Browsing by Author "Louvet, Alexandre"
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- ItemAlcohol‐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, KarnBackground 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.
- ItemAssociation between public health policies on alcohol and worldwide cancer, liver disease and cardiovascular disease outcomes(Elsevier B.V., 2023) Diaz Piga, Luis Antonio; Fuentes, López Eduardo; Idalsoaga Ferrer, Francisco Javier; Ayares Campos, Gustavo Ignacio; Corsi Sotelo, Oscar Felipe; Arnold Alvarez, Jorge Ignacio; Cannistra Cadiz, Macarena Rossella; Vio Quiroz, Danae Fernanda; Marquez Lomas, Andrea; Ramirez Cadiz, Carolina Andrea; Medel Salas, María Paz; Hernández Tejero, María; Ferreccio Readi, Fresia Catterina; Lazo Bravo, Mariana Carolina; Roblero Cum, Juan Pablo; Cotter, Thomas G.; Kulkarni ,Anand V.; Kim, Won; Brahmania, Mayur; Louvet, Alexandre; Tapper, Elliot B.; Dunn, Winston; Simonetto, Douglas; Shah, Vijay H.; Kamath, Patrick S.; Lazarus, Jeffrey V.; Singal, Ashwabi K.; Bataller, Ramón; Arrese Jimenez, Marco Antonio; Arab Verdugo, Juan Pablo© 2023 The Author(s)Background & Aims: The long-term impact of alcohol-related public health policies (PHPs) on disease burden is unclear. We aimed to assess the association between alcohol-related PHPs and alcohol-related health consequences. Methods: We conducted an ecological multi-national study including 169 countries. We collected data on alcohol-related PHPs from the WHO Global Information System of Alcohol and Health 2010. Data on alcohol-related health consequences between 2010–2019 were obtained from the Global Burden of Disease database. We classified PHPs into five items, including criteria for low, moderate, and strong PHP establishment. We estimated an alcohol preparedness index (API) using multiple correspondence analysis (0 lowest and 100 highest establishment). We estimated an incidence rate ratio (IRR) for outcomes according to API using adjusted multilevel generalized linear models with a Poisson family distribution. Results: The median API in the 169 countries was 54 [IQR 34.9–76.8]. The API was inversely associated with alcohol use disorder (AUD) prevalence (IRR 0.13; 95% CI 0.03–0.60; p = 0.010), alcohol-associated liver disease (ALD) mortality (IRR 0.14; 95% CI 0.03–0.79; p = 0.025), mortality due to neoplasms (IRR 0.09; 95% CI 0.02–0.40; p = 0.002), alcohol-attributable hepatocellular carcinoma (HCC) (IRR 0.13; 95% CI 0.02–0.65; p = 0.014), and cardiovascular diseases (IRR 0.09; 95% CI 0.02–0.41; p = 0.002). The highest associations were observed in the Americas, Africa, and Europe. These associations became stronger over time, and AUD prevalence was significantly lower after 2 years, while ALD mortality and alcohol-attributable HCC incidence decreased after 4 and 8 years from baseline API assessment, respectively (p <0.05). Conclusions: The API is a valuable instrument to quantify the robustness of alcohol-related PHP establishment. Lower AUD prevalence and lower mortality related to ALD, neoplasms, alcohol-attributable HCC, and cardiovascular diseases were observed in countries with a higher API. Our results encourage the development and strengthening of alcohol-related policies worldwide. Impact and implications: We first developed an alcohol preparedness index, an instrument to assess the existence of alcohol-related public policies for each country. We then evaluated the long-term association of the country's alcohol preparedness index in 2010 with the burden of chronic liver disease, hepatocellular carcinoma, other neoplasms, and cardiovascular disease. The strengthening of alcohol-related public health policies could impact long-term mortality rates from cardiovascular disease, neoplasms, and liver disease. These conditions are the main contributors to the global burden of disease related to alcohol use. Over time, this association has not only persisted but also grown stronger. Our results expand the preliminary evidence regarding the importance of public health policies in controlling alcohol-related health consequences.
- ItemClinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease(2025) Díaz Piga, Luis Antonio; Thiele, Maja; Louvet, Alexandre; Lee, Brian P.; Ajmera, Veeral; Tavaglione, Federica; Hsu, Cynthia L.; Huang, Daniel Q.; Pose, Elisa; Bataller, Ramon; McClain, Craig; Mellinger, Jessica; Tincopa, Monica; Mitchell, Mack C.; Ratziu, Vlad; Rinella, Mary E.; Sarin, Shiv K.; Shah, Vijay H.; Szabo, Gyongyi; Wong, Vincent Wai-Sun; Bansal, Meena B.; Leggio, Lorenzo; Kamath, Patrick S.; Krag, Aleksander; Sanyal, Arun J.; Arrese, Marco; Arab Verdugo, Juan Pablo; Anstee, Quentin M.; Mathurin, Philippe; Loomba, RohitMetabolic and alcohol-related liver disease (MetALD) is a newly defined entity within the spectrum of steatotic liver disease, characterized by the interplay of cardiometabolic risk factors and alcohol consumption. The evolving epidemiology and complex pathophysiology of MetALD present unique challenges and opportunities for clinical trial design. Inclusion criteria should require simultaneous evidence of metabolic dysfunction (at least two cardiometabolic features) and verified quantifiable alcohol exposure recorded over the preceding 3–6 months. Traditional histological end points are limited by invasiveness, sampling error and interpretative variability. Thus, imaging modalities, serum-based fibrosis biomarkers and quantitative measures of alcohol intake are gaining relevance as non-invasive, reproducible and patient-centric end points aiming to improve trial feasibility. Furthermore, incorporating alcohol biomarkers, stratifying patients by metabolic risk factor burden, and using adaptive designs of trials might enhance the precision and generalizability of MetALD clinical trials. Although uncertainties remain regarding optimal patient selection criteria, event rates and the dynamic interplay between metabolic dysfunction and alcohol intake, ongoing research efforts aim to refine diagnostic criteria, standardize methodologies and validate novel end points. These advances will ultimately accelerate drug development, improve trial efficiency and foster interventions to treat MetALD.
