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Sökning: WFRF:(Ramji A)

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1.
  • Blach, S., et al. (författare)
  • Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
  • 2022
  • Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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  • Bruggmann, P., et al. (författare)
  • Historical epidemiology of hepatitis C virus (HCV) in selected countries
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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  • Razavi, H., et al. (författare)
  • The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Wedemeyer, H., et al. (författare)
  • Strategies to manage hepatitis C virus (HCV) disease burden
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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  • Razavi-Shearer, Devin M., et al. (författare)
  • Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
  • 2024
  • Ingår i: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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  • Razavi, Homie A., et al. (författare)
  • Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
  • 2023
  • Ingår i: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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  • Lagging, Martin, 1965, et al. (författare)
  • Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial
  • 2016
  • Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504. ; 23:2, s. 80-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Grazoprevir (MK-5172, Merck & Co., Inc.) is a selective inhibitor of the hepatitis C virus (HCV) NS3/4a protease. The aim of this study was to evaluate the safety and efficacy of grazoprevir at doses of 25-100mg/day in combination with peginterferon and ribavirin (PEG-IFN/RBV). In this randomized, dose-ranging, multicentre trial, treatment-naive adults with chronic HCV genotype 1 infection received once-daily grazoprevir 25mg, 50mg or 100mg plus PEG-IFN/RBV for 12weeks. Patients with quantifiable HCV RNA (25IU/mL) at week 4 received an additional 12weeks of PEG-IFN/RBV. The primary endpoint was sustained virologic response (HCV RNA <25IU/mL 12weeks after completing therapy [SVR12]). Eighty-seven patients were randomly assigned and received 1 dose of therapy. Median time to undetectable HCV RNA was 16days in the 100-mg arm and 22days in the 25- and 50-mg arms. All patients except one had HCV RNA undetectable or unquantifiable at week 4 and received 12weeks of therapy. SVR12 was achieved by 13 of 24 (54.2%), 21 of 25 (84.0%) and 23 of 26 (88.5%) patients in the 25-, 50- and 100-mg arms, respectively (per-protocol analysis). Three patients discontinued as a result of nonserious adverse events (AEs) and three patients experienced serious AEs. Transaminase elevations occurred in two patients (one each in the 25- and 100-mg arms). Conclusion: These data support further study of the grazoprevir 100-mg dose. Phase 3 studies of grazoprevir 100mg in combination with elbasvir are currently ongoing (NCT01710501; protocol P038).
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