Dataset Information

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

ABSTRACT: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis.Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ?18 years, had chronic HCV genotype 1 infection (serum HCV RNA ?2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay.Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen.Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy.CT01805882.

SUBMITTER: Kattakuzhy S

PROVIDER: S-EPMC4725378 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

Kattakuzhy Sarah S Wilson Eleanor E Sidharthan Sreetha S Sims Zayani Z McLaughlin Mary M Price Angie A Silk Rachel R Gross Chloe C Akoth Elizabeth E McManus Maryellen M Emmanuel Benjamin B Shrivastava Shikha S Tang Lydia L Nelson Amy A Teferi Gebeyehu G Chavez Jose J Lam Brian B Mo Hongmei H Osinusi Anuoluwapo A Polis Michael A MA Masur Henry H Kohli Anita A Kottilil Shyamasundaran S

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20151026 4

<h4>Background</h4>Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis.<h4> ...[more]

PMID: 26503379

Similar Datasets

Project description:ImportanceSome payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection.ObjectiveTo evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR).Design, setting, and participantsThis retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023.ExposureAlcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.Main outcomes and measuresThe primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category.ResultsAmong 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30).Conclusions and relevanceIn this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.

Project description:BACKGROUND & AIMS:The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure. METHODS:We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12. RESULTS:The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI, 95%-99%). Factors that predicted SVR12 were higher albumin (?3.5 g/dL), lower total bilirubin (?1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use. CONCLUSIONS:Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.

Dataset Information

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

Publications

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets