Targeted next-generation sequencing of adult gliomas for retrospective prognostic evaluation and up-front diagnostics.

AIMS: We aimed to reclassify a population-based cohort of 529 adult glioma patients to evaluate the prognostic impact of the 2016 World Health Organization (WHO) central nervous system tumour classification. Moreover, we evaluated the feasibility of gene panel next-generation sequencing (NGS) in daily diagnostics of 225 prospective glioma patients. METHODS: The retrospective cohort was reclassified according to WHO 2016 criteria by immunohistochemistry for IDH-R132H, fluorescence in situ hybridization for 1p/19q-codeletion and gene panel NGS. All tumours of the prospective cohort were subjected to NGS analysis up-front. RESULTS: The entire population-based cohort was successfully reclassified according to WHO 2016 criteria. NGS results were obtained for 98% of the prospective patients. Survival analyses in the population-based cohort confirmed three major prognostic subgroups, that is, isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas, IDH-mutant astrocytomas and IDH-wildtype glioblastomas. The distinction between WHO grade II and III was prognostic in patients with IDH-mutant astrocytoma. The survival of patients with IDH-wildtype diffuse astrocytomas carrying TERT promoter mutation and/or EGFR amplification overlapped with the poor survival of IDH-wildtype glioblastoma patients. CONCLUSIONS: Gene panel NGS proved feasible in daily diagnostics. In addition, our study confirms the prognostic role of glioma classification according to WHO 2016 in a large population-based cohort. Molecular features of glioblastoma in IDH-wildtype diffuse glioma were linked to poor survival corresponding to IDH-wildtype glioblastoma patients. The distinction between WHO grade II and III retained prognostic significance in patients with IDH-mutant diffuse astrocytic gliomas.

Historical epidemiology of hepatitis C virus in select countries-volume 4.

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

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.

Achieving WHO recommendations for Hepatitis C Virus Elimination in Belgium.

BACKGROUD: The World Health Organization (WHO) released updated guidelines for the screening, care and treatment of patients with chronic hepatitis C virus (HCV) infection. METHODS: A previously described HCV disease burden model was used to develop a "WHO scenario" to achieve the WHO recommendations of a 90% reduction in incidence and 65% reduction in liver-related deaths. After determining the steps necessary to achieve this goal, the impact of realistic constraints was modeled. RESULTS: In 2015, there were 66.200 viremic infections, with 43% diagnosed and 1.350 treated. In order to reduce new infections, treatment must be extended to ≥ F0 patients, including people who inject drugs and other individuals at risk of transmitting HCV. -Additionally, diagnosis and treatment of 3.030 and 4.060 patients, respectively, would be required. The largest attenuation of the WHO scenario would occur if no new cases were diagnosed after 2018 (300% more viremic infections by 2030). Limiting treatment to ≥ F2 patients or treating fewer patients (3.000) would result in 220% or 140% more viremic cases, respectively, compared with the WHO scenario. CONCLUSION: Achieving the WHO guidelines in Belgium requires a coordinated effort to scale up treatment and prevention efforts and to allow treatment access to patients of all fibrosis stages. A scale-up of treatment, however, requires patients to be both diagnosed and linked to care, suggesting a need for increased awareness and expanded screening efforts. Finally, prevention of new HCV infections requires a comprehensive understanding of the population at risk of transmitting HCV.

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.

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

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).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.