Browsing by Author "Diaz Piga, Luis Antonio"

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    A Precision Medicine Guided Approach to the Utilization of Biomarkers in MASLD
    (2024) Thakral, Nimish; Desalegn, Hailemichael; Diaz Piga, Luis Antonio; Cabrera, Daniel; Loomba, Rohit; Arrese Jiménez, Marco Antonio; Arab Verdugo, Juan Pablo
    The new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes a positive diagnosis based on cardiometabolic risk factors. This definition is not only less stigmatizing but also allows for subclassification and stratification, thereby addressing the heterogeneity of what was historically referred to as nonalcoholic fatty liver disease. The heterogeneity within this spectrum is influenced by several factors which include but are not limited to demographic/dietary factors, the amount of alcohol use and drinking patterns, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The net effect of this dynamic and intricate system-level interaction is reflected in the phenotypic presentation of MASLD. Therefore, the application of precision medicine in this scenario aims at complex phenotyping with consequent individual risk prediction, development of individualized preventive strategies, and improvements in the clinical trial designs. In this review, we aim to highlight the importance of precision medicine approaches in MASLD, including the use of novel biomarkers of disease, and its subsequent utilization in future study designs.
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    Association 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.
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    Current situation of pediatric liver transplantation in Chile : Inequities associated with the MELD/PELD prioritization system
    (2020) Diaz Piga, Luis Antonio; López, M.; Sin, P.; Wolff, R.; Buckel, Erwin; Pattillo Silva, Juan Carlos; Jarufe Cassis, Nicolás; Martínez Castillo, Jorge; Guerra, Juan Francisco; Gana Ansaldo, Juan Cristóbal; González, G.; Muñoz, M. P.; Uribe, M.; Ananias, Á.; Bezama, I.; Zañartu, N.; Innocenti, F.; Elgueta S.
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    Editorial: Sounding the alarm—The rising global burden of adolescent and young adult alcohol-related liver disease. Author's reply
    (2024) Danpanichkul, Pojsakorn; Duangsonk, Kwanjit; Diaz Piga, Luis Antonio; Arab Verdugo, Juan Pablo; Liangpunsakul, Suthat; Wijarnpreecha, Karn
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    Emerging Drug Therapies for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Glimpse into the Horizon
    (2024) Arnold Álvarez, Jorge Ignacio; Idalsoaga Ferrer, Francisco Javier; Diaz Piga, Luis Antonio; Cabrera García, Daniel Alejandro; Barrera Álvarez, Francisco Benjamín; Arab Verdugo, Juan Pablo; Arrese Jiménez, Marco Antonio
    Purpose of Review Metabolic dysfunction–associated steatotic liver disease (MASLD) and its aggressive form, metabolic dysfunction-associated steatohepatitis (MASH), are highly prevalent and can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. Currently, there is no approved pharmacological treatment for MASLD. In this review, we aim to summarize recent data on therapeutic agents under study in phase 2 and 3 trials.Recent FindingsBuilding on a better understanding of MASLD/MASH pathophysiology, a myriad of drugs has been developed. Recent results from clinical trials show promise, with some candidates demonstrating positive outcomes in phase 3 trials that are predictably expected to be approved in the near future. Notably, resmetirom, a thyroid receptor β agonist, is likely to be approved in 2024.SummaryIn the coming years, results from several landmark trials will be available and will likely provide options to prevent progression to cirrhosis and adverse liver outcomes in patients with MASLD/MASH.
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    Granulocyte-colony stimulating factor use in alcohol-associated hepatitis: is it time to promote liver regeneration?
