Cost-effectiveness analysis of chronic hepatitis C treatment in the prison population in Spain.

OBJECTIVES: To evaluate the cost-effectiveness of direct-acting antiviral (DAAs) treatment versus non-treatment in prisoners awaiting treatment for chronic hepatitis C (CHC) and to analyse the clinical and economic impact of the treatment on liver complications and mortality. MATERIAL AND METHOD: A lifetime Markov model was developed to simulate treatment and disease progression from an estimated cohort of 4,408 CHC prisoners treated with DAAs over 2 years (50% of patient each year) versus no treatment. In the treated cohort, a sustained viral response of 95% was associated. Patient characteristics, transition probabilities, utilities and costs (pharmacological and healthcare states) were obtained from published literature. The model estimated healthcare costs and benefits, incremental cost-utility ratio (ICUR) based on total costs and the quality-adjusted life year (QALY) and avoided clinical events. A National Healthcare System perspective was adopted with a 3% annual discount rate for both costs and health outcomes. Sensitivity analyses were performed to assess uncertainty. RESULTS: In the DDA treated cohort, the model estimated a decrease of 92% of decompensated cirrhosis and 83% of hepatocellular carcinoma, 88% liver-related mortality cases were reduced, 132 liver transplants were avoided. The treatment achieved an additional 5.0/QALYs (21.2 vs. 16.2) with an incremental cost of €3,473 (€24,088 vs. €20,615) per patient with an ICUR of €690 per QALY gained. DISCUSSION: Considering the willingness-to-pay threshold used in Spain (€22,000-30,000/QALY), DAAs treatment for prisoners with CHC is a highly cost-effective strategy, reduces infection transmission, increases survival and reduces complications due to liver disease, as well as the cost associated with its management.

Treatment of HCV reduces viral hepatitis-associated liver-related mortality in patients: An ERCHIVES study.

BACKGROUND & AIMS: Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown. METHODS: We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR). RESULTS: Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p <0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality. CONCLUSIONS: Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies. LAY SUMMARY: Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

Cost-effectiveness and health-related outcomes of screening for hepatitis C in Korean population.

BACKGROUND/AIM: In the era of direct-acting antivirals (DAA), active screening for hidden hepatitis C virus (HCV) infection is important for HCV elimination. This study estimated the cost-effectiveness and health-related outcomes of HCV screening and DAA treatment of a targeted population in Korea, where anti-HCV prevalence was 0.6% in 2015. METHODS: A Markov model simulating the natural history of HCV infection was used to examine the cost-effectiveness of two strategies: no screening vs screening and DAA treatment. Screening was performed by integration of the anti-HCV test into the National Health Examination Program. From a healthcare system's perspective, the cost-utility and the impact on HCV-related health events of one-time anti-HCV screening and DAA treatment in Korean population aged 40-65 years was analysed with a lifetime horizon. RESULTS: The HCV screening and DAA treatment strategy increased quality-adjusted life years (QALY) by 0.0015 at a cost of $11.27 resulting in an incremental cost-effectiveness ratio (ICER) of $7435 per QALY gained compared with no screening. The probability of the screening strategy to be cost-effective was 98.8% at a willingness-to-pay of $27 205. Deterministic sensitivity analyses revealed the ICERs were from $4602 to $12 588 and sensitive to screening costs, discount rates and treatment acceptability. Moreover, it can prevent 32 HCV-related deaths, 19 hepatocellular carcinomas and 15 decompensated cirrhosis per 100 000 screened persons. CONCLUSIONS: A one-time HCV screening and DAA treatment of a Korean population aged 40-65 years would be highly cost-effective, and significantly reduce the HCV-related morbidity and mortality compared with no screening.

Reduced Incidence and Better Liver Disease Outcomes among Chronic HCV Infected Patients Who Consume Cannabis.

