Alcohol-related Disease Research Articles

Changes in gut microbiome correlate with intestinal barrier dysfunction and inflammation following a 3-day ethanol exposure in aged mice.

Alcohol use among older adults is on the rise. This increase is clinically relevant as older adults are at risk for increased morbidity and mortality from many alcohol-related chronic diseases compared to younger patients. However, little is known regarding the synergistic effects of alcohol and age. There are intriguing data suggesting that aging may lead to impaired intestinal barrier integrity and dysbiosis of the intestinal microbiome, which could increase susceptibility to alcohol's negative effects. To study the effects of alcohol in age we exposed aged and young mice to 3 days of moderate ethanol and evaluated changes in gut parameters. We found that these levels of drinking do not have obvious effects in young mice but cause significant alcohol-induced gut barrier dysfunction and expression of the pro-inflammatory cytokine TNFα in aged mice. Ethanol-induced downregulation of expression of the gut-protective antimicrobial peptides Defa-rs1, Reg3b, and Reg3g was observed in aged, but not young mice. Analysis of the fecal microbiome revealed age-associated shifts in microbial taxa, which correlated with intestinal and hepatic inflammatory gene expression. Taken together, these data demonstrate that age drives microbiome dysbiosis, while ethanol exposure in aged mice induces changes in the expression of antimicrobial genes important for separating these potentially damaging microbes from the intestinal lumen. These changes highlight potential mechanistic targets for prevention of the age-related exacerbation of effects of ethanol on the gut.

Alcoholism and its adverse effects

Alcoholism affects both adults and children, and it is a major medical issue. A high predominance of ailment, insufficiencies, and fatalities has been associated to alcoholism. It tends to be influenced by hereditary, psychological, social, and other elements. Misuse of alcohol is a main source of non-communicable diseases and mental illnesses and its all add weight to the alcohol-related disease. With regard to alcohol-related issues, medicine and public health face a conundrum. Early detection is critical for effective analysis and management of patients, hence primary prevention should be emphasized in medical care administrations.

A phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a single agent and in combination with standard of care in patients with hepatocellular carcinoma and other solid tumor types known for association with the MYC oncogene (MYCHELANGELO I).

TPS627 Background: MYC, or c-MYC, is a master regulator of gene expression that controls cell growth and proliferation. Dysregulation of MYC is frequently identified in various cancer types, including hepatocellular carcinoma (HCC), where it is overexpressed in up to 70% viral and alcohol-related disease.1 While MYC represents an attractive therapeutic target, it has historically been considered undruggable due to a lack of a structured binding pocket and its tightly autoregulated expression. OTX-2002 is a first-in-class, engineered and programable mRNA therapeutic called Omega Epigenomic Controllers (OECs) that modulates MYC gene expression pre-transcriptionally by creating epigenetic marks at two different structural and regulatory elements within the insulated genomic domain where MYC resides. In vitro studies have demonstrated that downregulation of MYC through OTX-2002 led to loss of viability in HCC cells while sparing normal hepatocytes. In HCC xenograft mouse models, OTX-2002 demonstrated anti-tumor activity as monotherapy and in combinations with standard of care therapies in HCC.2 Methods: OTX-2002 is being evaluated in an open-label, non-randomized, phase 1/2 study (MYCHELANGELO I) in patients with HCC and other advanced solid tumor types (NCT05497453). The study consists of two parts. Part 1 dose escalation explores ascending doses of intravenous OTX-2002 monotherapy given every 2 weeks to identify dose limiting toxicities, maximum tolerated dose, and recommended dose for expansion (RDE) in patients with HCC and other solid tumors using a classic 3+3 design. Upon identification of the RDE, a monotherapy expansion in advanced HCC patients is planned to explore the preliminary anti-tumor activity of OTX-2002. Part 2 will evaluate OTX-2002 in combination with HCC standard of care in the same HCC population as that of Part 1 expansion. The safety of OTX-2002 at the selected dose in combination with a tyrosine kinase inhibitor or immune checkpoint inhibitor will be evaluated in a safety run-in; expansion will follow to identify the preliminary anti-tumor activity of the combinations. Key eligibility criteria for HCC patients include: 1) Barcelona Clinical Liver Cancer (BCLC) stage B or C disease, 2) Child-Pugh A liver function, 3) received at least 1 prior systemic therapy. The MYCHELANGELO I study began enrollment in August 2022, and Part 1 dose escalation is ongoing in the US.