    (2024) Diaz Piga, Luis Antonio; Arab Verdugo, Juan Pablo; Leggio, Lorenzo
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    Impact of alcohol use on liver disease outcomes
    (Wolters Kluwer Medknow Publications, 2024) Desalegn, Hailemichael; Diaz Piga, Luis Antonio; Rehm, Jürgen; Arab Verdugo, Juan Pablo
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    Impact of Public Health Policies on Alcohol-Associated Liver Disease in Latin America: An Ecological Multinational Study
    (WILEY, 2021) Diaz Piga, Luis Antonio; Idalsoaga Ferrer, Francisco Javier; Fuentes López, Eduardo; Marquez Lomas, Andrea; Ramirez, Carolina A.; Pablo Roblero, Juan; Araujo, Roberta C.; Higuera de la Tijera, Fatima; Guillermo Toro, Luis; Pazmino, Galo; Montes, Pedro; Hernandez, Nelia; Mendizabal, Manuel; Corsi, Oscar; Ferreccio, Catterina; Lazo, Mariana; Brahmania, Mayur; Singal, Ashwani K.; Bataller, Ramon; Arrese Jimenez, Marco Antonio; Arab Verdugo, Juan Pablo
    Background and Aims Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality in Latin America, yet the impact of public health policies (PHP) on liver disease is unknown. We aimed to assess the association between alcohol PHP and deaths due to ALD in Latin American countries. Approach and Results We performed an ecological multinational study including 20 countries in Latin America (628,466,088 inhabitants). We obtained country-level sociodemographic information from the World Bank Open Data source. Alcohol-related PHP data for countries were obtained from the World Health Organization Global Information System of Alcohol and Health. We constructed generalized linear models to assess the association between the number of PHP (in 2010) and health outcomes (in 2016). In Latin America, the prevalence of obesity was 27% and 26.1% among male and female populations, respectively. The estimated alcohol per capita consumption among the population at 15 years old or older was 6.8 L of pure alcohol (5.6 recorded and 1.2 unrecorded). The overall prevalence of alcohol use disorders (AUD) was 4.9%. ALD was the main cause of cirrhosis in 64.7% of male and 40.0% of female populations. A total of 19 (95%) countries have at least one alcohol-related PHP on alcohol. The most frequent PHP were limiting drinking age (95%), tax regulations (90%), drunk-driving policies and countermeasures (90%), and government monitoring systems and community support (90%). A higher number of PHP was associated with a lower ALD mortality (PR, 0.76; 95% CI, 0.61-0.93; P = 0.009), lower AUD prevalence (PR, 0.80; 95% CI, 0.65-0.99; P = 0.045), and lower alcohol-attributable road traffic deaths (PR, 0.81; 95% CI, 0.65-1.00; P = 0.051). Conclusions Our study indicates that in Latin America, countries with higher number of PHP have lower mortality due to ALD, lower prevalence of AUD, and lower alcohol-attributable road traffic mortality.
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    Letter: Potential impact of Helicobacter pylori infection on oesophageal disorders in chronic liver disease—Authors' reply
    (2024) Idalsoaga Ferrer, Francisco Javier; Diaz Piga, Luis Antonio; Ayares Campos, Gustavo Ignacio; Cabrera, Daniel; Chahuan Abde, Javier Nicolas; Monrroy Bravo, Hugo Alfonso; Halawi, Houssam; Arrese Jiménez, Marco Antonio; Arab Verdugo, Juan Pablo
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    MELD 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.
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    New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease
    (Lippincott Williams & Wilkins, 2023) Diaz Piga, Luis Antonio; Winder, Gerald Scott; Leggio, Lorenzo; Bajaj, Jasmohan S.; Bataller, Ramon; Arab, Juan Pablo
    Alcohol use disorder (AUD) remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for AUD. In particular, a change in gut microbiota composition and function, especially bile acid homeostasis, and these changes can improve after alcohol cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors in turn promote liver and brain inflammation and progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, e.g.: the ghrelin system (ghrelin receptor blockade), incretin mimetics (GLP-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of AUD. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-related burden of disease.
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    Nutrition in Alcohol-Related Liver Disease
    (2022) Ayala-Valverde, María; Arnold Álvarez, Jorge Ignacio; Diaz Piga, Luis Antonio; Idalsoaga Ferrer, Francisco Javier; Arrese Jiménez, Marco Antonio; Arab Verdugo, Juan Pablo
    Purpose of Review Alcohol use represents one of the five major causes of morbimortality globally, and alcohol-related liver disease (ALD) is the most common cause of cirrhosis worldwide. Malnutrition is one of the most frequent complications in ALD and is associated with decreased survival. Additionally, protein-energy malnutrition causes sarcopenia, frailty, and immunosuppression. This review summarizes the diverse mechanisms involved in the pathophysiology of malnutrition in ALD and its management.Recent FindingsMechanisms regarding malnutrition in ALD have been recently described. There is also an important area of interest in patients with overnutrition and sarcopenic obesity. Early assessment of malnutrition is needed so the management and prognosis improve in ALD patients.SummaryMalnutrition worsens disease progression and increases infections and mortality risk, especially in decompensated patients. It is important to have early recognition and management of this ALD complication. It is also essential to stratify a patient’s risk for refeeding syndrome once the supplementation is given since this syndrome can increase morbimortality.
