Original Article
Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection
N Engl J Med 2009; 361:580-593August 6, 2009
- Abstract
Background
Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared.
Methods
At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen.
Results
Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P=0.20 for standard-dose vs. low-dose peginterferon alfa-2b; P=0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], −2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for low-dose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively.
Conclusions
In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon–ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.gov number, NCT00081770.)
Media in This Article
Figure 1
Screening, Treatment, and Follow-up of the Study Patients.Table 1
Baseline Demographic and Disease Characteristics of the Study Patients, According to Treatment Group.Article Activity
- Article
Hepatitis C virus (HCV) chronically infects approximately 180 million people worldwide1 and is a frequent cause of liver disease, including liver failure and hepatocellular carcinoma.2 HCV treatment is recommended for persons at the greatest risk for progression of liver disease.3 On the basis of noncomparative studies demonstrating similar safety and efficacy between the two treatments,4,5 consensus guidelines recommend the use of either peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for the treatment of chronic hepatitis C. However, differences between the peginterferons with respect to structural modifications and dosing (weight-adjusted vs. fixed) may lead to important differences in clinical outcomes, and there is some evidence of such differences.6-9 Randomized, comparative effectiveness trials are necessary to provide patients with evidence-based treatment options.
The Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) study was initiated to compare standard-dose and low-dose regimens of peginterferon alfa-2b, plus ribavirin, after it was observed that both dose levels yielded similar rates of sustained virologic response in the absence of ribavirin.10 A third treatment group, peginterferon alfa-2a plus ribavirin, was added to the study because (in addition to standard-dose peginterferon alfa-2b plus ribavirin) it is the other approved regimen. The objective was to compare the safety and efficacy of the two standard regimens and the experimental low-dose peginterferon alfa-2b regimen.
Methods
Study Patients
We enrolled patients from 118 centers in the United States. Eligible patients were 18 years of age or older, had compensated liver disease due to chronic HCV genotype 1 infection and a detectable plasma HCV RNA level, and had not been previously treated for hepatitis C infection. The patients had an absolute neutrophil count of 1500 or more per cubic millimeter, a platelet count of 80,000 or more per cubic millimeter, and hemoglobin level of 12 g (for women) or 13 g (for men) or more per deciliter. Patients were excluded if they had coinfection with human immunodeficiency virus or hepatitis B, any other cause of liver disease, poorly controlled diabetes mellitus (glycated hemoglobin value >8.5%), morbid obesity (weight >125 kg), severe depression or a severe psychiatric disorder, or active substance abuse. All patients had undergone liver biopsy within 3 years before screening. A pathologist at the central site, who was unaware of the treatment assignments, reviewed all the biopsy specimens and determined the METAVIR fibrosis stage and inflammatory grade, as well as the percentage of the tissue containing hepatocytes with steatosis.11
Study Oversight
The study sponsor and the academic principal investigators were jointly responsible for the study design, protocol, statistical analysis plan, and data analysis. The principal investigators had unrestricted access to the data, wrote the manuscript, and vouch for the accuracy and integrity of the data and analyses. A publication committee comprising the academic principal investigators and three independent experts prepared the prespecified data-analysis plan and ensured the unbiased interpretation of the data.
Study Design
Patients were randomly assigned, in a 1:1:1 ratio and with the use of an interactive voice system, to one of the three treatment groups and were stratified according to HCV RNA level (≤600,000 IU per milliliter or >600,000 IU per milliliter) and self-reported race (black or nonblack). The three treatment groups were as follows: peginterferon alfa-2b at the standard dose, 1.5 μg per kilogram of body weight per week, or at a lower dose, 1.0 μg per kilogram per week, both in combination with oral ribavirin at a dose according to body weight (40 to 65 kg, 800 mg per day; >65 to 85 kg, 1000 mg per day; >85 to 105 kg, 1200 mg per day; and >105 to 125 kg, 1400 mg per day); or peginterferon alfa-2a at a dose of 180 μg per week, plus oral ribavirin at a dose of 1000 to 1200 mg per day, according to body weight (<75 kg, 1000 mg per day; ≥75 kg, 1200 mg per day).
The study was double-blinded with regard to the dose of peginterferon alfa-2b. For patients receiving peginterferon alfa-2a, the dose of ribavirin was determined on the basis of prescribing information from the Food and Drug Administration (FDA). Because weight-based ribavirin dosing was not approved by the FDA for use with peginterferon alfa-2b when the study was initiated, the dose of ribavirin administered in the two groups receiving peginterferon alfa-2b was calculated to deliver a mean (±SD) of 13±2 mg per kilogram per day, on the basis of data derived from previous trials and from the product information from the European Medicines Agency.4,7,12 Patients underwent treatment for up to 48 weeks and follow-up for 24 weeks. The study was approved by each center's institutional review board and was conducted in accordance with provisions of the Declaration of Helsinki and Good Clinical Practice guidelines.
Efficacy Assessments
HCV RNA levels were measured with the use of the Cobas TaqMan assay (Roche), which has a lower limit of quantitation of 27 IU per milliliter. Measurements were obtained at screening visits 1 and 2 (baseline); weeks 2, 4, 12, 24, and 48 during the treatment period; and follow-up weeks 4, 12, and 24. Per established guidelines, patients with an insufficient virologic response at 12 weeks (a detectable HCV RNA level and a decrease of <2 log10 IU from the baseline level) or at 24 weeks (a detectable HCV RNA level) were considered to have treatment failure, and therapy was discontinued.
Safety Assessments
Adverse events were graded by the investigators as mild, moderate, severe, or life-threatening, according to a modified World Health Organization grading system. Non–life-threatening adverse events were managed by reduction of the dose of peginterferon alfa or ribavirin (or both). The peginterferon-dose reduction was a two-step process: the dose was reduced if the neutrophil count was below 750 per cubic millimeter, and treatment with both drugs was permanently discontinued if the neutrophil count was below 500 per cubic millimeter. For patients receiving peginterferon alfa-2b, the ribavirin-dose reduction occurred in two steps, as established by Jacobson et al.7 The first step was a reduction of either 200 mg (in patients receiving 800 to 1200 mg of ribavirin per day) or 400 mg (in patients receiving 1400 mg per day); the second step was reduction by another 200 mg, if required for resolution of the adverse event. For patients receiving peginterferon alfa-2a, ribavirin-dose reduction consisted of a reduction to 600 mg per day, on the basis of FDA-approved prescribing information. For all patients, ribavirin-dose reduction was required if the hemoglobin level was less than 10 g per deciliter; treatment with both drugs was permanently discontinued if the level was below 8.5 g per deciliter. In patients with a hemoglobin level less than 10 g per deciliter, use of erythrocyte-stimulating agents was permitted after ribavirin-dose reduction. Drug doses could be increased once the cytopenia resolved (i.e., the neutrophil count was ≥750 per cubic millimeter or the hemoglobin level was ≥10 g per deciliter).
End Points
Analyses included data from all patients who underwent randomization and who received at least one dose of study medication. The primary end point was a sustained virologic response, defined as undetectable HCV RNA levels 24 weeks after the completion of therapy. If the 24-week post-treatment HCV RNA measurement was missing, the 12-week post-treatment level was used. (This was done for 38, 21, and 25 patients receiving standard-dose and low-dose peginterferon alfa-2b and peginterferon alfa-2a, respectively, all of whom had had undetectable HCV RNA at 12 weeks after treatment.)
The study involved two primary comparisons: standard-dose versus low-dose peginterferon alfa-2b regimens and standard-dose peginterferon alfa-2b versus peginterferon alfa-2a. Secondary end points included the rates of virologic response during the treatment phase and relapse, defined as an undetectable HCV RNA level at the end of the treatment phase, with a detectable HCV RNA level during the follow-up period.
Statistical Analysis
For both primary comparisons, the trial was designed as a superiority study to detect clinically meaningful differences in the rates of sustained virologic response among the three regimens. The study had a statistical power of 80% to detect a significant absolute difference in rates of sustained virologic response of 6.5% between the standard-dose and low-dose peginterferon alfa-2b regimens and of 7% between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen. A one-sided test was used to compare the two peginterferon alfa-2b regimens, with an assumption that the standard-dose regimen would be at least as effective as the low-dose regimen. A two-sided test was used to compare standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Because there were two primary treatment comparisons, the Holm–Bonferroni method was used to maintain the overall type 1 error rate at 0.05. According to this method, the lowest P value must be below 0.025 to be considered to indicate statistical significance. If this criterion is met, then the higher P value must be below 0.05 to be considered to indicate statistical significance. If the lowest P value is greater than 0.025, no other tests are performed.
P values for the two primary treatment comparisons were calculated on the basis of a logistic-regression model controlling for the stratification factors (race and baseline HCV RNA level). Since neither of the two comparisons was significant, all P values are considered to be nominal and are labeled as such. Similarly, nominal two-sided 95% confidence intervals are reported, calculated for the two primary comparisons according to a Mantel–Haenszel approach controlling for the stratification factors. Summary statistics are reported for each of the three treatment regimens for subgroups of patients defined by prespecified baseline characteristics and one characteristic defined post hoc (baseline fasting glucose level). Multivariable logistic-regression analyses involving treatment regimen, prespecified baseline characteristics, and three post hoc factors (baseline fasting glucose level, hemoglobin value, and platelet count) were performed to study sustained virologic response and relapse. A stepwise procedure was used to identify independent predictors of sustained virologic response and relapse (with P=0.05 as the threshold level for variables to be entered into and retained in the final model). This type of approach was prespecified in the analysis plan for sustained virologic response but not for relapse. As was prespecified, we also explored the relationship between the magnitude and rapidity of virologic response during the treatment phase and the probability of achieving a sustained virologic response.
