Real-world use of elbasvir-grazoprevir in patients with chronic hepatitis C: retrospective analyses from the TRIO network.

BACKGROUND: Elbasvir-grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4. AIM: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir-grazoprevir in the United States. METHODS: We conducted a retrospective cohort study of adults treated with elbasvir-grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud-based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post-treatment (SVR12). RESULTS: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non-cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir-grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent-to-treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4. CONCLUSION: Elbasvir-grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12-week therapy without ribavirin.

Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan.

Hepatocellular carcinoma (HCC) is a serious complication of hepatitis C virus (HCV) infection. Sustained virologic response (SVR) for HCV is associated with a reduction in cirrhosis, HCC and mortality and their associated costs. Japanese HCV patients are older with higher prevalence of HCC. Here we used a decision-analytic Markov model to estimate the economic benefit of HCV cure by reducing HCC and DCC burden in Japan. A cohort of 10 000 HCV genotype 1b (GT1b) Japanese patients was modelled with a hybrid decision tree and Markov state-transition model capturing natural history of HCV over a lifetime horizon. Treatment options were approved all-oral direct-acting anti-virals (DAAs) vs no treatment. Treatment efficacy was based on clinical trials and transition rates and costs obtained from Japan-specific data. Cases of HCC, decompensated cirrhosis (DCC) and quality-adjusted life years (QALYs) were projected for patients treated with DAAs vs NT. QALYs were monetized using a willingness-to-pay threshold of ¥4-to-¥6 million. Incremental savings with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. The model showed that DAA treatment vs no treatment, reduces 2057 cases of HCC and 1478 cases of decompensated cirrhosis and saves ¥850 446.73 and ¥338 229.90 per patient (ppt). Additionally, treatment can lead to additional 2.64 QALYs gained per patient. The indirect economic gains associated with treatment-related QALY improvements were ¥10 576 000, ¥13 220 000 and ¥15 864 000 ppt (willingness-to-pay thresholds of ¥4 million, ¥5 million and ¥6 million). Total economic savings of treatment with DAAs (vs no treatment) was ¥7 526 372.63, ¥10 170 372.63 and ¥12 814 372.63, at these different willingness-to-pay thresholds. In conclusion treatment of HCV GT1b with all-oral DAAs in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.

Direct medical costs associated with the extrahepatic manifestations of hepatitis C infection in Europe.

Hepatitis C virus (HCV) infection is a systemic disease associated with both hepatic and extrahepatic manifestations. The burden associated with the hepatic manifestation of HCV infection has been well documented in Europe, although that of HCV extrahepatic manifestations remains unknown. In this study, we estimated the annual direct medical costs associated with HCV extrahepatic manifestations in five European countries. A previously validated economic model was used to estimate the annual direct medical cost associated with HCV extrahepatic manifestations. Global excess prevalence of extrahepatic manifestations in HCV patients relative to that in non-HCV patients was obtained from a recent meta-analysis. Per-patient per-year inpatient, outpatient and medication costs to treat each extrahepatic manifestation were from the literature, national databases or expert opinion if unavailable otherwise. All costs were adjusted to 2016 euros (€). The overall direct medical costs associated with HCV extrahepatic manifestations were calculated by multiplying the total per-patient per-year costs of each by the respective excess prevalence rates and then by the size of the HCV-infected population in each country. Treatment impact with direct-acting antivirals (DAAs) was explored using HCV extrahepatic manifestations excess prevalence rates among cured patients compared to untreated HCV patients, as sourced from a meta-analysis. The total annual direct medical cost associated with HCV extrahepatic manifestations was estimated to be 2.17 billion euro (€), with a per-HCV-patient cost ranging from €899 to €1647 annually. DAA treatment was projected to result in cost savings of €316 million per year. We find that the annual economic burden of extrahepatic manifestations is significant and may be partly mitigated by treatment with DAAs.

Hospice care in Medicare patients with primary liver cancer: the impact on resource utilisation and mortality.