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    Public Health Measures and Prevention of Alcohol-Associated Liver Disease
    (2022) Ayares Campos, Gustavo Ignacio; Idalsoaga Ferrer, Francisco Javier; Arnold Álvarez, Jorge Ignacio; Fuentes López, Eduardo; Arab Verdugo, Juan Pablo; Diaz Piga, Luis Antonio
    Hazardous alcohol consumption causes approximately 4% of deaths globally, constituting one of the leading risk factors for the burden of the disease worldwide. Alcohol has several health consequences, such as alcohol-associated liver disease, hepatocellular carcinoma, nonliver neoplasms, physical injury, cardiac disease, and psychiatric disorders. Alcohol misuse significantly affects workforce productivity, with elevated direct and indirect economic costs. Due to the high impact of alcohol consumption on the population, public health has led to the development of a range of strategies to reduce its harmful effects. Regulatory public health policies (PHP) for alcohol can exist at the global, regional, international, national, or subnational levels. Effective strategies incorporate a multilevel, multicomponent approach, targeting multiple determinants of drinking and alcohol-related harms. The World Health Organization categorizes the PHP into eight categories: national plan to fight the harmful consequences of alcohol, national license and production and selling control, taxes control and pricing policies, limiting drinking age, restrictions on alcohol access, driving-related alcohol policies, control over advertising and promotion, and government monitoring systems. These policies are supported by evidence from different populations, demonstrating that determinants of alcohol use depend on several factors such as socioeconomic level, age, sex, ethnicity, production, availability, marketing, and others. Although most policies have a significant individual effect, a higher number of PHP are associated with a lower burden of disease due to alcohol. The excessive consequences of alcohol constitute a call for action, and clinicians should advocate for developing and implementing a new PHP on alcohol consumption.
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    Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States
    (WILEY, 2024) Ayares Campos, Gustavo Ignacio; Diaz Piga, Luis Antonio; Fuentes Lopez, Eduardo; Idalsoaga Ferrer, Francisco Javier; Cotter, Thomas G.; Dunn, Winston; Simonetto, Douglas; Shah, Vijay H.; Kamath, Patrick S.; Lazarus, Jeffrey V.; Bataller, Ramon; Arrese, Marco; Wong, Robert J.; Singal, Ashwani K.; Arab, Juan Pablo
    Background: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown.MethodsWe conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis.ResultsBlack individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62).ConclusionsAfter accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients., image
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    Review article: Oesophageal disorders in chronic liver disease
    (WILEY, 2024) Idalsoaga Ferrer, Francisco Javier; Diaz Piga, Luis Antonio; Ayares Campos, Gustavo Ignacio; Cabrera, Daniel; Chahuan Abde, Javier Nicolas; Monrroy Bravo, Hugo Alfonso; Halawi, Houssam; Arrese Jimenez, Marco Antonio; Arab Verdugo, Juan Pablo
    Background: Oesophageal disorders and chronic liver disease are common worldwide and significantly impact quality of life. The intricate link between these conditions, including how oesophageal disorders like GERD, Barrett's oesophagus and oesophageal cancer affect and are affected by chronic liver disease, remains poorly understood. Aims: To review the relationship between oesophageal disorders and chronic liver disease, evaluating epidemiology, pathophysiology and therapeutic factors. Methods: We reviewed the literature on the relationship between oesophageal disorders and chronic liver disease, including cirrhosis, using the PubMed database Results: Oesophageal disorders such as gastroesophageal reflux disease, Barrett's oesophagus, oesophageal cancer, oesophageal motor disorders and oesophageal candidiasis are prevalent among individuals with cirrhosis, exacerbating the burden of liver disease. These diseases have a multifaceted symptomatology and pathogenic basis, posing a significant challenge in cirrhotic patients that necessitates careful diagnosis and management. Additionally, therapies frequently used for these diseases, such as proton pump inhibitors, require careful consideration in cirrhotic patients due to potential adverse effects and altered pharmacokinetics. Managing oesophageal disorders in cirrhotic patients requires a cautious approach due to possible interactions with medications and the risk of adverse effects. Furthermore, symptoms associated with these conditions are often exacerbated by common interventions in patients with cirrhosis, such as band ligation for oesophageal varices. Conclusions: Oesophageal disorders are common in cirrhosis and increase the disease burden. These conditions require careful management due to complex symptoms and treatment risks. Proton pump inhibitors and other therapies must be used cautiously, as cirrhosis interventions can worsen symptoms.