Injectable heat-sensitive nanocomposite hydrogel for regulating gene expression in the treatment of alcohol-induced osteonecrosis of the femoral head.

For repairing lesions, it is important to recover physiological and cellular activities. Gene therapy can restore these activities by regulating the expression of genes in lesion cells; however, in chronic diseases, such as alcohol-induced osteonecrosis of the femoral head (ONFH), gene therapy has failed to provide long-term effects. In this study, we developed a heat-sensitive nanocomposite hydrogel system with a secondary nanostructure that can regulate gene expression and achieve long-term gene regulation in lesion cells. This nanocomposite hydrogel exists in a liquid state at 25 °C and is injectable. Once injected into the body, the hydrogel can undergo solidification induced by body heat, thereby gaining the ability to be retained in the body for a prolonged time period. With the gradual degradation of the hydrogel in vivo, the internal secondary nanostructures are continuously released. These nanoparticles carry plasmids and siRNA into lesion stem cells to promote the expression of B-cell lymphoma 2 (inhibiting the apoptosis of stem cells) and inhibit the secretion of peroxisome proliferators-activated receptors γ (PPARγ, inhibiting the adipogenic differentiation of stem cells). Finally, the physiological activity of the stem cells in the ONFH area was restored and ONFH repair was promoted. In vivo experiments demonstrated that this nanocomposite hydrogel can be indwelled for a long time, thereby providing long-term treatment effects. As a result, bone reconstruction occurs in the ONFH area, thus enabling the treatment of alcohol-induced ONFH. Our nanocomposite hydrogel provides a novel treatment option for alcohol-related diseases and may serve as a useful biomaterial for other gene therapy applications.

Role of the ghrelin system in alcohol use disorder and alcohol-associated liver disease: A narrative review.

Unhealthy alcohol consumption is a global health problem. Adverse individual, public health, and socioeconomic consequences are attributable to harmful alcohol use. Epidemiological studies have shown that alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) are the top two pathologies among alcohol-related diseases. Consistent with the major role that the liver plays in alcohol metabolism, uncontrolled drinking may cause significant damage to the liver. This damage is initiated by excessive fat accumulation in the liver, which can further progress to advanced liver disease. The only effective therapeutic strategies currently available for ALD are alcohol abstinence or liver transplantation. Any molecule with dual-pronged effects at the central and peripheral organs controlling addictive behaviors and associated metabolic pathways are a potentially important therapeutic target for treating AUD and ALD. Ghrelin, a hormone primarily derived from the stomach, has such properties, and regulates both behavioral and metabolic functions. In this review, we highlight recent advances in understanding the peripheral and central functions of the ghrelin system and its role in AUD and ALD pathogenesis. We first discuss the correlation between blood ghrelin concentrations and alcohol use or abstinence. Next, we discuss the role of ghrelin in alcohol-seeking behaviors and finally its role in the development of fatty liver by metabolic regulations and organ crosstalk. We propose that a better understanding of the ghrelin system could open an innovative avenue for improved treatments for AUD and associated medical consequences, including ALD.

Increased incidence of alcohol use disorder and alcohol-related psychiatric disorders in patients with obstructive sleep apnea: A nationwide population-based cohort study

BackgroundObstructive sleep apnea (OSA) and alcohol-related diseases (ARDs), including alcohol use disorder, alcohol-related psychiatric disorders, alcoholic liver disease, alcoholic polyneuropathy alcoholic cardiomyopathy, and alcoholic gastritis, are both highly prevalent conditions. Alcohol consumption is associated with a higher risk of sleep apnea. However, whether OSA increases the risk of ARD has not, as yet, been studied comprehensively. Our study aimed to determine whether OSA increases the subsequent risk of ARD. MethodsThis study utilized the data from Taiwan's National Health Insurance Database between 2000 and 2015. We identified 7722 individuals newly diagnosed with OSA and randomly selected sex-, age-, and index date-matched (1:3) 22,166 controls without OSA, with a total of 29,888 subjects. We used the Fine and Gray's survival analysis to estimate the effects of OSA on ARD. ResultsThe OSA cohort had an adjusted hazard ratio of subsequent ARDs as 1.486 (95% Confidence Interval: 1.301–1.698), when comparing the cohort without OSA. The Kaplan-Meier analysis showed that the cumulative incidence of ARDs was significantly higher in the OSA cohort than in the controls in the first year of follow-up, till the end of the follow-up. A post-hoc analysis showed that OSA was associated with alcohol use disorder, alcohol-related psychiatric disorders, and alcoholic liver disease, but not alcoholic polyneuropathy, alcoholic cardiomyopathy, and alcoholic gastritis. The use of psychoactive medication, including the sedative-hypnotics, antidepressants or antipsychotics were associated with a lower risk of ARDs. ConclusionsOur study demonstrates that the OSA patients are at a higher risk of developing ARDs.

