Browsing by Author "Noureddin, Mazen"

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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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    Alcohol‐Attributable Cancer: Update From the Global Burden of Disease 2021 Study
    (2025) Danpanichkul, Pojsakorn; Pang, Yanfang; Díaz Piga, Luis Antonio; White, Trenton M.; Sirimangklanurak, Supapitch; Auttapracha, Thanida; Suparan, Kanokphong; Syn, Nicholas; Jatupornpakdee, Pimtawan; Saowapa, Sakditad; Ng, Cheng Han; Kaewdech, Apichat; Lui, Rashid N.; Fallon, Michael B.; Yang, Ju Dong; Louvet, Alexandre; Noureddin, Mazen; Liangpunsakul, Suthat; Jepsen, Peter; Lazarus, Jeffrey V.; Arab, Juan Pablo; Wijarnpreecha, Karn
    Background and AimsAlcohol is a major risk factor for cancer development. Our study aimed to provide the updated global, regional and national burden of alcohol-attributable cancer.Approach and ResultsWe analysed the Global Burden of Disease Study 2021 to determine the death and age-standardised death rate (ASDR) from alcohol-attributable cancer and the change of these measures between 2000 and 2021 (reflected as annual percent change [APC]), classified by region, nation and country's developmental status, which is based on the sociodemographic index (SDI).ResultsIn 2021, there were 343,370 deaths globally from alcohol-attributable cancer, which was an increase from 2000 by 51%. Alcohol-attributable cancer accounted for 3.5% of all cancer deaths. Among alcohol-attributable cancer, liver cancer (27%) accounted for the highest mortality from alcohol, followed by oesophageal (24%) and colorectal cancer (16%). From 2000 to 2021, ASDR from alcohol-attributable cancer decreased (APC: −0.66%). Regionally, from 2000 to 2021, the fastest-growing ASDR was observed in South Asia. Classified by SDI, low (APC: 0.33%) and low-to-middle SDI countries (APC: 1.58%) exhibited an uptrend in ASDR from alcohol-attributable cancer. While the ASDR from all other cancers decreased, ASDR from early-onset (15–49 years) lip and oral cavity cancer increased (APC: 0.40%).ConclusionsFrom 2000 to 2021, although the ASDR from alcohol-attributable cancer declined, the total number of deaths continued to rise. This trend was accompanied by variations across sociodemographic groups and cancer types, particularly gastrointestinal cancers. Urgent efforts are needed both globally and at regional levels to address the burden of alcohol-attributable cancers.
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    Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019
    (2024) Danpanichkul, Pojsakorn; Suparan, Kanokphong; Dutta, Priyata; Kaeosri, Chuthathip; Sukphutanan, Banthoon; Pang, Yanfang; Kulthamrongsri, Narathorn; Jaisa-aad, Methasit; Ng, Cheng Han; Teng, Margaret; Nakano, Masahito; Morishita, Asahiro; Alkhouri, Naim; Yang, Ju Dong; Chen, Vincent L.; Kim, Donghee; Fallon, Michael B.; Diaz, Luis Antonio; Arab, Juan Pablo; Mantzoros, Christos S.; Noureddin, Mazen; Lazarus, Jeffrey, V; Wijarnpreecha, Karn
    Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary. Methods: From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data. Results: Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase ( +134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/ AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average. Conclusion: The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher (DALYs) disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.
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    Disparities in steatosis prevalence in the United States by Race or Ethnicity according to the 2023 criteria
    (2024) Díaz, Luis Antonio; Lazarus, Jeffrey V.; Fuentes López, Eduardo; Idalsoaga Ferrer, Francisco Javier; Ayares Campos, Gustavo Ignacio; Desaleng, Hailemichael; Danpanichkul, Pojsakorn; Cotter, Thomas G.; Dunn, Winston; Barrera Martínez, Francisco; Wijarnpreecha, Karn; Noureddin, Mazen; Alkhouri, Naim; Singal, Ashwani K.; Wong, Robert J.; Younossi, Zobair M.; Rinella, Mary E.; Kamath, Patrick S.; Bataller, Ramon; Loomba, Rohit; Arrese Jiménez, Marco; Arab Verdugo, Juan Pablo
    © The Author(s) 2024.Introduction: The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature. Methods: We undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed. Results: A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk. Conclusions: MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.
