Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection

Bourlière, Marc; Gordon, Stuart C.; Flamm, Steven L.; Cooper, Curtis; Ramji, Alnoor; Tong, Myron J.; Ravendhran, Natarajan; Vierling, John M.; Tran, Tram T.; Pianko, Stephen; Bansal, Meena B.; Lédinghen, Victor de; Hyland, Robert H.; Stamm, Luisa M.; Dvory‐Sobol, Hadas; Svarovskaia, Evguenia S.; Zhang, Jie; Huang, K.C.; Subramanian, G. Mani; Brainard, Diana M.; McHutchison, John G.; Verna, Elizabeth C.; Buggisch, Peter; Landis, Charles; Younes, Ziad; Curry, Michael P.; Strasser, Simone I.; Schiff, Eugene R.; Reddy, K. Rajender; Manns, Michael P.; Kowdley, Kris V.; Zeuzem, Stefan

doi:10.1056/nejmoa1613512

Cited by 506 publications

(533 citation statements)

References 16 publications

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“…Especially the grade of fibrosis or cirrhosis is of utmost importance. Current therapies with DAAs are associated with high rates of SVR, generally exceeding 90% even among patients with cirrhosis or prior treatment failure [23, 24]. Therefore, one of the most interesting current questions concerns the impact of DAAs on HCC incidence.…”

Section: Discussionmentioning

confidence: 99%

Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals

et al. 2018

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Background and Aims: The aim of the study was to evaluate the risk of hepatocellular carcinoma (HCC) development after treatment with direct-acting antivirals (DAAs) and to compare HCC occurrence in these patients with that among patients treated with interferon (IFN)-based therapies. Methods: We analyzed a large cohort with chronic hepatitis C virus patients for the onset of new HCC after DAA treatment. A historical IFN-treated cohort was investigated for comparison. Results: A total of 819 patients were included in the DAA group. The median follow-up period was 263 days (0–1,001). Twenty-five patients (3.6 HCCs/100 person-years; 3.1%) were diagnosed with de novo HCC within the time of observation. No patient without cirrhosis had developed HCC. Patients with newly diagnosed HCC were mostly male, older, and treatment-experienced and had a lower 12-week sustained virologic response (SVR12) rate and higher levels of liver inflammation markers. The median time to HCC was 312 days (0–880). Investigation of the subcohort of 269 cirrhotic patients yielded an HCC rate of 8.9 HCCs/100 person-years. In this cohort, non-SVR12 was an independent risk factor for de novo HCC (HR 4.48; 95% CI 1.51–13.12; p = 0.007). Twenty-four patients (96%) with new HCC were Child-Pugh class A and 17 (68%) were diagnosed in early BCLC stage A. For the IFN-treated patients, we calculated an overall risk of HCC occurrence of 1.3/100 person-years (19 patients out of 351; 5.4%). The median time to diagnosis was 38.8 months (0–113). Conclusion: The de novo HCC rates did not differ between the DAA-treated patients and those who received IFN. Achievement of SVR is of utmost importance for HCC prevention.

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Section: Discussionmentioning

confidence: 99%

Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals

et al. 2018

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“…From October 2012 to May 2016, participants were enrolled in 10 multicenter, randomized clinical studies, including ION-1–3 (ClinicalTrials.gov identifier: NCT01701401, NCT01768286, and NCT01851330, respectively [24–26]), ASTRAL-1–3 (ClinicalTrials.gov: NCT02201940, NCT02220998, and NCT02201953, respectively [27, 28]), and POLARIS-1–4 (ClinicalTrials.gov: NCT02607735, NCT02607800, NCT02639338, and NCT02639247 [29, 30]).…”

Section: Methodsmentioning

confidence: 99%

“…In the ASTRAL-1–3 studies, a fixed-dose combination tablet of sofosbuvir/velpatasvir 400 mg/100 mg was administered for 12 weeks in patients with chronic HCV genotypes 1–6 [27, 28]. In the POLARIS studies, a fixed-dose combination tablet of sofosbuvir/velpatasvir 400 mg/100 mg was administered for 12 weeks or a fixed-dose combination tablet of sofosbuvir/velpatasvir/voxilaprevir 400 mg/100 mg/100 mg was administered for 8 or 12 weeks in patients with chronic HCV genotypes 1–6 [29, 30]. …”

Section: Methodsmentioning

confidence: 99%

Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies

Grebely

Feld

Wyles

et al. 2018

Open Forum Infectious Diseases

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BackgroundHepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST.MethodsTen phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible.ResultsAmong 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P = .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25) or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%).ConclusionSofosbuvir-based therapies are effective and safe in patients receiving OST.

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“…The fixeddose combination singletablet regimen of sofosbuvir/ velpatasvir/voxilaprevir for 12 weeks is effective against all HCV genotypes with sustained virologic response rates above 95% in patients who did not achieve sustained virologic response after a course of firstline antiviral therapy based on directacting antiviral agents. 82 Other salvage regimens, including the combination of glecaprevir/pibrentasvir, have been less well studied for retreat ment. 83 Details about retreatment are included in Appendix 1.…”

Section: 81mentioning

confidence: 99%

The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver

Shah¹,

Bilodeau

Burak

et al. 2018

CMAJ

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103

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Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection

Cited by 506 publications

References 16 publications

Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals

Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals

Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies

The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver

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