Faldaprevir, pegylated interferon, and ribavirin for treatment-naïve HCV genotype-1: pooled analysis of two phase 3 trials.

INTRODUCTION & AIM: Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection. MATERIAL AND METHODS: Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively. CONCLUSION: Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270.

STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection.

BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.

A tool for selecting patients with a high probability of sustained virological response to peginterferon alfa-2a (40kD)/ribavirin.

BACKGROUND & AIMS: Pretreatment identification of patients likely to achieve a sustained virological response (SVR) with peginterferon alfa-2a/ribavirin would be useful for individualizing treatment choices. The aim of this analysis was to devise a simple scoring system to identify patients with high probability of achieving an SVR with peginterferon alfa-2a/ribavirin. METHODS: Using data from 2109 Caucasian treatment-naive hepatitis C virus (HCV) genotype 1 mono-infected patients from the PROPHESYS cohorts, the relationship between favourable baseline characteristics and SVR was explored using generalized additive model analysis, and a scoring system was devised to predict SVR. RESULTS: Points were assigned for: age (years) (≤35: 2; >35, ≤45: 1; >45: 0); body mass index (kg/m(2)) (≤20: 2; >20, ≤22: 1; >22: 0); HCV RNA (IU/ml) (≤100,000: 3; >100,000-400,000: 2; >400,000-800,000: 1; >800,000: 0); platelets (>150 ×10(9)/l: 1; ≤150 ×10(9)/l: 0); alanine aminotransferase [×upper limit of normal (ULN)] (>3: 1; ≤3: 0); serum aspartate aminotransferase (×ULN) (≤1: 1; >1: 0). 1029, 698 and 382 patients had scores of 0-2, 3-4 and ≥5, respectively, among whom SVR rates were 35.0, 54.9 and 76.7%. SVR in patients with scores ≥5 and undetectable HCV RNA by week 4 was 86.7%. The score was tested against two databases of patients who received peginterferon alfa-2a/ribavirin in other clinical trials; similar high SVR rates in patients with scores ≥5 were reported. CONCLUSIONS: The scoring system can reliably identify treatment-naive HCV genotype 1 mono-infected Caucasian patients who have a high probability of achieving an SVR with peginterferon alfa-2a/ribavirin and will be particularly useful where protease inhibitors are not readily available.

In routine clinical practice, few physicians use early viral kinetics to guide HCV dual therapy treatment decisions.

BACKGROUND & AIMS: PROPHESYS is a large, multinational, non-interventional prospective cohort study of chronic hepatitis C patients treated with peginterferon alfa/ribavirin. This subanalysis assesses rates of premature treatment discontinuation stratified by on-treatment virological response (VR). METHODS: This PROPHESYS subanalysis is restricted to treatment-naive, hepatitis C virus (HCV) genotype (G)1/2/3 mono-infected patients who received peginterferon alfa-2a (40KD)/ribavirin with intended treatment duration of 48 (G1) or 24 weeks (G2/3). Early virological responses were classified into four mutually exclusive categories [rapid VR (RVR), complete early VR (cEVR), partial EVR (pEVR), no RVR/EVR], using standard criteria. RESULTS: The likelihood for shortening treatment owing to good efficacy was highest among patients with an RVR and HCV RNA≤400 000 IU/ml (G1 10.0%; G2/3 5.8%) whereas for poor efficacy, it was highest in G1 non-RVR/EVR patients with HCV RNA>400 000 IU/ml (56.6%). Factors significantly associated with early treatment discontinuation as a result of good efficacy in G1 patients included RVR vs. no RVR/EVR and, at baseline, lower HCV RNA, lower FIB-4 score, HCV infection via injection drug use. For G2/3 patients, factors included lower baseline HCV RNA and G2 vs. G3 infection. Most patients started with the recommended peginterferon alfa-2a dose, but a high proportion received a higher-than-recommended ribavirin dose. CONCLUSIONS: Despite international guidelines, few physicians used early viral kinetics to abbreviate treatment. Therefore, relatively few patients with an RVR and low baseline HCV RNA abbreviated treatment. In addition, there were deviations in ribavirin starting doses, suggesting that physicians tailor treatment according to local guidelines or previous experience.