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    From Shadows to Spotlight: Exploring the Escalating Burden of Alcohol-Associated Liver Disease and Alcohol Use Disorder in Young Women
    (2024) Danpanichkul, Pojsakorn; Ng, Cheng Han; Muthiah, Mark; Suparan, Kanokphong; Tan, Darren Jun Hao; Duangsonk, Kwanjit; Sukphutanan, Banthoon; Kongarin, Siwanart; Harinwan, Nateeluck; Panpradist, Nuttada; Takahashi, Hirokazu; Kawaguchi, Takumi; Vichitkunakorn, Polathep; Chaiyakunapruk, Nathorn; Nathisuwan, Surakit; Huang, Daniel; Arab, Juan Pablo; Noureddin, Mazen; Mellinger, Jessica Leigh; Wijarnpreecha, Karn
    INTRODUCTION: The burden of alcohol-related complications is considerable, particularly alcohol-associated liver disease and alcohol use disorder (AUD). However, there are deficiencies in comprehensive epidemiological research focusing on these issues, especially among young women who display higher susceptibility to such complications compared with their male counterparts. We thus aimed to determine the global burden of these conditions in this vulnerable group.
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    Global and regional burden of alcohol-associated liver disease and alcohol use disorder in the elderly
    (2024) Danpanichkul, Pojsakorn; Suparan, Kanokphong; Ng, Cheng Han; Dejvajara, Disatorn; Kongarin, Siwanart; Panpradist, Nuttada; Chaiyakunapruk, Nathorn; Muthiah, Mark D.; Chen, Vincent L.; Huang, Daniel Q.; Diaz, Luis Antonio; Noureddin, Mazen; Arab, Juan Pablo; Wijarnpreecha, Karn
    Background & Aims: Alcohol -associated liver diseases (ALDs) and alcohol use disorder (AUD) pose a global health risk. AUD is underrecognized in the elderly, and the burden of AUD complications, including ALD, may increase with aging populations and rising alcohol intake. However, there is a lack of epidemiological evidence on AUD and ALD in the elderly. Methods: Using the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, disability -adjusted life years (DALYs), age -standardized rates (ASRs), and temporal change from 2000 to 2019 of ALD and AUD in the overall population and the elderly (65-89 years). The findings were categorized by sex, region, nation, and sociodemographic index. Results: The prevalence rates of ALD in the elderly were higher than those in adolescents and young adults, whereas AUD levels were lower than those in adolescents and young adults. In 2019, there were 9.39 million cases (8.69% of cases in the overall population) of AUD, 3.23 million cases (21.8% of cases in the overall population) of alcohol -associated cirrhosis, and 68,468 cases (51.27% of cases in the overall population) of liver cancer from alcohol among the elderly. ASRs of the prevalence of ALD and AUD in the elderly increased in most regions; on the contrary, ASRs of death and DALYs decreased in most regions. Nevertheless, ASRs of death and DALYs from liver cancer from alcohol increased in many areas. Conclusions: Our findings highlighted the increased prevalence of ALD in the elderly, with a burden of AUD comparable with that in the overall population. Public health strategies on ALD and AUD targeting the elderly are urgently needed. Impact and implications: The burden of alcohol -associated liver disease (ALD) and alcohol use disorder (AUD) is increasing. Advances in healthcare and education have resulted in a remarkable spike in life expectancy and a consequential population aging. Nevertheless, little is known about the epidemiology of ALD and AUD in the elderly. Our study indicates the increasing burden of ALD and AUD in the elderly population, necessitating early detection, intervention, and tailored care to the unique needs and complexities faced by older individuals grappling with these conditions. (c) 2024 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 -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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    Global epidemiology of alcohol-associated liver disease in adolescents and young adults
    (2024) Danpanichkul, Pojsakorn; Chen, Vincent L.; Tothanarungroj, Primrose; Kaewdech, Apichat; Kanjanakot, Yatawee; Fangsaard, Panisara; Wattanachayakul, Phuuwadith; Duangsonk, Kwanjit; Kongarin, Siwanart; Yang, Ju Dong; Wong, Robert J.; Noureddin, Mazen; Diaz, Luis Antonio; Arab, Juan Pablo; Liangpunsakul, Suthat; Wijarnpreecha, Karn
    Background and AimsThe objective of the study was to analyse the prevalence, incidence, and death of alcohol-associated liver disease (ALD) among adolescents and young adults globally, continentally, and nationally, focusing on trends over time.MethodsThe study analysed data from the Global Burden of Disease (GBD) study between 2000 and 2019. It examined ALD's prevalence, incidence, and death in adolescents and young adults aged 15-29, segmented by region, nation, and sociodemographic index. The analysis utilised Joinpoint regression modelling to calculate the annual per cent change (APC) in the rate of these parameters over time.ResultsIn 2019, there were 281,450 ALD prevalences, 18,930 incidences, and 3190 deaths among adolescents and young adults globally. From 2000 to 2019, the age-adjusted prevalence rate per 100,000 increased in the 25-29 age group (APC: +0.6%, p = 0.003), remained stable among ages 20-24 (p = 0.302) and ages 15-19 (p = 0.160). Prevalence increased significantly from age 15-19 to 20-24 (19-fold increase) and from age 20-24 to 25-29 (2.5-fold increase). ALD prevalence rates increased in all age groups in adolescents and young adults in Africa and the Eastern Mediterranean region. Around three-quarters of countries and territories experienced an increase in ALD incidence rates in young adults.ConclusionOver two decades, the burden of ALD among adolescents and young adults has increased globally. The study emphasises the importance of public health policies aimed at reducing alcohol consumption and preventing ALD among younger populations.