Background and Aim: The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals. Methods: We analyzed hospital discharge records of adults (age ≥ 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to nonusers on 1:1 ratio (4,728:4,728), using a propensity-based matching system, with a stringent algorithm. We then used conditional regression models with generalized estimating equations to measure the adjusted prevalence rate ratio (aPRR) for having liver cirrhosis (and its complications), carcinoma, mortality, discharge disposition, and the adjusted mean ratio (aMR) of total hospital cost and length of stay (LOS) [SAS 9.4]. Results: Our study revealed that cannabis users (CUs) had decreased prevalence of liver cirrhosis (aPRR: 0.81[0.72-0.91]), unfavorable discharge disposition (0.87[0.78-0.96]), and lower total health care cost ($39,642[36,220-43,387] versus $45,566[$42,244-$49,150]), compared to noncannabis users (NCUs). However, there was no difference among CUs and NCUs on the incidence of liver carcinoma (0.79[0.55-1.13]), in-hospital mortality (0.84[0.60-1.17]), and LOS (5.58[5.10-6.09] versus 5.66[5.25-6.01]). Among CUs, dependent cannabis use was associated with lower prevalence of liver cirrhosis, compared to nondependent use (0.62[0.41-0.93]). Conclusions: Our findings suggest that cannabis use is associated with decreased incidence of liver cirrhosis, but no change in mortality nor LOS among HCV patients. These novel observations warrant further molecular mechanistic studies.

Changing Trends in Etiology-Based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016.

BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied trends in age-standardized mortality of chronic liver diseases in adults at least 20 years old in the United States from 2007 through 2016. METHODS: We collected data from the US Census and National Center for Health Statistics mortality records and identified individuals with HCV infection, ALD, nonalcoholic fatty liver disease, or hepatitis B virus infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC). RESULTS: Age-standardized HCV-related mortality increased from 7.17 per 100,000 persons in 2007 to 8.14 per 100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09 per 100,000 persons in 2014 to 7.15 per 100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014 but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC 2.3% from 2007 through 2013 and APC 5.5% from 2013 through 2016) and nonalcoholic fatty liver disease (APC 6.1% from 2007 through 2013 and APC 11.3% from 2013 through 2016). Mortality related to hepatitis B virus decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI -3.0 to -1.2). Etiology-based mortality in minority populations was higher. HCV-related mortality (per 100,000 persons) was highest in non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest in non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for hepatitis B virus infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks and 0.47 for non-Hispanic whites). CONCLUSION: In our population-based analysis of chronic liver disease mortality in the United States, the decrease in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, whereas mortality from ALD and nonalcoholic fatty liver disease increased during the same period. Minorities in the United States have disproportionately higher mortality related to chronic liver disease.

Hepatitis C virus infection and hospital-related outcomes: a systematic review protocol.

INTRODUCTION: People living with hepatitis C virus (HCV) infection are disproportionately over-represented in the healthcare system due to various individual and contextual circumstances, including comorbidities and socioeconomic marginalisation. With growing trends in morbidity and mortality related to HCV infection, HCV is becoming a significant health and financial burden on the healthcare system, particularly in acute hospital settings. It is noteworthy that with the advent of direct-acting antiviral therapy the increasing number of patients who are cured of HCV could potentially result in different patterns of hospital-related outcomes over time. METHODS AND ANALYSIS: We will conduct a systematic review of published literature to retrieve quantitative research articles pertaining to hospital outcomes among patients living with HCV. Primary outcomes include hospitalisation rates, length of stay, leaving against medical advice, readmission and in-hospital mortality. In total, five databases will be searched (MEDLINE, EMBASE, CINAHL, PsycINFO and Web of Science). Titles, abstracts and full texts will be independently reviewed by two investigators in three separate stages. The methodological quality of included quantitative research studies will be assessed using a validated tool. Data from included articles will be extracted using a standardised form and synthesised in a narrative account. ETHICS AND DISSEMINATION: Results of this systematic review could provide a better understanding on how to optimise health systems and services to improve patient outcomes and care. The results of this study may provide future research with a foundation to guide decision-making and for designing and implementing systems-level interventions to improve treatment and care delivery for people living with HCV. Ethical approval for this study was received by the University of British Columbia/Providence Health Care Research Ethics Board. Findings from this study will be disseminated through peer-reviewed publications, presentations, reports and community forums PROSPERO REGISTRATION NUMBER: CRD42017081082; Pre-results.

Economic and clinical burden of viral hepatitis in California: A population-based study with longitudinal analysis.

