. Patients from all IL28B genotypes achieved high SVR rates, thus IL28B may not be predictive of response to QUAD therapy in treatment-naive patients with genotype 1 chronic HCV.

C型慢性肝炎に対するpegylated interferon &amp;alpha;-2b/ribavirin併用療法の無効・再燃例におけるpegylated interferon &amp;alpha;-2a/ribavirin併用療法の効果

We investigated the efficacy of peginterferon alfa-2a plus ribavirin (α-2a therapy) for chronic hepatitis C patients who relapsed or did not respond to peginterferon alfa-2b plus ribavirin (α-2b therapy). Eleven patients with relapse and 5 non-responders to α-2b therapy received α-2a therapy for 48 to 72 weeks. In those with relapse, the rate of RVR, complete EVR and SVR were 54.5%, 72.7% and 72.7%, respectively. In non-responders, the rate of RVR, complete EVR and SVR were all 0%. Three of 5 LVR patients on α-2b therapy achieved SVR on α-2a therapy. Our findings suggest that patients showing relapse on α-2b therapy could achieve an early viral response and high SVR rate on α-2a therapy, non-responders could not.

Ribavirin dosage in patients with HCV genotypes 2 and 3 who completed short therapy with peg‐interferon α‐2b and ribavirin

Aliment Pharmacol Ther 31, 1346–1353SummaryBackground The optimal dose of ribavirin to be used in combination with Peg‐IFN in patients with HCV genotypes 2 and 3 undergoing short treatment has not been established.Aim To explore the relationship between starting ribavirin doses, expressed as mg/kg body weight and both rapid viral response at treatment week 4 (RVR) and sustained virological response (SVR) in patients treated for 12–14 weeks with peg‐interferon α‐2b and ribavirin.Methods A post hoc analysis of data collected from two multicenter clinical trials was performed. Multiple regression analyses were employed to identify independent baseline and on‐treatment predictors of RVR and SVR. For each dose of ribavirin, the empirical estimated probability of response was computed and the continuous exposure index was dichotomized by using a recursive partitioning and amalgamation method.Results A nonlinear relationship was ascertained between ribavirin dose and RVR, but not SVR. A dose of 15.2 mg/kg was selected as the best splitting value for discriminating RVR vs. non‐RVR. Regression analysis identified low baseline viraemia, genotype 2 and high ribavirin dose as independent prognostic factors for RVR. The likelihood of an SVR was not correlated with baseline ribavirin dose, but was independently predicted by adherence to the full dose throughout treatment and normal platelet counts.Conclusions Starting high ribavirin doses appears capable of increasing the rate of RVR in patients with HCV genotypes 2 and 3 undergoing short treatment. Maintenance of the full planned dose throughout treatment is essential for achieving optimal SVR rates.

Preemptive Erythropoietin Plus High Ribavirin Doses to Increase Rapid Virological Responses in HIV Patients Treated for Chronic Hepatitis C

Chronic hepatitis C affects one-third of HIV(+) patients worldwide. High ribavirin (RBV) exposure is crucial to maximize the response to hepatitis C therapy in this population, although it may increase the risk for hemolytic anemia. PERICO is a prospective multicenter trial in which HIV/HCV-coinfected patients are randomized to receive peginterferon (pegIFN) alfa-2a 180 microg/week plus either weight-based RBV (1000-1200 mg/day) or RBV 2000 mg/day, the latest along with erythropoietin alfa (EPO) 30,000 IU/week from the first day until week 4. A total of 149 patients were assessed in a planned interim analysis at week 4. In both arms, 22% of patients achieved negative HCV-RNA (rapid virological response, RVR). Multivariate analysis [OR (IC 95%), p] showed that factors associated with RVR were HCV genotypes 2/3 vs. 1/4 [20 (5-100), <0.01] and baseline HCV-RNA [0.16 (0.07-0.37) per log IU/ml, <0.01]. The occurrence of severe anemia (hemoglobin <10 g/dl) did not differ when comparing RBV vs. high RBV + EPO (7% vs. 3%; p = 0.4). Moreover, RBV plasma trough levels were comparable at week 4 (1.9 vs. 2.4 microg/ml; p = 0.2). Use of high RBV doses with preemptive EPO during the first 4 weeks of hepatitis C therapy is safe, but fails to enhance significantly RBV plasma exposure and RVR rates. Extensive intraerythrocyte accumulation of RBV following boosted production of red blood cells by EPO could explain these findings.

