Mortality outcomes in individuals with MASLD versus MASLD and increased alcohol intake.

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.

Review article: Oesophageal disorders in chronic liver disease.

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.

Socio-economic association of alcohol use disorder and cardiovascular and alcohol-associated liver disease from 2010 to 2019.

BACKGROUNDS AND AIMS: Alcohol 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. METHODS: We 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. RESULTS: In 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. CONCLUSION: The 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.

Incidence of liver cancer in young adults according to the Global Burden of Disease database 2019.

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.

Alcohol-related liver disease: A global perspective.

Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences of excessive alcohol use. It represents 5.1 % of the global burden of disease, mainly involving the productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular disease, neoplasms, and liver disease, among others, accounting for 5.3 % of global deaths. Daily alcohol consumption, binge drinking (BD), and heavy episodic drinking (HED) are the patterns associated with a higher risk of developing ALD. The escalating global burden of ALD, even exceeding what was predicted, is the result of a complex interaction between the lack of public policies that regulate alcohol consumption, low awareness of the scope of the disease, late referral to specialists, underuse of available medications, insufficient funds allocated to ALD research, and non-predictable events such as the COVID-19 pandemic, where increases of up to 477 % in online alcohol sales were registered in the United States. Early diagnosis, referral, and treatment are pivotal to achieving the therapeutic goal in patients with alcohol use disorder (AUD) and ALD, where complete alcohol abstinence and prevention of alcohol relapse are expected to enhance overall survival. This can be achieved through a combination of cognitive behavioral, motivational enhancement and pharmacological therapy. Furthermore, the appropriate use of available pharmacological therapy and implementation of public policies that comprehensively address this disease will make a real difference.

Is There a Safe Alcohol Consumption Limit for the General Population and in Patients with Liver Disease?

Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.

Global and regional burden of alcohol-associated liver disease and alcohol use disorder in the elderly.

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.

Association between public health policies on alcohol and worldwide cancer, liver disease and cardiovascular disease outcomes.

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.

From Shadows to Spotlight: Exploring the Escalating Burden of Alcohol-Associated Liver Disease and Alcohol Use Disorder in Young Women.

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. METHODS: Leveraging data from the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, and disability-adjusted life years of alcohol-associated cirrhosis (AC), liver cancer from alcohol, and AUD in young women. The findings were categorized by region, nation, and sociodemographic index. RESULTS: The highest age-standardized prevalence rates were observed in AUD (895.96 [95% uncertainty interval (UI) 722.6-1,103.58]), followed by AC (65.33 [95% UI 48.37-86.49]) and liver cancer from alcohol (0.13 [95% UI 0.09-0.19]) per 100,000 people. The highest age-standardized mortality rates were observed in AC (0.75 [95% UI 0.55-0.97]), followed by AUD (0.48 [95% UI 0.43-0.53]) and liver cancer from alcohol (0.06 [95% UI 0.04-0.09]). The highest burdens of AC and AUD were observed in Central Europe, whereas the high-income Asia Pacific had the highest burden of liver cancer from alcohol. DISCUSSION: Throughout the past decade, the trend of AUD varied among regions while the impact of alcohol-associated liver disease has increased, requiring urgent public health strategy to mitigate these complications, particularly in female patients in Europe and the Asia-Pacific region.

Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Global burden of liver disease: 2023 update.

Liver disease accounts for two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and non-alcoholic fatty liver disease. Hepatotropic viruses are the aetiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.

Immunotherapy for Cancer: Common Gastrointestinal, Liver, and Pancreatic Side Effects and Their Management.

Cancer cells can block the activation of T lymphocytes by deploying inhibitory signals to cell surface receptors that downregulate the immune response. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that regulate the immune response by acting on these receptors. The use of ICI has been successful for cancer types that do not respond well to conventional chemotherapy, showing clinical benefit in various advanced and metastatic cancers and supporting the promise of cancer immunotherapy. However, in some cases, these treatments are associated with immune-related adverse events, many of which affect the digestive system. The treatment of immune-related adverse events depends on the affected organ and the severity of symptoms. Here, we review the commonly used US FDA-approved ICI and briefly outline their mechanism of action. We also describe the resulting collateral effects on the gastrointestinal tract, liver, and pancreas and discuss their management and prognosis.