- ItemDefective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis(2019) Argemie, Josepmaria; Latasa, Maria U.; Atkinson, Stephen R.; Blokhin, Ilya O.; Massey, Verónica; Gue, Joel P.; Cabezas, Joaquín; Lozano, Juan J.; Van Booven, Derek; Arab Verdugo, Juan Pablo; Bell, Aaron; Cao, Sheng; Vernetti, Lawrence A.; Ventura Cots, Maritxell; Edmunds, Lia R.; Fondevilla, Constantino; Starkel, Peter; Dubuquoy, Laurent; Louvet, Alexandre; Odena, Gemma; Gómez, Juan L.; Aragón, Tomás; Altamirano, José; Caballeria, Juan; Jurczak, Michael J.; Taylor, D. Lansing; Berasain, Carmen; Wahlestedt, Claes; Monga, Satdaeshan P.; Morgan, Marsha Y.; Sancho Bru, Pau; Mathurin, Philippe; Furuya, Shinji; Lackner, Carolin; Rusyn, Ivan; Shah, Vijay H.; Thursz, Mark R.; Mann, Jelena; Ávila, Matías A.; Bataller, Ramón
- ItemGlobal 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 PabloBackground/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.
- ItemMELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis(Elsevier B.V., 2023) Diaz Piga, Luis Antonio; Fuentes Lopez, Eduardo; Ayares Campos, Gustavo Ignacio; Idalsoaga Ferrer, Francisco Javier; Arnold Álvarez, Jorge Ignacio; Valverde, María Ayala; Perez, Diego; Gómez, Jaime; Escarate, Rodrigo; Villalon Friedrich, Alejandro Andrés; Ramírez, Carolina A.; Hernández-Tejero, María; Zhang, Wei; Qian, Steve; Simonetto, Douglas; Ahn, Joseph C.; Buryska, Seth; Dunn, Winston; Mehta, Heer; Agrawal, Rohit; Cabezas, Joaquín; Garcia Carrera, Inés; Cuyas, Berta; Poca, Maria; Soriano, German; Sarin, Shiv K.; Maiwall, Rakhi; Jalal, Prasun K.; Abdulsada, Saba; Higuera de la Tijera, Fátima; Kulkarni, Anand V.; Rao, P. Nagaraja; Guerra Salazar, Patricia; Skladany, Lubomir; Bystrianska, Natália; Clemente Sánchez, Ana; Villaseca Gómez, Clara; Haider, Tehseen; Chacko, Kristina R.; Romero, Gustavo A.; Pollarsky Florencia D.; Restrepo, Juan Carlos; Castro Sánchez, Susan; Toro, Luis G.; Yaquich, Pamela; Mendizabal, Manuel; Garrido, María Laura; Marciano, Sebastián; Dirchwolf, Melisa; Vargas, Víctor; Jimenez, César; Louvet, Alexandre; Garcia Tsao, Guadalupe; Roblero, Juan Pablo; Abraldes, Juan G.; Shah, Vijay H.; Kamath, Patrick S.; Arrese Jimenez, Marco Antonio; Singal, Ashwani K.; Bataller, Ramón; Arab Verdugo, Juan Pablo© 2023 The Author(s)Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20–33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732–0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713–0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691–0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723–0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727–0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724–0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708–0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687–0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805–0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.
- ItemTrajectory of Serum Bilirubin Predicts Spontaneous Recovery in a Real-World Cohort of Patients With Alcoholic Hepatitis(2022) Parker, Richard; Cabezas, Joaquin; Altamirano, Jose; Arab, Juan Pablo; Ventura-Cots, Meritxell; Sinha, Ashish; Dhanda, Ashwin; Arrese, Marco; McCune, C. Anne; Rowe, Ian A.; Schnabl, Bernd; Mathurin, Phillipe; Shawcross, Debbie; Abraldes, Juan G.; Lucey, Michael R.; Garcia-Tsao, Guadalupe; Verna, Elizabeth; Brown, Robert S., Jr.; Bosques-Padilla, Francisco; Vargas, Victor; Louvet, Alexandre; Holt, Andrew P.; Bataller, RamonBACKGROUND AND AIMS: Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments.