Direct-acting antivirals for chronic hepatitis C

doi:10.1002/14651858.CD012143.pub2

Meta-Analysis

. 2017 Jun 6;6(6):CD012143.

doi: 10.1002/14651858.CD012143.pub2.

Direct-acting antivirals for chronic hepatitis C

Janus C Jakobsen¹, Emil Eik Nielsen, Joshua Feinberg, Kiran Kumar Katakam, Kristina Fobian, Goran Hauser, Goran Poropat, Snezana Djurisic, Karl Heinz Weiss, Milica Bjelakovic, Goran Bjelakovic, Sarah Louise Klingenberg, Jian Ping Liu, Dimitrinka Nikolova, Ronald L Koretz, Christian Gluud

Affiliations

Affiliation

¹ The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Sjælland, Denmark, DK-2100.

PMID: 28585310
PMCID: PMC6484383
DOI: 10.1002/14651858.CD012143.pub2

Meta-Analysis

Direct-acting antivirals for chronic hepatitis C

Janus C Jakobsen et al. Cochrane Database Syst Rev. 2017.

. 2017 Jun 6;6(6):CD012143.

doi: 10.1002/14651858.CD012143.pub2.

Authors

Affiliation

¹ The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Sjælland, Denmark, DK-2100.

PMID: 28585310
PMCID: PMC6484383
DOI: 10.1002/14651858.CD012143.pub2

Update in

Direct-acting antivirals for chronic hepatitis C.
Jakobsen JC, Nielsen EE, Feinberg J, Katakam KK, Fobian K, Hauser G, Poropat G, Djurisic S, Weiss KH, Bjelakovic M, Bjelakovic G, Klingenberg SL, Liu JP, Nikolova D, Koretz RL, Gluud C. Jakobsen JC, et al. Cochrane Database Syst Rev. 2017 Sep 18;9(9):CD012143. doi: 10.1002/14651858.CD012143.pub3. Cochrane Database Syst Rev. 2017. PMID: 28922704 Free PMC article.

Abstract

Background: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). However, it is still questionable if eradication of hepatitis C virus in the blood eliminates hepatitis C in the body, and improves survival and leads to fewer complications.

Objectives: To assess the benefits and harms of DAAs in people with chronic HCV.

Search methods: We searched for all published and unpublished trials in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, LILACS, and BIOSIS; the Chinese Biomedical Literature Database (CBM), China Network Knowledge Information (CNKI), the Chinese Science Journal Database (VIP), Google Scholar, The Turning Research into Practice (TRIP) Database, ClinicalTrials.gov, European Medicines Agency (EMA) (www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp), the Food and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016.

Selection criteria: Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic HCV. We included trials irrespective of publication type, publication status, and language.

Data collection and analysis: We used standard methodological procedures expected by Cochrane. Our primary outcomes were hepatitis C-related morbidity, serious adverse events, and quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and sustained virological response. We systematically assessed risks of bias, performed Trial Sequential Analysis, and followed an eight-step procedure to assess thresholds for statistical and clinical significance. The overall quality of the evidence was evaluated using GRADE.