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    Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021
    (2025) Danpanichkul, Pojsakorn; Díaz Piga, Luis Antonio; Suparan, Kanokphong; Tothanarungroj, Primrose; Sirimangklanurak, Supapitch; Auttapracha, Thanida; Blaney, Hanna L.; Sukphutanan, Banthoon; Pang, Yanfang; Kongarin, Siwanart; Idalsoaga, Francisco; Fuentes-López, Eduardo; Leggio, Lorenzo; Noureddin, Mazen; White, Trenton M.; Louvet, Alexandre; Mathurin, Philippe; Loomba, Rohit; Kamath, Patrick S.; Rehm, Jürgen; Lazarus, Jeffrey V.; Wijarnpreecha, Karn; Arab Verdugo, Juan Pablo
    Background/Aims Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000–2021. Methods We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time. Results In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC 0.59%; 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC –0.71%; 95% CI –0.75 to –0.67%) and AUD (APC –0.90%; 95% CI –0.94 to –0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019–2021), the prevalence, incidence, and death of ALD increased to a greater extent in females. Conclusions Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.
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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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    Incidence of liver cancer in young adults according to the Global Burden of Disease database 2019
    (2024) Danpanichkul, Pojsakorn; Aboona, Majd B.; Sukphutanan, Banthoon; Kongarin, Siwanart; Duangsonk, Kwanjit; Ng, Cheng Han; Muthiah, Mark D.; Huang, Daniel Q.; Seko, Yuya; Diaz Piga, Luis Antonio; Arab Verdugo, Juan Pablo; Yang, Ju Dong; Chen, Vincent L.; Kim, Donghee; Noureddin, Mazen; Liangpunsakul, Suthat; Wijarnpreecha, Karn
    Background and Aims: The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms., Approach and Results: This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million disability-adjusted life years in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010 and 2019. More than half of the countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease database include reliance on the quality of primary data and possible underestimation of alcohol consumption., Conclusions: Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.
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    Letter to the Editor: Serum Identification of At-Risk MASH: The Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF)
    (2024) Noureddin, Mazen; Truong, Emily; Mayo, Rebeca; Martínez-Arranz, Ibon; Mincholé, Itziar; Banales, Jesús M.; Arrese Jiménez, Marco Antonio; Cusi, Kenneth; Arias-Loste, María Teresa; Bruha, Radan; Romero-Gómez, Manuel; Iruzubieta, Paula; Aller, Rocío; Ampuero, Javier; Calleja, José Luis; Ibáñez-Samaniego, Luis; Aspichueta, Patricia; Marín-Duce, Antonio; Kushner, Tatyana; Ortiz, Pablo
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    Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
    (2022) Martinez-Arranz, Ibon; Bruzzone, Chiara; Noureddin, Mazen; Gil-Redondo, Ruben; Minchole, Itziar; Bizkarguenaga, Maider; Arretxe, Enara; Iruarrizaga-Lejarreta, Marta; Fernandez-Ramos, David; Lopitz-Otsoa, Fernando; Mayo, Rebeca; Embade, Nieves; Newberry, Elizabeth; Mittendorf, Bettina; Izquierdo-Sanchez, Laura; Smid, Vaclav; Arnold, Jorge; Iruzubieta, Paula; Perez Castano, Ylenia; Krawczyk, Marcin; Marigorta, Urko M.; Morrison, Martine C.; Kleemann, Robert; Martin-Duce, Antonio; Hayardeny, Liat; Vitek, Libor; Bruha, Radan; Aller de la Fuente, Rocio; Crespo, Javier; Romero-Gomez, Manuel; Banales, Jesus M.; Arrese, Marco; Cusi, Kenneth; Bugianesi, Elisabetta; Klein, Samuel; Lu, Shelly C.; Anstee, Quentin M.; Millet, Oscar; Davidson, Nicholas O.; Alonso, Cristina; Mato, Jose M.