Results
Characteristics of the Study Patients
Between March 2004 and June 2006, a total of 4469 patients were screened, and 3070 underwent randomization and treatment (Figure 1Figure 1
Screening, Treatment, and Follow-up of the Study Patients.). Baseline demographic characteristics were balanced among the three treatment groups (Table 1Table 1Baseline Demographic and Disease Characteristics of the Study Patients, According to Treatment Group.). The majority of patients were men in their 40s; 18.6% of the patients were black; and the mean body weight was 83.4 kg. After stratification on the basis of body weight, 1061 of 2035 patients (52.1%) receiving peginterferon alfa-2b were assigned to receive the same dose of ribavirin as the corresponding patients receiving peginterferon alfa-2a, whereas 773 of the 2035 patients (38.0%) were assigned a lower dose of ribavirin, and 201 of the 2035 (9.9%) were assigned a higher dose. During the treatment period, the mean and median daily ribavirin doses received were significantly higher among patients receiving peginterferon alfa-2a than those in either peginterferon alfa-2b group, regardless of ribavirin-dose reduction, use of erythrocyte-stimulating agents, or efficacy outcome (sustained virologic response, relapse, or nonresponse). The proportion of patients who received, on average, more than 13 mg of ribavirin per kilogram per day was greater in the peginterferon alfa-2a group (56.0%) than in either peginterferon alfa-2b group (29.1% in the standard-dose group and 32.6% in the low-dose group) (P<0.001 for each comparison).Efficacy
The rates of sustained virologic response did not differ significantly among the three treatment groups, with a rate of 39.8% (95% confidence interval [CI], 36.8 to 42.8) for standard-dose peginterferon alfa-2b, 38.0% (95% CI, 35.0 to 41.0) for low-dose peginterferon alfa-2b, and 40.9% (95% CI, 37.9 to 43.9%) for peginterferon alfa-2a, (P=0.20 for standard-dose vs. low-dose peginterferon alfa-2b; P=0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a) (Table 2Table 2
Virologic Response during and after Treatment, According to Treatment Group.). Estimated differences in response rates were 1.8% (95% CI, −2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Therefore, the two primary trial end points of superiority were not met. Response rates at the end of the treatment phase were higher with peginterferon alfa-2a than with either peginterferon alfa-2b regimen, but the virologic relapse rate was also higher. In all three groups, HCV RNA suppression at treatment weeks 4 and 12 was strongly associated with achievement of sustained virologic response (Table 3Table 3
Responses to Treatment, According to Treatment Group.). Fewer than 5% of patients who had a reduction from the baseline HCV RNA level of less than 1 log10 IU per milliliter at week 4 also had a sustained virologic response. A prolonged time (>12 weeks of therapy) to undetectable HCV RNA level was associated with a higher likelihood of relapse after treatment (Table 3). Stepwise multivariable logistic-regression analyses identified several baseline factors as independent predictors of sustained virologic response: baseline HCV RNA level (≤600,000 IU per milliliter), race (nonblack), minimal fibrosis (METAVIR score of F0, F1, or F2), absence of steatosis, normal baseline fasting glucose level, and elevated baseline serum alanine aminotransferase level. Using the same method, we found that these factors were independently associated with relapse, as were age over 40 years and peginterferon alfa-2a treatment (Table 1 of the Supplementary Appendix, available with the full text of this article at NEJM.org).Ribavirin Dosing
Rates of sustained virologic response were similar among the three treatment groups, within the subgroups of patients receiving the same dose of ribavirin (those weighing >65 to <75 kg and those weighing >85 to 105 kg) (Table 2). The ribavirin dose was reduced, owing to an adverse event, in 30.2% of patients. The rate of sustained virologic response among these patients was 52.2% in the peginterferon alfa-2a, 51.8% in the standard-dose peginterferon-2b group, and 49.3% in the low-dose peginterferon alfa-2b group. In comparison, the rate of sustained virologic response was higher among patients who had a hemoglobin level that was less than 10 g per deciliter during the treatment phase but who required a ribavirin-dose reduction, as compared with those with levels of 10 g per deciliter or above: 48.8% (422 of 865 patients) versus 36.7% (793 of 2158 patients) (P<0.001).
Safety
The types and frequencies of adverse events were similar among the three groups (Table 4Table 4
Adverse Events, Discontinuations of Treatment, and Dose Reductions, According to Treatment Group.). The most common adverse events included influenza-like symptoms, depression, and the hematologic events of anemia and neutropenia. The proportions of patients with neutropenia who met the criterion for peginterferon-dose reduction (a neutrophil count of <750 and ≥500 per cubic millimeter were 21.1% receiving peginterferon alfa-2a, 19.4% receiving standard-dose peginterferon alfa-2b, and 12.5% receiving low-dose peginterferon alfa-2b. However, only 2.1 to 5.9% of patients met the discontinuation criterion based on neutropenia. The proportion of patients meeting the hemoglobin criterion for ribavirin-dose reduction (a hemoglobin level <10 and ≥8.5 g per deciliter) was somewhat higher with standard-dose peginterferon alfa-2b (28.2%) and peginterferon alfa-2a (25.8%) than with low-dose peginterferon alfa-2b (23.2%); only 2.1 to 3.8% of patients met the discontinuation criterion (hemoglobin level <8.5 g per deciliter).Most psychiatric adverse events were mild or moderate and were not treatment-limiting; however, 1.8 to 2.6% of patients did discontinue treatment. Twelve patients (0.4%) died during the study: seven during the treatment period and five during or after the follow-up period. Two of these deaths were considered by the investigator to be possibly related to study medications: a suicide at 6 months after the end of treatment with standard-dose peginterferon alfa-2b and a myocardial infarction during treatment with peginterferon alfa-2a.
Discussion
Treatment with peginterferon alfa-2a or peginterferon alfa-2b, plus ribavirin, for 48 weeks is recommended for patients infected with HCV genotype 1, the most common variant in the United States and Europe.13 Despite this recommendation, few data comparing these treatment regimens are available. Accordingly, several findings of our large, randomized comparative study affect the care of these patients.
The safety and adverse-event profiles and the efficacy data were similar among patients treated with low-dose or standard-dose peginterferon alfa-2b or peginterferon alfa-2a, in combination with differing ribavirin regimens. The finding that low-dose peginterferon alfa-2b resulted in a similar rate of sustained virologic response as the other regimens was unexpected. Since monotherapy with standard-dose peginterferon alfa-2b has been associated with higher rates of virologic response during the treatment period,10 we aimed to test the hypothesis that use of standard-dose peginterferon alfa-2b with ribavirin would result in a higher rate of sustained virologic response than with the low-dose regimen. Although our data do not support this hypothesis, a significant interaction between treatment group and sex (P=0.01) (Table 2 in the Supplementary Appendix) suggests that women may have higher rates of sustained virologic response with standard-dose than with low-dose peginterferon alfa-2b. Although the interaction with race was not significant, blacks tended to have higher rates of sustained virologic response with the standard dose of peginterferon alfa-2b. Host, virologic, and treatment factors associated with eradication of HCV genotype 1 infection were identified. Consistent with previous observations,14-20 a sustained virologic response was less frequent among blacks, persons with advanced hepatic fibrosis and steatosis, and those with high baseline HCV RNA levels. Although it was not a prespecified covariate, impaired fasting glucose was also associated with a lower likelihood of sustained virologic response. These data suggest a need for additional research to test the hypothesis that dietary and pharmacologic interventions to correct glucose intolerance can improve treatment response. The magnitude of HCV RNA suppression during the treatment phase was also closely linked to the likelihood of having a sustained virologic response. Among the 10% of patients with undetectable HCV RNA levels at treatment week 4, 86% had a sustained virologic response. The 24% of patients with a minimal decline in HCV RNA level (decline of <1 log10 IU from the baseline value) at treatment week 4 had a probability of sustained virologic response of less than 5%. Thus, virologic response at treatment week 4 is an important predictor of sustained virologic response; HCV RNA levels should be routinely assessed at this time point.
The time to the first undetectable HCV RNA level was associated with the probability of virologic relapse after the end of treatment. Approximately 50% of patients who had HCV suppression for the first time by treatment week 24 also had virologic relapse, as compared with less than 10% of patients who had HCV suppression at treatment week 4. After week 4, patients receiving peginterferon alfa-2a had a higher rate of HCV RNA suppression than did those who were receiving peginterferon alfa-2b; however, this difference was not sustained after the end of the treatment period. Thus, although the rates of sustained virologic response were similar among the three groups, patients treated with peginterferon alfa-2a were more likely to have a response while receiving therapy, followed by relapse after the completion of therapy, whereas patients treated with peginterferon alfa-2b were more likely to discontinue therapy at treatment week 12 or 24 because of an insufficient virologic response.
Increased ribavirin exposure during the treatment phase was associated with an increased likelihood of sustained virologic response among all treated patients. Ribavirin exposure was lower in patients who received peginterferon alfa-2b, which was administered according to four dosing categories (based on body weight), as compared with those who received peginterferon alfa-2a, which was administered according to two. Patients weighing between 75 and 85 kg received 1000 mg of ribavirin per day if they were also receiving peginterferon alfa-2b, as compared with 1200 mg per day if they were also receiving peginterferon alfa-2a. In this large weight group (792 patients), the rate of sustained virologic response was higher by approximately 10 percentage points in the peginterferon alfa-2a group, suggesting that the ribavirin dose for persons who weigh between 75 and 85 kg should be 1200 mg per day in the peginterferon alfa-2b groups. Surprisingly, reducing the ribavirin dose because of treatment-related anemia (as was done in 30% of patients) did not appear to reduce the likelihood of sustained virologic response. Despite the reduction of ribavirin dose by as much as 50% in patients receiving peginterferon alfa-2a, patients with anemia had a higher rate of sustained virologic response than did those without anemia, suggesting that the magnitude of anemia may be a pharmacodynamic marker of drug exposure. The data indicate that the initial ribavirin dose should be at least 13 mg per kilogram per day and that the conservative management of anemia, involving a ribavirin-dose reduction in either one or two steps, appears to maintain safety and not to compromise efficacy.
The findings are subject to several limitations. Because the initial ribavirin dose varied among the patients, the study compares HCV treatment regimens and is not a direct comparison of the type of peginterferon. Nonetheless, more than 51% of patients received the same dose of ribavirin in combination with either peginterferon alfa-2a or peginterferon alfa-2b, and their rates of sustained virologic response were similar. Second, the procedure for ribavirin-dose reduction differed between the peginterferon alfa-2a group and the peginterferon alfa-2b groups. Yet, the rate of sustained virologic response was higher among patients who had the ribavirin dose reduced because of anemia than among those who did not. Third, since the study was conducted in the United States, these comparative data may not be generalizable to other regions or HCV genotypes. Fourth, owing to insurmountable differences in drug formulation (lyophilized powder in the case of peginterferon alfa-2b or solution in the case of peginterferon alfa-2a), patients and investigators were aware of the type of peginterferon being given. After careful inspection, however, no irregularity in data collection or reporting was detected.
In conclusion, the rates of sustained virologic response and the safety and adverse-event profiles were similar among patients infected with HCV genotype 1 who received standard-dose or low-dose peginterferon alfa-2b or peginterferon alfa-2a, in combination with ribavirin.
Supported by grants from Schering-Plough.