Right Lobe Liver Donation After Bariatric Surgery. A Case Series of 4 Living Donors.

BACKGROUND: The increasing prevalence of obesity and need for bariatric surgery as well as the expanding use of living donors for liver transplantation means that potential donors could present with this surgical history. We present 4 cases of liver donors with previous bariatric surgery in our living donor liver transplant program. METHODS: A retrospective descriptive analysis of patients with a bariatric surgery history who underwent right hepatectomy in our living donor liver transplant program is presented. RESULTS: Case 1: A 53-year-old man with body mass index (BMI) of 33 who underwent laparoscopic sleeve gastrectomy (LSG). Pretransplant BMI was 21.5. Case 2: A 46-year-old woman with a BMI maximum of 40.8 who underwent LSG and required conversion to Roux-en-Y gastric bypass. Pretransplant BMI was 35.1. Case 3: A 53-year-old woman with a BMI maximum of 31.6 who underwent LSG. Pretransplant BMI was 24.2. Case 4: A 38-year-old man with a BMI maximum of 41.5 who underwent Roux-en-Y gastric bypass 6 years before the hepatectomy. Pretransplant BMI was 29.4. No complications were observed. Average operative time was 367.5 minutes, with a hospital stay of 5.8 days and 100% graft survival to date. DISCUSSION: Utilization of selected donors with previous bariatric surgery appears to be a safe option and increases the donor pool.

Liver Diseases in Latin America: Current Status, Unmet Needs, and Opportunities for Improvement.

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.

Trasplante hepático por metástasis hepáticas irresecables de cáncer colorrectal: revisión de la literatura / Liver transplantation for non-resectable colorectal liver metastases: A review

In Chile, colorectal cancer ranks third in incidence and fifth in mortality. Half of these patients have liver metastases at the diagnosis, and only 30% of them are resectable. Despite the development of many complex hepatobiliary procedures to achieve the total resection of metastases, the long-term survival with these techniques is not good. Liver transplantation is an alternative to treat unresectable liver metastasis from colorectal cancer with a good outcome. Several prognostic scores allow the selection of patients with good tumor biology. These patients have better overall and disease-free survival after liver transplantation. The use of immunosuppressive treatment doesn't increase recurrence, and even the pattern of tumor growth is slower in liver transplant recipients. The purpose of this review is to summarize the current evidence in this topic and to highlight the need for a formal protocol for liver transplantation for unresectable colorectal liver metastases, using living donors or marginal grafts to avoid competition with the rest of the national waiting list.

Alcohol Consumption: Medical Implications, the Liver and Beyond.

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.

[Liver transplantation for non-resectable colorectal liver metastases: A review]. / Trasplante hepático por metástasis hepáticas irresecables de cáncer colorrectal: revisión de la literatura.

In Chile, colorectal cancer ranks third in incidence and fifth in mortality. Half of these patients have liver metastases at the diagnosis, and only 30% of them are resectable. Despite the development of many complex hepatobiliary procedures to achieve the total resection of metastases, the long-term survival with these techniques is not good. Liver transplantation is an alternative to treat unresectable liver metastasis from colorectal cancer with a good outcome. Several prognostic scores allow the selection of patients with good tumor biology. These patients have better overall and disease-free survival after liver transplantation. The use of immunosuppressive treatment doesn't increase recurrence, and even the pattern of tumor growth is slower in liver transplant recipients. The purpose of this review is to summarize the current evidence in this topic and to highlight the need for a formal protocol for liver transplantation for unresectable colorectal liver metastases, using living donors or marginal grafts to avoid competition with the rest of the national waiting list.