High sustained virologic response rates in rapid virologic response patients in the large real-world PROPHESYS cohort confirm results from randomized clinical trials.

UNLABELLED: The ability to predict which patients are most likely to achieve a sustained virologic response (SVR) with peginterferon/ribavirin would be useful in optimizing treatment for hepatitis C virus (HCV). The objective of this large international noninterventional cohort study was to investigate the predictive value (PV) of a virologic response (VR) by weeks 2, 4, and 12 of treatment on SVR. Treatment-naive HCV monoinfected patients (N = 7,163) age ≥ 18 years were prescribed peginterferon/ribavirin at the discretion of the treating physician according to country-specific requirements in accordance with the local label. The main outcome measure was the PV of a VR (HCV RNA <50 IU/mL) by weeks 2, 4, and 12 of treatment for SVR24 (HCV RNA <50 IU/mL after 24 weeks of untreated follow-up) by HCV genotype. The overall SVR24 rate was 49.4% (3,541/7,163; 95% confidence interval [CI]: 48.3-50.6%). SVR24 rates in patients with an HCV RNA titer <50 IU/mL by weeks 2, 4, and 12, respectively, were 66.2% (95% CI: 60.4-71.7%), 68.4% (95% CI: 65.7-71.0%), and 60.3% (95% CI: 58.5-62.1%) among genotype 1 patients; 82.0% (95% CI: 76.8-86.5%), 76.3% (95% CI: 73.3-79.1%), and 74.2% (95% CI: 71.3-76.9%) among genotype 2 patients; 67.3% (95% CI: 61.1-73.1%), 67.3% (95% CI: 64.2-70.3%), and 63.8% (95% CI: 61.0-66.6%) among genotype 3 patients; and 59.4% (95% CI: 40.6-76.3%), 63.3% (95% CI: 54.3-71.6%), and 54.3% (95% CI: 47.5-60.9%) among genotype 4 patients. The absence of a VR by week 12 had the highest negative PV across all genotypes. CONCLUSION: A VR by week 2 or 4 had the highest positive PV for SVR24 and differed according to HCV genotype.

Adherence to treatment and quality of life during hepatitis C therapy: a prospective, real-life, observational study.

BACKGROUND: Adherence is important for therapy of chronic diseases, but has still not been well studied in real life in chronic hepatitis C. AIMS: To assess adherence to hepatitis C combination therapy in routine clinical practice and to identify factors associated with imperfect adherence. METHODS: This cohort study included unselected chronic hepatitis C patients initiating peginterferon α-2b plus ribavirin. 100% adherence was defined by taking all the prescribed doses of both drugs for the full initially intended duration, as declared by the patient or believed by the physician. Quality of life was assessed using the short-form health survey (SF-36) questionnaire. RESULTS: 1860 patients were analysed, including 72% treatment-naive, 36% genotype 2/3, 23% psychiatric, 44% drug addicts and 3% human immunodeficiency virus (HIV)-positive patients. Early treatment discontinuation occurred in 30% of patients. Overall, 38% of patients reported 100% adherence. Patient- and physician-reported adherences were discordant, with a 20-30% overestimation by physicians. HIV co-infection [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.36-4.67], no drug use during follow-up (2.37, 1.30-4.31), genotype 3 (1.55, 1.20-2.00) and treatment-naive (1.32, 1.03-1.69) were associated with 100% adherence. Quality of life worsened during treatment but returned to baseline after the end of treatment. CONCLUSIONS: Imperfect adherence to combination therapy is common in routine patients. Adherence is markedly overestimated by physicians and is associated with some patient's baseline characteristics. Knowledge of these factors might help identify patients who are most in need of intervention and plan more frequent and accurate follow-up.

Final analysis of the international observational S-Collate study of peginterferon alfa-2a in patients with chronic hepatitis B.

BACKGROUND AND AIMS: Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. METHODS: A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. RESULTS: The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. CONCLUSIONS: Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.

Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection: a prospective, real-life, observational study.

AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin). Adherence to bitherapy was defined as adherence to the two drugs for >or= 20 wk. SVR was defined as undetectable RNA >or= 12 wk after the end of treatment. RESULTS: 370/674 patients received education during the first 3 mo of treatment. After 6 mo, adherence to bitherapy was higher in educated patients (61% vs 47%, P = 0.01). Adherence to peg-interferon was 78% vs 69% (P = 0.06). Adherence to ribavirin was 70% vs 56% (P = 0.006). The SVR (77% vs 70%, P = 0.05) and relapse (10% vs 16%, P = 0.09) rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio (OR) 1.58, P = 0.04] but not the SVR (OR 1.54, P = 0.06). CONCLUSION: In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy.

Satisfaction of patients treated for chronic hepatitis C with the peginterferon alfa-2b pen device: the VISA observational study.

OBJECTIVES: This observational study aimed at evaluating the satisfaction of patients with chronic hepatitis C using the peginterferon (peg-IFN) alfa-2b pen device. METHODS: Consecutive patients were included when prescribed the pen device. Self-administered questionnaires relating to the progress brought by the pen, convenience/comfort, and the mode and security of injection were completed after the first injection and at 12 weeks. RESULTS: Six hundred and forty eight patients aged 45.7 +/- 12.1 years completed the 1st questionnaire; 70% were naive for any hepatitis C treatment. Five hundred and twenty five (81%) patients completed the 2nd questionnaire. Adherence to the pen device was >or=80% in more than 80% of the patients. Most (85%) patients declared that the pen brought important progress compared to traditional syringes. Satisfaction was high after the 1st injection and further increased 12 weeks later, with ease of use scoring 7.7 then 8.0 (P=0.007, 10-point scale), and rapidity of use scoring 8.0 then 8.2 (P=0.008); less painful injection scoring 7.9 at both time points. The proportion of self-injectors (no intervention of a health professional) increased from 32% to 58% (P<0.0001). Reasons for self-injecting were: easier injection (58%), no product/syringe handling (50%/41%), and assurance of exact dosing (45%). CONCLUSION: Patients were satisfied with the peg-IFN alfa-2b pen device. The proportion of self-injectors doubled over 12 weeks. Good treatment adherence, which is mandatory for therapeutic success, is expected from use if this device.

Safety and efficacy of combination therapy with peginterferon alfa-2a (40kD) and ribavirin in the outpatient setting: prospective analysis of 197 patients with chronic hepatitis C viral infection.

OBJECTIVES: Combination therapy using peginterferon alfa-2a (40 kD) plus ribavirin achieves viral eradication in nearly 60% of patients with chronic hepatitis C viral infection. However, because of the numerous side effects, use of the combination regimen might be restricted for patients consulting private practitioners specialized in hepatogastroenterology. PATIENTS AND METHOD: Conducted in this specific context, this prospective clinical trial investigated the safety and efficacy of combination therapy in 197 patients. Therapy was given in compliance with the recommendations of the French consensus conference on hepatitis C treatment. RESULTS: Commonly reported adverse effects were noted in 90% of patients, most occurring during the first three months, with a stable prevalence thereafter and resolution after treatment end. The most frequent adverse events were asthenia (35 to 37.5% according to the treatment group pruritus (25 to 26.3%) and flu-like syndrome (19 to 21.7%). A depressive syndrome was reported in 20 to 21% of patients. Grade 4 neutropenia was exceptional and never led to severe infections. At intent-to-treat analysis, the rate of sustained virological response was 54.8% for the entire population. It was 71.1% for patients with genotypes 2 or 3 (mainly treated for 24 weeks) and 44.6% for patients with genotype 1 (all treated 48 weeks). CONCLUSION: The characteristic features of combination therapy observed in the context of private hepatogastroenterology consultations are similar to those observed in randomized clinical trials.