779 PF-03491390 PAN-CASPASE INHIBITOR DECREASES LIVER INJURY AND FIBROSIS IN A MURINE MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)

with 5% of patients who received the BAP placebo in the SOC arm. Lymphopenia was the most common reason for discontinuation of BAP. There were 2 deaths reported in the study (primary varicella and B-cell lymphoma) and these were considered related to study medication and a potential consequence of the lymphopenia. Conclusions: When combined with the SOC, BAP increased the rate of RVR and cEVR in genotype 1 patients; however, the drug did not confer an SVR advantage due in part to frequent safetyrelated dose reductions and discontinuations for both BAP and SOC. Further development of BAP has been halted because of the unfavourable benefit:risk ratio. Investigations are ongoing to explore the mechanism of BAP-related toxicity.

909 CHARACTERISTICS OF HBeAg-POSITIVE PATIENTS WITH HBsAg LOSS/SEROCONVERSION FOLLOWING TREATMENT WITH TENOFOVIR DISOPROXIL FUMARATE (TDF)

achieved RVR and of these, 77 (89.5%) had SVR. RVR rates for genotype 1 patients (53.2%) were significantly lower (86.8%) than genotype 2 and 3 (chi(2)=16.563, p=0.000). SVR rates for genotype 1 patients who had achieved RVR (90.4%) were significantly higher than those (9.6%) who had not achieved RVR (chi(2)= 3.232, p=0.000). Of 33 patients with genotype 1 who had achieved RVR, 27 (81.8%) had SVR and of 29 patients who did not achieve RVR, only 4 (13.7%) had SVR. Similarly, of 53 patients with genotypes 2 and 3 who had RVR, 50 (94.3%) had SVR and of 8 patients who did not have RVR, 4 (50%) had SVR. Significant factors associated with SVR were RVR (chi(2)=56.011, p=0.000), genotype (chi(2)=19.319, p=0.000), baseline AST level (p=0.031) and baseline viral load (p=0.049). The positive and negative predictive values of RVR in genotype 1 patients were 82% and 86% respectively and in genotype 2 and 3, 94% and 50% respectively. Conclusion: RVR in patients with chronic hepatitis C, genotype 1 was significantly lower than genotypes 2 and 3. SVR rates were significantly higher in patients who had achieved RVR. RVR predicts SVR in genotypes 1, 2 and 3. RVR, Genotype, baseline viral load and baseline AST level were significant factors for predicting SVR.

Rapid virological response to peginterferon and ribavirin for hepatitis C genotype 1: The role of weight-based ribavirin exposure

We read with great interest the report by Mangia et al. in a recent issue of HEPATOLOGY.1 They assigned 696 patients with hepatitis C virus genotype 1 (HCV-1) to peginterferon plus ribavirin 1000–1200 mg/day for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if patients were HCV-RNA–negative at weeks 4, 8, or 12, respectively (variable, n = 459). The sustained virological response (SVR) was comparable between the standard group (45.1%) and the variable group (48.8%). Patients with rapid virological response (RVR; HCV-RNA–negative at weeks 4) achieved a high SVR rate with either standard 48-week (87.0%) or abbreviated 24-week (77.2%) treatment, respectively. However, only 26.7% of patients attained an RVR, indicating the urgency of increasing RVR rate to ensure treatment efficacy. Although the RVR rate in the study by Mangia et al. was substantially higher than those in previous reports from Europe and the United States (10%–22.6%),2-5 it was considerably lower than that of our recent study in Taiwan (43.5%).6 Similarly, the RVR rate of patients with HCV-2 was noticeably higher in Taiwanese patients (86.7%)7 than in whites (71.1%).8 Several factors have been predictors of an RVR for HCV-1, such as lower viremia,1, 5, 6 young age,1, 5, 9 and HCV-1b.2 However, these factors are unchangeable. Recently, ribavirin dose,2 low body weight,9 and the first 4 weeks of weight-based ribavirin exposure with a cut-off point of 13 mg/kg/day5 have been associated with the achievement of an RVR. These findings suggest the role of weight-based ribavirin exposure, an adjustable factor, in achieving an RVR. Table 1 summarizes the relationship among ribavirin dose, body weight, and RVR rate in patients with HCV-1 in recent large clinical trials. A regimen with the standard dose of ribavirin (1000–12000 mg/day) had a considerably higher rate of RVR (22.6%–43.5%) than that with a lower dose of ribavirin (800 mg/day, 10%–21.6%). Moreover, a negative linear trend was observed between the body weight and the chance of attaining an RVR in either the lower or standard ribavirin groups. A study by Loustaud-Ratti et al. demonstrated that plasma concentration of ribavirin after the first dose, expressed by ribavirin area under the concentration-time curves (AUC0–12h), was associated with RVR.10 These observations highlight the potential role of weight-based ribavirin exposure during the first 4 weeks of combination therapy on the achievement of an RVR. Because RVR is the most important single predictor of an SVR, further prospective studies are encouraged to explore the crucial dose of weight-based ribavirin exposure during first 4 weeks for achieving an RVR to maximize the treatment efficacy. Ming-Lung Yu* , Chia-Yen Dai* , Jee-Fu Huang , Wan-Long Chuang* , * Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.