Mortality and causes of death in different celiac disease phenotypes during long-term follow-up.

Celiac disease has been associated with increased mortality, but data on long-term mortality are scarce. To determine long-term mortality in celiac disease. The study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 - 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time. During the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85-1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38-4.24 and HR 2.14, 95% CI 1.05-4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09-1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortality CONCLUSIONS: Overall mortality was not increased in any celiac disease phenotype during a very long-term follow-up.

Estimated Deaths Attributable to Excessive Alcohol Use Among US Adults Aged 20 to 64 Years, 2015 to 2019

Alcohol consumption is a leading preventable cause of death in the US, and death rates from fully alcohol-attributable causes (eg, alcoholic liver disease) have increased in the past decade, including among adults aged 20 to 64 years. However, a comprehensive assessment of alcohol-attributable deaths among this population, including from partially alcohol-attributable causes, is lacking. To estimate the mean annual number of deaths from excessive alcohol use relative to total deaths among adults aged 20 to 64 years overall; by sex, age group, and state; and as a proportion of total deaths. This population-based cross-sectional study of mean annual alcohol-attributable deaths among US residents between January 1, 2015, and December 31, 2019, used population-attributable fractions. Data were analyzed from January 6, 2021, to May 2, 2022. Mean daily alcohol consumption among the 2 089 287 respondents to the 2015-2019 Behavioral Risk Factor Surveillance System was adjusted using national per capita alcohol sales to correct for underreporting. Adjusted mean daily alcohol consumption prevalence estimates were applied to relative risks to generate alcohol-attributable fractions for chronic partially alcohol-attributable conditions. Alcohol-attributable fractions based on blood alcohol concentrations were used to assess acute partially alcohol-attributable deaths. Alcohol-attributable deaths for 58 causes of death, as defined in the Centers for Disease Control and Prevention's Alcohol-Related Disease Impact application. Mortality data were from the National Vital Statistics System. During the 2015-2019 study period, of 694 660 mean deaths per year among adults aged 20 to 64 years (men: 432 575 [66.3%]; women: 262 085 [37.7%]), an estimated 12.9% (89 697 per year) were attributable to excessive alcohol consumption. This percentage was higher among men (15.0%) than women (9.4%). By state, alcohol-attributable deaths ranged from 9.3% of total deaths in Mississippi to 21.7% in New Mexico. Among adults aged 20 to 49 years, alcohol-attributable deaths (44 981 mean annual deaths) accounted for an estimated 20.3% of total deaths. The findings of this cross-sectional study suggest that an estimated 1 in 8 total deaths among US adults aged 20 to 64 years were attributable to excessive alcohol use, including 1 in 5 deaths among adults aged 20 to 49 years. The number of premature deaths could be reduced with increased implementation of evidenced-based, population-level alcohol policies, such as increasing alcohol taxes or regulating alcohol outlet density.

Gender-Specific Renal Function and Urinary Syndrome in Patients with Liver Cirrhosis of Alcoholic Etiology: Observational Study