Drs. McHutchison, Lawitz, Shiffman, Muir, Galler, McCone, Nyberg, Lee, Ghalib, Schiff, Galati, Bacon, Davis, and Sulkowski report receiving research and grant support from Schering-Plough; Drs. McHutchison, Lawitz, Shiffman, Nyberg, Schiff, and Sulkowski, research and grant support from Roche; Drs. McHutchison, Lawitz, Muir, Galler, McCone, Nyberg, Lee, Ghalib, Schiff, Galati, Bacon and Sulkowski, lecture fees from Schering-Plough; Drs. McHutchison, Shiffman, Muir, Galler, McCone, Schiff, Galati, Bacon, Noviello, and Sulkowski, consulting or advisory fees from Schering-Plough; Drs. McHutchison, Shiffman, Muir, Nyberg, Lee, Schiff, and Sulkowski, research and grant support from Vertex Pharmaceuticals; Dr. Shiffman, research and grant support from Pharmassett, Johnson and Johnson and Tibotec, ZymoGenetics, and Biolex, and consulting or advisory fees from ZymoGenetics; Drs. Shiffman, Muir, Nyberg, and Bacon, consulting or advisory fees from Vertex Pharmaceuticals; Drs. Shiffman, McCone, Davis, and Sulkowski, lecture fees from Roche; Drs. Shiffman, McCone, and Sulkowski, consulting or advisory fees from Roche; Drs. Shiffman and Nyberg, research and grant support from Idenix; Drs. Shiffman, Nyberg, and Schiff, research and grant support from Conatus Pharmaceuticals; Drs. Shiffman, Lee, and Schiff, research and grant support from GlobeImmune; Drs. Shiffman, Lee, Schiff, and Bacon, research and grant support from Bristol-Myers Squibb; Drs. Shiffman, Lee, and Bacon, research and grant support from GlaxoSmithKline and consulting or advisory fees from Gilead; Drs. Shiffman and Schiff, research and grant support from Coley Pharmaceuticals, Gilead, and Pfizer; Drs. Shiffman and Bacon, research and grant support from Wyeth, Valeant, and Romark Laboratories and lecture fees from Gilead; Drs. Nyberg and Bacon, research and grant support from Human Genome Sciences; Dr. Lee, consulting or advisory fees from Lilly, Novartis, and Westat; Drs. Lee and Schiff, research and grant support from Beckman; Dr. Schiff, research and grant support from Bayer Corporation, FibroScan, Kendle Phynova, LabCorp, Merck, Orasure Technologies, Ortho Diagnostics, Scripps Clinic Liver Research Consortium, and Siemens; Drs. Schiff and Sulkowski, research and grant support from Duke University Medical Center and Debio Pharmaceuticals; Dr. Bacon, research and grant support from Intarcia and Intercept, consulting or advisory fees from GlaxoSmithKline, Genentech, Human Genome Sciences, Isis Pharmaceuticals, and Three Rivers Pharmaceuticals, and lecture fees from Three Rivers Pharmaceuticals; and Dr. Sulkowski, research and grant support from Peregrine Pharmaceuticals. Drs. Mukhopadhyay, Koury, Noviello, Pedicone, Brass, and Albrecht report being employees of Schering-Plough and stockholders in the company.
No other potential conflict of interest relevant to this article was reported.
This article (10.1056/NEJMoa0808010) was published on July 22, 2009, at NEJM.org.
We thank the study coordinators, nurses, and patients involved in the study; Weiping Deng, Michael Geffner, Joann Harvey, Karen Kelly, Misti Linaberry, Helen Nguyen, Peter Savino of Schering-Plough Research Institute for their contributions to the conduct of the study; and Jennifer King, Ph.D., for editorial assistance in preparing the manuscript.
Source Information
From the Duke Clinical Research Institute and Duke University Medical Center, Durham, NC (J.G.M., A.J.M.); Alamo Medical Research, San Antonio, TX (E.J.L.); Kelsey Research Foundation, Houston (G.W.G.); University of Texas Southwestern Medical Center, Dallas (W.M.L.); the Liver Institute at Methodist Dallas Medical Center, Dallas (R.H.G.); and Liver Specialists of Texas, Houston (J.S.G.); Virginia Commonwealth University, Richmond (M.L.S.); and Mount Vernon Endoscopy Center, Alexandria, VA (J.M.); Kaiser Permanente, San Diego Medical Center, San Diego, CA (L.M.N.); University of Miami Center for Liver Diseases, Miami (E.R.S.); and South Florida Center of Gastroenterology, Wellington (M.N.D.); Saint Louis University School of Medicine, St. Louis (B.R.B.); Schering-Plough Research Institute, Kenilworth, NJ (P.M., K.K., S.N., L.D.P., C.A.B., J.K.A.), and Johns Hopkins University School of Medicine, Baltimore (M.S.S.).
Address reprint requests to Dr. McHutchison at Duke Clinical Research Institute, Duke University Medical Center, P.O. Box 17969, Durham, NC 27715, or at mchut001@mc.duke.edu.
Additional members of the Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) study team are listed in the Appendix.
Appendix
In addition to the authors, other participants and members of the IDEAL study team include the following: N. Afdhal, A. Al-Osaimi, L. Balart, M. Bennett, D. Bernstein, E. Bini, M. Black, J. Bloomer, H. Bonilla, T. Box, T. Boyer, N. Brau, K. Brown, R. Brown, C. Bruno, W. Cassidy, R. Chung, D. Clain, J. Crippin, D. Dalke, C. Davis, G. Davis, F. Felizarta, R. Firpi-Morell, S. Flamm, J. Franco, B. Freilich, A. Gibas, E. Godofsky, F. Gordon, J. Gross, S. Harrison, J. Herrera, S. Herrine, R. Herring, K.-Q. Hu, J. Israel, I. Jacobson, S. Joshi, M. Khalili, A. Kilby, J. King, P. King, A. Koch, E. Krawitt, M. Kugelmas, P. Kwo, L. Lambiase, E. Lebovics, J. Levin, R. Levine, S. Lidofsky, M. Lucey, M. Mailliard, L. Marsano, P. Martin, T. McGarrity, D. Mikolich, T. Morgan, K. Mullen, S. Munoz, D. Nelson, F. Nunes, A. Nyberg, S. Oh, P. Pandya, M. P. Pauly, C. Peine, R. Perillo, G. Poleynard, F. Poordad, A. Post, J. Poulos, D. Pound, M. Rabinovitz, N. Ravendhran, J. Ready, R. Reddy, R. Reindollar, A. Reuben, L. Rossaro, L. Rothman, R. Rubin, V. Rustgi, M. Ryan, W. Schmidt, W. Semon, T. Sepe, K. Sherman, M. Sjogren, R. Sjogren, C. Smith, L. Stein, R. Strauss, M. Swaim, G. Szabo, J. Thurn, M. Tong, J. Vierling, G. Wu, R. Yapp, Z. Younes, A. Zaman.
- References
References
1
Hepatitis C fact sheet. Geneva: World Health Organization. (Accessed July 13, 2009, at http://www.who.int/mediacentre/factsheets/fs164/en/.)
2
Perz JF ,Armstrong GL ,Farrington LA ,Hutin YJ ,Bell BP . The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529-538
CrossRef | Web of Science | Medline3
National Institutes of Health Consensus Development Conference Statement: management of hepatitis C: 2002 --June 10-12, 2002. Hepatology 2002;36:Suppl 1:S3-S20
CrossRef | Web of Science | Medline4
Manns MP ,McHutchison JG ,Gordon SC , et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-965
CrossRef | Web of Science | Medline5
Fried MW ,Shiffman ML ,Reddy KR , et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-982
Full Text | Web of Science | Medline6
Hadziyannis SJ ,Sette H Jr ,Morgan TR , et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346-355
Web of Science | Medline7
Jacobson IM ,Brown RS Jr ,Freilich B , et al. Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial. Hepatology 2007;46:971-981
CrossRef | Web of Science | Medline8
Rustgi VK ,Esposito S ,Hamzeh FM ,Shiffman ML . Peginterferon alfa-2a/ribavirin in hepatitis C virus patients nontolerant or nonresponsive to peginterferon alfa-2b/ribavirin. Aliment Pharmacol Ther 2008;27:433-440
CrossRef | Web of Science | Medline9
McHutchison J ,Sulkowski M . Scientific rationale and study design of the Individualized Dosing Efficacy vs Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) trial: determining optimal dosing in patients with genotype 1 chronic hepatitis C. J Viral Hepat 2008;15:475-481
CrossRef | Web of Science | Medline10
Lindsay KL ,Trepo C ,Heintges T , et al. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 2001;34:395-403
CrossRef | Web of Science | Medline11
Bedossa P ,Poynard T . An algorithm for the grading of activity in chronic hepatitis C. Hepatology 1996;24:289-293
CrossRef | Web of Science | Medline12
Summary of product characteristics: Rebetol. London: European Medicines Agency. (Accessed July 13, 2009, at http://www.emea.europa.eu/humandocs/PDFs/EPAR/Rebetol/H-246-PI-en.pdf.)
13
Global surveillance and control of hepatitis C: report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepat 1999;6:35-47
CrossRef | Web of Science | Medline14
Muir AJ ,Bornstein JD ,Killenberg PG . Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004;350:2265-2271[Erratum, N Engl J Med 2004;351:1268.]
