Browsing by Author "Tsochatzis, Emmanuel A."

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    A global action agenda for turning the tide on fatty liver disease
    (2024) Lazarus, Jeffrey V.; Mark, Henry E.; Allen, Alina M.; Arab, Juan Pablo; Carrieri, Patrizia; Noureddin, Mazen; Alazawi, William; Alkhouri, Naim; Alqahtani, Saleh A.; Anstee, Quentin M.; Arrese, Marco; Bataller, Ramon; Berg, Thomas; Brennan, Paul N.; Burra, Patrizia; Castro-Narro, Graciela E.; Cortez-Pinto, Helena; Cusi, Kenneth; Dedes, Nikos; Duseja, Ajay; Francque, Sven M.; Gastaldelli, Amalia; Hagstrom, Hannes; Huang, Terry T. K.; Wajcman, Dana Ivancovsky; Kautz, Achim; Kopka, Christopher J.; Krag, Aleksander; Newsome, Philip N.; Rinella, Mary E.; Romero, Diana; Sarin, Shiv Kumar; Silva, Marcelo; Spearman, C. Wendy; Terrault, Norah A.; Tsochatzis, Emmanuel A.; Valenti, Luca; Villota-Rivas, Marcela; Zelber-Sagi, Shira; Schattenberg, Joern M.; Wong, Vincent Wai-Sun; Younossi, Zobair M.
    Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care.Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance.Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.
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    A global research priority agenda to advance public health responses to fatty liver disease
    (2023) Lazarus, Jeffrey V.; Mark, Henry E.; Allen, Alina M.; Arab, Juan Pablo; Carrieri, Patrizia; Noureddin, Mazen; Alazawi, William; Alkhouri, Naim; Alqahtani, Saleh A.; Arrese, Marco; Bataller, Ramon; Berg, Thomas; Brennan, Paul N.; Burra, Patrizia; Castro-Narro, Graciela E.; Cortez-Pinto, Helena; Cusi, Kenneth; Dedes, Nikos; Duseja, Ajay; Francque, Sven M.; Hagstrom, Hannes; Huang, Terry T. -K.; Wajcman, Dana Ivancovsky; Kautz, Achim; Kopka, Christopher J.; Krag, Aleksander; Miller, Veronica; Newsome, Philip N.; Rinella, Mary E.; Romero, Diana; Sarin, Shiv Kumar; Silva, Marcelo; Spearman, C. Wendy; Tsochatzis, Emmanuel A.; Valenti, Luca; Villota-Rivas, Marcela; Zelber-Sagi, Shira; Schattenberg, Jorn M.; Wong, Vincent Wai-Sun; Younossi, Zobair M.
    Background & aims: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community.
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    Advancing the global public health agenda for NAFLD: a consensus statement
    (2022) Lazarus, Jeffrey, V; Mark, Henry E.; Anstee, Quentin M.; Arab, Juan Pablo; Batterham, Rachel L.; Castera, Laurent; Cortez-Pinto, Helena; Crespo, Javier; Cusi, Kenneth; Dirac, M. Ashworth; Francque, Sven; George, Jacob; Hagstrom, Hannes; Huang, Terry T-K; Ismail, Mona H.; Kautz, Achim; Sarin, Shiv Kumar; Loomba, Rohit; Miller, Veronica; Newsome, Philip N.; Ninburg, Michael; Ocama, Ponsiano; Ratziu, Vlad; Rinella, Mary; Romero, Diana; Romero-Gomez, Manuel; Schattenberg, Jorn M.; Tsochatzis, Emmanuel A.; Valenti, Luca; Wong, Vincent Wai-Sun; Yilmaz, Yusuf; Younossi, Zobair M.; Zelber-Sagi, Shira
    Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.
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    Consensus Statement on the definition and classification of metabolic hyperferritinaemia
    (2023) Valenti, Luca; Corradini, Elena; Adams, Leon A.; Aigner, Elmar; Alqahtani, Saleh; Arrese, Marco; Bardou-Jacquet, Edouard; Bugianesi, Elisabetta; Fernandez-Real, Jose-Manuel; Girelli, Domenico; Hagstrom, Hannes; Henninger, Benjamin; Kowdley, Kris; Ligabue, Guido; McClain, Donald; Laine, Fabrice; Miyanishi, Koji; Muckenthaler, Martina U.; Pagani, Alessia; Pedrotti, Patrizia; Pietrangelo, Antonello; Prati, Daniele; Ryan, John D.; Silvestri, Laura; Spearman, C. Wendy; Stal, Per; Tsochatzis, Emmanuel A.; Vinchi, Francesca; Zheng, Ming-Hua; Zoller, Heinz
    Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.