    Background and Aims We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. Approach and Results We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Conclusions Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.
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    MetALD: New Perspectives on an Old Overlooked Disease
    (WILEY, 2025) Ayares, Gustavo; Díaz, Luis Antonio; Idalsoaga, Francisco; Alkhouri, Naim; Noureddin, Mazen; Bataller, Ramon; Loomba, Rohit; Arab, Juan Pablo; Arrese, Marco
    Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) are the major contributors to the liver disease burden globally. The rise in these conditions is linked to obesity, type 2 diabetes, metabolic syndrome and increased alcohol consumption. MASLD and ALD share risk factors, pathophysiology and histological features but differ in their thresholds for alcohol use, and the ALD definition does not require the presence of metabolic dysfunction. A recent multi-society consensus overhauled the nomenclature of liver steatosis and introduced the term MetALD to describe patients with metabolic dysfunction who drink more than those with MASLD and less than those with ALD. This new terminology aims to enhance the understanding and management of liver disease but poses challenges, such as the need to accurately measure alcohol consumption in research and clinical practice settings. Recent studies show that MetALD has significant implications for patient management, as it is associated with increased mortality risks and more severe liver outcomes compared to MASLD alone. MetALD patients face increased risks of liver disease progression, cancer and cardiovascular disease. The diagnosis of MetALD involves the adequate quantification of alcohol use through standardised questionnaires and/or biomarkers as well as proper assessment of liver disease stage and progression risk using non-invasive tools including serologic markers, imaging, elastography techniques and genetic testing. Effective management requires addressing both metabolic and alcohol-related factors to improve outcomes. This review intends to provide a comprehensive overview of MetALD, covering pathogenesis, potential diagnostic approaches, management strategies and emerging therapies.
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    Mortality outcomes in individuals with MASLD versus MASLD and increased alcohol intake
    (2024) Aboona, Majd B.; Danpanichkul, Pojsakorn; Chen, Vincent L.; Rangan, Pooja; Kim, Donghee; Alkhouri, Naim; Fallon, Michael B.; Noureddin, Mazen; Arab, Juan Pablo; Wijarnpreecha, Karn
    Background and Aim Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease worldwide. A new entity termed MetALD has also been described and is defined as individuals with MASLD and increased alcohol intake. However, the natural history of MetALD compared with MASLD is unknown. We aimed to compare longitudinal outcomes in patients with MASLD versus MetALD. Methods This study was performed using data from the National Health and Nutrition Examination Survey from 2011 to 2018. MASLD patients (defined by the United States Fatty Liver Index > 30) who met cardiometabolic criteria including body mass index (BMI) > 25 (BMI > 23 in Asians), hypertension, diabetes mellitus, dyslipidemia, and hypertriglyceridemia were included. MetALD was defined as MASLD with increased alcohol intake (3-6 standard drinks per day in males; 2-5 standard drinks per day in females). A comparison of overall, cardiovascular, cancer-related, and other causes of mortality in patients with MASLD versus MetALD was performed. Results A total of 2838 individuals with MASLD and 2557 individuals with MetALD were included with a median follow-up time of 56 months. MetALD patients were at increased risk of cancer-related mortality compared with patients with MASLD (hazard ratio 1.32; 95% confidence interval 1.14-1.53; P < 0.01). However, there was no significant difference in overall, cardiovascular, and other causes of mortality. Conclusions Patients with MetALD were at higher risk for cancer-related mortality than MASLD. Close attention to regular cancer surveillance and accurate classification of alcohol consumption in individuals with diagnosed MASLD is warranted to help improve patient care and outcome.