Main results: We included a total of 138 trials randomising a total of 25,232 participants. The 138 trials assessed the effects of 51 different DAAs. Of these, 128 trials employed matching placebo in the control group. All included trials were at high risk of bias. Eighty-four trials involved DAAs on the market or under development (13,466 participants). Fifty-seven trials administered withdrawn or discontinued DAAs. Trial participants were treatment-naive (95 trials), treatment-experienced (17 trials), or both treatment-naive and treatment-experienced (24 trials). The HCV genotypes were genotype 1 (119 trials), genotype 2 (eight trials), genotype 3 (six trials), genotype 4 (nine trials), and genotype 6 (one trial). We identified two ongoing trials.Meta-analysis of the effects of all DAAs on the market or under development showed no evidence of a difference when assessing hepatitis C-related morbidity or all-cause mortality (OR 3.72, 95% CI 0.53 to 26.18, P = 0.19, I² = 0%, 2,996 participants, 11 trials, very low-quality evidence). As there were no data on hepatitis C-related morbidity and very few data on mortality (DAA 15/2377 (0.63%) versus control 1/617 (0.16%)), it was not possible to perform Trial Sequential Analysis on hepatitis C-related morbidity or all-cause mortality.Meta-analysis of all DAAs on the market or under development showed no evidence of a difference when assessing serious adverse events (OR 0.93, 95% CI 0.75 to 1.15, P = 0.52, I² = 0%, 15,817 participants, 43 trials, very low-quality evidence). The Trial Sequential Analysis showed that the cumulative Z-score crossed the trial sequential boundary for futility, showing that there was sufficient information to rule out that DAAs compared with placebo reduced the relative risk of a serious adverse event by 20%. The only DAA that showed a significant difference on risk of serious adverse events when meta-analysed separately was simeprevir (OR 0.62, 95% CI 0.45 to 0.86). However, Trial Sequential Analysis showed that there was not enough information to confirm or reject a relative risk reduction of 20%, and when one trial with an extreme result was excluded, then the meta-analysis result showed no evidence of a difference.DAAs on the market or under development seemed to reduce the risk of no sustained virological response (RR 0.44, 95% CI 0.37 to 0.52, P < 0.00001, I² = 77%, 6886 participants, 32 trials, very low-quality evidence) and Trial Sequential Analysis confirmed this meta-analysis result.Only 1/84 trials on the market or under development assessed the effects of DAAs on health-related quality of life (SF-36 mental score and SF-36 physical score).Withdrawn or discontinued DAAs had no evidence of a difference when assessing hepatitis C-related morbidity and all-cause mortality (OR 0.64, 95% CI 0.23 to 1.79, P = 0.40, I² = 0%; 5 trials, very low-quality evidence). However, withdrawn DAAs seemed to increase the risk of serious adverse events (OR 1.45, 95% CI 1.22 to 1.73, P = 0.001, I² = 0%, 29 trials, very low-quality evidence), and Trial Sequential Analysis confirmed this meta-analysis result.Most of all outcome results were short-term results; therefore, we could neither confirm nor reject any long-term effects of DAAs. None of the 138 trials provided useful data to assess the effects of DAAs on the remaining secondary outcomes (ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, and hepatocellular carcinoma).

Authors' conclusions: Overall, DAAs on the market or under development do not seem to have any effects on risk of serious adverse events. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses, we could neither confirm nor reject that DAAs had any clinical effects. DAAs seemed to reduce the risk of no sustained virological response. The clinical relevance of the effects of DAAs on no sustained virological response is questionable, as it is a non-validated surrogate outcome. All trials and outcome results were at high risk of bias, so our results presumably overestimate benefit and underestimate harm. The quality of the evidence was very low.

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Conflict of interest statement

JCJ: none declared. EN: none declared. JF: none declared. KK: none declared. KF: none declared. GH: none declared. GP: none declared. SD: none declared. KW: none declared. MB: none declared. GB: none declared. SK: none declared. JP: none declared. DN: none declared. RK: none declared. CG: none declared.

Figures

**Figure 3**
Trial Sequential Analysis of the effects of direct‐acting antivirals on the market or under development versus placebo or no intervention on risk of serious adverse events. The analysis was based on a proportion in the control group (Pc) of 4.5%, a relative risk reduction (RRR) of 20%, and alfa of 2.5%, a beta of 20%, and a diversity of 0%. The cumulative Z‐curve enters the futility area after the randomisation of about 6000 participants.

**Figure 4**
Trial Sequential Analysis of the effects of simeprevir versus placebo or no intervention on risk of serious adverse events. The analysis was based on a proportion in the control group (Pc) of 8.4%, a relative risk reduction (RRR) of 20%, and alfa of 2.5%, a beta of 20%, and a diversity of 0%. The cumulative Z‐curve crosses the naive type I error level of 5%, but does not cross the trial monitoring boundary for benefit.

**Figure 5**
Trial Sequential Analysis of the effects of direct‐acting antivirals on the market or under development versus placebo or no intervention on risk of no sustained virological response. The analysis was based on a proportion in the control group (Pc) of 60.2%, a RRR of 20%, and alfa of 2.5%, a beta of 20%, and a diversity of 83%. After randomisation of about 1000 participants the cumulative Z‐curve crosses the trial sequential monitoring boundary for benefit.

**Figure 6**
Trial Sequential Analysis of the effects of withdrawn direct‐acting antivirals versus placebo or no intervention on risk of serious adverse events. The analysis was based on a proportion in the control group (Pc) of 7.5%, a RRR of 20%, and alfa of 2.5%, a beta of 20%, and a diversity of 0%. After randomisation of about 5000 participants, the cumulative Z‐curve crosses the trial sequential monitoring boundary for harm.

**Analysis 1.1**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 1 Hepatitis C‐related morbidity or all‐cause mortality.

**Analysis 1.2**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 2 Hepatitis C‐related morbidity or all‐cause mortality ‐ bias risk.

**Analysis 1.3**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 3 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to type of DAA.

**Analysis 1.4**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 4 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to group of DAA.

**Analysis 1.5**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 5 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to HIV‐infection.

**Analysis 1.6**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 6 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to comorbidity.

**Analysis 1.7**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 7 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to viral genotype.

**Analysis 1.8**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 8 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to human genotype (IL28b).

**Analysis 1.9**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 9 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to Asian‐region.

**Analysis 1.10**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 10 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to specific ethnicities.

**Analysis 1.11**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 11 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to reaching planned sample size.

**Analysis 1.12**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 12 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to prior treatment.

**Analysis 1.13**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 13 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to interferon.

**Analysis 1.14**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 14 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to ribavirin.

**Analysis 1.15**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 15 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to chronic kidney disease.

**Analysis 1.16**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 16 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to cryoglobulinaemia.

**Analysis 1.17**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 17 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to DAA group as co‐intervention.

**Analysis 1.18**
Comparison 1 DAA on or on the way to the market versus placebo/no intervention, Outcome 18 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to median dose.

**Analysis 2.1**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 1 Serious adverse events.

**Analysis 2.2**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 2 Serious adverse events ‐ bias risk.

**Analysis 2.3**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 3 Serious adverse events ‐ according to type of DAA.

**Analysis 2.4**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 4 Serious adverse events ‐ according to group of DAA.

**Analysis 2.5**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 5 Serious adverse events ‐ according to HIV‐infection.

**Analysis 2.6**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 6 Serious adverse events ‐ according to comorbidity.

**Analysis 2.7**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 7 Serious adverse events ‐ according to viral genotype.

**Analysis 2.8**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 8 Serious adverse events ‐ according to human genotype (IL28b).

**Analysis 2.9**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 9 Serious adverse events ‐ according to Asian‐region.

**Analysis 2.10**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 10 Serious adverse events ‐ according to specific ethnicities.

**Analysis 2.11**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 11 Serious adverse events ‐ according to reaching planned sample size.

**Analysis 2.12**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 12 Serious adverse events ‐ according to prior treatment.

**Analysis 2.13**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 13 Serious adverse events ‐ according to interferon.

**Analysis 2.14**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 14 Serious adverse events ‐ according to ribavirin.

**Analysis 2.15**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 15 Serious adverse events ‐ according to chronic kidney disease.

**Analysis 2.16**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 16 Serious adverse events ‐ according to cryoglobulinaemia.

**Analysis 2.17**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 17 Serious adverse events ‐ according to DAA group as co‐intervention.

**Analysis 2.18**
Comparison 2 DAA on or on the way to the market versus placebo/no intervention, Outcome 18 Serious adverse events ‐ according to median dose.

**Analysis 3.1**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 1 Without sustained virological response.

**Analysis 3.2**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 2 Without sustained virological response ‐ bias risk.

**Analysis 3.3**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 3 Without sustained virological response ‐ according to type of DAA.

**Analysis 3.4**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 4 Without sustained virological response ‐ according to group of DAA.

**Analysis 3.5**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 5 Without sustained virological response ‐ according to HIV‐infection.

**Analysis 3.6**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 6 Without sustained virological response ‐ according to comorbidity.

**Analysis 3.7**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 7 Without sustained virological response ‐ according to viral genotype.

**Analysis 3.8**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 8 Without sustained virological response ‐ according to human genotype (IL28b).

**Analysis 3.9**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 9 Without sustained virological response ‐ according to Asian‐region.

**Analysis 3.10**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 10 Without sustained virological response ‐ according to specific ethnicities.

**Analysis 3.11**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 11 Without sustained virological response ‐ according to reaching planned sample size.

**Analysis 3.12**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 12 Without sustained virological response ‐ according to prior treatment.

**Analysis 3.13**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 13 Without sustained virological response ‐ according to interferon.

**Analysis 3.14**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 14 Without sustained virological response ‐ according to ribavirin.

**Analysis 3.15**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 15 Without sustained virological response ‐ according to chronic kidney disease.

**Analysis 3.16**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 16 Without sustained virological response ‐ according to cryoglobulinaemia.

**Analysis 3.17**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 17 Without sustained virological response ‐ according to DAA group as co‐intervention.

**Analysis 3.18**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 18 Without sustained virological response ‐ 'Best‐worst case' scenario.

**Analysis 3.19**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 19 Without sustained virological response ‐ 'Worst‐best case' scenario.

**Analysis 3.20**
Comparison 3 DAA on or on the way to the market versus placebo/no intervention, Outcome 20 Without sustained virological response ‐ according to median dose.

**Analysis 4.1**
Comparison 4 Danoprevir versus placebo/no intervention, Outcome 1 Hepatitis C‐related morbidity or all‐cause mortality.

**Analysis 4.2**
Comparison 4 Danoprevir versus placebo/no intervention, Outcome 2 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to dose.