Full Text | Web of Science | Medline15
Myers RP ,Patel K ,Pianko S ,Poynard T ,McHutchison JG . The rate of fibrosis progression is an independent predictor of the response to antiviral therapy in chronic hepatitis C. J Viral Hepat 2003;10:16-22
CrossRef | Web of Science | Medline16
Soresi M ,Tripi S ,Franco V , et al. Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis. Liver Int 2006;26:1119-1125
CrossRef | Web of Science | Medline17
Reddy KR ,Govindarajan S ,Marcellin P , et al. Hepatic steatosis in chronic hepatitis C: baseline host and viral characteristics and influence on response to therapy with peginterferon alpha-2a plus ribavirin. J Viral Hepat 2008;15:129-136
Web of Science | Medline18
Bronowicki JP ,Ouzan D ,Asselah T , et al. Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin. Gastroenterology 2006;131:1040-1048
CrossRef | Web of Science | Medline19
Moucari R ,Ripault MP ,Oules V , et al. High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy. J Hepatol 2007;46:596-604
CrossRef | Web of Science | Medline20
Yu ML ,Dai CY ,Huang JF , et al. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology 2008;47:1884-1893
CrossRef | Web of Science | Medline
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CrossRef2
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CrossRef3
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CrossRef5
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CrossRef6
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CrossRef7
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CrossRef8
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CrossRef9
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CrossRef10
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CrossRef11
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CrossRef12
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CrossRef13
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CrossRef14
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CrossRef15
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CrossRef16
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CrossRef17
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CrossRef18
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CrossRef19
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Full Text20
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CrossRef21
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CrossRef22
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CrossRef23
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CrossRef24
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CrossRef25
E. W. Hwang, I.-C. Thomas, R. Cheung, L. I. Backus. (2012) Implications of rapid virological response in hepatitis C therapy in the US veteran population. Alimentary Pharmacology & Therapeutics 35:1, 105-115
CrossRef26
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CrossRef27
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CrossRef28
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CrossRef29
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CrossRef30
Giel R. Gaajetaan, Tanja H. Geelen, Gert E. Grauls, Cathrien A. Bruggeman, Frank R. Stassen. (2012) CpG and poly(I:C) stimulation of dendritic cells and fibroblasts limits herpes simplex virus type 1 infection in an IFNβ-dependent and -independent way. Antiviral Research 93:1, 39-47
CrossRef31
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CrossRef32
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CrossRef33
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CrossRef34
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CrossRef35
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CrossRef36
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CrossRef37
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CrossRef38
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CrossRef39
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CrossRef40
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CrossRef41
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CrossRef42
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CrossRef43
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CrossRef44
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CrossRef45
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CrossRef46
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CrossRef47
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CrossRef48
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CrossRef49
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CrossRef50
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CrossRef51
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CrossRef52
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CrossRef53
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CrossRef54
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CrossRef55
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CrossRef56
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CrossRef57
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CrossRef58
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CrossRef59
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CrossRef60
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CrossRef61
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CrossRef62
P. D. Griffiths. (2011) Mixed results from combination therapy. Reviews in Medical Virology 21:6, 333-335
CrossRef63
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CrossRef64
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CrossRef65
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CrossRef66
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CrossRef67
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CrossRef68
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CrossRef69
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CrossRef70
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CrossRef71
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CrossRef72
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CrossRef73
Chalermrat Bunchorntavakul, K. Rajender Reddy. (2011) Ribavirin: How Does it Work and is it Still Needed?. Current Hepatitis Reports 10:3, 168-178
CrossRef74
Michael Manns, Stefan Zeuzem, Ajit Sood, Yoav Lurie, Markus Cornberg, Hartwig Klinker, Peter Buggisch, Martin Rössle, Holger Hinrichsen, Ismail Merican, Yaron Ilan, Stefan Mauss, Saif Abu-Mouch, Andryes Horban, Thomas H. Müller, Christoph Welsch, Rongdean Chen, Rab Faruqi, Lisa D. Pedicone, Heiner Wedemeyer. (2011) Reduced dose and duration of peginterferon alfa-2b and weight-based ribavirin in patients with genotype 2 and 3 chronic hepatitis C. Journal of Hepatology 55:3, 554-563
CrossRef75
Alison B. Jazwinski, Andrew J. Muir. (2011) Emerging Therapies in Hepatitis C: Dawn of the Era of the Direct-Acting Antivirals. Gastroenterology Clinics of North America 40:3, 481-494
CrossRef76
Arjmand R. Mufti, Nancy Reau. (2011) IL28B: Implications for Therapy. Current Hepatitis Reports 10:3, 153-161
CrossRef77
Anne-Laure Grillot, Luc J. Farmer, B. Govinda Rao, William P. Taylor, Ilan S. Weisberg, Ira M. Jacobson, Robert B. Perni, Ann D. Kwong. 2011. Discovery and Development of Telaprevir. , 207-224.
CrossRef78
Jacinta A. Holmes, Paul V. Desmond, Alexander J. Thompson. (2011) Redefining Baseline Demographics: The Role of Genetic Testing in Hepatitis C Virus Infection. Clinics in Liver Disease 15:3, 497-513
CrossRef79
Archita P. Desai, Nancy Reau. (2011) Naives, Nonresponders, Relapsers: Who Is There Left to Treat?. Clinics in Liver Disease 15:3, 483-495
CrossRef80
Koray Ergünay, Burçin Şener, Alpaslan Alp, Jale Karakaya, Gülşen Hasçelik. (2011) Utility of a commercial quantitative hepatitis C virus core antigen assay in a diagnostic laboratory setting. Diagnostic Microbiology and Infectious Disease 70:4, 486-491
CrossRef81
Andres Duarte-Rojo, Elizabeth Jenny Heathcote, Jordan Jay Feld. (2011) ‘Easy to treat’ genotypes were not created equal: Can rapid virological response (RVR) level the playing field?. Journal of Hepatology 55:2, 466-473
CrossRef82
Mitchell L. Shiffman. (2011) Interferon-Free Regimens: The Near Future, the Likely and the Not So Likely. Clinics in Liver Disease 15:3, 665-675
CrossRef83
Fernando E. Membreno, Eric J. Lawitz. (2011) The HCV NS5B Nucleoside and Non-Nucleoside Inhibitors. Clinics in Liver Disease 15:3, 611-626
CrossRef84
Mary Olson, Ira M. Jacobson. (2011) Role of the nurse practitioner in the management of patients with chronic hepatitis C. Journal of the American Academy of Nurse Practitioners 23:8, 410-420
CrossRef85
Tsugiko Oze, Naoki Hiramatsu, Takayuki Yakushijin, Kiyoshi Mochizuki, Masahide Oshita, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Yoshiaki Inui, Hiroyuki Fukui, Taizo Hijioka, Kazuhiro Katayama, Shinji Tamura, Harumasa Yoshihara, Atsuo Inoue, Yasuharu Imai, Eijiro Hayashi, Michio Kato, Atsushi Hosui, Takuya Miyagi, Hisashi Ishida, Yuichi Yoshida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Tetsuo Takehara, Norio Hayashi. (2011) Efficacy of re-treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan. Journal of Gastroenterology 46:8, 1031-1037
CrossRef86
Jacinta A Holmes, William Sievert, Alexander J Thompson. (2011) IL28B polymorphism and genetic biomarkers of viral clearance in hepatitis C virus infection. Biomarkers in Medicine 5:4, 461-478
CrossRef87
Maria Buti, Rafael Esteban. (2011) 1990–2010: Two Decades of Interferon-Based Therapy. Clinics in Liver Disease 15:3, 473-482
CrossRef88
Paul Y. Kwo, Rong Zhao. (2011) Boceprevir: A User’s Guide. Clinics in Liver Disease 15:3, 537-553