Background. Gender has now been proven to have a significant impact on the development, course and outcome of a large number of diseases, including alcoholic liver disease. Alcohol consumption is one of the leading risk factors for various diseases. Alcohol-related diseases cause 10% of all deaths worldwide among young and middle-aged people. The occurrence of renal dysfunction in cirrhosis of the liver is an integral part of the natural course of the disease. At the moment, the diagnosis of gender-specific renal dysfunction that occurs against the background of liver cirrhosis is essential for the development of effective treatment strategies and the improvement of survival.Objectives. The study is aimed at identifying the features of the gender-specific renal function and urinary syndrome in patients with liver cirrhosis of alcoholic etiology and assessing the comprehensive prognostic significance of the indicators of common urine analysis in the diagnosis of renal dysfunction.Methods. An observational study was carried out using data from medical records of 158 patients with alcoholic liver cirrhosis (95 men and 63 women), aged 36 to 72 years, who were inpatients between February 2016 and March 2020. Physical examination and laboratory diagnostic data were taken into account. Binary predictors of renal dysfunction progression in patients with alcoholic liver cirrhosis were determined based on the analysis of descriptive statistics. Statistical data processing was performed using computer program Statistica 10 (StatSoft, Inc., USA) and standard Microsoft Excel software package (Microsoft Office 2016). Non-parametric statistical methods were used to describe the results. Quantitative results were analyzed using the Mann-Whitney test; comparison of two samples by a qualitatively defined feature was performed by means of the Fisher angular transformation method. Differences were considered significant at p ˂ 0.05. A multilayer neural network function from the Statistica 10 Neural Networks software was used to construct a classification scheme for renal dysfunction (yes/no). Neural network performance was assessed using descriptive and inductive statistics, calculating sensitivity, specificity, performing ROC analysis and constructing cumulative gains charts.Results. A renal function test revealed a significant decrease in glomerular filtration rate (p = 0.029) and a significant increase in urinary albumin/creatinine ratio (p < 0.0001) in women with alcoholic liver cirrhosis as compared with men. Women are also reported to have a high incidence of proteinuria, leukocyturia and bacteriuria. According to ROC-analysis, the urinalysis indicators have a high prognostic significance in identifying renal dysfunction in men and women with alcoholic liver cirrhosis (AUROC = 0.902 and sensitivity 81.82%, AUROC = 0.881 and sensitivity 75.00%, respectively).Conclusion. Renal dysfunction develops earlier and occurs twice as often in women with alcoholic cirrhosis than in men of the same age. The application of a neural network mechanism to predict renal dysfunction in men and women with alcoholic liver cirrhosis according to the indicators of urinalysis provides a high prognostic ability.

The profile and causes of death among medical doctors and dental surgeons in Uganda: 1986 to 2016.

The loss of health workers through death is of great importance and interest to the public, media and the medical profession as it has very profound social and professional consequences on the delivery of health services. To describe the profile, causes and patterns of death among medical doctors and dental surgeons in Uganda between 1986 and 2016. We conducted a retrospective descriptive study of mortality among registered medical doctors and dental surgeons. Information on each case was collected using a standard questionnaire and analysed. Cause of death was determined using pathology reports, and if unavailable, verbal autopsies. We summarized our findings across decades using means and standard deviations, proportions and line graphs as appropriate. Cuzick's test for trend was used to assess crude change in characteristics across the three decades. To estimate the change in deaths across decades adjusted for age and sex, we fit a logistic regression model, and used the margins command with a dy/dx option. All analyses were done in Stata version 14.0 (Stata Corp, College Station, TX). There were 489 deaths registered between 1986 and 2016. Of these, 59 (12.1%) were female. The mean age at death was 48.8 years (Standard Deviation (SD) 15.1) among male and 40.1 years (SD 12.8) among females. We ascertained the cause of death for 468/489 (95.7%). The most common causes of death were HIV/AIDS (218/468, 46.6%), cancer (68/468, 14.5%), non-communicable diseases (62/48, 13.3%), alcohol related deaths (36, 7.7%), road traffic accidents (34, 7.3%), gunshots (11, 2.4%), among others. After adjusting for age and sex, HIV/AIDs attributable deaths decreased by 33 percentage points between the decade of 1986 to1995 and that of 2006 to 2016 -0.33 (-0.44, -0.21. During the same period, cancer attributable deaths increased by 13 percentage periods 0.13 (0.05,0.20). The main causes of death were HIV/AIDS, cancer, non-communicable diseases, alcohol-related diseases and road traffic accidents. There was a general downward trend in the HIV/AIDS related deaths and a general upward trend in cancer related deaths. Doctors should be targeted for preventive and support services especially for both communicable and non-communicable diseases.

Imaging and Editing the Phospholipidome.