BACKGROUND: Few studies have assessed the impact of hospice care in patients with primary liver cancer. AIM: To examine the determinants of hospice care and its effects on resource utilisation and survival among Medicare beneficiaries with primary liver cancer. METHODS: We utilised the Surveillance, Epidemiology and End result Registry (SEER) database from 2002 to 2009 for this cross-sectional study. A total of 3385 patients with primary liver cancer were included. We used logistic regression to discern variables associated with hospice and Cox proportional hazards models to evaluate one-year mortality risk. RESULTS: Compared to patients who enrolled in a hospice, those patients who did not, were younger, non-White and sicker (P < .05 for all). Half of all patients with primary liver cancer died within six months of diagnosis, and one-year mortality was similar in both groups (P = .413). After adjusting for baseline characteristics [age at diagnosis, race, disease severity, tumour stage and treatment], shorter time to hospice care was associated with reduced mortality (HR per day: 0.99 [95% CI, 0.98-0.99]). Older age, decompensated cirrhosis and advanced tumours stage were associated with decreased time to hospice, while Asian/Pacific Islander race and history of radiosurgery were associated with increased time to hospice (all P < .05). Hospitalisations were more costly for those who never enrolled in a hospice compared to hospice enrollees (median $31 607 [$18 394-$54 254] vs $22 316 [$13 741-$36 170], P < .0001). CONCLUSIONS: Hospice enrolment of patients with primary liver cancer provides survival and resource utilisation benefits. Some clinical and demographic factors may represent barriers to hospice enrolment. Further studies are needed to fully understand these barriers in patients with primary liver cancer.

Sofosbuvir and velpatasvir with or without voxilaprevir in direct-acting antiviral-naïve chronic hepatitis C: patient-reported outcomes from POLARIS 2 and 3.

BACKGROUND: Chronic hepatitis C infection leads to impairment of patient-reported outcomes (PROs). Treatment with direct-acting antiviral regimens results in short- and long-term improvement of these outcomes. AIM: To assess PROs in patients treated with a newly developed direct-acting antiviral, a fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX). METHODS: The PRO data were collected from participants of POLARIS-2 and POLARIS-3 clinical trials (DAA-naïve, all HCV genotypes). Participants self-administered SF-36v2, FACIT-F, CLDQ-HCV and WPAI:SHP instruments at baseline, during treatment, and in follow-up. RESULTS: Of 1160 patients, 611 received SOF/VEL/VOX and 549 received SOF/VEL (52.8 ± 11.0 years, 55.9% male, 75.4% treatment-naïve, 33.9% cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%-98%. During treatment, improvements in most PRO scores were significant (all but one P < .01) and ranged from, on average, +2.3 to +15.0 points (on a 0-100 scale) by the end of treatment. These improvements were similar between SOF/VEL/VOX and SOF/VEL arms (all P > .05). After treatment discontinuation, patients treated with both regimens achieved significant and clinically meaningful PRO gains (+2.7 to +16.7 by post-treatment week 12, +3.9 to +20.1 by post-treatment week 24; all but one P < .001). Multivariate analysis showed that depression, anxiety and cirrhosis were the most consistent independent predictors of PRO impairment while no association of PROs with the treatment regimen choice was found (all P > .05). CONCLUSIONS: The pan-genotypic regimens with SOF/VEL with or without VOX not only have excellent efficacy and safety, but also significantly positively impact patients' experience both during treatment and after achieving sustained virologic response in DAA-naïve patients with HCV.

Impact of ledipasvir/sofosbuvir on the work productivity of genotype 1 chronic hepatitis C patients in Asia.

Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor clinical prognosis and a detrimental impact on patients' lives, including on work productivity. To estimate the value of productivity losses due to genotype 1 (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to estimate the potential productivity gains associated with treating patients with ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a time horizon of 1 year. Hepatitis C virus patients entered the model at 12 weeks post-treatment, having achieved or not achieved sustained virological response (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of data from the ION 1-3 studies. These rates were converted into hours of lost productivity, multiplied by the average wage and applied to the total employed, adult GT1 population in each country. Results were compared assuming no treatment, and assuming all patients were treated with LDV/SOF. Total productivity losses due to untreated HCV were: $11.3 million, $17.1 m, $146.0 m and $349.1 m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment resulted in economic gains of $4.5 m, $6.8 m, $58.7 m and $138 m, respectively. These gains were due to reduced presenteeism. The results were sensitive to changes in the prevalence of HCV and the average wage. In conclusion, productivity losses due to untreated HCV infection represent a substantial economic burden. By instituting universal HCV treatment with LDV/SOF (or other therapies with high SVR rates), productivity gains can be achieved.

Direct medical costs associated with the extrahepatic manifestations of hepatitis C virus infection in France.

BACKGROUND: The economic impact of extrahepatic manifestations of hepatitis C virus (HCV) infection remains unknown for France. AIM: To estimate the prevalence of extrahepatic manifestations of HCV and the direct medical costs associated with them. METHODS: Estimates of 13 extrahepatic manifestations prevalence were obtained from (1) a retrospective data analysis of HCV-infected patients in a specialised centre and the baseline prevalence in the general French population and (2) an international systematic review. Per-patient-per-year costs to treat these manifestations were obtained from the literature, national databases or expert opinion. The impact of achieving HCV cure after anti-viral therapy was applied to the French healthcare costs. RESULTS: Using approach (1), increased prevalence rates in HCV patients compared to the general population were observed for most extrahepatic manifestations. The mean per-patient-per-year cost of these manifestations in the tertiary centre was 3296 € [95% CI 1829; 5540]. In France, HCV-extrahepatic manifestations amounted to a total cost of 215 million (M) € per year [144; 299]. Using approach (2), the mean per-patient-per-year cost was estimated to be 1117 €. The estimated total cost reduction in France associated with HCV cure was 13.9 M€ for diabetes, 8.6 M€ for cryoglobulinemia vasculitis, 6.7 M€ for myocardial infarction, 2.4 M€ for end-stage renal disease and 1.4 M€ for stroke. CONCLUSION: Extrahepatic manifestations of HCV infection substantially add to the overall economic burden of the disease in France. HCV cure after anti-viral therapy is expected to significantly reduce the total costs of managing these manifestations in France.

Quality of life in adolescents with hepatitis C treated with sofosbuvir and ribavirin.

Chronic HCV infection has been associated with impairment of HRQL in both adults and paediatric patients. Our aim was to assess the HRQL of HCV-positive children treated with SOF + RBV. The data for this post hoc analysis were collected in a phase 2 open-label multinational study that evaluated safety and efficacy of SOF (400 mg/day) plus RBV (weight-based up to 1400 mg/day) for 12 or 24 weeks in adolescents with chronic HCV (GS-US-334-1112). Patients and their parents/guardians completed the PedsQL-4.0-SF-15 questionnaire at baseline, at the end of treatment and in post-treatment follow-up. We included 50 adolescents with HCV genotype 2 and 3 without cirrhosis (14.8 ± 1.9 years; male: 58%; treatment-naïve: 82%; vertically transmitted HCV: 70%). After treatment, 100% of patients with HCV genotype 2 and 95% with genotype 3 achieved SVR-12. During treatment with SOF + RBV, there were no significant decrements in any of patients' self-reported or parent-proxy-reported PRO scores regardless of treatment duration (all P > .05). After treatment cessation, we recorded a statistically significant improvement in patients' self-reported Social Functioning score by post-treatment week 12: on average, +4.8 points on a 0-100 scale (P = .02). By post-treatment week 24, parent-proxy-reported School Functioning score increased by, on average, +13.0 points (P = .0065). In multivariate analysis, history of abdominal pain and psychiatric disorders were predictive of impaired HRQL in adolescents with HCV (P < .05). Adolescents with HCV do not seem to experience any HRQL decrement during treatment with SOF + RBV and experience some improvement of their HRQL scores after achieving SVR.

