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Background and Aims: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model., Approach and Results: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts., Conclusions: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ ., (Copyright © 2024 American Association for the Study of Liver Diseases.)

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., (© 2024. The Author(s).)

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., Methods: We 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., Results: Black 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)., Conclusions: After 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., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

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., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Acute-on-chronic liver failure (ACLF) is a severe clinical entity associated with elevated short-term mortality. We aimed to characterize patients with decompensated cirrhosis according to presence of ACLF, their association with active alcohol intake, and long-term survival in Latin America., Methods: Retrospective cohort study of decompensated cirrhotic in three Chilean university centers (2017-2019). ACLF was diagnosed according EASL-CLIF criteria. We assessed survival using competing-risk and time-to-event analyses. We evaluated the time to death using accelerated failure time (AFT) models., Results: We included 320 patients, median age of 65.3±11.7 years old, and 48.4% were women. 92 (28.7%) patients met ACLF criteria (ACLF-1: 29.3%, ACLF-2: 27.1%, and ACLF-3: 43.4%). The most common precipitants were infections (39.1%), and the leading organ failure was kidney (59.8%). Active alcohol consumption was frequent (27.7%), even in patients with a prior diagnosis of non-alcoholic fatty liver disease (NAFLD) (16.2%). Ninety-two (28.7%) patients had ACLF (ACLF-1: 8.4%, ACLF-2: 7.8%, and ACLF-3: 12.5%). ACLF patients had a higher MELD-Na score at admission (27 [22-31] versus 16 [12-21], p<0.0001), a higher frequency of alcohol-associated liver disease (36.7% versus 24.9%, p=0.039), and a more frequent active alcohol intake (37.2% versus 23.8%, p=0.019). In a multivariate model, ACLF was associated with higher mortality (subdistribution hazard ratio 1.735, 95%CI: 1.153-2.609; p<0.008). In the AFT models, the presence of ACLF during hospitalization correlated with a shorter time to death: ACLF-1 shortens the time to death by 4.7 times (time ratio [TR] 0.214, 95%CI: 0.075-0.615; p<0.004), ACLF-2 by 4.4 times (TR 0.224, 95%CI: 0.070-0.713; p<0.011), and ACLF-3 by 37 times (TR 0.027, 95%CI: 0.006-0.129; p<0.001)., Conclusions: Patients with decompensated cirrhosis and ACLF exhibited a high frequency ofactive alcohol consumption. Patients with ACLF showed higher mortality and shorter time todeath than those without ACLF., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Introduction: Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been suggested that it may play a crucial role in reducing infections in these populations., Aim: To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections [spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia], Clostridioides difficil e infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug., Methods: A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching., Results: We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 [95% confidence interval (CI) (0.47-0.89); p  = 0.008]. However, no discernible impact on mortality outcome was observed [IRR 1.9, 95% CI (0.9-4.0); p  = 0.09]. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects., Conclusion: The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2023 The Author(s).)

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., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) affects 20-25% of the general population and is associated with morbidity, increased mortality, and elevated health-care costs. Most NAFLD risk factors are modifiable and, therefore, potentially amenable to being reduced by public health policies. To date, there is no information about NAFLD-related public health policies in the Americas. In this study, we analysed data from 17 American countries and found that none have established national public health policies to decrease NAFLD-related burden. There is notable heterogeneity in the existence of public health policies to prevent NAFLD-related conditions. The most common public health policies were related to diabetes (15 [88%] countries), hypertension (14 [82%] countries), cardiovascular diseases (14 [82%] countries), obesity (nine [53%] countries), and dyslipidaemia (six [35%] of countries). Only seven (41%) countries had a registry of the burden of NAFLD, and efforts to raise awareness in the Americas were scarce. The implementation of public health policies are urgently needed in the Americas to decrease the burden of NAFLD., Competing Interests: Declaration of interests NC-T received speaking fees from Bayer. The other authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alcohol consumption represents a major factor of morbidity and mortality, with a wide range of adverse medical implications that practically affect every organ system. It is the fifth major cause of deaths in men and women and causes up to 139 million disability-adjusted life years. Solid evidence places the risk as undoubtedly correlated to the length of time and amount of alcohol consumption. While alcohol-related liver disease represents one of the most studied and well-known consequences of alcohol use, the term itself embodies a wide spectrum of progressive disease stages that are responsible for almost half of the liver-related mortality worldwide. We discuss the staged alcohol-related fatty liver, alcohol-related steatohepatitis and, finally, fibrosis and cirrhosis, which ultimately may end up in a hepatocellular carcinoma. Other comorbidities such as acute and chronic pancreatitis; central nervous system; cardiovascular, respiratory and endocrine system; renal disease; urological pathologies; type 2 diabetes mellitus and even infectious diseases are reviewed in their relation to alcohol consumption. This article reviews the impact of alcohol use on different systems and organs, summarizing available evidence regarding its medical implications. It examines current basic and clinical data regarding mechanisms to highlight factors and processes that may be targetable to improve patient outcomes. Although alcohol use is a part of many cultural and social practices, as healthcare providers we must identify populations at high risk of alcohol abuse, educate patients about the potential alcohol-related harm and provide appropriate treatment., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Purpose of Review: To assess the current challenges regarding liver diseases, including the burden of disease, access to care, screening, and treatment needs in Latin America., Recent Findings: Latin America is a region with a rich multicultural heritage and important socioeconomic differences. The burden of liver diseases is high and mainly determined by a high level of alcohol intake and the surge of risk factors associated with NAFLD (i.e., sedentary lifestyles, broader access to highly processed foods, obesity, and type 2 diabetes mellitus). Hepatotropic viruses also play a role in the development of chronic liver diseases, although their comparative frequency has been decreasing over the last decades. There are important disparities in access to screening and treatment for liver diseases in Latin America, which are reflected in low access to critical treatments such as direct-acting antiviral agents and drugs to treat hepatocellular carcinoma. Also, important barriers to liver transplantation are present in multiple countries, including a low deceased donors' rate and a lack of availability in several countries (especially in Central America). Our region also has disadvantages in research and education in liver diseases, which limits regional academic development and improvement in quality of care of liver diseases., Summary: In order to tackle an increasing health burden due to liver diseases, Latin America urgently needs tailored interventions aiming to control the main risk factors for these disorders through the establishment of effective public health policies. Also, development of liver transplantation programs and improvement of medical education and research capabilities as well as extensive collaboration between all stakeholders are keys to address the liver disease agenda in the region., Competing Interests: Conflict of interestLuis Antonio Díaz declares that he has no conflict of interest. Gustavo Ayares declares that he has no conflict of interest. Jorge Arnold declares that he has no conflict of interest. Francisco Idalsoaga declares that he has no conflict of interest. Oscar Corsi declares that he has no conflict of interest. Marco Arrese declares that he has no conflict of interest. Juan Pablo Arab declares that he has no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