Membranes are multifunctional supramolecular assemblies that encapsulate our cells and the organelles within them. Glycerophospholipids are the most abundant component of membranes. They make up the majority of the lipid bilayer and play both structural and functional roles. Each organelle has a different phospholipid composition critical for its function that results from dynamic interplay and regulation of numerous lipid-metabolizing enzymes and lipid transporters. Because lipid structures and localizations are not directly genetically encoded, chemistry has much to offer to the world of lipid biology in the form of precision tools for visualizing lipid localization and abundance, manipulating lipid composition, and in general decoding the functions of lipids in cells.In this Account, we provide an overview of our recent efforts in this space focused on two overarching and complementary goals: imaging and editing the phospholipidome. On the imaging front, we have harnessed the power of bioorthogonal chemistry to develop fluorescent reporters of specific lipid pathways. Substantial efforts have centered on phospholipase D (PLD) signaling, which generates the humble lipid phosphatidic acid (PA) that acts variably as a biosynthetic intermediate and signaling agent. Though PLD is a hydrolase that generates PA from abundant phosphatidylcholine (PC) lipids, we have exploited its transphosphatidylation activity with exogenous clickable alcohols followed by bioorthogonal tagging to generate fluorescent lipid reporters of PLD signaling in a set of methods termed IMPACT.IMPACT and its variants have facilitated many biological discoveries. Using the rapid and fluorogenic tetrazine ligation, it has revealed the spatiotemporal dynamics of disease-relevant G protein-coupled receptor signaling and interorganelle lipid transport. IMPACT using diazirine photo-cross-linkers has enabled identification of lipid-protein interactions relevant to alcohol-related diseases. Varying the alcohol reporter can allow for organelle-selective labeling, and varying the bioorthogonal detection reagent can afford super-resolution lipid imaging via expansion microscopy. Combination of IMPACT with genome-wide CRISPR screening has revealed genes that regulate physiological PLD signaling.PLD enzymes themselves can also act as tools for precision editing of the phospholipid content of membranes. An optogenetic PLD for conditional blue-light-stimulated synthesis of PA on defined organelle compartments led to the discovery of the role of organelle-specific pools of PA in regulating oncogenic Hippo signaling. Directed enzyme evolution of PLD, enabled by IMPACT, has yielded highly active superPLDs with broad substrate tolerance and an ability to edit membrane phospholipid content and synthesize designer phospholipids in vitro. Finally, azobenzene-containing PA analogues represent an alternative, all-chemical strategy for light-mediated control of PA signaling.Collectively, the strategies described here summarize our progress to date in tackling the challenge of assigning precise functions to defined pools of phospholipids in cells. They also point to new challenges and directions for future study, including extension of imaging and membrane editing tools to other classes of lipids. We envision that continued application of bioorthogonal chemistry, optogenetics, and directed evolution will yield new tools and discoveries to interrogate the phospholipidome and reveal new mechanisms regulating phospholipid homeostasis and roles for phospholipids in cell signaling.

Astaxanthin Is Able to Prevent Alcohol-Induced Dysfunction of Liver Mitochondria.

The search for new targets for the pathological action of ethanol remains an urgent task of biomedicine. Since degenerative changes in the liver are associated with the development of oxidative stress, antioxidants are promising agents for the treatment of alcohol-related diseases. In this work, we studied the ability of the carotenoid antioxidant, astaxanthin (AX), to prevent ethanol-induced changes in the liver of rats. It was shown that AX is able to protect the structure of mitochondria from degenerative changes caused by ethanol to improve mitochondrial functions. AX positively influences the activity and expression of proteins of the mitochondrial respiratory chain complexes and ATPase. In addition, a protective effect of AX on the rate and activity of mitochondrial respiration was demonstrated in the work. Thus, studies have shown that AX is involved in protective mechanisms in response to ethanol-induced mitochondrial dysfunction.

Mortality and its association with chronic alcohol-related diseases in patients admitted to the emergency department for acute alcoholic intoxication: retrospective cohort study

We assessed long-term mortality and its association with chronic alcohol-related diseases in patients admitted to the emergency department (ED) because of acute alcoholic intoxication (AAI). A retrospective cohort study was performed at the ED of Sant’Orsola-Malpighi Hospital, Bologna, Italy. 3304 patients, corresponding to 6415 admissions for AAI, who accessed the ED from January 1, 2005, to December 31, 2017, were studied. The ED electronic registry system was used to assess living status on 08 May 2020 and to obtain the prespecified potential predictors, i.e., age at first admission, sex, alcohol use disorder (AUD), substance use disorder (SUD), more than 1 admission to ED for trauma, mental and behavioral disorders, neurological disorders, and cardiovascular disease. The median follow-up time was 9.3 years and the time on risk was 30,053 person years (PY) with a death rate corresponding to 4.42 (95% CI 3.74–5.26) per 1000 PY (n = 133 deaths). The death rate was higher in patients with AUD (17.30) than in those without AUD (1.98) and in those with SUD (13.58) than in those without SUD (3.80). Lastly, there was a clearly higher death rate among AUD+ SUD+ (20.89) compared to AUD–SUD–patients (1.74). At multivariable Cox regression, AUD, SUD, and liver cirrhosis were strong and independent predictors of time-to-death. Using standardized mortality ratios, a clear excess of mortality was evident for all the age bands from (40–45] to (60–65] years. Mortality is higher in AAI than in the general population and chronic alcohol-related diseases are strongly associated with it.