Effectiveness of 8- or 12-weeks of ledipasvir and sofosbuvir in real-world treatment-naïve, genotype 1 hepatitis C infected patients.

BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS: In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.

Long-term trends in chronic hepatitis B virus infection associated liver transplantation outcomes in the United States.

With effective antiviral therapies, rates of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and decompensated liver disease requiring liver transplantation (LT) are expected to decrease. We aim to evaluate overall trends in LT waitlist registrations, waitlist survival and likelihood of receiving LT among chronic HBV patients in the United States. Using the United Network for Organ Sharing database, we retrospectively evaluated adults (age≥18) with chronic HBV (with and without HCC) listed for LT from 1992 to 1996 (Era 1) vs 1997 to 2004 (Era 2) vs 2005-2015 (Era 3). Multivariate Cox-regression models evaluated probability of waitlist survival and receiving LT. Overall, 6797 chronic HBV adults were listed for LT. While the total number of HBV patients listed for LT remained stable, the proportion of HBV patients with HCC increased from 5.4% in Era 1 to 39.0% in Era 3. Compared to Era 1, waitlist mortality was higher in Era 2 (HR: 4.55, P<.001) and Era 3 (HR: 3.63, P<.001). However, in the most recent era, waitlist mortality significantly improved (compared to 2005-2007: 2008-2011: HR: 0.74, P=.05, 95% CI: 0.55-0.99; 2012-2015: HR: 0.53, P<.001, 95% CI: 0.38-0.75). Probability of receiving LT was also lower with latter time periods (compared to 2005-2007: 2008-2011: HR: 0.77, P<.001 95% CI: 0.68-0.86; 2012-2015: HR: 0.61, P<.001, 95% CI: 0.54-0.69). Although the number of HBV patients requiring LT remained stable, the proportion of HBV patients with HCC continues to rise. The decrease in waitlist mortality and lower likelihood of LT among HBV patients may reflect the effectiveness of antiviral therapies in delaying disease progression in the current era.

Real-world effectiveness for 12 weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: the Trio Health study.

Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.

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

Long-term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the U.S. transplant registry.

BACKGROUND: Chronic hepatitis C patients in need of a lung transplant are often considered ineligible due to their infection. AIM: To assess the association of hepatitis C virus (HCV) infection with long-term outcomes of lung transplants. METHODS: From the Scientific Registry of Transplant Recipients (1995-2011), we selected all adults with and without HCV infection who underwent lung transplantation. RESULTS: A total of 17 762 lung transplant recipients were included (55.5% bilateral). Of those, 319 (1.83%) had positive HCV serology. The HCV-positive recipients were 1.6 years younger, less Caucasian and more African-American, and had a significantly higher rate of co-infection with hepatitis B virus (all P < 0.001). Post-transplant patients were discharged alive at similar rates regardless of HCV status: 88.4% in HCV+ vs. 90.3% in HCV- (P = 0.25). The mortality rates were also similar at 1 and 2 years after transplantation (20.7% in HCV+ vs. 19.2% in HCV- and 31.6% in HCV+ vs. 28.9% in HCV-, respectively; both P > 0.05), but at post-transplant year 3 year, mortality rate in HCV+ became significantly higher (42.5% vs. 36.4%, P = 0.04) and remained higher for the duration of the follow-up (mean 9.1 years, max 18.4 years). In multivariate survival analysis, after adjustment for confounders, being HCV+ was associated with higher mortality: adjusted hazard ratio 1.24 (1.04-1.46), P = 0.01. No association of HCV infection with time to graft loss was found (P = 0.92). CONCLUSIONS: Chronic HCV infection is associated with a moderate increase in post-lung transplant mortality. Treatment of HCV in lung transplant recipients may, therefore, result in improvement of post-transplant outcomes.

Presence of hepatitis C (HCV) infection in Baby Boomers with Medicare is independently associated with mortality and resource utilisation.

BACKGROUND: Hepatitis C virus is common among Baby Boomers (BB). As this cohort ages, they will increasingly become Medicare eligible. AIM: To evaluate resource utilisation and mortality of BB-Medicare recipients with HCV. METHODS: We used in-patient and out-patient Medicare databases (2005-2010). HCV was identified using ICD-9 codes. Outcomes included resource utilisation [payment/case and in-patient length of stay (LOS)] and short-term mortality. RESULTS: Of 1 153 862 BB Medicare recipients (2005-2010), 3.2% (N = 37 365) had HCV. During this period, in-patient Medicare-BB (39 793-55 235) and their claims (78 924-106 232) increased. Furthermore, their overall mortality increased from 8.94% to 10.25% (P < 0.0001). In multivariate analysis, HCV [OR = 1.23 (1.16-1.29)], older age [OR = 1.98 (1.82-2.14)], male gender [OR = 1.25 (1.22-1.29)], ESRD [OR = 1.31 (1.26-1.36)], Charlson score [OR = 1.41 (1.40-1.42)] and LOS [OR = 1.02 (1.02-1.02)] predicted mortality. LOS decreased from 12.98 to 11.74 days (P < 0.0001), whereas total payments increased from $22 157 to $23 185 (P < .0001). During the study, the number of out-patient Medicare BB patients (123 097-192 110) and claims (863 978-1 340 260) also increased. Furthermore, overall mortality increased from 3.15% to 3.31% (P = 0.0131). Again, HCV [OR = 1.23 (1.16-1.30)], older age [OR = 2.03 (1.89-2.17)], ESRD [OR = 3.40 (3.28-3.51)], disabled status [OR = 1.49 (1.40-1.58)] and Charlson score [OR = 1.39 (1.38-1.40)] predicted mortality. Annual total out-patient payments increased from $3781 to $4001 (P < 0.0001). HCV [36.04% [34.28-37.82%)], 45-49 age [4.21% (3.14-5.28%)], ESRD [966.31% (954.86-977.88%)], disabled status [43.22% (41.67-44.80%)], Charlson score [46.78% (46.31-47.26%)] and study year [2.72% (2.58-2.85%)] independently predicted increases in payments. CONCLUSIONS: In Baby Boomer Medicare recipients, diagnosis of HCV is independently associated with higher mortality and resource utilisation.

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

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.

Disparate access to treatment regimens in chronic hepatitis C patients: data from the TRIO network.

Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid-covered group, must be resolved.

Impact of eradicating hepatitis C virus on the work productivity of chronic hepatitis C (CH-C) patients: an economic model from five European countries.

CH-C negatively affects work productivity (WP), creating a large economic burden. The aim of this study was to model the impact of sustained virologic response (SVR) on WP in CHC genotype 1 (GT1) patients in five European countries (EU5). Work Productivity and Activity Index-Specific Health Problem questionnaire was administered to patients across the ION clinical trials (n = 629 European patients). The analysis modelled a population of GT1 CHC patients over one year, who had been either not treated or treated with LDV/SOF. Sensitivity analyses assessed the possibility that CHC patients' labour costs were lower than the general population's and presented results by fibrosis stage. Before initiation of treatment, EU patients with CHC GT1 exhibited absenteeism and presenteeism impairments of 3.54% and 9.12%, respectively. About 91.8% of EU patients in the ION trials achieved SVR and improved absenteeism and presenteeism impairments by 16.3% and 19.5%, respectively. Monetizing these data, treatment with LDV/SOF resulted in an annual productivity gain of €435 million and a weighted average per-employed patient (PEP) gain of €900 in the EU5. PEP gains from treatment are projected to be higher in cirrhotic than in noncirrhotic patients. If CHC patients are assumed to earn 20% less than the general population, gains of €348 million (€720 PEP) annually are projected. CHC results in a significant economic burden to European society. Due to improvements in WP, SVR with treatment could provide substantial economic gains, partly offsetting the direct costs related to its widespread use.