S. Hunt

Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients

BACKGROUND & AIMSnHepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75-80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens.nnnMETHODSnA decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all, and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5 years until age 70. The reference case was a treatment-naïve 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs).nnnRESULTSnTreatment of all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of

Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the ION-1, -2, and -3 clinical trials.

15,709/QALY at baseline cost of oral therapy. The ICER remained below

Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir

50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease.nnnCONCLUSIONSnTreating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials.

Sofosbuvir and ledipasvir improve patient-reported outcomes in patients co-infected with hepatitis C and human immunodeficiency virus.

Treatment with interferon (IFN) and ribavirin (RBV) significantly impairs quality of life and other patient‐reported outcomes (PROs). Patient experience with IFN‐ and RBV‐free anti‐HCV (hepatitis C virus) regimens has not been reported. We assessed PROs in patients treated with ledipasvir and sofosbuvir (LDV/SOF) with and without RBV. Four different PRO questionnaires were administered at baseline, during, and post‐treatment in HCV genotype 1 patients treated with LDV/SOF±RBV (ION‐1, ‐2, and ‐3). A total of 1,952 patients were enrolled to be treated for 8 (Nu2009=u2009431), 12 (Nu2009=u2009867), or 24 weeks (Nu2009=u2009654) with LDV/SOF (Nu2009=u20091,080) or LDV/SOF+RBV (Nu2009=u2009872). Baseline demographics and psychiatric disorders were similar between treatment groups (all Pu2009>u20090.05). Patients receiving LDV/SOF regimens showed significant improvement of PRO scores during treatment (up to +7.4%, +7.0%, and +6.7% on a normalized 0%‐100% scale in the 8‐, 12‐, and 24‐week‐long treatment groups, respectively (all Pu2009<u20090.0001). These PRO improvements coincided with early viral suppression after 2 weeks of treatment and maximized by the end of treatment. On the other hand, during treatment with LDV/SOF+RBV, PRO scores declined (up to −5.5% regardless of treatment duration; Pu2009<u20090.0001). Receiving RBV was an independent predictor of PRO impairment in multivariate analysis (beta up to −5.9%; Pu2009<u20090.0001). Patients who achieved sustained virological response at 12 weeks showed significant improvement of their PROs post‐treatment (up to +8.3%; Pu2009<u20090.0001). Conclusion: IFN‐ and RBV‐free regimens with LDV/SOF result in early HCV suppression with simultaneous improvement in PROs that continued throughout the duration of treatment and post‐treatment. (Hepatology 2015;61:1798‐1808)

Patient-reported outcomes with sofosbuvir and velpatasvir with or without ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory analysis from the randomised, open-label ASTRAL-4 phase 3 trial

BACKGROUND & AIMSnNew interferon-free anti-HCV regimens are highly efficacious with a favorable safety profile. We assessed health-related quality of life (HRQL) and work productivity in patients with different stages of hepatic fibrosis treated with sofosbuvir+ledipasvir.nnnMETHODSnFour questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index:Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment with sofosbuvir+ledipasvir+ribavirin or sofosbuvir+ledipasvir (ION-1,2,3 clinical trials). Metavir fibrosis stage was determined from pre-treatment liver biopsies.nnnRESULTSnThere were 1005 patients included (stage F0: n=94; F1: n=311; F2: n=301; F3: n=197; F4: n=102). At baseline, patients with more advanced fibrosis had more HRQL impairments, predominantly related to physical functioning (stage 0 vs. stage 4 by up to 0.126 on a normalized 0-1 scale p<0.0001). During and post-treatment, HRQL remained lower in patients with advanced fibrosis. After achieving sustained virologic response, significant improvements from baseline in most HRQL domains were observed regardless of fibrosis stage (by 0.024-0.103 on a 0-1 scale; all p>0.05 across fibrosis stages). In multivariate analysis, advanced fibrosis was independently associated with impairment of HRQL and work productivity (beta up to -0.056 in comparison with none-to-mild fibrosis, p<0.05). However, improvement of HRQL and work productivity after viral clearance was not related to the stage of fibrosis (all p>0.05).nnnCONCLUSIONSnAlthough advanced hepatic fibrosis is associated with HRQL and work productivity impairment, viral eradication with sofosbuvir+ledipasvir leads to HRQL improvement regardless of fibrosis stage. HCV patients with early fibrosis experience similar improvement of patient reported outcomes as those with advanced fibrosis.