CrossRef89
Ashwani K. Singal, Sarat C. Jampana, Bhupinderjit S. Anand. (2011) Peginterferon Alfa-2a Is Superior to Peginterferon Alfa-2b in the Treatment of Naïve Patients with Hepatitis C Virus Infection: Meta-Analysis of Randomized Controlled Trials. Digestive Diseases and Sciences 56:8, 2221-2226
CrossRef90
(2011) EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology 55:2, 245-264
CrossRef91
Christophe Lallemand, Michael G. Tovey. 2011. A Novel One-Step Cell-Based Assay for Quantification of Neutralizing Antibodies to Biopharmaceuticals. , 383-398.
CrossRef92
Eric Trépo, Pierre Pradat, Andrej Potthoff, Yukihide Momozawa, Eric Quertinmont, Thierry Gustot, Arnaud Lemmers, Pascale Berthillon, Leila Amininejad, Michéle Chevallier, Jerome Schlué, Hans Kreipe, Jacques Devière, Michael Manns, Christian Trépo, John Sninsky, Heiner Wedemeyer, Denis Franchimont, Christophe Moreno. (2011) Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C. Hepatology 54:1, 60-69
CrossRef93
Roberta Melis, Christiane Fauron, Gwendolyn McMillin, Elaine Lyon, Brian Shirts, Lindsey M. Hubley, Patricia R. Slev. (2011) Simultaneous Genotyping of rs12979860 and rs8099917 Variants Near the IL28B Locus Associated with HCV Clearance and Treatment Response. The Journal of Molecular Diagnostics 13:4, 446-451
CrossRef94
Tsugiko Oze, Naoki Hiramatsu, Takayuki Yakushijin, Kiyoshi Mochizuki, Kazuho Imanaka, Akira Yamada, Masahide Oshita, Akira Kaneko, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Toshihiko Nagase, Yoshiaki Inui, Taizo Hijioka, Shinji Tamura, Harumasa Yoshihara, Eijiro Hayashi, Yasuharu Imai, Michio Kato, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Hisashi Ishida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Tetsuo Takehara, Norio Hayashi. (2011) The efficacy of extended treatment with pegylated interferon plus ribavirin in patients with HCV genotype 1 and slow virologic response in Japan. Journal of Gastroenterology 46:7, 944-952
CrossRef95
Lei Y. Lim, Paul Y. Kwo, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein. (2011) A glimpse at the future of hepatitis C therapy: The INFORM trial. Hepatology 54:1, 360-363
CrossRef96
Peter Ferenci. (2011) Safety and efficacy of treatment for chronic hepatitis C with a focus on pegylated interferons: the backbone of therapy today and in the future. Expert Opinion on Drug Safety 10:4, 529-544
CrossRef97
Norman D. Grace. (2011) Patients With Clinically Significant Portal Hypertension Caused by Hepatitis C Virus Cirrhosis Respond Poorly to Antiviral Therapy. Clinical Gastroenterology and Hepatology 9:7, 536-538
CrossRef98
Michael T. Melia, Andrew J. Muir, Jonathan McCone, Mitchell L. Shiffman, John W. King, Steven K. Herrine, Greg W. Galler, Joseph R. Bloomer, Frederick A. Nunes, Kimberly A. Brown, Kevin D. Mullen, Natarajan Ravendhran, Reem H. Ghalib, Navdeep Boparai, Ruiyun Jiang, Stephanie Noviello, Clifford A. Brass, Janice K. Albrecht, John G. McHutchison, Mark S. Sulkowski, . (2011) Racial differences in hepatitis C treatment eligibility. Hepatology 54:1, 70-78
CrossRef99
David Kershenobich, Homie A. Razavi, Juan Francisco Sánchez-Avila, Fernando Bessone, Henrique S. Coelho, Lucy Dagher, Fernando L. Gonçales, Jorge F. Quiroz, Federico Rodriguez-Perez, Barbara Rosado, Carolyn Wallace, Francesco Negro, Marcelo Silva. (2011) Trends and projections of hepatitis C virus epidemiology in Latin America. Liver International 31, 18-29
CrossRef100
Zeuzem, Stefan, Andreone, Pietro, Pol, Stanislas, Lawitz, Eric, Diago, Moises, Roberts, Stuart, Focaccia, Roberto, Younossi, Zobair, Foster, Graham R., Horban, Andrzej, Ferenci, Peter, Nevens, Frederik, Müllhaupt, Beat, Pockros, Paul, Terg, Ruben, Shouval, Daniel, van Hoek, Bart, Weiland, Ola, Van Heeswijk, Rolf, De Meyer, Sandra, Luo, Don, Boogaerts, Griet, Polo, Ramon, Picchio, Gaston, Beumont, Maria, . (2011) Telaprevir for Retreatment of HCV Infection. New England Journal of Medicine 364:25, 2417-2428
Full Text101
Jacobson, Ira M., McHutchison, John G., Dusheiko, Geoffrey, Di Bisceglie, Adrian M., Reddy, K. Rajender, Bzowej, Natalie H., Marcellin, Patrick, Muir, Andrew J., Ferenci, Peter, Flisiak, Robert, George, Jacob, Rizzetto, Mario, Shouval, Daniel, Sola, Ricard, Terg, Ruben A., Yoshida, Eric M., Adda, Nathalie, Bengtsson, Leif, Sankoh, Abdul J., Kieffer, Tara L., George, Shelley, Kauffman, Robert S., M.D., Stefan Zeuzem. (2011) Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection. New England Journal of Medicine 364:25, 2405-2416
Full Text102
Rosen, Hugo R., . (2011) Chronic Hepatitis C Infection. New England Journal of Medicine 364:25, 2429-2438
Full Text103
A K Smith, J S Simon, E L Gustafson, S Noviello, J F Cubells, M P Epstein, D J Devlin, P Qiu, J K Albrecht, C A Brass, M S Sulkowski, J G McHutchinson, A H Miller. (2011) Association of a polymorphism in the indoleamine- 2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C. Molecular Psychiatry
CrossRef104
Michael P. Manns, Marc Bourlière, Yves Benhamou, Stanislas Pol, Maurizio Bonacini, Christian Trepo, David Wright, Thomas Berg, José L. Calleja, Peter W. White, Jerry O. Stern, Gerhard Steinmann, Chan-Loi Yong, George Kukolj, Joe Scherer, Wulf O. Boecher. (2011) Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. Journal of Hepatology 54:6, 1114-1122
CrossRef105
J. H. Hoofnagle, S. Sarkar. (2011) Fatigue and serum carnitine levels in chronic liver disease. Alimentary Pharmacology & Therapeutics 33:11, 1252-1253
CrossRef106
Joseph Torresi, Doug Johnson, Heiner Wedemeyer. (2011) Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. Journal of Hepatology 54:6, 1273-1285
CrossRef107
Elena Vezali, Alessio Aghemo, Pietro Lampertico, Massimo Colombo. (2011) Does interferon therapy prevent hepatocellular carcinoma in patients with chronic viral hepatitis?. Clinics and Research in Hepatology and Gastroenterology 35:6-7, 455-464
CrossRef108
Yoshimasa Hashimoto, Hidenori Ochi, Hiromi Abe, Yasufumi Hayashida, Masataka Tsuge, Fukiko Mitsui, Nobuhiko Hiraga, Michio Imamura, Shoichi Takahashi, C. Nelson Hayes, Waka Ohishi, Michaki Kubo, Tatsuhiko Tsunoda, Naoyuki Kamatani, Yusuke Nakamura, Kazuaki Chayama. (2011) Prediction of response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b. Journal of Medical Virology 83:6, 981-988
CrossRef109
Julien Vergniol, Juliette Foucher, Eric Terrebonne, Pierre–Henri Bernard, Brigitte le Bail, Wassil Merrouche, Patrice Couzigou, Victor de Ledinghen. (2011) Noninvasive Tests for Fibrosis and Liver Stiffness Predict 5-Year Outcomes of Patients With Chronic Hepatitis C. Gastroenterology 140:7, 1970-1979.e3
CrossRef110
J. T. WILDE, D. MUTIMER, G. DOLAN, C. MILLAR, H. G. WATSON, T. T. YEE, M. MAKRIS. (2011) UKHCDO guidelines on the management of HCV in patients with hereditary bleeding disorders 2011. Haemophiliano-no
CrossRef111
Alison A Murphy, Eva Herrmann, Anu O Osinusi, Lynn Wu, William Sachau, Richard A Lempicki, Jun Yang, Tei L Chung, Brad J Wood, Bart L Haagmans, Shyam Kottilil, Michael A Polis. (2011) Twice-weekly pegylated interferon-α-2a and ribavirin results in superior viral kinetics in HIV/hepatitis C virus co-infected patients compared to standard therapy. AIDS 25:9, 1179-1187
CrossRef112
Nagraj Mani, Bhisetti G. Rao, Tara L. Kieffer, Ann D. Kwong. 2011. Recent Progress in the Development of HCV Protease Inhibitors. , 307-328.
CrossRef113
Mario Masarone, Marcello Persico. (2011) Antiviral therapy: why does it fail in HCV-related chronic hepatitis?. Expert Review of Anti-infective Therapy 9:5, 535-543
CrossRef114
Lotte G. van Vlerken, Martijn G.H. van Oijen, Karel J. van Erpecum. (2011) Ribavirin Concentration Is a More Important Predictor of Sustained Viral Response Than Anemia in Hepatitis C Patients. Gastroenterology 140:5, 1693-1694
CrossRef115
Thomas-Matthias Scherzer, Harald Hofer, Albert Friedrich Staettermayer, Karoline Rutter, Sandra Beinhardt, Petra Steindl-Munda, Heidrun Kerschner, Harald H. Kessler, Peter Ferenci. (2011) Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin. Journal of Hepatology 54:5, 866-871
CrossRef116
Naoya Sakamoto, Mina Nakagawa, Yasuhito Tanaka, Yuko Sekine-Osajima, Mayumi Ueyama, Masayuki Kurosaki, Nao Nishida, Akihiro Tamori, Nishimura-Sakurai Yuki, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Shuhei Hige, Yoshito Itoh, Eiji Tanaka, Yoichi Hiasa, Namiki Izumi, Katsushi Tokunaga, Masashi Mizokami, Mamoru Watanabe, . (2011) Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b. Journal of Medical Virology 83:5, 871-878
CrossRef117
Geoffrey Dusheiko. 2011. Hepatitis C. , 406-426.
CrossRef118
Hong-ming Nie. (2011) Syndrome distribution among patients with chronic hepatitis C and interventions of integrated traditional Chinese and Western medicine: study protocol. Journal of Chinese Integrative Medicine 9:4, 365-373
CrossRef119
A. J. Muir, K. -Q. Hu, S. C. Gordon, K. Koury, N. Boparai, S. Noviello, J. K. Albrecht, M. S. Sulkowski, J. McCone. (2011) Hepatitis C treatment among racial and ethnic groups in the IDEAL trial. Journal of Viral Hepatitis 18:4, e134-e143
CrossRef120
Yuki Hitomi, Elizabeth T. Cirulli, Jacques Fellay, John G. McHutchison, Alexander J. Thompson, Curtis E. Gumbs, Kevin V. Shianna, Thomas J. Urban, David B. Goldstein. (2011) Inosine Triphosphate Protects Against Ribavirin-Induced Adenosine Triphosphate Loss by Adenylosuccinate Synthase Function. Gastroenterology 140:4, 1314-1321
CrossRef121
Christoph Sarrazin. (2011) Viral kinetics for individualized treatment durations. Journal of Hepatology 54:4, 836-837
CrossRef122
Mark S. Sulkowski, Curtis Cooper, Bela Hunyady, Jidong Jia, Pavel Ogurtsov, Markus Peck-Radosavljevic, Mitchell L. Shiffman, Cihan Yurdaydin, Olav Dalgard. (2011) Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C. Nature Reviews Gastroenterology & Hepatology 8:4, 212-223
CrossRef123
Zong-Gen Peng, Zhi-Yun Zhao, Yan-Ping Li, Yu-Ping Wang, Lan-Hu Hao, Bo Fan, Yu-Huan Li, Yue-Ming Wang, Yong-Qiang Shan, Yan-Xing Han, Yan-Ping Zhu, Jian-Rui Li, Xue-Fu You, Zhuo-Rong Li, Jian-Dong Jiang. (2011) Host apolipoprotein b messenger RNA-editing enzyme catalytic polypeptide-like 3G is an innate defensive factor and drug target against hepatitis C virus. Hepatology 53:4, 1080-1089
CrossRef124
Davide Bitetto, Giovanna Fattovich, Carlo Fabris, Elisa Ceriani, Edmondo Falleti, Ezio Fornasiere, Michela Pasino, Donatella Ieluzzi, Annarosa Cussigh, Sara Cmet, Mario Pirisi, Pierluigi Toniutto. (2011) Complementary role of vitamin D deficiency and the interleukin-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C. Hepatology 53:4, 1118-1126
CrossRef125
S. Mauss, D. Hueppe, C. John, J Goelz, R. Heyne, B. Moeller, R. Link, G. Teuber, A. Herrmann, M. Spelter, S. Wollschlaeger, A. Baumgarten, K.-G. Simon, N. Dikopoulos, T. Witthoeft. (2011) Estimating the likelihood of sustained virological response in chronic hepatitis C therapy. Journal of Viral Hepatitis 18:4, e81-e90
CrossRef126
Deepak Joshi, John O'Grady, Doug Dieterich, Brian Gazzard, Kosh Agarwal. (2011) Increasing burden of liver disease in patients with HIV infection. The Lancet 377:9772, 1198-1209
CrossRef127
Albert Friedrich Stättermayer, Rudolf Stauber, Harald Hofer, Karoline Rutter, Sandra Beinhardt, Thomas Matthias Scherzer, Kerstin Zinober, Christian Datz, Andreas Maieron, Emina Dulic–Lakovic, Harald H. Kessler, Petra Steindl–Munda, Michael Strasser, Christoph Krall, Peter Ferenci. (2011) Impact of IL28B Genotype on the Early and Sustained Virologic Response in Treatment-Naïve Patients With Chronic Hepatitis C. Clinical Gastroenterology and Hepatology 9:4, 344-350.e2
CrossRef128
Poordad, Fred, McCone, Jonathan Jr., Bacon, Bruce R., Bruno, Savino, Manns, Michael P., Sulkowski, Mark S., Jacobson, Ira M., Reddy, K. Rajender, Goodman, Zachary D., Boparai, Navdeep, DiNubile, Mark J., Sniukiene, Vilma, Brass, Clifford A., Albrecht, Janice K., Bronowicki, Jean-Pierre, . (2011) Boceprevir for Untreated Chronic HCV Genotype 1 Infection. New England Journal of Medicine 364:13, 1195-1206
Full Text129
Jensen, Donald M., . (2011) A New Era of Hepatitis C Therapy Begins. New England Journal of Medicine 364:13, 1272-1274
Full Text130
Bacon, Bruce R., Gordon, Stuart C., Lawitz, Eric, Marcellin, Patrick, Vierling, John M., Zeuzem, Stefan, Poordad, Fred, Goodman, Zachary D., Sings, Heather L., Boparai, Navdeep, Burroughs, Margaret, Brass, Clifford A., Albrecht, Janice K., Esteban, Rafael, . (2011) Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection. New England Journal of Medicine 364:13, 1207-1217
Full Text131
Edward L. Korn, Boris Freidlin. (2011) Inefficacy Interim Monitoring Procedures in Randomized Clinical Trials: The Need to Report. The American Journal of Bioethics 11:3, 2-10
CrossRef132
Sanaa M. Kamal, Amany Ahmed, Sara Mahmoud, Leila Nabegh, Iman El Gohary, Isi Obadan, Tamer Hafez, Dahlia Ghoraba, Ahmed A. Aziz, Mona Metaoei. (2011) Enhanced efficacy of pegylated interferon alpha-2a over pegylated interferon and ribavirin in chronic hepatitis C genotype 4A randomized trial and quality of life analysis. Liver International 31:3, 401-411
CrossRef133
Stevan A. Gonzalez. (2011) Consensus Interferon: Tailored Therapy and the Impact of Adherence. Digestive Diseases and Sciences 56:3, 631-634
CrossRef134
Alajos Pár, Péter Kisfali, Béla Melegh, István Tornai, Judit Gervain, Ferenc Szalay, Márta Varga, Mária Papp, János Schuller, Anna Tusnádi, János Fehér, Gabriella Lengyel, Zsuzsanna Nemes, Zoltán Péterfi, Béla Hunyady, Áron Vincze, Gabriella Pár. (2011) Cytokine (IL-10, IL-28B and LT-A) gene polymorphisms in chronic hepatitis C virus infection. Clinical and Experimental Medical Journal 5:1, 9-19
CrossRef135
Dong Hyun Sinn, Su Rin Shin, Jae Sook Kil, Jeong Kim, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Byung Chul Yoo, Seung Woon Paik. (2011) Efficacy of peg-interferon-α-2a plus ribavirin for patients aged 60 years and older with chronic hepatitis C in Korea. Journal of Gastroenterology and Hepatology 26:3, 469-476
CrossRef136
Elena Vezali, Alessio Aghemo, Massimo Colombo. (2011) Interferon in the treatment of chronic hepatitis C: a drug caught between past and future. Expert Opinion on Biological Therapy 11:3, 301-313
CrossRef137
Arjmand Mufti. (2011) IL28B Polymorphisms as a Predictor of Response to Therapy in Genotype 1 Chronic Hepatitis C Infections. Current Hepatitis Reports 10:1, 1-3
CrossRef138
Xiaogang Xiang, Jie Lu, Zhixia Dong, Huijuan Zhou, Wanyin Tao, Qing Guo, Xiaqiu Zhou, Shisan Bao, Qing Xie, Jin Zhong. (2011) Viral sequence evolution in Chinese genotype 1b chronic hepatitis C patients experiencing unsuccessful interferon treatment. Infection, Genetics and Evolution 11:2, 382-390
CrossRef139
Jean-Marc Costa, Dmytro Telehin, Mona Munteanu, Tetiana Kobryn, Yen Ngo, Vincent Thibault, Moussalli Joseph, Vlad Ratziu, Yves Benhamou, Volodymyr Koz’ko, Galyna Dubins’ka, Jean-Dominique Poveda, Thierry Poynard. (2011) HCV-GenoFibrotest: A combination of viral, liver and genomic (IL28b, ITPA, UGT1A1) biomarkers for predicting treatment response in patients with chronic hepatitis C. Clinics and Research in Hepatology and Gastroenterology 35:3, 204-213
CrossRef140
Saumya Jayakumar, Vincent Bain. (2011) Rational Guide to the Use of Erythropoietin in the Treatment of HCV Infection. Current Hepatitis Reports 10:1, 62-69
CrossRef141
Yuko Inoue, Naoki Hiramatsu, Tsugiko Oze, Takayuki Yakushijin, Kiyoshi Mochizuki, Kazuto Fukuda, Eiji Mita, Yoshimichi Haruna, Atsuo Inoue, Yasuharu Imai, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Tetsuo Takehara, Norio Hayashi. (2011) Amino acid substitution in the core protein has no impact on relapse in hepatitis C genotype 1 patients treated with peginterferon and ribavirin. Journal of Medical Virology 83:3, 419-427
CrossRef142
Paul J. Clark, Alexander J. V. Thompson, Andrew J. Muir. (2011) IL28B Polymorphisms and Treatment of Hepatitis C. Current Hepatitis Reports 10:1, 70-78
CrossRef143
Samuel B. Ho, Bashar Aqel, Eric Dieperink, Shanglei Liu, Lori Tetrick, Yngve Falck-Ytter, Charles DeComarmond, Coleman I. Smith, Daniel P. McKee, William Boyd, Clark C. Kulig, Edmund J. Bini, Marcos C. Pedrosa. (2011) U.S. Multicenter Pilot Study of Daily Consensus Interferon (CIFN) Plus Ribavirin for “Difficult-to-Treat” HCV Genotype 1 Patients. Digestive Diseases and Sciences 56:3, 880-888
CrossRef144
Kimberly A. Forde, K. Rajender Reddy. (2011) Hormones: A Potential Explanation for Differences in Response Rates to Therapy for Chronic Hepatitis C Infection. Gastroenterology 140:3, 776-779
CrossRef145
S. Chevaliez. (2011) Virological tools to diagnose and monitor hepatitis C virus infection. Clinical Microbiology and Infection 17:2, 116-121
CrossRef146
Fred Poordad. (2011) Big Changes Are Coming in Hepatitis C. Current Gastroenterology Reports 13:1, 72-77
CrossRef147
Serena Slavenburg, Hanneke W H A Huntjens-Fleuren, Ton S M Dofferhoff, Clemens Richter, Peter P Koopmans, Corrien P W G M Verwey-Van Wissen, Joost P H Drenth, David M Burger. (2011) Ribavirin Plasma Concentration Measurements in Patients With Hepatitis C: Early Ribavirin Concentrations Predict Steady-State Concentrations. Therapeutic Drug Monitoring 33:1, 40-44
CrossRef148
Stéphane Chevaliez. (2011) Nouveaux outils pour le diagnostic et le suivi des hépatites virales chroniques. Revue Francophone des Laboratoires 2011:429, 48-50
CrossRef149
Fumitaka Suzuki, Yoshiyuki Suzuki, Norio Akuta, Hitomi Sezaki, Miharu Hirakawa, Yusuke Kawamura, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saito, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Kazuaki Chayama, Naoyuki Kamatani, Yusuke Nakamura, Yuzo Miyakawa, Hiromitsu Kumada. (2011) Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir. Hepatology 53:2, 415-421
CrossRef150
Alexander J. Thompson, Rosanna Santoro, Valeria Piazzolla, Paul J. Clark, Susanna Naggie, Hans L. Tillmann, Keyur Patel, Andrew J. Muir, Kevin V. Shianna, Leonardo Mottola, Daniela Petruzzellis, Mario Romano, Fernando Sogari, Domenico Facciorusso, David B. Goldstein, John G. McHutchison, Alessandra Mangia. (2011) Inosine triphosphatase genetic variants are protective against anemia during antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or increase SVR. Hepatology 53:2, 389-395
CrossRef151
Brian L. Pearlman. (2011) The IL-28 Genotype: How It Will Affect the Care of Patients with Hepatitis C Virus Infection. Current Gastroenterology Reports 13:1, 78-86
CrossRef152
Kathleen B. Schwarz, Regino P. Gonzalez–Peralta, Karen F. Murray, Jean P. Molleston, Barbara A. Haber, Maureen M. Jonas, Philip Rosenthal, Parvathi Mohan, William F. Balistreri, Michael R. Narkewicz, Lesley Smith, Steven J. Lobritto, Stephen Rossi, Alexandra Valsamakis, Zachary Goodman, Patricia R. Robuck, Bruce A. Barton. (2011) The Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents With Chronic Hepatitis C. Gastroenterology 140:2, 450-458.e1
CrossRef153
Patrick Marcellin, Xavier Forns, Tobias Goeser, Peter Ferenci, Frederik Nevens, Giampiero Carosi, Joost P. Drenth, Lawrence Serfaty, Koen De Backer, Rolf Van Heeswijk, Donghan Luo, Gaston Picchio, Maria Beumont. (2011) Telaprevir Is Effective Given Every 8 or 12 Hours With Ribavirin and Peginterferon Alfa-2a or -2b to Patients With Chronic Hepatitis C. Gastroenterology 140:2, 459-468.e1
CrossRef154
Alessandra Mangia. (2011) Individualizing treatment duration in hepatitis C virus genotype 2/3-infected patients. Liver International 31:1, 36-41
CrossRef155
Kazuaki Chayama, C Nelson Hayes. (2011) Hepatitis C virus: How genetic variability affects pathobiology of disease. Journal of Gastroenterology and Hepatology 26, 83-95
CrossRef156
Yasuhito Tanaka. (2011) Interleukin28B and Inosine Triphosphatase Help to Personalize Hepatitis C Treatment. Digestion 84:s1, 50-55
CrossRef157
Masaya Sugiyama, Yasuhito Tanaka, Makoto Nakanishi, Masashi Mizokami. (2011) Novel Findings for the Development of Drug Therapy for Various Liver Diseases: Genetic Variation in IL-28B Is Associated With Response to the Therapy for Chronic Hepatitis C. Journal of Pharmacological Sciences 115:3, 263-269
CrossRef158
Reem R Al Olaby, Hassan ME Azzazy. (2011) Hepatitis C virus RNA assays: current and emerging technologies and their clinical applications. Expert Review of Molecular Diagnostics 11:1, 53-64
CrossRef159
Olav Dalgard, Zbigniew Konopski, Franziskus Bosse, Berit Nordstrand, Per Sandvei, Lars Karlsen, Jon Florholmen, Astrid Rojahn, Rune Almaas, Steinar Skrede, Arne Eskesen, Bjørn Myrvang. (2011) Hepatitt C - utredning og behandling. Tidsskrift for Den norske legeforening 131:1, 2-9
CrossRef160
Bertus Eksteen. (2011) Infections and the Liver. Digestive Diseases 29:2, 184-190
CrossRef161
John G. McHutchison. (2011) The role of genetic markers in hepatitis C virus therapy: a major step for individualized care. Liver International 31, 29-35
CrossRef162
Paul J Clark, Alex J Thompson, John G McHutchison. (2011) IL28B Genomic-Based Treatment Paradigms for Patients With Chronic Hepatitis C Infection: The Future of Personalized HCV Therapies. The American Journal of Gastroenterology 106:1, 38-45
CrossRef163
Melanie C.M. Murray, Rolando Barrios, Wendy Zhang, Mark Hull, Valentina Montessori, Robert S. Hogg, Julio S.G. Montaner. (2011) Hepatitis C virus treatment rates and outcomes in HIV/hepatitis C virus co-infected individuals at an urban HIV clinic. European Journal of Gastroenterology & Hepatology 23:1, 45-50
CrossRef164
Philipp de Leuw, Christoph Sarrazin, Stefan Zeuzem. (2011) How to use virological tools for the optimal management of chronic hepatitis C. Liver International 31, 3-12
CrossRef165
McKenzie C Ferguson. (2011) Current Therapies for Chronic Hepatitis C. Pharmacotherapy 31:1, 92-111
CrossRef166
Gowtham A. Rao, Prashant K. Pandya. (2011) Statin Therapy Improves Sustained Virologic Response Among Diabetic Patients With Chronic Hepatitis C. Gastroenterology 140:1, 144-152.e2
CrossRef167
Theo Dingermann, Ilse Zündorf. (2011) Alfa-Interferone. Gentechnisch hergestellte Virustatika. Pharmazie in unserer Zeit 40:1, 68-77
CrossRef168
Kazuaki Chayama, Shoichi Takahashi, Joji Toyota, Yoshiyasu Karino, Kenji Ikeda, Hiroki Ishikawa, Hideaki Watanabe, Fiona McPhee, Eric Hughes, Hiromitsu Kumada. (2011) Dual therapy with the NS5A inhibitor BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected null responders. Hepatologyn/a-n/a
CrossRef169
Pierre-Yves Bochud, Stéphanie Bibert, Zoltán Kutalik, Etienne Patin, Julien Guergnon, Bertrand Nalpas, Nicolas Goossens, Lorenz Kuske, Beat Müllhaupt, Tillman Gerlach, Markus H. Heim, Darius Moradpour, Andreas Cerny, Raffaele Malinverni, Stephan Regenass, Guenter Dollenmaier, Hans Hirsch, Gladys Martinetti, Meri Gorgiewski, Marc Bourlière, Thierry Poynard, Ioannis Theodorou, Laurent Abel, Stanislas Pol, Jean-François Dufour, Francesco Negro, . (2011) IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes. Hepatologyn/a-n/a
CrossRef170
Venessa Pattullo, E. Jenny Heathcote, David K. H. Wong. (2010) Superior response to pegylated interferon and ribavirin in Asians with chronic hepatitis C. Hepatology International 4:4, 723-731
CrossRef171
Elena Vezali, Alessio Aghemo, Massimo Colombo. (2010) A review of the treatment of chronic hepatitis C virus infection in cirrhosis. Clinical Therapeutics 32:13, 2117-2138
CrossRef172
Raymond T. Chung, Fred F. Poordad, Tarek Hassanein, Xiaolei Zhou, Ellen Lentz, Avinash Prabhakar, Adrian M. Di Bisceglie. (2010) Association of host pharmacodynamic effects with virologic response to pegylated interferon alfa-2a/ribavirin in chronic hepatitis C. Hepatology 52:6, 1906-1914
CrossRef173
Tarik Asselah, Eric Pasmant, Saïd Lyoumi. (2010) Unraveling the genetic predisposition of ribavirin-induced anaemia. Journal of Hepatology 53:5, 971-973
CrossRef174
Naoya Sakamoto, Yasuhito Tanaka, Mina Nakagawa, Hiroshi Yatsuhashi, Shuhei Nishiguchi, Nobuyuki Enomoto, Seishin Azuma, Yuki Nishimura-Sakurai, Sei Kakinuma, Nao Nishida, Katsushi Tokunaga, Masao Honda, Kiyoaki Ito, Masashi Mizokami, Mamoru Watanabe. (2010) ITPA gene variant protects against anemia induced by pegylated interferon-α and ribavirin therapy for Japanese patients with chronic hepatitis C. Hepatology Research 40:11, 1063-1071
CrossRef175
Joep de Bruijne, Jilling F. Bergmann, Henk W. Reesink, Christine J. Weegink, Richard Molenkamp, Janke Schinkel, Xiao Tong, Jing Li, Michelle A. Treitel, Eric A. Hughes, Jan Jaap van Lier, Andre A. van Vliet, Harry L. A. Janssen, Robert J. de Knegt. (2010) Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients. Hepatology 52:5, 1590-1599
CrossRef176
Mark S. Sulkowski, Mitchell L. Shiffman, Nezam H. Afdhal, K. Rajender Reddy, Jonathan McCone, William M. Lee, Steven K. Herrine, Stephen A. Harrison, F. Fred Poordad, Kenneth Koury, Weiping Deng, Stephanie Noviello, Lisa D. Pedicone, Clifford A. Brass, Janice K. Albrecht, John G. McHutchison. (2010) Hepatitis C Virus Treatment-Related Anemia Is Associated With Higher Sustained Virologic Response Rate. Gastroenterology 139:5, 1602-1611.e1
CrossRef177
Maria Buti, Yoav Lurie, Natalia G. Zakharova, Natalia P. Blokhina, Andrzej Horban, Gerlinde Teuber, Christoph Sarrazin, Ligita Balciuniene, Saya V. Feinman, Rab Faruqi, Lisa D. Pedicone, Rafael Esteban. (2010) Randomized trial of peginterferon alfa-2b and ribavirin for 48 or 72 weeks in patients with hepatitis C virus genotype 1 and slow virologic response. Hepatology 52:4, 1201-1207
CrossRef178
Srunthron Akkarathamrongsin, Masaya Sugiyama, Kentaro Matsuura, Fuat Kurbanov, Yong Poovorawan, Yasuhito Tanaka, Masashi Mizokami. (2010) High sensitivity assay using serum sample for IL28B genotyping to predict treatment response in chronic hepatitis C patients. Hepatology Research 40:10, 956-962
CrossRef179
David L Thomas. (2010) Curing hepatitis C with pills: a step toward global control. The Lancet 376:9751, 1441-1442
CrossRef180
Paul Y. Kwo, Rakesh Vinayek. (2010) The next step for taribavirin. Hepatology 52:4, 1185-1188
CrossRef181
Stefan Zeuzem, Mark S. Sulkowski, Eric J. Lawitz, Vinod K. Rustgi, Maribel Rodriguez–Torres, Bruce R. Bacon, Mircea Grigorescu, Alan D. Tice, Yoav Lurie, Janusz Cianciara, Andrew J. Muir, Patrick W. Cronin, Erik Pulkstenis, G. Mani Subramanian, John G. McHutchison. (2010) Albinterferon Alfa-2b Was Not Inferior to Pegylated Interferon-α in a Randomized Trial of Patients With Chronic Hepatitis C Virus Genotype 1. Gastroenterology 139:4, 1257-1266
CrossRef182
Mazen Noureddin, Marc G. Ghany. (2010) Pharmacokinetics and Pharmacodynamics of Peginterferon and Ribavirin: Implications for Clinical Efficacy in the Treatment of Chronic Hepatitis C. Gastroenterology Clinics of North America 39:3, 649-658
CrossRef183
Tatsuo Kanda, Fumio Imazeki, Osamu Yokosuka. (2010) New antiviral therapies for chronic hepatitis C. Hepatology International 4:3, 548-561
CrossRef184
Seyed-Moayed Alavian, Seyed Vahid Tabatabaei, Maryam Keshvari, Bita Behnava, Seyyed Mohammad Miri, Pegah Karimi Elizee, Kamran Bagheri Lankarani. (2010) Peginterferon α-2a and ribavirin treatment of patients with haemophilia and hepatitis C virus infection: a single-centre study of 367 cases. Liver International 30:8, 1173-1180
CrossRef185
Zong-Gen Peng, Bo Fan, Na-Na Du, Yu-Ping Wang, Li-Mei Gao, Ying-Hong Li, Yu-Huan Li, Fei Liu, Xue-Fu You, Yan-Xing Han, Zhi-Yun Zhao, Shan Cen, Jian-Rui Li, Dan-Qing Song, Jian-Dong Jiang. (2010) Small molecular compounds that inhibit hepatitis C virus replication through destabilizing heat shock cognate 70 messenger RNA. Hepatology 52:3, 845-853
CrossRef186
Alessio Aghemo, Maria Grazia Rumi, Massimo Colombo. (2010) Pegylated interferons α2a and α2b in the treatment of chronic hepatitis C. Nature Reviews Gastroenterology & Hepatology 7:9, 485-494
CrossRef187
Andrew J. Muir, Mitchell L. Shiffman, Atif Zaman, Boris Yoffe, Andrew de la Torre, Steven Flamm, Stuart C. Gordon, Paul Marotta, John M. Vierling, Juan Carlos Lopez-Talavera, Kelly Byrnes-Blake, David Fontana, Jeremy Freeman, Todd Gray, Diana Hausman, Naomi N. Hunder, Eric Lawitz. (2010) Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 52:3, 822-832
CrossRef188
Stephen A. Harrison, Lorenzo Rossaro, Ke-Qin Hu, Keyur Patel, Hans Tillmann, Sandeep Dhaliwal, Dawn M. Torres, Kenneth Koury, Venkata S. Goteti, Stephanie Noviello, Clifford A. Brass, Janice K. Albrecht, John G. McHutchison, Mark S. Sulkowski. (2010) Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy. Hepatology 52:3, 864-874
CrossRef189
Chanunta Hongthanakorn, Anna S.F. Lok. (2010) New Pharmacologic Therapies in Chronic Hepatitis B. Gastroenterology Clinics of North America 39:3, 659-680
CrossRef190
Dawn McDowell Torres. (2010) Update on Specifically Targeted Antiviral Therapy for Hepatitis C Infection: Progress and Pitfalls on the Road to Viral Eradication. Current Hepatitis Reports 9:3, 125-132
CrossRef191
Paul Y Kwo, Eric J Lawitz, Jonathan McCone, Eugene R Schiff, John M Vierling, David Pound, Mitchell N Davis, Joseph S Galati, Stuart C Gordon, Natarajan Ravendhran, Lorenzo Rossaro, Frank H Anderson, Ira M Jacobson, Raymond Rubin, Kenneth Koury, Lisa D Pedicone, Clifford A Brass, Eirum Chaudhri, Janice K Albrecht. (2010) Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. The Lancet 376:9742, 705-716