BACKGROUND: Economic burden of HBV and HCV infection are trending upwards. AIMS: Compare hepatitis B virus (HBV) and hepatitis C virus (HCV) related hospital admission rates, charges, mortality rates, causes of death in a US population-based study. METHODS: Retrospective cohort analysis of HBV and HCV patients from the California Office of Statewide Health Planning and Development (2006-2013) database. RESULTS: A total of 23,891 HBV and 148,229 HCV patients were identified. Across the 8-year period, the mean increase for all-cause ($1,863 vs $1,388) and liver-related hospitalization charges ($1,175 vs $675) were significantly higher for the HBV cohort compared to the HCV cohort. HBV patients had significantly higher liver-related hospital charges per person per year than HCV patients after controlling for covariates ($123,239 vs $111,837; p = 0.002). Compared to HCV patients, adjusted mortality hazard ratio was slightly lower in HBV patients (relative risk = 0.96; 95% CI 0.94-0.99). The major causes and places of death were different. The three major causes of death for HBV were: other malignant neoplasms (35%), cardiovascular disease/other circulatory disorders (17%), and liver-related disease (15%) whereas for HCV patients were: liver-related disease (22%), other malignant neoplasms (20%), and cardiovascular disease (16%). Regarding the place of death, 53% of HBV patients and 44% of HCV patients died in hospital inpatient, respectively. CONCLUSIONS: HBV patients incurred higher liver-related hospital charges and higher mean increase for all-cause and liver-related hospitalization charges over the 8-year period compared to HCV patients. HBV patients had slightly lower mortality rate and their major causes and places of death were noticeably different from HCV patients.

Monitoring response to hepatitis B and C in EU/EEA: testing policies, availability of data on care cascade and chronic viral hepatitis-related mortality - results from two surveys (2016).

OBJECTIVES: The World Health Organization (WHO) developed a European Regional Action Plan (EAP) to fast-track action towards the goal of eliminating viral hepatitis. Robust monitoring is essential to assess national programme performance. The purpose of this study was to assess the availability of selected monitoring data sources in European Union/European Economic Area (EU/EEA) Member States (MS). METHODS: Availability of data sources at EU/EEA level was assessed using two surveys distributed to 31 EU/EEA MS in 2016. The two surveys covered (A) availability of policy documents on testing; testing practices and monitoring; monitoring of diagnosis and treatment initiation, and; (B) availability of data on mortality attributable to chronic viral hepatitis. RESULTS: Just over two-thirds of EU/EEA MS responded to the surveys. 86% (18/21) reported national testing guidance covering HBV, and 81% (17/21) covering HCV; while 33% (7/21) and 38% (8/21) of countries, respectively, monitored the number of tests performed. 71% (15/21) of countries monitored the number of chronic HBV cases diagnosed and 33% (7/21) the number of people treated. Corresponding figures for HCV were 48% (10/21) and 57% (12/21). 27% (6/22) of countries reported availability of data on mortality attributable to chronic viral hepatitis. CONCLUSIONS: The results of this study suggest that sources of information in EU/EEA Member States to monitor the progress towards the EAP milestones and targets related to viral hepatitis diagnosis, cascade of care and attributable mortality are limited. Our analysis should raise awareness among EU/EEA policy makers and stimulate higher prioritisation of efforts to improve the monitoring of national viral hepatitis programmes.

Neighborhood Inequalities in Hepatitis C Mortality: Spatial and Temporal Patterns and Associated Factors.

Deaths attributable to hepatitis C (HCV) infection are increasing in the USA even as highly effective treatments become available. Neighborhood-level inequalities create barriers to care and treatment for many vulnerable populations. We seek to characterize citywide trends in HCV mortality rates over time and identify and describe neighborhoods in New York City (NYC) with disproportionately high rates and associated factors. We used a multiple cause of death (MCOD) definition for HCV mortality. Cases identified between January 1, 2006, and December 31, 2014, were geocoded to NYC census tracts (CT). We calculated age-adjusted HCV mortality rates and identified spatial clustering using a local Moran's I test. Temporal trends were analyzed using joinpoint regression. A multistep global and local Poisson modeling approach was used to test for neighborhood associations with sociodemographic indicators. During the study period, 3697 HCV-related deaths occurred in NYC, with an average annual percent increase of 2.6% (p = 0.02). The HCV mortality rates ranged from 0 to 373.6 per 100,000 by CT, and cluster analysis identified significant clustering of HCV mortality (I = 0.23). Regression identified positive associations between HCV mortality and the proportion of non-Hispanic black or Hispanic residents, neighborhood poverty, education, and non-English-speaking households. Local regression estimates identified spatially varying patterns in these associations. The rates of HCV mortality in NYC are increasing and vary by neighborhood. HCV mortality is associated with many indicators of geographic inequality. Results identified neighborhoods in greatest need for place-based interventions to address social determinants that may perpetuate inequalities in HCV mortality.