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    Research and clinical trial design in patients with metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD): a narrative review
    (2025) Acuña Valenzuela, Pedro Pablo; Albhaisi, Omar; Idalsoaga Ferrer, Francisco Javier; Alkhouri, Naim; Noureddin, Mazen; Diaz Piga, Luis Antonio; Arab Verdugo, Juan Pablo
    This narrative review examines current trial design strategies and highlights the limitations of traditional models in capturing the heterogeneity and dynamic nature of metabolic dysfunction and alcohol-associated liver disease (MetALD). MetALD represents an increasingly prevalent and clinically distinct phenotype that reflects the convergence of metabolic risk factors and alcohol-related liver injury. Designing effective clinical and translational research in MetALD presents unique challenges as its burden continues to rise. Novel frameworks, such as adaptive and enrichment designs, offer improved pathways for patient stratification and intervention testing. The integration of molecular and translational biomarkers to inform diagnosis, prognosis, and therapeutic responsiveness is central to this evolution. This review also addresses critical methodological issues, including the need for harmonized definitions, careful endpoint selection, and real-world applicability of findings. Emerging therapies targeting steatosis, inflammation, fibrosis, gut-liver axis dysfunction, and metabolic pathways are now entering clinical development and require trial designs tailored to the multifaceted biology of MetALD. In this context, the article also discusses the importance of early-phase proof-of-concept studies and innovative approaches for combination therapies. Ethical and operational considerations, such as alcohol use thresholds, stigma, and disparities in access to care, further influence trial feasibility and generalizability. Finally, multidisciplinary collaboration across hepatology, addiction medicine, endocrinology, and trial methodology is essential to advance this field.
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    Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF)
    (2024) Noureddin, Mazen; Truong, Emily; Mayo, Rebeca; Martinez-Arranz, Ibon; Banales, Jesus M.; Minchole, Itziar; Arrese, Marco; Cusi, Kenneth; Arias-Loste, Maria Teresa; Bruha, Radan; Romero-Gomez, Manuel; Iruzubieta, Paula; Aller, Rocio; Ampuero, Javier; Calleja, Jose Luis; Ibanez-Samaniego, Luis; Aspichueta, Patricia; Martin-Duce, Antonio; Kushner, Tatyana; Ortiz, Pablo; Harrison, Stephen A.; Anstee, Quentin M.; Crespo, Javier; Mato, Jose M.; Sanyal, Arun J.
    Background: Early identification of those with NAFLD activity score >= 4 and significant fibrosis (>= F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.
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    Socio-economic association of alcohol use disorder and cardiovascular and alcohol-associated liver disease from 2010 to 2019
    (2024) Danpanichkul, Pojsakorn; Chen, Vincent L.; Chaiyakunapruk, Nathorn; Auttapracha, Thanida; Kongarin, Siwanart; Ng, Cheng Han; Duangsonk, Kwanjit; Muthiah, Mark D.; Sukphutanan, Banthoon; Sim, Benedix; Huang, Daniel Q.; Seko, Yuya; Lee, Brian P.; Takahashi, Hirokazu; Noureddin, Mazen; Lazarus, Jeffrey V.; Diaz, Luis Antonio; Arab, Juan Pablo; Mellinger, Jessica Leigh; Liangpunsakul, Suthat; Wijarnpreecha, Karn
    Backgrounds and AimsAlcohol use leads to disabilities and deaths worldwide. It not only harms the liver but also causes alcohol use disorder (AUD) and heart disease. Additionally, alcohol consumption contributes to health disparities among different socio-economic groups.MethodsWe estimated global and regional trends in the burden of AUD, liver disease, and cardiovascular disease from alcohol using the methodology of the Global Burden of Disease study.ResultsIn 2019, the highest disability-adjusted life years rate per 100,000 population was due to AUD (207.31 [95% Uncertainty interval (UI) 163.71-261.66]), followed by alcohol-associated liver disease (ALD) (133.31 [95% UI 112.68-156.17]). The prevalence rate decreased for AUD (APC [annual percentage change] -0.38%) and alcohol-induced cardiomyopathy (APC -1.85%) but increased for ALD (APC 0.44%) and liver cancer (APC 0.53%). Although the mortality rate for liver cancer from alcohol increased (APC 0.30%), mortality rates from other diseases decreased. Between 2010 and 2019, the burden of alcohol-associated complications increased in countries with low and low-middle sociodemographic index (SDI), contributing more significantly to the global burden.ConclusionThe global burden of AUD, liver, and cardiovascular disease has been high and increasing over the past decade, particularly for liver complications. Lower SDI countries are contributing more to this global burden. There is a pressing need for effective strategies to address this escalating burden.