CrossRef192
Paul Kwo. (2010) Viral Kinetics and Duration of Hepatitis C Therapy. Current Hepatitis Reports 9:3, 140-146
CrossRef193
Eleanor L. Ramos. (2010) Preclinical and Clinical Development of Pegylated Interferon-Lambda 1 in Chronic Hepatitis C. Journal of Interferon & Cytokine Research 30:8, 591-595
CrossRef194
Valerianna K. Amorosa. (2010) New Frontiers of HCV Therapy in HIV/HCV Co-infection. Current HIV/AIDS Reports 7:3, 117-126
CrossRef195
Alexander J. Thompson, Andrew J. Muir, Mark S. Sulkowski, Dongliang Ge, Jacques Fellay, Kevin V. Shianna, Thomas Urban, Nezam H. Afdhal, Ira M. Jacobson, Rafael Esteban, Fred Poordad, Eric J. Lawitz, Jonathan McCone, Mitchell L. Shiffman, Greg W. Galler, William M. Lee, Robert Reindollar, John W. King, Paul Y. Kwo, Reem H. Ghalib, Bradley Freilich, Lisa M. Nyberg, Stefan Zeuzem, Thierry Poynard, David M. Vock, Karen S. Pieper, Keyur Patel, Hans L. Tillmann, Stephanie Noviello, Kenneth Koury, Lisa D. Pedicone, Clifford A. Brass, Janice K. Albrecht, David B. Goldstein, John G. McHutchison. (2010) Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus. Gastroenterology 139:1, 120-129.e18
CrossRef196
Jenny Nilsson, Ola Weiland. (2010) Effect of control selection on sustained viral response rates in genotype 2/3 HCV mono-infected versus HIV/HCV co-infected patients. Scandinavian Journal of Infectious Diseases 42:6-7, 533-539
CrossRef197
Stefan Zeuzem, Fred Poordad. (2010) Pegylated-interferon plus ribavirin therapy in the treatment of CHC: individualization of treatment duration according to on-treatment virologic response. Current Medical Research and Opinion 26:7, 1733-1743
CrossRef198
F. F. POORDAD. (2010) Review article: the role of rapid virological response in determining treatment duration for chronic hepatitis C. Alimentary Pharmacology & Therapeutics 31:12, 1251-1267
CrossRef199
Kathleen T Berg, Bruce Nelson, Andrew R Harrison, Linda K McLoon, Michael S Lee. (2010) Pegylated Interferon Alpha-Associated Optic Neuropathy. Journal of Neuro-Ophthalmology 30:2, 117-122
CrossRef200
T.J.S. Cross, A. Quaglia, J. Nolan, S. Hughes, P.M. Harrison. (2010) Do steatosis and steatohepatitis impact on sustained virological response (SVR) rates in patients receiving pegylated interferon and ribavirin for chronic hepatitis C infection?. Journal of Medical Virology 82:6, 958-964
CrossRef201
Christophe Lallemand, Jean-Francois Meritet, Brigitte Blanchard, Pierre Lebon, Michael G. Tovey. (2010) One-step assay for quantification of neutralizing antibodies to biopharmaceuticals. Journal of Immunological Methods 356:1-2, 18-28
CrossRef202
Tahany Awad, Kristian Thorlund, Goran Hauser, Davor Stimac, Mahasen Mabrouk, Christian Gluud. (2010) Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: Systematic review of randomized trials. Hepatology 51:4, 1176-1184
CrossRef203
Frank Bennett, Yuhua Huang, Siska Hendrata, Raymond Lovey, Stephane L. Bogen, Weidong Pan, Zhuyan Guo, Andrew Prongay, Kevin X. Chen, Ashok Arasappan, Srikanth Venkatraman, Francisco Velazquez, Latha Nair, Mousumi Sannigrahi, Xiao Tong, John Pichardo, Kuo-Chi Cheng, Viyyoor M. Girijavallabhan, Anil K. Saksena, F. George Njoroge. (2010) The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir®: A change in direction in the search for a second generation HCV NS3 protease inhibitor. Bioorganic & Medicinal Chemistry Letters 20:8, 2617-2621
CrossRef204
Eva Van den Eynde, Juan Manuel Tiraboschi, Cristina Tural, Ricard Solà, José Antonio Mira, Daniel Podzamczer, Antoni Jou, Nuria Cañete, Juan Antonio Pineda, Albert Pahissa, Manuel Crespo. (2010) Ability of treatment week 12 viral response to predict long-term outcome in genotype 1 hepatitis C virus/HIV coinfected patients. AIDS 24:7, 975-982
CrossRef205
Bertram Bengsch, Robert Thimme. (2010) Ribavirin ante portas: Uptake transporters into hepatocytes dissected. Journal of Hepatology 52:4, 469-471
CrossRef206
Jacques Fellay, Alexander J. Thompson, Dongliang Ge, Curtis E. Gumbs, Thomas J. Urban, Kevin V. Shianna, Latasha D. Little, Ping Qiu, Arthur H. Bertelsen, Mark Watson, Amelia Warner, Andrew J. Muir, Clifford Brass, Janice Albrecht, Mark Sulkowski, John G. McHutchison, David B. Goldstein. (2010) ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature 464:7287, 405-408
CrossRef207
Alajos Pár. (2010) Hepatitis C-vírus- (HCV-) infekció – 20 év után. Orvosi Hetilap 151:12, 485-493
CrossRef208
Kara L Norman, Peter Sarnow. (2010) Hepatitis C virus' Achilles' heel – dependence on liver-specific microRNA miR-122. Cell Research 20:3, 247-249
CrossRef209
Ferenc Szalay. (2010) Peginterferon-alfa-2b vagy -alfa-2a és ribavirin kombinált kezelés hepatitis C-infekcióban. Orvosi Hetilap 151:7, 271-273
CrossRef210
Mitchell L. Shiffman. (2010) Treatment of Hepatitis C in 2011: What Can We Expect?. Current Gastroenterology Reports 12:1, 70-75
CrossRef211
T. Witthoeft, D. Hueppe, C. John, J. Goelz, R. Heyne, B. Moeller, G. Teuber, S. Wollschlaeger, A. Baumgarten, K.-G. Simon, G. Moog, N. Dikopoulos, S. Mauss. (2010) Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: The PRACTICE Study. Journal of Viral Hepatitis
CrossRef212
Alexander J. Thompson, Jacques Fellay, John G. McHutchison. (2010) How the Human Genome Can Predict Response to Hepatitis C Therapy. Current Hepatitis Reports 9:1, 1-8
CrossRef213
AnnMarie Liapakis, Ira Jacobson. (2010) Research Highlights: Pharmacogenetics of hepatitis C therapy. Pharmacogenomics 11:2, 135-139
CrossRef214
Chun-Hao Chen, Ming-Lung Yu. (2010) Evolution of Interferon-Based Therapy for Chronic Hepatitis C. Hepatitis Research and Treatment 2010, 1-12
CrossRef215
Graham R. Foster. (2010) Pegylated Interferons for the Treatment of Chronic Hepatitis C. Drugs 70:2, 147-165
CrossRef216
Antonio Craxì. (2010) PEG IFN alfa-2a vs. alfa-2b: And the winner is …?. Journal of Hepatology 52:1, 133-135
CrossRef217
Maria Grazia Rumi, Alessio Aghemo, Gian Maria Prati, Roberta D'Ambrosio, Maria Francesca Donato, Roberta Soffredini, Ersilio Del Ninno, Antonio Russo, Massimo Colombo. (2010) Randomized Study of Peginterferon-α2a Plus Ribavirin vs Peginterferon-α2b Plus Ribavirin in Chronic Hepatitis C. Gastroenterology 138:1, 108-115
CrossRef218
Stefan Zeuzem. (2010) Do Differences in Pegylation of Interferon Alfa Matter?. Gastroenterology 138:1, 34-36
CrossRef219
Douglas F. Meyer, Hillel Tobias, Albert D. Min, Arathi Rajendra, Ivanka Zic, Edward Brettholz, David J. Clain, Franklin Klion, David Bernstein, Henry C. Bodenheimer. (2010) Retreatment of Patients Nonresponsive to Pegylated Interferon and Ribavirin with Daily High-Dose Consensus Interferon. Hepatitis Research and Treatment 2010, 1-5
CrossRef220
Antonio Ascione, Massimo De Luca, Maria Teresa Tartaglione, Filippo Lampasi, Giovan Giuseppe Di Costanzo, Alfonso Galeota Lanza, Francesco Paolo Picciotto, Giuseppina Marino–Marsilia, Luca Fontanella, Gioacchino Leandro. (2010) Peginterferon Alfa-2a Plus Ribavirin Is More Effective Than Peginterferon Alfa-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus Infection. Gastroenterology 138:1, 116-122
CrossRef221
Robert M. Friedman, Sara Contente. (2010) Treatment of Hepatitis C Infections with Interferon: A Historical Perspective. Hepatitis Research and Treatment 2010, 1-4
CrossRef222
C. Kent Martin, Jeffrey E. Hostetter, John J. Hagan. (2010) New Opportunities for the Management and Therapy of Hepatitis C in Correctional Settings. American Journal of Public Health 100:1, 13-17
CrossRef223
Tetsuo TAKEHARA. (2010) Antiviral Therapy for Chronic Hepatitis C: Current Status and Perspectives. YAKUGAKU ZASSHI 130:2, 143-156
CrossRef224
Julian Schulze zur Wiesch, Ansgar W. Lohse, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein. (2009) Results of the IDEAL trial: “Mirror, mirror on the wall … Which's the fairest peg-interferon of them all?”. Hepatology 50:6, 2034-2037
CrossRef225
Anna C. Need, David B. Goldstein. (2009) Next generation disparities in human genomics: concerns and remedies. Trends in Genetics 25:11, 489-494
CrossRef226
(2009) Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Hepatitis C. New England Journal of Medicine 361:18, 1808-1809
Full Text227
David L. Thomas, Chloe L. Thio, Maureen P. Martin, Ying Qi, Dongliang Ge, Colm O’hUigin, Judith Kidd, Kenneth Kidd, Salim I. Khakoo, Graeme Alexander, James J. Goedert, Gregory D. Kirk, Sharyne M. Donfield, Hugo R. Rosen, Leslie H. Tobler, Michael P. Busch, John G. McHutchison, David B. Goldstein, Mary Carrington. (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:7265, 798-801
CrossRef228
Alessio Aghemo, Maria Grazia Rumi, Massimo Colombo. (2009) Pegylated IFN-α2a and ribavirin in the treatment of hepatitis C. Expert Review of Anti-infective Therapy 7:8, 925-935
CrossRef229
Thomas R O'Brien. (2009) Interferon-alfa, interferon-λ and hepatitis C. Nature Genetics 41:10, 1048-1050
CrossRef230
Dongliang Ge, Jacques Fellay, Alexander J. Thompson, Jason S. Simon, Kevin V. Shianna, Thomas J. Urban, Erin L. Heinzen, Ping Qiu, Arthur H. Bertelsen, Andrew J. Muir, Mark Sulkowski, John G. McHutchison, David B. Goldstein. (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:7262, 399-401
CrossRef231
Shawn P. Iadonato, Michael G. Katze. (2009) Genomics: Hepatitis C virus gets personal. Nature 461:7262, 357-358
CrossRef232
Noritomo Shimada, Kai Yoshizawa, Makiko Ika, Akira Dobashi, Naoto Nomura, Gotaro Toda, Akihito Tsubota, Hiroshi Abe, Yoshio Aizawa. (2009) Response-guided therapy in Japanese chronic hepatitis C patients infected with genotype 1b and high viral load. Kanzo 50:12, 687-702
CrossRef
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