Hepatitis C: The beginning of the end-key elements for successful European and national strategies to eliminate HCV in Europe.

Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely "silent pandemic," its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high-level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.

Chronic hepatitis C virus (HCV) burden in Rhode Island: modelling treatment scale-up and elimination.

We utilized a disease progression model to predict the number of viraemic infections, cirrhotic cases, and liver-related deaths in the state of Rhode Island (RI) under four treatment scenarios: (1) current HCV treatment paradigm (about 215 patients treated annually, Medicaid reimbursement criteria fibrosis stage ⩾F3); (2) immediate scale-up of treatment (to 430 annually) and less restrictive Medicaid reimbursement criteria (fibrosis stage ⩾F2); (3) immediate treatment scale-up and no fibrosis stage-specific Medicaid reimbursement criteria (⩾F0); (4) an 'elimination' scenario (i.e. a continued treatment scale-up needed to achieve >90% reduction in viraemic cases by 2030). Under current treatment models, the number of cirrhotic cases and liver-related deaths will plateau and peak by 2030, respectively. Treatment scale-up with ⩾F2 and ⩾F0 fibrosis stage treatment criteria could reduce the number of cirrhotic cases by 21·7% and 10·0%, and the number of liver-related deaths by 19·3% and 7·4%, respectively by 2030. To achieve a >90% reduction in viraemic cases by 2030, over 2000 persons will need to be treated annually by 2020. This strategy could reduce cirrhosis cases and liver-related deaths by 78·9% and 72·4%, respectively by 2030. Increased HCV treatment uptake is needed to substantially reduce the burden of HCV by 2030 in Rhode Island.

Mitigating the burden of hepatitis C virus among people who inject drugs in Belgium.

BACKGROUD AND AIMS: In 2010, there were an estimated 10 100 PWID in Belgium and 43% (34%-57%) were HCV infected. Understanding HCV transmission dynamics in high-risk populations and assessing the potential impact of improved HCV treatment strategies requires robust epidemiological data and mathematical modeling. METHODS: CV transmission was modeled using cohorts to track HCV incidence and prevalence among active PWID in the general PWID population, OST and NSP. Model assumptions were derived from published literature and expert consensus. The relative impact of increasing the number of PWID treated with new oral DAAs was considered. RESULTS: If the current transmission paradigm continues, there will be 2645 HCV-infected PWID in 2030. Annually treating 30 (1% of 2015 population) or 120 (4% of 2015 population) HCV-infected PWID with oral DAAs will result in 5% and 25% reductions, respectively, in HCV-infected PWID by 2030. Treating 370 PWID annually (12.5% of 2015 population) will result in a > 90% reduction by 2030. CONCLUSION: Treating a small number of PWID can result in substantial reduction in HCV prevalence in this population ; however, high levels of treatment are necessary to reduce the viral pool and thus the risk of secondary infections. This analysis supports implementation of a screening and treatment strategy among PWID when combined with an expansion of harm reduction programs.

Making the case for looking beyond WHO estimates for the global burden of hepatitis C and B.

The article by Basnayake and Easterbrook on variation of global estimates for HBV, HCV and HIV co-infection is a comprehensive study of cited World Health Organization (WHO) estimates in the literature between 2010 and 2014. The authors reviewed 488 articles published during this period and showed that a wide range of estimates have been quoted using different WHO estimates, and they attempt to set the record straight by listing the most recent/appropriate WHO estimates that should be used going forward.

The estimated future disease burden of hepatitis C virus in the Netherlands with different treatment paradigms.

BACKGROUND & AIMS: Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. METHODS: Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. RESULTS: The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2. CONCLUSIONS: A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands.

Economic burden of hepatitis C in Egypt: the future impact of highly effective therapies.

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in Egypt is the highest in the world, yet the total economic burden has not been quantified. Improved understanding of costs and the impact of treatment strategies will provide for better allocation of resources to reduce HCV disease and economic burden. AIM: A modelling approach was used to quantify the current HCV-infected population, future disease progression and associated costs in Egypt. METHODS: Direct healthcare costs were calculated from a nationally representative hospital and a disability adjusted life year (DALY) template was used with monetary value assigned to lost life years. Three scenarios were considered: (i) Historical treatment scenario: 50% SVR; 65,000 treated annually, (ii) Current treatment scenario: 90% sustained virologic response (SVR); 65,000 treated annually, (iii) Increased treatment scenario: 90% SVR; 325,000 treated annually by 2018. RESULTS: Cumulative DALYs (2015-2030) under Scenario 1 were estimated at 7.88 million and cumulative costs estimated at $89.07 billion. Annual DALYs increased 16% during 2015-2030 while annual costs more than doubled. Scenario 2 reduced cumulative DALYs and costs by 7% and 4%, respectively. Under Scenario 3, total costs declined 73% to $1047 million during 2015-2030. As compared to Scenario 1, cumulative DALYs and costs decreased 37% and 35%, respectively. CONCLUSIONS: This is the first estimate of the total economic burden of HCV in Egypt. Extraordinary measures are necessary to substantially reduce HCV disease and cost burden. With newer therapies, strategies to reduce disease burden are feasible and cost-effective.

The Disease Burden of Hepatitis C in Belgium : An update of a realistic disease control strategy.

BACKGROUND: This manuscript serves as an update to position papers published in 2014 based on the available Belgian hepatitis C virus (HCV) epidemiological data. METHODS: Building on the current standard of care (2015 : 900 ≥ F3 patients treated with 70-85% SVR), four new scenarios were developed to achieve the goals of near viral elimination and prevention of HCV associated morbidity and mortality by 2026 and 2031. Increases in treatment efficacy were assumed in 2016 (90% SVR) and 2017 (95% SVR). RESULTS: Scenario 1: Treating 6,670 patients annually by 2018 (≥ F0 beginning in 2017) and diagnosing 3,790 patients annually by 2020, a 90% reduction in viremic cases and advanced outcomes was observed by 2026. Scenario 2: Treating 4,300 patients annually by 2018 (≥ F0 beginning in 2020) without increasing the number diagnosed, a 90% reduction in viremic cases and 85%-95% reduction in advanced outcomes was observed by 2031. Scenario 3: Treating 5,000 ≥ F2 patients annually by 2018, and diagnosing 3,620 patients annually by 2020, a 90% reduction in advanced outcomes and 50% reduction in viremic cases was observed by 2026. Scenario 4: Treating 3,100 ≥ F2 patients annually by 2018 without increasing the number diagnosed, a 90%-95% reduction in advanced outcomes and 55% reduction in viremic cases was observed by 2031. CONCLUSIONS: Scenario 2 would provide the most favorable balance of outcomes (90% reduction in viremic prevalence and advanced outcomes) and realistic requirements for implementation (gradual increase in treatment, delayed incorporation of patients with no/mild fibrosis).

The disease burden of hepatitis C in Belgium: development of a realistic disease control strategy.

BACKGROUND: Novel direct antiviral agents (DAAs) will become available soon with higher sustained viral response (SVR), fewer side-effects and higher compliance. Our aim was to evaluate different realistic strategies to control the projected increase in HCV-related disease burden in Belgium. METHODS: Based on literature review, expert opinions and historical assumptions, HCV-disease progression and mortality in Belgium was modeled to 2030. Strategies exploring the impact of increased treatment, treatment delay, and treatment restrictions were developed. RESULTS: Although the overall HCV prevalence is decreasing in Belgium, the burden of advanced stage HCV, including cirrhosis and hepatocellular carcinoma (HCC), is expected to increase under current treatment and cure rates. By increasing SVR to 90% from 2016 onward and the number of treated cases (from 710 to 2,050), in 2030 the cases with cirrhosis, decompensated cirrhosis and HCC would be significantly lower than in 2013. This strategy was found most efficient when applied to F2-F4 cases. To obtain comparable outcomes with F0-F4 cases, 3,490 patients should be treated. A two year delayed access to the DAAs increased HCV related morbidity and mortality by 15% relative to our strategy. CONCLUSIONS: Considering the evolving burden of HCV disease and the need for efficacious usage of healthcare resources, primary application of new DAAs in Belgium should focus on patients with significant and advanced fibrosis (F2-F4), providing these new drugs without delay upon availability and increasing access to therapy.

Hepatitis C epidemiology in Belgium.

BACKGROUND: The burden of hepatitis C virus (HCV) infection is significant and is increasing with the aging population. The results of a modeling study that included Belgium, along with many other countries, was published in April 2014. An in depth discussion surrounding the epidemiology of HCV in Belgium will be presented here. METHODS: A systematic literature review was conducted to assess the historical and current clinical burden of HCV in Belgium. Two expert panels were convened to discuss the strengths and limitations surrounding the available data and to generate consensus regarding the best estimates for total number of HCV cases, number of cases diagnosed, and the number of patients treated and cured, including potential HCV control strategies. RESULTS: Although no national studies exist, there were an estimated 70,000 (10,000-91,000) viremic HCV infections in 1994. By 2010 there were an estimated 22,900 individuals diagnosed with viremic HCV, and in 2011 approximately 710 patients were treated annually. An estimated 13% of liver transplants were attributable to HCV in 2011. Genotype 1 predominated (59%), followed by genotypes 3 (19%) and 4 (14%). CONCLUSIONS: Estimates of HCV prevalence, diagnosed cases and liver transplants due to HCV were available through published studies. However these publications were subject to bias and were occasionally outdated. Improved estimates of HCV prevalence would be useful for informing treatment, prevention and policy efforts in Belgium.