**Analysis 4.3**
Comparison 4 Danoprevir versus placebo/no intervention, Outcome 3 Serious adverse events.

**Analysis 4.4**
Comparison 4 Danoprevir versus placebo/no intervention, Outcome 4 Serious adverse events ‐ according to median dose.

**Analysis 4.5**
Comparison 4 Danoprevir versus placebo/no intervention, Outcome 5 Without sustained virological response.

**Analysis 4.6**
Comparison 4 Danoprevir versus placebo/no intervention, Outcome 6 Without sustained virological response ‐ according to median dose.

**Analysis 5.1**
Comparison 5 All DAA versus placebo/no intervention/other medical intervention, Outcome 1 Hepatitis C‐related morbidity or all‐cause mortality.

**Analysis 6.1**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 1 Serious adverse events.

**Analysis 6.2**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 2 Serious adverse events ‐ bias risk.

**Analysis 6.3**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 3 Serious adverse events ‐ according to type of DAA.

**Analysis 6.4**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 4 Serious adverse events ‐ according to group of DAA.

**Analysis 6.5**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 5 Serious adverse events ‐ according to HIV‐infection.

**Analysis 6.6**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 6 Serious adverse events ‐ according to comorbidity.

**Analysis 6.7**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 7 Serious adverse events ‐ according to viral genotype.

**Analysis 6.8**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 8 Serious adverse events ‐ according to human genotype (IL28b).

**Analysis 6.9**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 9 Serious adverse events ‐ according to Asian‐region.

**Analysis 6.10**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 10 Serious adverse events ‐ according to specific ethnicities.

**Analysis 6.12**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 12 Serious adverse events ‐ according to prior treatment.

**Analysis 6.13**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 13 Serious adverse events ‐ according to interferon.

**Analysis 6.14**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 14 Serious adverse events ‐ according to ribavirin.

**Analysis 6.15**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 15 Serious adverse events ‐ according to chronic kidney disease.

**Analysis 6.16**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 16 Serious adverse events ‐ according to cryoglobulinaemia.

**Analysis 6.17**
Comparison 6 All DAA versus placebo/no intervention/other medical intervention, Outcome 17 Serious adverse events ‐ according to DAA group as co‐intervention.

**Analysis 7.1**
Comparison 7 All DAA versus placebo/no intervention/other medical intervention, Outcome 1 Without sustained virological response.

**Analysis 8.1**
Comparison 8 All DAA versus placebo/no intervention/other medical intervention, Outcome 1 SF‐36 physical score.

**Analysis 8.2**
Comparison 8 All DAA versus placebo/no intervention/other medical intervention, Outcome 2 SF‐36 mental score.

**Analysis 9.1**
Comparison 9 Daclatasvir versus placebo/no intervention, Outcome 1 Hepatitis C‐related morbidity or all‐cause mortality.

**Analysis 9.2**
Comparison 9 Daclatasvir versus placebo/no intervention, Outcome 2 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to dose.

**Analysis 9.3**
Comparison 9 Daclatasvir versus placebo/no intervention, Outcome 3 Serious adverse events.

**Analysis 9.4**
Comparison 9 Daclatasvir versus placebo/no intervention, Outcome 4 Serious adverse events ‐ according to median dose.

**Analysis 9.5**
Comparison 9 Daclatasvir versus placebo/no intervention, Outcome 5 Without sustained virological response.

**Analysis 9.6**
Comparison 9 Daclatasvir versus placebo/no intervention, Outcome 6 Without sustained virological response ‐ according to median dose.

**Analysis 10.1**
Comparison 10 Simeprevir versus placebo/no intervention, Outcome 1 Hepatitis C‐related morbidity or all‐cause mortality.

**Analysis 10.2**
Comparison 10 Simeprevir versus placebo/no intervention, Outcome 2 Hepatitis C‐related morbidity or all‐cause mortality ‐ according to dose.

**Analysis 10.3**
Comparison 10 Simeprevir versus placebo/no intervention, Outcome 3 Serious adverse events.

**Analysis 10.4**
Comparison 10 Simeprevir versus placebo/no intervention, Outcome 4 Serious adverse events ‐ according to median dose.

**Analysis 10.5**
Comparison 10 Simeprevir versus placebo/no intervention, Outcome 5 Without sustained virological response.

**Analysis 10.6**
Comparison 10 Simeprevir versus placebo/no intervention, Outcome 6 Without sustained virological response ‐ according to median dose.

**Analysis 12.1**
Comparison 12 All DAA versus placebo/no intervention, Outcome 1 Without significant reductions in ALT/AST serum levels.

**Analysis 12.2**
Comparison 12 All DAA versus placebo/no intervention, Outcome 2 Without significant reductions in ALT/AST serum levels ‐ according to DAA status.