Association of work productivity with clinical and patient-reported factors in patients infected with hepatitis C virus.

A fixed‐dose combination of ledipasvir and sofosbuvir (LDV/SOF) has been approved for treatment of HCV patients. We assessed the effect of LDV/SOF on patient‐reported outcomes (PROs) in HIV–HCV‐co‐infected patients. Patient‐reported outcomes data from HIV–HCV‐co‐infected patients who were treated with LDV/SOF for 12 weeks were collected as a part of a clinical trial (ION‐4). Historical controls were HIV–HCV‐co‐infected patients treated with SOF and ribavirin (RBV) in PHOTON‐1. We included 335 HIV–HCV‐co‐infected patients (SVR‐12 in HCV genotype 1 was 96%) who received LDV/SOF, while 223 patients (SVR‐12 in HCV genotype 1 was 76.3%) received SOF/RBV. During treatment, patients receiving LDV/SOF showed improvement in all of their PRO scores (+6.0% in activity/energy of CLDQ‐HCV, +5.0% in fatigue score of FACIT‐F, +6.8% in physical component of SF‐36; all P < 0.0001) while those receiving SOF+RBV showed moderate decline in some of their PRO scores (−4.8% in physical functioning of SF‐36, −4.4% in fatigue score of FACIT‐F, both P < 0.001). Patients who achieved sustained virologic response with LDV/SOF also showed improvement of PROs (average +5.1%) while those treated with SOF/RBV showed less or no improvement (average +1.4%). In a multivariate analysis, in addition to depression and fatigue, receiving SOF+RBV (vs LDV/SOF) was independently associated with more PRO impairment during treatment (beta −6.1 to −12.1%, P < 0.001). Hence, HIV–HCV patients treated with LDV/SOF show significant improvement of their health‐related quality of life and other patient‐reported outcomes during treatment and after treatment cessation.

Inpatient resource utilization, disease severity, mortality and insurance coverage for patients hospitalized for hepatitis C virus in the United States.

BACKGROUNDnHepatitis C virus (HCV) treatment regimens with direct-acting antivirals have not been extensively studied in patients with decompensated cirrhosis. We assessed patient-reported outcomes (PROs) in patients with decompensated cirrhosis given a fixed-dose combination of sofosbuvir and velpatasvir with and without ribavirin.nnnMETHODSnThis study was an exploratory analysis of data collected in a randomised, open-label phase 3 trial (ASTRAL-4) in which patients with HCV-related decompensated cirrhosis were randomly assigned to an all-oral fixed-dose combination of sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks, sofosbuvir and velpatasvir plus oral ribavirin (weight-based 1000 mg or 1200 mg) for 12 weeks, or sofosbuvir and velpatasvir for 24 weeks. Eligible patients were aged 18 years or older with any HCV genotype and decompensated cirrhosis at screening. PROs were collected for the intention-to-treat population using four questionnaires, Short Form (36) Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), the Chronic Liver Disease Questionnaire-HCV Version (CLDQ-HCV), and the Work Productivity Activity Index:HCV (WPAI), which were given prospectively to patients before, during, and after treatment. The ASTRAL-4 study is registered with ClinicalTrials.gov, number NCT02201901.nnnFINDINGSnPatients were enrolled at 47 hepatology outpatient practices in the USA from Aug 19, 2014, to Dec 19, 2014. 267 patients with HCV-related decompensated cirrhosis were included. In patients given sofosbuvir and velpatasvir for 12 weeks (n=90), clinically significant improvements in PROs started 4 weeks after treatment initiation (+4·4 to +7·5 points on a 0-100 scale at treatment week 4). By the end of treatment, mean improvements in PROs of +5·3 to +16·0 points were noted in all PROs except for role emotional, mental component summary, and social wellbeing scores and work productivity metrics by WPAI:HCV. Similar end-of-treatment improvements (+3·8 to +17·0 points) were observed in patients given sofosbuvir and velpatasvir for 24 weeks (n=90). In patients given sofosbuvir and velpatasvir plus ribavirin (n=87), PRO scores decreased within 4 weeks of treatment (-3·6 to -6·9 points), although scores returned to the baseline levels by the end of treatment. After treatment cessation, significant improvements in all PROs were similar between the treatment groups (all p>0·01) and, by post-treatment week 24, improvements were between +4·9 and +21·2 points. In multivariate analysis, predictors of PRO impairment were treatment naivety, anxiety, use of anxiolytics, use of antidepressants, use of opioids, ribavirin use, the presence of ascites, encephalopathy, insomnia, and depression.nnnINTERPRETATIONnA clinically significant early (within 4 weeks) and sustained improvement in PROs was observed in patients with HCV-related decompensated cirrhosis who were given sofosbuvir and velpatasvir without ribavirin. A similar regimen with ribavirin resulted in a temporary decrease in PROs, which completely resolved after 8 weeks of treatment. Accompanied by high efficacy, the favourable effect of treatment on PROs improves patients experience in this difficult-to-treat population with HCV.nnnFUNDINGnGilead Sciences.

Resource utilization and survival among Medicare patients with advanced liver disease.

Patients with HCV infection have reduced work productivity (WP), in terms of both presenteeism (impairment in work productivity while working) and absenteeism (productivity loss due to absence from work). The aim of this study was to identify clinical and patient‐reported factors that are predictive of WP in HCV‐infected patients. HCV‐infected patients enrolled in clinical trials completed 3 PRO questionnaires (CLDQ‐HCV, SF‐36 and FACIT‐F) and one work productivity (WPAI:SHP) questionnaire. In employed subjects, work productivity and its absenteeism and presenteeism components were calculated using WPAI:SHP instrument. Of 4121 HCV‐infected patients with work productivity data, 2480 (60.2%) reported to be employed, and of those, 2190 had completed all PRO questionnaires before treatment initiation. Of the study cohort, 519/2190 (23.7%) had severe work impairment. In multiple linear regression analysis, work productivity was predicted by lower scores in activity/energy domain of CLDQ‐HCV, physical well‐being domain of FACIT‐F, worry domain of CLDQ‐HCV and role physical domain of SF‐36 (all P < 0.0005). Furthermore, presenteeism was independently predicted by the activity/energy of CLDQ‐HCV, physical well‐being of FACIT‐F, worry domain of CLDQ‐HCV, role physical scale of SF‐36 and fatigue scale of FACIT‐F (P < 0.002). Finally, absenteeism was independently predicted by physical well‐being scale of FACIT‐F and role physical scale of SF‐36 (all P < 0.002). Clinically, work productivity impairment was predicted by the presence of cirrhosis, anxiety, depression and clinically overt fatigue (P < 0.01). Thus, the most important drivers of WP in HCV are impairment of physical aspects of PROs and clinical history of depression, anxiety, fatigue and cirrhosis.

Anti-adipocyte antibody response in patients with non-alcoholic fatty liver disease.

Although the incidence of new hepatitis C virus (HCV) infection has fallen, HCV‐related complications are on the rise. Our aim was to assess and describe the 2005–2009 national inpatient mortality and resource utilization trends for patients with HCV. Data from the National Inpatient Sample (NIS) and the National Hospital Discharge Survey (NHDS) between 2005 and 2009 were analyzed. Included were all adult hospital discharges with HCV‐related ICD‐9 codes. Incremental hospital charge, in‐hospital mortality and length of stay (LOS) were estimated using n = 1000 bootstrap replicates clustered by unique hospital identifier. A total of 123 939 (0.38%) discharges were related to HCV (primary or secondary diagnosis). In‐hospital mortality increased from 1.7% (2005) to 2.6% (2009) (P < 0.001). Inflation‐adjusted charges increased 2% annually from 2005 (

P717 IMPROVEMENT OF CENTRAL FATIGUE IS ASSOCIATED WITH SUSTAINED VIROLOGIC RESPONSE (SVR) FOLLOWING SOFOSBUVIR (SOF) CONTAINING REGIMENS

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