[Treatment of chronic hepatitis viral C: new associations]. / Traitement de l'hépatite chronique virale C par trithérapie.

The current treatment of patients with chronic HCV infection since ten years is pegylated interferon combined with ribavirin. This association allows a virological eradication in 55% of patients, all genotype and 40% of those infected with genotype 1, the most prevalent. Two protease inhibitors (telaprevir and boceprevir) were approved in 2011, in combination with pegylated interferon and ribavirin in both naïve and non-responder patients infected with HCV genotype 1. These new drugs allow obtaining a viral eradication in 70% of cases. Other direct acting antiviral drugs are also currently being tested and likely to radically change treatment strategies for patients with chronic hepatitis due to HCV.

Add-on peg-interferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs.

BACKGROUND AND OBJECTIVE: The aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment. STUDY DESIGN: We analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years. RESULTS: HBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up. CONCLUSIONS: In HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12-18 months of follow up. HBs seroconversion was observed in two patients.

Pegylated interferon-α2a plus ribavirin for chronic hepatitis C in a real-life setting: the Hepatys French cohort (2003-2007).

BACKGROUND: The aim of this study was to document in real life the characteristics and management of hepatitis C patients treated with pegylated interferon-α2a and ribavirin, and the efficacy of treatment (sustained virological response [SVR]). METHODS: This observational study enrolled hepatitis C patients initiating pegylated interferon-α2a and ribavirin treatment. RESULTS: A total of 2,066 patients were included, of which 70% were treatment-naive, 53% had genotype (G) 1 and 38% G2 or G3 infection, and 35% had an F3-F4 Metavir score. In total, 18% of patients treated for 24 weeks and 39% of patients treated for 48 weeks prematurely stopped treatment, mainly because of side effects. The SVR rate (intent-to-treat population) was 39%: 43% in naive patients and 31% in treatment-failure patients. In the complete case analysis population, this was 49%: 54% in naive patients and 37% in treatment-failure patients. Among naive patients, the SVR rate was 42% in G1 carriers and 69% in G2 or G3 carriers. The SVR rate was 69% in naive G1 patients without fibrosis (F0; versus 44% in F1-F2 versus 31% in F3-F4; P<0.001). In naive patients, G2 or G3, low viral load (<800,000 IU/ml) and age ≤40 years were predictive factors for SVR. In treatment-failure patients, low viral load, no or low fibrosis stage (F0-F1) and no treatment modification were predictive factors of SVR. CONCLUSIONS: In patients treated in a real-life setting, adherence to therapy, SVR rates, predictive factors of SVR and safety results were close to those observed in randomized trials. A high SVR in G1 naive patients with no fibrosis warrants further study and might suggest earlier treatment.

Pegylated interferon-alpha2b plus ribavirin therapy in patients with hepatitis C and psychiatric disorders: results of a cohort study.

BACKGROUND: Hepatitis C antiviral therapies have significant psychiatric side effects. It is therefore believed that they might exacerbate mental illness in patients with pre-existing psychiatric disorders, resulting in poor adherence and response to antiviral treatment. We aimed to assess adherence to treatment, virological outcomes and mental safety in psychiatric patients, compared with non-psychiatric patients, treated for hepatitis C. METHODS: A cohort study involved unselected hepatitis C patients on scheduled therapy with pegylated interferon-alpha2b and ribavirin, between 2002 and 2005 in France, and followed-up until 6 months after the end of treatment. Virological response was reported by the physician according to standard definitions and adverse events were monitored. Adherence to treatment was assessed by patient report. RESULTS: Among 1,860 patients, 403 (22%) had pre-existing psychiatric disorders, mostly depressive and anxiety disorders. Strict adherence was similar in psychiatric and non-psychiatric patients (35% versus 39%; P=0.20) as was the rate of sustained virological response (52% versus 51%; P=0.75). Conversely the rate of mental adverse events was higher in psychiatric patients (78% versus 57%; P<0.001). Baseline characteristics independently associated with the risk of later mental adverse events were history of depression, initial pegylated interferon-alpha2b dose and female gender. CONCLUSIONS: Antiviral therapy in hepatitis C patients with associated psychiatric disease appears as effective as in other patients but results in a higher rate of mental adverse events, emphasizing the need for close monitoring of these psychiatric patients.

Effectiveness of chronic hepatitis C treatment in drug users in routine clinical practice: results of a prospective cohort study.

OBJECTIVE: Injection drug users are often excluded from hepatitis C virus (HCV) treatment. This study compares sustained virological response, adherence, and quality of life in patients with or without a history of illicit drug use in routine clinical practice. METHODS: This is a post-hoc analysis of a prospective, observational study conducted in 1860 patients who received peginterferon alpha-2b/ribavirin combination therapy. Nondrug users (NDUs) were defined as patients without a history of drug addiction; former drug users (FDUs) as patients who had stopped using illicit drugs or opioid maintenance therapy and active drug users (ADUs) as patients using illicit drugs or on opioid maintenance therapy. Virological response, adherence, and the health-related quality of life were assessed by the measure of HCV RNA in the serum, self-report and 36-item short-form health survey Questionnaire, respectively. RESULTS: The analyzed population included 1038 (56%) NDUs, 578 (31%) FDUs, and 244 (13%) ADUs. About 85% of ADUs were on opioid maintenance therapy and 25% used illicit drugs. Although ADUs had a more chaotic lifestyle and more psychiatric disorders, sustained virological response of ADUs (58%) did not differ from that of NDUs (49%) and FDUs (51%) (P=0.133). Adherence rates were 39% in NDUs and FDUs, and 37% in ADUs (P=0.883). Health-related quality of life was improved in the three groups after the end of treatment. CONCLUSION: Our study suggests that HCV therapy in ADUs on opioid maintenance therapy is as effective as in other HCV patients. The effectiveness of HCV therapy in illicit drug users needs to be evaluated in further studies.

Assessment of early virological response to antiviral therapy by comparing four assays for HCV RNA quantitation using the international unit standard: implications for clinical management of patients with chronic hepatitis C virus infection.

WHO International Standards for nucleic acid tests are used widely to compare the different assays used in HCV RNA quantitation. The aim of the study was to assess the impact of the international unit standard for measuring HCV RNA in the management of patients with chronic hepatitis C virus (HCV) infection. Twenty-seven naïve patients infected chronically by HCV were treated with ribavirin plus PEG-interferon-alfa-2b for 48 weeks. SVR was obtained for 16 patients (the other were non-responders). For HCV RNA quantitation, four assays were undertaken: Versant HCV RNA 3.0 (Bayer), Real time PCR (TaqMan, Roche), LCx HCV RNA (Abbott), and Cobas Amplicor-Monitor v2 (Roche). Considering a 2-log decline at Week 12 after the beginning of therapy, discordant results were found with the four HCV RNA methods in predicting SVR or non-response. At Week 4 and Week 12, significant differences were observed between Versant HCV RNA 3.0 versus PCR HCV Taqman, Versant HCV RNA 3.0 versus LCx HCV RNA, Cobas Monitor Amplicor HCV 2.0 versus LCx HCV RNA, and Cobas Monitor Amplicor HCV 2.0 versus PCR HCV Taqman (P < 0.001). The HCV RNA cutoff, given a 100% negative predictive value at Week 4 and Week 12, differed with the assays used to quantify HCV RNA, despite the use of the IU/ml units. Eighty-nine percent of serum values for HCV RNA were concordant by the IU standard. All assays, however, failed to detect HCV RNA in some cases. Despite the use of the IU standard HCV-infected patients might be monitored with only one assay.

Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin.

BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. METHODS: A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone. RESULTS: Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2. CONCLUSIONS: We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.