**Analysis 12.3**
Comparison 12 All DAA versus placebo/no intervention, Outcome 3 Without significant reductions in ALT/AST serum levels ‐ according to type of drug.

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Comment in

Response to the Cochrane systematic review on DAA-based treatment of chronic hepatitis C.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. J Hepatol. 2017 Oct;67(4):663-664. doi: 10.1016/j.jhep.2017.06.022. Epub 2017 Jun 29. J Hepatol. 2017. PMID: 28669753 No abstract available.
New hepatitis C antiviral treatments eliminate the virus.
Doyle JS, Thompson AJ, Higgs P, Stoove M, Dietze PM, Hellard ME. Doyle JS, et al. Lancet. 2017 Jul 22;390(10092):358-359. doi: 10.1016/S0140-6736(17)31817-2. Epub 2017 Jul 7. Lancet. 2017. PMID: 28689663 No abstract available.
What is the impact of treatment for hepatitis C virus infection?
Wiktor SZ, Scott JD. Wiktor SZ, et al. Lancet. 2017 Jul 8;390(10090):107-109. doi: 10.1016/S0140-6736(17)31762-2. Lancet. 2017. PMID: 28699578 No abstract available.
IDSA/AASLD Response to Cochrane Review on Direct-Acting Antivirals for Hepatitis C.
Powderly WG, Naggie S, Kim AY, Vargas HE, Chung RT, Lok AS. Powderly WG, et al. Clin Infect Dis. 2017 Nov 13;65(11):1773-1775. doi: 10.1093/cid/cix620. Clin Infect Dis. 2017. PMID: 29020156 No abstract available.

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References

References to studies included in this review

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3. Bisceglie AM, Dusheiko GM, Muir AJ, Zeuzem S, Marcellin P, Bzowej NH. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Gastroenterology 2011;140(5 Suppl 1):S908.
4. Dusheiko GM, Bengtsson L, Adda N, Kauffman R, Jacobson IM. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 Advance study. Gut 2011;60(Suppl 2):A32‐3.
5. Everson G, Dusheiko G, Pol S, Nelson D, Muir A, Andreone P, et al. Telaprevir in combination with peginterferon alfa‐2a and ribavirin increased sustained virologic response in genotype 1 chronic HCV and allowed for shorter treatment duration in treatment‐naive and prior relapser patients. American Journal of Gastroenterology 2011;106(2S):S113‐4.
6. Jacobson IM, McHutchison JG, Dusheiko G, Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. New England Journal of Medicine 2011;364(25):2405‐16. - PubMed
7. Jacobson IM, McHutchison JG, Dusheiko GM, Bisceglie AM, Reddy R, Bzowej NH, et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 ADVANCE study. Hepatology 2010;52(Suppl S1):427A.
8. Kieffer TL, Bartels DJ, Sullivan J, Adiwijaya BS, Zhang EZ, Tigges A, et al. Clinical virology results from telaprevir phase 3 study ADVANCE. Hepatology 2010;52(Suppl S1):879A.
9. Luo D, Zeuzem S, Jacobson IM, Sherman K, Adda N, Wright CI, et al. High concordance between SVR12 and SVR24 in patients receiving telaprevir plus peginterferon and ribavirin in three phase iii clinical trials: Advance, Illuminate and Realize. Journal of Hepatology 2012;56(Suppl 2):S446‐7.
10. Marcellin P, Jacobson IM, Zeuzem S, Bzowej N, Muir AJ, Dusheiko G. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Journal of Hepatology 2011;54(Suppl 1):S183‐4.
11. Rizzetto M, Andreone P, Colombo M, Scuteri A, Ciancio A, Smedile A, et al. ADVANCE study: final results of the phase III trial with telaprevir in combination with PEG‐IFN and RBV in treatment‐naive genotype 1 HCV. Digestive and Liver Disease 2011;43(Suppl 2):S69.
12. Sulkowski MS, Reddy R, Afdhal NH, Bisceglie AM, Zeuzem S, Poordad F, et al. Anemia had no effect on efficacy outcomes in treatment‐naive patients who received telaprevir‐based regimen in the Advance and Illuminate phase 3 studies. Journal of Hepatology 2011;54(Suppl 1):S195.
1. Brogan AJ, Talbird SE, Thompson JR, Miller JD, Rubin J, Deniz B. Cost‐effectiveness of telaprevir combination therapy for chronic hepatitis C. PLoS ONE 2014;9(3):e90295. - PMC - PubMed
2. Curtis S, Cure S, Gavart S, Dearden L, Fleischmann J, Ouwens M, et al. The cost‐effectiveness of telaprevir (TVR) in combination with pegylated interferon‐alfa and ribavirin (PR) for the treatment of genotype 1 chronic hepatitis C patients. Journal of Hepatology2012; Vol. 56, issue Suppl 2:S434.
3. Bisceglie AM, Dusheiko GM, Muir AJ, Zeuzem S, Marcellin P, Bzowej NH. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Gastroenterology 2011;140(5 Suppl 1):S908.
4. Dusheiko GM, Bengtsson L, Adda N, Kauffman R, Jacobson IM. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 Advance study. Gut 2011;60(Suppl 2):A32‐3.
5. Everson G, Dusheiko G, Pol S, Nelson D, Muir A, Andreone P, et al. Telaprevir in combination with peginterferon alfa‐2a and ribavirin increased sustained virologic response in genotype 1 chronic HCV and allowed for shorter treatment duration in treatment‐naive and prior relapser patients. American Journal of Gastroenterology 2011;106(2S):S113‐4.
6. Jacobson IM, McHutchison JG, Dusheiko G, Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. New England Journal of Medicine 2011;364(25):2405‐16. - PubMed
7. Jacobson IM, McHutchison JG, Dusheiko GM, Bisceglie AM, Reddy R, Bzowej NH, et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 ADVANCE study. Hepatology 2010;52(Suppl S1):427A.
8. Kieffer TL, Bartels DJ, Sullivan J, Adiwijaya BS, Zhang EZ, Tigges A, et al. Clinical virology results from telaprevir phase 3 study ADVANCE. Hepatology 2010;52(Suppl S1):879A.
9. Luo D, Zeuzem S, Jacobson IM, Sherman K, Adda N, Wright CI, et al. High concordance between SVR12 and SVR24 in patients receiving telaprevir plus peginterferon and ribavirin in three phase iii clinical trials: Advance, Illuminate and Realize. Journal of Hepatology 2012;56(Suppl 2):S446‐7.
10. Marcellin P, Jacobson IM, Zeuzem S, Bzowej N, Muir AJ, Dusheiko G. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Journal of Hepatology 2011;54(Suppl 1):S183‐4.
11. Rizzetto M, Andreone P, Colombo M, Scuteri A, Ciancio A, Smedile A, et al. ADVANCE study: final results of the phase III trial with telaprevir in combination with PEG‐IFN and RBV in treatment‐naive genotype 1 HCV. Digestive and Liver Disease 2011;43(Suppl 2):S69.
12. Sulkowski MS, Reddy R, Afdhal NH, Bisceglie AM, Zeuzem S, Poordad F, et al. Anemia had no effect on efficacy outcomes in treatment‐naive patients who received telaprevir‐based regimen in the Advance and Illuminate phase 3 studies. Journal of Hepatology 2011;54(Suppl 1):S195.
1. Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed
2. Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.
3. Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.
1. Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed
2. Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.
3. Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.
1. Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed
2. Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.
3. Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.