Current and future health and economic impact of hepatitis C in Belgium.

BACKGROUND AND STUDY AIMS: Chronic hepatitis C virus (HCV) infection is a serious global health problem affecting 150 million individuals worldwide. Although infection rates are decreasing, an aging population with progressing disease is expected to result in increased burden of advanced stage disease with high associated costs. This analysis describes the current and projected future economic impact of HCV sequelae in Belgium. METHODS: A previously described and validated model was populated with Belgian inputs and calibrated to project the current and future health and economic burden of HCV. Monte Carlo and sensitivity analyses were run to quantify uncertainty. All estimates exclude the cost of antiviral therapy. RESULTS: Costs associated with HCV were projected to peak in 2026 at Euro126M (Euro30M-Euro257M), while decompensated cirrhosis and hepatocellular carcinoma costs were projected to increase until 2031 and 2034. The projected 2014-2030 cumulative cost of HCV under current conditions was Euro1,850M. Scenarios to reduce the burden of HCV could result in Euro70M-Euro400M in cumulative cost savings. Starting treatment (1,000 patients) in 2015 could result in Euro150M cost savings. The lifetime cost of HCV increases with life expectancy, with highest future costs projected among young females with early stage disease. CONCLUSIONS: The economic burden of HCV and advanced stage disease were projected to further increase. Cost reductions are possible with timely interventions aimed at minimizing the health burden of advanced stage disease.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Does consumption of polyunsaturated fatty acids influence on neurorehabilitation in traumatic spinal cord-injured individuals? A double-blinded clinical trial.

STUDY DESIGN: A double-blinded randomized clinical trial. OBJECTIVES: The anti-inflammatory and neuroprotective effect of omega-3 fatty acids have been shown so far, but still its influence on clinical measures in spinal cord-injured human models were not known. We tried to investigate changes in disability and dependency scores in chronic traumatic spinal cord-injured patients after 14 months of ω-3 fatty-acid consumption. METHODS: Main inclusion criteria were: traumatic spinal cord injury (SCI) and post injury duration longer than 1 year. Disability and dependency was assessed using U.K Functional Independence Measure and Functional Assessment Measure (FIM+FAM) scale. MorDHA capsules (435 mg of docosahexaenoic acid and 65 mg of eicosapentaenoic acid) were administered in treatment group, whereas control group received placebo capsules for 14 months. U.K. FIM+FAM scale were estimated before intervention and at the end of the trial. RESULTS: Fifty-four patients in treatment group and 50 patients in placebo group completed the trial. Highest scores were detected in cognitive domain in both groups before and after intervention. Most dependency was observed in locomotion subscale and secondly in sphincter control. Scores of none of these components were changed by ω-3 fatty-acid consumption. CONCLUSION: Although omega-3 fatty acids have been shown to have neuroprotective effect in acute phase of SCI, it seems that they have no significant influence in chronic inflammatory state of SCI. The positive effect of ω-3 fatty acid in chronic neurorecovery process, if exists, is weaker to exert any significant improvement in UK FIM+FAM scores in spinal cord-injured individuals.

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

Economic burden of hepatitis C-associated diseases in the United States.

There are approximately 100 drugs in development to treat hepatitis C. Over the next decade, a number of new therapies will become available. A good understanding of the cost of hepatitis C sequelae is important for assessing the value of new treatments. The objective of this study was to assess the economic burden data sources for hepatitis C in the United States. A systematic literature search was conducted to identify studies reporting the costs of hepatitis C sequelae in the United States. Over 400 references were identified, of which 50 were pertinent. The costs were compiled and adjusted to 2010 constant US dollars using the medical component of the consumer price index (CPI). The cost of liver transplants was estimated at $201 110 ($178 760-$223 460), hepatocellular carcinoma (HCC) at $23 755-$44 200, variceal haemorrhage at $25 595, compensated cirrhosis at $585-$1110, refractory ascites at $24 755, hepatic encephalopathy at $16 430, sensitive ascites at $2450, moderate chronic hepatitis C at $155, and mild chronic hepatitis C at $145 per year per person. All studies were traced back to a handful of publications in the 1990s, which have provided the basis for all sequelae-based cost estimates to date. Hepatitis C imposes a high economic burden. Most cost analysis is more than 10 years old, and more research is required to update the sequelae costs associated with HCV infection.

Comparison between optimized geometries and vibrational frequencies calculated by the DFT methods for the Anderson-type heteropolyanion: hexamolybdoaluminate(III), [AlIII(OH)6Mo6O18]3-.

Optimized geometries and vibrational frequencies were calculated for the hexamolybdoaluminate(III), [AlIII(OH)6Mo6O18]3-, Anderson-type heteropolyanion with the HF, B3LYP, B3PW91, B3P86 and B1LYP methods of theory using the LanL2DZ, SDD and combination of LanL2DZ with 6-31G (d, p) basis sets. The agreement between the optimized and experimental geometries was in the decreasing order: HF, B3P86, B3PW91, B1LYP and B3LYP. The calculated frequencies by the B3LYP have the smallest mean root mean square (RMS) error. The effect of the basis set on the calculated bond lengths and frequencies by the density functional calculations (DFT) methods was minor. The agreement between the previously reported IR and Raman spectra and the calculated values is, in general, good.

Effects of macrophage inducible nitric oxide synthase in murine septic lung injury.

Inducible nitric oxide synthase (iNOS) contributes importantly to septic pulmonary protein leak in mice with septic acute lung injury (ALI). However, the role of alveolar macrophage (AM) iNOS in septic ALI is not known. Thus we assessed the specific effects of AM iNOS in murine septic ALI through selective AM depletion (via intratracheal instillation of clodronate liposomes) and subsequent AM reconstitution (via intratracheal instillation of donor iNOS+/+ or iNOS-/- AM). Sepsis was induced by cecal ligation and perforation, and ALI was assessed at 4 h: protein leak by the Evans blue (EB) dye method, neutrophil infiltration via myeloperoxidase (MPO) activity, and pulmonary iNOS mRNA expression via RT-PCR. In iNOS+/+ mice, AM depletion attenuated the sepsis-induced increases in pulmonary microvascular protein leak (0.3 +/- 0.1 vs. 1.4 +/- 0.1 microg EB.g lung(-1).min(-1); P < 0.05) and MPO activity (37 +/- 4 vs. 67 +/- 8 U/g lung; P < 0.05) compared with that shown in non-AM-depleted mice. In AM-depleted iNOS+/+ mice, septic pulmonary protein leak was restored by AM reconstitution with iNOS+/+ AM (0.9 +/- 0.3 microg EB.g lung(-1).min(-1)) but not with iNOS-/- donor AM. In iNOS-/- mice, sepsis did not induce pulmonary protein leak or iNOS mRNA expression, despite increased pulmonary MPO activity. However, AM depletion in iNOS-/- mice and subsequent reconstitution with iNOS+/+ donor AM resulted in significant sepsis-induced pulmonary protein leak and iNOS expression. Septic pulmonary MPO levels were similar in all AM-reconstituted groups. Thus septic pulmonary protein leak is absolutely dependent on the presence of functional AM and specifically on iNOS in AM. AM iNOS-dependent pulmonary protein leak was not mediated through changes in pulmonary neutrophil influx.

Occupational and environmental causes of bronchogenic carcinoma.

Occupational and environmental carcinogens account for an important minority of cases of bronchogenic carcinoma. From a public health perspective, it is important to characterize occupational and environmental carcinogens and to define disease risk to reduce preventable lung cancer. From a clinician's perspective, it is important to distinguish individual cases of occupational lung cancer from nonoccupational cases, because cancer acquired from work may be compensable through worker's compensation claims and litigation. Important carcinogens include asbestos, radon daughters, diesel exhaust, and metals. Epidemiologic investigations identify excess cases of lung cancer in populations exposed to carcinogens. Experimental animal and ex vivo human research provide complementary information supporting causal relationships between exposure and carcinogenesis. Clinical challenges include proving that a given case of lung cancer is due to an occupational exposure. Research challenges include determining safe exposure thresholds. Only a small percentage of all chemicals used in industry have been extensively analyzed for their carcinogenic potential. Scientific and regulatory information about pulmonary occupational and environmental health and safety is available from several important agencies and organizations, including the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, the International Agency for Research on Cancer, the American Lung Association, and the Environmental Protection Agency.