Advanced Alcohol-related Liver Disease Research Articles

Efficacy of prophylactic antibiotics in the adjuvant treatment of alcohol-related liver disease (ALD): A systematic review and meta-analysisProphylactic antibiotics in ALD

Introduction and ObjectivesThis research aims to evaluate the efficacy and safety of prophylactic antibiotics in patients with alcohol-related liver disease (ALD). Materials and MethodsWe systematically searched databases including PubMed, Embase, Cochrane, and Web of Science up to October 2023. Our scope encompassed the influence of prophylactic antibiotics on all-cause mortality, infection, variceal bleeding, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), adverse events (AE), fungal infection, clostridioides difficile infection (CDI), and multidrug-resistant (MDR) bacterial infection. Additionally, total bilirubin, creatinine, platelet counts, and plasma endotoxin levels were also analyzed. ResultsAfter comprehensive selection, 10 studies with 974 participants were included for further analysis. The study demonstrated that prophylactic antibiotic therapy was associated with reductions in infection rates, HE incidence, variceal bleeding, and all-cause mortality. The treatment did not increase the incidence of AE, fungal infection, and CDI, but it did raise the MDR bacteria infection rate. The analysis revealed no significant protective effect of antibiotic prophylaxis on total bilirubin and creatinine levels. Furthermore, the administration of antibiotics led to marginal increases in platelet counts, a minor reduction in endotoxin concentrations, and a subtle enhancement in HRS; however, these changes did not reach statistical significance. ConclusionsProphylactic antibiotic therapy was an effective and safe treatment for advanced ALD. To mitigate the risk of MDR bacterial infections, a strategy of selective intestinal decontamination could be advisable. Future investigations should prioritize varied ALD patient populations with extended follow-up periods and assorted antibiotic regimens to solidify the efficacy and safety of ALD treatments.

Alcohol use disorder in community management of chronic liver diseases.

Rising rates of alcohol use disorder (AUD) combined with increases in alcohol-related liver disease (ALD) and other liver disease have resulted in the need to develop alcohol management strategies at all levels of patient care. For those with pre-existing liver disease, whether ALD or others, attention to alcohol use treatment and abstinence becomes critical to avoiding worsening liver-related consequences. Modalities to help patients reduce or stop alcohol include screening/brief intervention/referral to treatment, various therapeutic modalities including cognitive behavioral therapy, motivational enhancement therapy and 12-step facilitation, and alcohol relapse prevention medications. Harm reduction approaches versus total abstinence may be considered, but for those with existing ALD, particularly advanced ALD (cirrhosis or acute alcoholic hepatitis), total abstinence from alcohol is the recommendation, given clear data that ongoing alcohol use worsens mortality and liver-related morbidity. For certain populations, alcohol cessation is even more critically important. For those with hepatitis C or NAFLD, alcohol use accelerates negative liver-related outcomes. In women, alcohol use accelerates liver damage and results in worsened liver-related mortality. Efforts to integrate AUD and liver disease care are urgently needed and can occur at several levels, with establishment of multidisciplinary ALD clinics for fully integrated co-management as an important goal.

Diagnosis and Treatment of Alcohol-Associated Liver Disease: A Patient-Friendly Summary of the 2019 AASLD Guidelines.

Diagnosis and Treatment of Alcohol-Associated Liver Disease: A Patient-Friendly Summary of the 2019 AASLD Guidelines.

Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis: A population-based study.

Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n=1222) or high-risk drinkers (n=275) (>21units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n=263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS≥8kPa and 3.9 and 9.2kPa for LS≥9.1kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Public health policies and alcohol-related liver disease.

SummaryAlcohol-related liver disease (ALD) represents a major public health problem worldwide. According to the World Health Organization, the highest levels of per capita alcohol consumption are observed in countries of the European Region. Alcohol consumption is also alarmingly increasing in developing countries. ALD is one of the main contributors to the burden of alcohol-attributable deaths and disability. In the United States, severe forms of ALD such alcoholic hepatitis have increased in the last decade and in the United Kingdom, three-quarters of liver-related mortality results from alcohol consumption. Besides genetic factors, there is strong evidence that the amount of alcohol consumed plays a major role in the development of advanced ALD. Establishing effective public health policies is therefore mandatory to reduce the burden of ALD. Since the 90s, major public health institutions and governments have developed a variety of policies in order to reduce the harm caused by excessive drinking. These policies encompass multiple factors, from pricing and taxation to advertising regulation. Measures focused on taxation and price regulation have been shown to be the most effective at reducing alcohol-related mortality. However, there are few studies focused on the effect of public policies on ALD. This review article summarises the factors influencing ALD burden and the role of different public health policies.