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    Implementation of a liver health check in people with type 2 diabetes
    (2024) Abeysekera, Kushala W. M.; Valenti, Luca; Younossi, Zobair; Dillon, John F.; Allen, Alina M.; Noureddin, Mazen; Rinella, Mary E.; Tacke, Frank; Francque, Sven; Gines, Pere; Thiele, Maja; Newsome, Philip N.; Guha, Indra Neil; Eslam, Mohammed; Schattenberg, Joern M.; Alqahtani, Saleh A.; Arrese, Marco; Berzigotti, Annalisa; Holleboom, Adriaan G.; Caussy, Cyrielle; Cusi, Kenneth; Roden, Michael; Hagstroem, Hannes; Wong, Vincent Wai-Sun; Mallet, Vincent; Castera, Laurent; Lazarus, Jeffrey V.; Tsochatzis, Emmanuel A.
    As morbidity and mortality related to potentially preventable liver diseases are on the rise globally, early detection of liver fibrosis offers a window of opportunity to prevent disease progression. Early detection of non-alcoholic fatty liver disease allows for initiation and reinforcement of guidance on bodyweight management, risk stratification for advanced liver fibrosis, and treatment optimisation of diabetes and other metabolic complications. Identification of alcohol-related liver disease provides the opportunity to support patients with detoxification and abstinence programmes. In all patient groups, identification of cirrhosis ensures that patients are enrolled in surveillance programmes for hepatocellular carcinoma and portal hypertension. When considering early detection strategies, success can be achieved from applying ad-hoc screening for liver fibrosis in established frameworks of care. Patients with type 2 diabetes are an important group to consider case findings of advanced liver fibrosis and cirrhosis, as up to 19% have advanced fibrosis (which is ten times higher than the general population) and almost 70% have non-alcoholic fatty liver disease. Additionally, patients with type 2 diabetes with alcohol use disorders have the highest proportion of liver-related morbidity of people with type 2 diabetes generally. Patients with type 2 diabetes receive an annual diabetes review as part of their routine clinical care, in which the health of many organs are considered. Yet, liver health is seldom included in this review. This Viewpoint argues that augmenting the existing risk stratification strategy with an additional liver health check provides the opportunity to detect advanced liver fibrosis, thereby opening a window for early interventions to prevent end-stage liver disease and its complications, including hepatocellular carcinoma
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    Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease
    (2021) Shribman, Samuel; Heller, Carolin; Burrows, Maggie; Heslegrave, Amanda; Swift, Imogen; Foiani, Martha S.; Gillett, Godfrey T.; Tsochatzis, Emmanuel A.; Rowe, James B.; Gerhard, Alex; Butler, Chris R.; Masellis, Mario; Bremner, Fion; Martin, Alison; Jung, Lynne; Cook, Paul; Zetterberg, Henrik; Bandmann, Oliver; Rohrer, Jonathan D.; Warner, Thomas T.
    Background Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage. Objective To identify a biomarker for neurological involvement in WD. Methods Neuronal and glial-specific proteins were measured in plasma samples from 40 patients and 38 age-matched controls. Patients were divided into neurological or hepatic presentations and those with recent neurological presentations or deterioration associated with non-adherence were subcategorized as having active neurological disease. Unified WD Rating Scale scores and copper indices were recorded. Results Unlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients. Conclusion NfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments. (c) 2020 University College London.Movement Disorderspublished by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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    Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice
    (2023) Lazarus, Jeffrey, V; Castera, Laurent; Mark, Henry E.; Allen, Alina M.; Adams, Leon A.; Anstee, Quentin M.; Arrese, Marco; Alqahtani, Saleh A.; Bugianesi, Elisabetta; Colombo, Massimo; Cusi, Kenneth; Hagstrom, Hannes; Loomba, Rohit; Romero-Gomez, Manuel; Schattenberg, Jorn M.; Thiele, Maja; Valenti, Luca; Wong, Vincent Wai-Sun; Yilmaz, Yusuf; Younossi, Zobair M.; Francque, Sven M.; Tsochatzis, Emmanuel A.
    Background & Aims: Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings. Methods: A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas.Results: There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan & REG;), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan & REG;, 21% of respondents used a single liver stiffness cut-off: 8 kPa in 50%, while the rest used 7.2 kPa, 7.8 kPa and 8.7 kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10 kPa and >7.5 to >20 kPa, respectively).Conclusions: The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management. Lay summary: Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.& COPY; 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).