Impact of universal access to hepatitis C therapy on HIV-infected patients: implementation of the Spanish national hepatitis C strategy.

In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population.

Treatment of Chronic Hepatitis C in the Aged - Does It Impact Life Expectancy? A Decision Analysis.

BACKGROUND AND AIMS: Recent studies have demonstrated that the efficacy of interferon-free direct-acting antiviral agents (DAAs) in patients over 70 is similar to that of younger age groups. Evidence continues to mount that life expectancy (LE) increases with successful treatment of hepatitis C (HCV) patients with advanced fibrosis. The evidence in older people is more limited. Our aim was to estimate the life year (LY) and quality-adjusted life year (QALY) gained by treatment of naïve patients with HCV as a function of patient's age and fibrosis stage. METHODS: We constructed a Markov model of HCV progression toward advanced liver disease. The primary outcome was LY and QALY saved. The model and the sustained virological response of HCV infected subjects treated with a fixed-dose combination of the NS5B polymerase inhibitor Sofosbuvir and the NS5A replication complex inhibitor Ledipasvir were based on the published literature and expert opinion. RESULTS: Generally, both the number of LY gained and QALY gained gradually decreased with advancing age but the rate of decline was slower with more advanced fibrosis stage. For patients with fibrosis stage F1, F2 and F3, LY gained dropped below six months if treated by the age of 55, 65 or 70 years, respectively, while for a patient with fibrosis stage F4, the gain was one LY if treated by the age of 75. The QALY gained for treated over untreated elderly were reasonably high even for those treated at early fibrosis stage. CONCLUSIONS: There is a significant life expectancy benefit to HCV treatment in patients up to age 75 with advanced-stage fibrosis.

Chronic Hepatitis B Is Associated with Higher Inpatient Resource Utilization and Mortality Versus Chronic Hepatitis C.

BACKGROUND: Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections remain one of the leading causes of chronic liver disease and hepatocellular carcinoma. Healthcare initiatives for chronic viral hepatitis to facilitate early diagnosis and linkage to care in an effort to reduce inpatient resource utilization associated with late diagnosis and end-stage liver disease have been partially successful. AIMS: Our objective was to determine the impact of liver-related complications from chronic HBV and HCV infections on inpatient cost of care, length of stay, and mortality. METHODS: Using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS), we studied the impact of chronic HBV and HCV infections on inpatient healthcare system following hospitalizations from 2003 to 2012. RESULTS: Of the 79,185,729 million hospitalizations among adult patients in the USA from 2003 to 2012, 143,896 (0.18 %) hospitalizations were HBV related and 1,073,269 (1.36 %) hospitalizations HCV related. HBV hospitalizations had a higher inpatient mortality (OR 1.34; 95 % CI 1.30, 1.38), median cost of care per hospitalization (+$2100.33; 95 % CI 1982.53, 2217.53), and increased length of hospitalization stay (+0.64 days; 95 % CI 0.60, 0.68; p < 0.01) compared to HCV. CONCLUSIONS: Despite higher per case resource utilization following hospitalization, HBV-infected patients demonstrate a lower inpatient survival in comparison with chronic HCV infection. These disparate observations underscore the need for early diagnosis of chronic HBV infection in at-risk population and prompt linkage to care.

Predictors of Inpatient Mortality and Resource Utilization for the Elderly Patients With Chronic Hepatitis C (CH-C) in the United States.

New incidents of chronic hepatitis C (CH-C) have stabilized yet the full impact of CH-C is not realized.Assess inpatient mortality and resource utilization for CH-C patients hospitalized in the United States.Adult CH-C patients were identified from The National Inpatient Sample (NIS) 2005 to 2009 database using the International Classification of Disease, Ninth Revision (ICD-9) diagnosis codes (070.51, 070.54, 070.70, 070.71, 070.41, and 070.44) also used to identify comorbidities.324,823 hospitalized CH-C patients were identified. Of these, 13.63% (N = 44,288) were older than 65. The rate of hospitalization for the elderly cohort steadily increased over the study period with Medicare as the payer for the majority (86%). This cohort had higher inpatient charges, approximately a half day longer hospital stay (P < 0.001) and more moderate or severe illness. During the index hospitalization, older CH-C patients were twice more likely to die than the younger age-group (5% versus 2%, P < 0.001). In the adjusted model, older age (OR: 1.02 [95% CI, 1.02-1.03]), severity of illness (OR: 12.06 [95% CI, 10.68-13.62]), and number of diagnoses (OR: 1.10 [95% CI, 1.09-1.11]) were associated with higher in-hospital mortality; severity of illness and having private insurance were significantly associated with charge per hospital stay (P < 0.001).The number of CH-C patients 65 and older increased due to the aging of the baby boomer population. Early treatment of CH-C patients with highly effective, well-tolerated, new anti-HCV regimens may prevent this significant societal burden.

Cost-effectiveness of treating chronic hepatitis C virus with direct-acting antivirals in people who inject drugs in Australia.

BACKGROUND AND AIM: Reducing the burden of hepatitis C virus (HCV) related liver disease will require treating people who inject drugs (PWID), the group at most risk of infection and transmission. We determine the cost-effectiveness of treating PWID with interferon-free direct-acting antiviral therapy in Australia. METHODS: Using a deterministic model of HCV treatment and liver disease progression, including a fixed rate of re-infection, the expected healthcare costs and quality-adjusted life years (QALYs) of a cohort of newly HCV-infected PWID were calculated for: no treatment; treatment after initial infection ("early-treatment"); and treatment prior to developing compensated cirrhosis ("late-treatment"). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. RESULTS: Late-treatment was cost-effective compared to no treatment, with a discounted average gain of 2.98 (95%confidence interval 2.88-5.22) QALYs per person for an additional cost of $15,132 ($11,246-18,922), giving an ICER of $5078 ($2847-5295) per QALY gained. Compared to late-treatment, early-treatment gained a further discounted average of 2.27 (0.58-4.80) QALYs per person for $38,794 ($34,789-41,367), giving an ICER of $17,090 ($2847-63,282), which was cost-effective in approximately 90% of Monte-Carlo uncertainty simulations. For every 100 newly HCV-infected PWID, there were an estimated 40 (39-56) eventual liver-related deaths without treatment, compared to 7 (6-11) and 8 (7-13) with early-treatment and late-treatment available respectively. CONCLUSIONS: Treating HCV-infected PWID with new therapies is cost-effective and could prevent a significant number of liver-related deaths. Although late-treatment was the most cost-effective option, the cost per QALY gained for early-treatment compared to late-treatment is likely to be below unofficial Australian willingness to pay thresholds.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Boceprevir for Chronic Genotype 1 Hepatitis C Virus in the Current Health Care Setting in Greece: A Cost-effectiveness Analysis.