Overcoming Alcohol Addiction in Patients with Alcohol-Related Liver Disease

This review provides a brief overview of key concepts in addiction medicine and provides tips and tricks as it pertains to treating patients with alcohol addiction in the setting of advanced alcohol-related liver disease (ALD). Understanding the brain disease model of addiction by both providers and patients is a vital springboard for establishing a therapeutic relationship. Despite a paucity of high-quality evidence, psychosocial treatments have withstood the test of time and still form the foundation of alcohol use disorder (AUD) treatment in advanced ALD. Despite the inescapable link between AUD) and advanced ALD, there are no FDA-approved medications for use in this special population. In this urgent subgroup, only baclofen, used off-label, has been shown to be effective for AUD in randomized controlled trials. An integrated, multidisciplinary and longitudinal approach remains the best option for the management of AUD in advanced ALD.

Alcohol-Related Liver Disease Is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide

Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

THU-300 - Nutritional, Metabolic and Immunological Effects of Intravenous Lipid Emulsions in Patients with Advanced Alcohol Related Liver Disease

THU-300 - Nutritional, Metabolic and Immunological Effects of Intravenous Lipid Emulsions in Patients with Advanced Alcohol Related Liver Disease

Insulin resistance, ceramide accumulation, and endoplasmic reticulum stress in human chronic alcohol-related liver disease.

Background. Chronic alcohol-related liver disease (ALD) is mediated by insulin resistance, mitochondrial dysfunction, inflammation, oxidative stress, and DNA damage. Recent studies suggest that dysregulated lipid metabolism with accumulation of ceramides, together with ER stress potentiate hepatic insulin resistance and may cause steatohepatitis to progress. Objective. We examined the degree to which hepatic insulin resistance in advanced human ALD is correlated with ER stress, dysregulated lipid metabolism, and ceramide accumulation. Methods. We assessed the integrity of insulin signaling through the Akt pathway and measured proceramide and ER stress gene expression, ER stress signaling proteins, and ceramide profiles in liver tissue. Results. Chronic ALD was associated with increased expression of insulin, IGF-1, and IGF-2 receptors, impaired signaling through IGF-1R and IRS1, increased expression of multiple proceramide and ER stress genes and proteins, and higher levels of the C14, C16, C18, and C20 ceramide species relative to control. Conclusions. In human chronic ALD, persistent hepatic insulin resistance is associated with dysregulated lipid metabolism, ceramide accumulation, and striking upregulation of multiple ER stress signaling molecules. Given the role of ceramides as mediators of ER stress and insulin resistance, treatment with ceramide enzyme inhibitors may help reverse or halt progression of chronic ALD.

Advanced liver disease in a homeless population

IntroductionResidents at St Mungo's with alcohol related liver disease frequently experience sudden deaths. There were no prognostic indicators to alert staff that a resident may be nearing the end of...

Association of Inflammation Genes with Alcohol Dependence/Abuse: A Systematic Review and a Meta-Analysis

The aim of the present work was to systematically review all association studies of inflammation genes with alcohol dependence/alcohol abuse (AD/AA) and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the ‘high-risk’ versus ‘low-risk’ alleles in AD/AA cases versus controls. Data reported in at least three published studies were available for four genetic polymorphisms [TNF-α -238 (rs361525, G/A); TNF-α -308 (rs1800629, G/A); IL-1RA (VNTR [86 bp]_n); IL-10 -592 (rs1800896, C/A)]. In total, nine meta-analyses were performed. Of these, only the TNF-α -238 polymorphism showed a significant association with AD/AA (OR = 1.36, 95% CI: 1.05–1.76). This risk remained significant and increased slightly when we considered only patients with advanced alcohol-related liver disease (AALD) (OR = 1.5, 95% CI: 1.13–1.98) but not when we considered only patients without AALD (OR = 1.08, 95% CI: 0.5–2.35). Sensitivity analysis showed that this genetic association is derived from the AALD phenotype rather than from AD. Our approach is limited by our phenotype definition; some studies included chronic heavy drinkers (minimal daily consumption of 80 g for a minimal duration of 10 years) but without a standardized psychiatric assessment.