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., (© 2021 by the American Association for the Study of Liver Diseases.)

Background & Aims: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH., Methods: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method., Results: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247)., Conclusion: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39., Lay Summary: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51)., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules ("cytokine storm"), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease., Competing Interests: The authors have no conflict of interests related to this publication., (© 2021 Authors.)

Background: Coronavirus disease 2019 (COVID-19) disease can frequently affect the liver. Data on hepatic histopathological findings in COVID-19 is scarce., Aim: To characterize hepatic pathological findings in patients with COVID-19., Methods: We conducted a systematic review with meta-analysis registered on PROSPERO (CRD42020192813), following PRISMA guidelines. Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test. Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed. Articles including less than ten patients were excluded. Proportions were pooled using random-effects models. Q statistic and I 2 were used to assess heterogeneity and levels of evidence, respectively., Results: We identified 18 studies from 7 countries; all were case reports and case series from autopsies. All the patients were over 15 years old, and 67.2% were male. We performed a meta-analysis of 5 studies, including 116 patients. Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1% [95% confidence interval (CI): 46.2-63.8], congestion of hepatic sinuses 34.7% (95%CI: 7.9-68.4), vascular thrombosis 29.4% (95%CI: 0.4-87.2), fibrosis 20.5% (95%CI: 0.6-57.9), Kupffer cell hyperplasia 13.5% (95%CI: 0.6-54.3), portal inflammation 13.2% (95%CI: 0.1-48.8), and lobular inflammation 11.6% (95%CI: 0.3-35.7). We also identified the presence of venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis., Conclusion: We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features. Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation. Further studies are needed to establish the mechanisms and implications of these findings., Competing Interests: Conflict-of-interest statement: The authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with a prevalence of 25-30%. Since its first description in 1980, NAFLD has been conceived as a different entity from alcohol-related fatty liver disease (ALD), despite that, both diseases have an overlap in the pathophysiology, share genetic-epigenetic factors, and frequently coexist. Both entities are characterized by a broad spectrum of histological features ranging from isolated steatosis to steatohepatitis and cirrhosis. Distinction between NAFLD and ALD is based on the amount of consumed alcohol, which has been arbitrarily established. In this context, a proposal of positive criteria for NAFLD diagnosis not considering exclusion of alcohol consumption as a prerequisite criterion for diagnosis had emerged, recognizing the possibility of a dual etiology of fatty liver in some individuals. The impact of moderate alcohol use on the severity of NAFLD is ill-defined. Some studies suggest protective effects in moderate doses, but current evidence shows that there is no safe threshold for alcohol consumption for NAFLD. In fact, given the synergistic effect between alcohol consumption, obesity, and metabolic dysfunction, it is likely that alcohol use serves as a significant risk factor for the progression of liver disease in NAFLD and metabolic syndrome. This also affects the incidence of hepatocellular carcinoma. In this review, we summarize the overlapping pathophysiology of NAFLD and ALD, the current data on alcohol consumption in patients with NAFLD, and the effects of metabolic dysfunction and overweight in ALD., (Copyright © 2020 Idalsoaga, Kulkarni, Mousa, Arrese and Arab.)