PURPOSE: Boceprevir, as an add-on to the standard of care (SOC) for chronic genotype 1 hepatitis C virus (G1 HCV), pegylated interferon + ribavirin for 48 weeks (PEG + RBV), has been reported to have a clinical profile superior to that of SOC alone. The objective of the present study was to compare the cost-effectiveness of triple therapy with PEG + RBV + boceprevir to that of SOC in treatment-naive and treatment-experienced patients with G1 HCV in Greece. METHODS: A Markov model that simulated the quality-adjusted life expectancy and corresponding costs of treating G1 HCV infection provided the basis of the analysis. Treatment strategies under consideration were those in the Phase III boceprevir trials: (1) boceprevir response-guided therapy (shortened treatment duration for early responders); (2) fixed-duration (4-week) SOC plus 44 weeks of triple therapy; and (3) 48-week SOC. Efficacy data and the baseline characteristics of the study population were based on data from the SPRINT-2 (Serine Protease Inhibitor Therapy 2) and RESPOND-2 (Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2) clinical trials. Health care resource utilization and costs reflect the local clinical setting, with a 3% discount per annum, and were assessed from a third-party payer perspective. FINDINGS: Triple therapy was projected to reduce liver complications (eg, decompensated cirrhosis, hepatocellular carcinoma, need for liver transplantation, and liver-related death) by 44% to 45% and 49% to 53% in treatment-naive and treatment-experienced patients, respectively, over a lifetime horizon, leading to corresponding gains of 0.87 and 1.25 quality-adjusted life-years gained per patient. Taking into account the costs of medications, treatment, and outcomes management, the estimated incremental cost-effectiveness ratios of triple therapy versus SOC were €10,003 and €10,852 per quality-adjusted life-years gained in treatment-naïve and treatment-experienced patients. Extensive sensitivity analyses suggested that the findings were robust over a wide range of inputs. IMPLICATIONS: Based on the findings from the present analysis, the addition of boceprevir to PEG + RBV for the treatment of patients with G1 HCV may be a cost-effective alternative in the health care setting in Greece.

Management of hepatitis C infection before and after liver transplantation.

Chronic hepatitis C (CHC) is the most common indication for liver transplantation (LT). Aggressive treatment of hepatitis C virus (HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon (IFN)-based regimens can be used in dual-agent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals (e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free anti-HCV therapy for pre- and post-LT remains high.

Labour productivity losses caused by premature death associated with hepatitis C in Spain.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection places a huge burden on healthcare systems. There is no study assessing the impact of HCV infection on premature deaths in Spain. The aim of this study was to estimate productivity losses because of premature deaths attributable to hepatitis C occurring in Spain during 2007-2011. MATERIALS AND METHODS: We use data from several sources (Registry of Deaths, Labour Force Survey and Wage Structure Survey) to develop a simulation model based on the human capital approach and to estimate the flows in labour productivity losses in the period considered. The attributable fraction method was used to estimate the numbers of deaths associated with HCV infection. Two sensitivity analyses were developed to test the robustness of the results. RESULTS: Our model shows total productivity losses attributable to HCV infection of 1054.7 million euros over the period analysed. The trend in productivity losses is decreasing over the period. This result is because of improvements in health outcomes, reflected in the reduction of the number of years of potential productive life lost. Of the total estimated losses, 18.6% were because of hepatitis C, 24.6% because of hepatocellular carcinoma, 30.1% because of cirrhosis, 15.9% because of other liver diseases and 10.7% because of HIV-HCV coinfection. CONCLUSION: The results show that premature mortality attributable to hepatitis C involves significant productivity losses. This highlights the need to extend the analysis to consider other social costs and obtain a more complete picture of the actual economic impact of hepatitis C infection.

The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus.

BACKGROUND: New hepatitis C virus (HCV) treatments deliver higher cure rates with fewer contraindications, increasing demand for treatment and healthcare costs. The cost-effectiveness of new treatments is unknown. METHODS: We conducted a microsimulation of guideline testing followed by alternative treatment regimens for HCV among the US population aged 20 and older to estimate cases identified, treated, sustained viral response, deaths, medical costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) of different treatment options expressed as discounted lifetime costs and benefits from the healthcare perspective. RESULTS: Compared to treatment with pegylated interferon and ribavirin (PR), and a protease inhibitor for HCV genotype (G) 1 and PR alone for G2/3, treatment with PR and Sofosbuvir (PRS) for G1/4 and treatment with Sofosbuvir and ribavirin (SR) for G2/3 increased QALYs by 555 226, reduced deaths by 80 682, and increased costs by $26.2 billion at an ICER of $47 304 per QALY gained. As compared to PRS/SR, treating with an all oral regimen of Sofosbuvir and Simeprevir (SS) for G1/4 and SR for G2/3, increased QALYs by 1 110 451 and reduced deaths by an additional 164 540 at an incremental cost of $80.1 billion and an ICER of $72 169. In sensitivity analysis, where treatment with SS effectiveness was set to the list price of Viekira Pak and then Harvoni, treatment cost $24 921 and $25 405 per QALY gained as compared to PRS/SR. CONCLUSIONS: New treatments are cost-effectiveness per person treated, but pent-up demand for treatment may create challenges for financing.