References to studies excluded from this review

1. Asselah T, Hassanein TI, Qaqish RB, Feld JJ, Hezode C, Zeuzem S, et al. Efficacy and safety of ombitasvir/paritaprevir/ritonavir co‐administered with ribavirin in adults with genotype 4 chronic hepatitis C infection and cirrhosis (AGATE‐I). Hepatology 2015;62(Suppl S1):563A‐4A. - PubMed
1. Wyles D, Ruane P, Sulkowski M, Dieterich D, Luetkemeyer A, Morgan T, et al. Daclatasvir in combination with sofosbuvir for HIV/HCV coinfection: ALLY‐2 study. Topics in Antiviral Medicine2015; Vol. 23, issue e‐1:62.
1. Jensen DM, Brunda M, Elston R, Gane EJ, George J, Glavini K, et al. Interferon‐free regimen containing setrobuvir (STV) in combination with ritonavir‐boosted danoprevir (DNVr) and ribavirin (R) with or without mericitabine (MCB) in HCV genotype (G)1 treatment‐naive patients: interim SVR4 results from the ANNAPURNA study. Hepatology 2013;58(S1):741A.
1. APRICOT Study Group. APRICOT Study evaluated. Surprisingly high virologic response in HIV‐HCV coinfection. MMW Fortschritte der Medizin 2004;146(Spec No 1):74‐5. - PubMed
1. Kowdley KV, Lawitz E, Crespo I, Hassanein T, Davis MN, Demicco M, et al. Sofosbuvir with pegylated interferon alfa‐2a and ribavirin for treatment‐naive patients with hepatitis C genotype‐1 infection (ATOMIC): an open‐label, randomised, multicentre phase 2 trial. Lancet 2013;381(9883):2100‐7. - PubMed

References to ongoing studies

1. Izumi N, LaTaillade M, Chayama K, Toyota J, Mochida S, Kawada N, et al. First report of peginterferon lambda/ribavirin in combination with either daclatasvir or asunaprevir in HCV genotype 1 Japanese subjects: early sustained virologic response (SVR4) results from the D‐LITE Japanese sub‐study. Hepatology 2012;56(S1):310A.
1. Lawitz E, Rodriguez‐Torres M, Nguyen T, Sheikh A, Tobias H, Galati J, et al. A phase II study of samatasvir (IDX719) in combination with simeprevir and ribavirin in treatment‐naive HCV‐infected subjects with genotypes 1B and 4 (helix‐1 study). Journal of Hepatology 2014;60(1 Suppl S):S495‐6.

Additional references

1. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. New England Journal of Medicine 2014;370(20):1889‐98. - PubMed
1. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. New England Journal of Medicine 2011;364(13):1207‐17. - PMC - PubMed
1. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011;64(4):401‐6. [PUBMED: 21208779] - PubMed
1. Basile N. Sofosbuvir‐ribavirin duo for chronic hepatitis C. Connecticut Medicine 2014;78(6):355‐6. - PMC - PubMed
1. Berger CT, Kim AY. IL28B polymorphisms as a pre‐treatment predictor of response to HCV treatment. Infectious Disease Clinics of North America 2012;26(4):863‐77. [DOI: 10.1016/j.idc.2012.08.010] - DOI - PMC - PubMed

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[2] Brogan AJ, Talbird SE, Thompson JR, Miller JD, Rubin J, Deniz B. Cost‐effectiveness of telaprevir combination therapy for chronic hepatitis C. PLoS ONE 2014;9(3):e90295. - PMC - PubMed

[3] Curtis S, Cure S, Gavart S, Dearden L, Fleischmann J, Ouwens M, et al. The cost‐effectiveness of telaprevir (TVR) in combination with pegylated interferon‐alfa and ribavirin (PR) for the treatment of genotype 1 chronic hepatitis C patients. Journal of Hepatology2012; Vol. 56, issue Suppl 2:S434.

[4] Bisceglie AM, Dusheiko GM, Muir AJ, Zeuzem S, Marcellin P, Bzowej NH. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Gastroenterology 2011;140(5 Suppl 1):S908.

[5] Dusheiko GM, Bengtsson L, Adda N, Kauffman R, Jacobson IM. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 Advance study. Gut 2011;60(Suppl 2):A32‐3.

[6] Everson G, Dusheiko G, Pol S, Nelson D, Muir A, Andreone P, et al. Telaprevir in combination with peginterferon alfa‐2a and ribavirin increased sustained virologic response in genotype 1 chronic HCV and allowed for shorter treatment duration in treatment‐naive and prior relapser patients. American Journal of Gastroenterology 2011;106(2S):S113‐4.

[7] Jacobson IM, McHutchison JG, Dusheiko G, Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. New England Journal of Medicine 2011;364(25):2405‐16. - PubMed

[8] Jacobson IM, McHutchison JG, Dusheiko GM, Bisceglie AM, Reddy R, Bzowej NH, et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 ADVANCE study. Hepatology 2010;52(Suppl S1):427A.

[9] Kieffer TL, Bartels DJ, Sullivan J, Adiwijaya BS, Zhang EZ, Tigges A, et al. Clinical virology results from telaprevir phase 3 study ADVANCE. Hepatology 2010;52(Suppl S1):879A.

[10] Luo D, Zeuzem S, Jacobson IM, Sherman K, Adda N, Wright CI, et al. High concordance between SVR12 and SVR24 in patients receiving telaprevir plus peginterferon and ribavirin in three phase iii clinical trials: Advance, Illuminate and Realize. Journal of Hepatology 2012;56(Suppl 2):S446‐7.

[11] Marcellin P, Jacobson IM, Zeuzem S, Bzowej N, Muir AJ, Dusheiko G. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Journal of Hepatology 2011;54(Suppl 1):S183‐4.

[12] Rizzetto M, Andreone P, Colombo M, Scuteri A, Ciancio A, Smedile A, et al. ADVANCE study: final results of the phase III trial with telaprevir in combination with PEG‐IFN and RBV in treatment‐naive genotype 1 HCV. Digestive and Liver Disease 2011;43(Suppl 2):S69.

[13] Sulkowski MS, Reddy R, Afdhal NH, Bisceglie AM, Zeuzem S, Poordad F, et al. Anemia had no effect on efficacy outcomes in treatment‐naive patients who received telaprevir‐based regimen in the Advance and Illuminate phase 3 studies. Journal of Hepatology 2011;54(Suppl 1):S195.

[15] Brogan AJ, Talbird SE, Thompson JR, Miller JD, Rubin J, Deniz B. Cost‐effectiveness of telaprevir combination therapy for chronic hepatitis C. PLoS ONE 2014;9(3):e90295. - PMC - PubMed

[16] Curtis S, Cure S, Gavart S, Dearden L, Fleischmann J, Ouwens M, et al. The cost‐effectiveness of telaprevir (TVR) in combination with pegylated interferon‐alfa and ribavirin (PR) for the treatment of genotype 1 chronic hepatitis C patients. Journal of Hepatology2012; Vol. 56, issue Suppl 2:S434.

[17] Bisceglie AM, Dusheiko GM, Muir AJ, Zeuzem S, Marcellin P, Bzowej NH. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Gastroenterology 2011;140(5 Suppl 1):S908.

[18] Dusheiko GM, Bengtsson L, Adda N, Kauffman R, Jacobson IM. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 Advance study. Gut 2011;60(Suppl 2):A32‐3.

[19] Everson G, Dusheiko G, Pol S, Nelson D, Muir A, Andreone P, et al. Telaprevir in combination with peginterferon alfa‐2a and ribavirin increased sustained virologic response in genotype 1 chronic HCV and allowed for shorter treatment duration in treatment‐naive and prior relapser patients. American Journal of Gastroenterology 2011;106(2S):S113‐4.

[20] Jacobson IM, McHutchison JG, Dusheiko G, Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. New England Journal of Medicine 2011;364(25):2405‐16. - PubMed

[21] Jacobson IM, McHutchison JG, Dusheiko GM, Bisceglie AM, Reddy R, Bzowej NH, et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment‐naive patients: final results of phase 3 ADVANCE study. Hepatology 2010;52(Suppl S1):427A.

[22] Kieffer TL, Bartels DJ, Sullivan J, Adiwijaya BS, Zhang EZ, Tigges A, et al. Clinical virology results from telaprevir phase 3 study ADVANCE. Hepatology 2010;52(Suppl S1):879A.

[23] Luo D, Zeuzem S, Jacobson IM, Sherman K, Adda N, Wright CI, et al. High concordance between SVR12 and SVR24 in patients receiving telaprevir plus peginterferon and ribavirin in three phase iii clinical trials: Advance, Illuminate and Realize. Journal of Hepatology 2012;56(Suppl 2):S446‐7.

[24] Marcellin P, Jacobson IM, Zeuzem S, Bzowej N, Muir AJ, Dusheiko G. Telaprevir in combination with peginterferon alfa‐2a and ribavirin: analyses of pre‐defined subpopulations in the phase 3 ADVANCE trial. Journal of Hepatology 2011;54(Suppl 1):S183‐4.

[25] Rizzetto M, Andreone P, Colombo M, Scuteri A, Ciancio A, Smedile A, et al. ADVANCE study: final results of the phase III trial with telaprevir in combination with PEG‐IFN and RBV in treatment‐naive genotype 1 HCV. Digestive and Liver Disease 2011;43(Suppl 2):S69.

[26] Sulkowski MS, Reddy R, Afdhal NH, Bisceglie AM, Zeuzem S, Poordad F, et al. Anemia had no effect on efficacy outcomes in treatment‐naive patients who received telaprevir‐based regimen in the Advance and Illuminate phase 3 studies. Journal of Hepatology 2011;54(Suppl 1):S195.

[27] Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed

Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.

Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.

[28] Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed

[29] Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.

[30] Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.

[31] Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed

Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.

Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.

[32] Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed

[33] Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.

[34] Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.

[35] Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed

Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.

Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.

[36] Anderson RT, Baran RW, Erickson P, Revicki DA, Dietz B, Gooch K. Psychometric evaluation of the hepatitis C virus patient‐reported outcomes (HCV‐PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial. Quality of Life Research 2014;23(3):877‐86. - PubMed

[37] Gaultier I, Cohen DE, Bhathena A, Idler K, Larsen LM, Podsadecki T, et al. The effect of IL28B polymorphisms on virologic response to treatment with pegylated interferon alpha‐2A and ribavirin (SOC) added to ABT‐450/ritonavir (ABT‐450/R), ABT‐333, or ABT‐072. Journal of Hepatology 2011;54(Suppl 1):S523.

[38] Pilot‐Matias TJ, Tripathi RL, Dekhtyar T, Menon RM, Gaultier IA, Cohen DE, et al. Genotypic and phenotypic characterization of NS3 variants selected in HCV‐infected patients treated with ABT‐450. Journal of Hepatology 2011;54(Suppl 1):S485‐6.

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