Risk of Recurrent Venous Thromboembolism in Selected Subgroups of Men: A Danish Nationwide Cohort Study.

Background Although men are considered at high risk for recurrent venous thromboembolism (VTE), sex-specific data on prognostic factors are lacking. We estimated the cumulative recurrence risks associated with clinical characteristics and comorbidities known or suspected to be associated with the development of VTE recurrence: major surgery, trauma, history of cancer, rheumatic disorder, ischemic heart disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes, chronic renal disease, varicose veins, alcohol-related diseases, and arterial hypertension. Methods We linked nationwide Danish health registries to identify all incident VTE in- and outpatients in men from 2008 through 2018. Recurrent VTE risk 2 years after anticoagulant discontinuation was calculated using the Aalen-Johansen estimator, stratified by age above/below 50 years. Results The study included 13,932 men with VTE, of whom 21% ( n = 2,898) were aged <50 years. For men aged <50 years with at least one of the clinical characteristics, 2-year recurrence risk ranged from 6% (major surgery) to 16% (history of cancer). For men ≥50 years with at least one of the characteristics, recurrence risk ranged from 7% (major surgery) to 12% (ischemic heart disease, chronic obstructive pulmonary disease, and chronic renal disease). Men aged <50 and ≥50 years without the clinical characteristics all had a recurrence risk of 10%. Discussion We demonstrated a 2-year recurrence risk of at least 6%, regardless of age category and disease status, in this nationwide cohort of men with VTE. The recurrence risk must be balanced against bleeding risk. However, the high recurrence risk across all subgroups might ultimately lead to greater emphasis on male sex in future guidelines focusing on optimized secondary VTE prevention.

Alcohol use disorders, self-help groups as a supplement to pharmacological and psychological therapy? A retrospective study in a population with alcohol related liver disease.

According to the new criteria in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V), the prevalence of alcohol use disorders (AUDs) is 20-30% in men and 10-15% in women worldwide.2,3 The anticraving therapy/psychotherapy combination is currently used routinely in clinical practice. However, the results after one year are unsatisfactory. Meta-analytic studies found failure rates of 57 to 75%. These percentages vary in relation to the intensity and length of the treatment. In addition, the abstinence rates gradually decrease over time. In this study, the clinical outcome of alcohol related liver disease (ALD) patients who spontaneously attended self-help groups (SHGs) (club of alcoholics in treatment - multi-family community/ alcoholics anonymous) regularly versus those who did not want to start the path or did not complete it was evaluated. From January 2005 to December 2010, 1337 alcohol use disorder patients affected by compensated alcohol related liver disease, were prospectively followed and retrospectively assessed. Two hundred thirty-one patients were enrolled: 74 attended self-help groups assiduously, 27 attended sporadically and 130 refused participation in SHGs. Constant attendance at SHGs compared to non-attendance allows for a significant increase (<0.0001) in the period of sobriety found in the median of distribution. Frequent attendance at SHGs is effectively "preventive," reducing the fraction of relapses by about 30%. The percentage of cases of cirrhosis is significantly different (P=0.0007) between those who have regularly attended SHG meetings (about 1% of patients) and those who have never attended or only occasionally (various percentages between 21 and 31% of patients); in both groups the incidence of new cases would seem to be 0.014 cases/ year. Similar difference in percentages regarding the onset of hepatocellular carcinomas (HCCs), although with a lower level of significance (P=0.017) among those who attended regularly, 4% of patients with an incidence of 0.006 cases/ year, compared to those who have never attended or only occasionally: over 14% of patients with an incidence of 0.022 cases/year. This study suggests the importance of attending SHGs not only for the long-term achievement of alcoholic abstention, but also in positively influencing the course of alcohol-related diseases.

Alcohol-Attributable Medical Costs in Commercially Insured and Medicaid Populations

Despite its social acceptance, excessive alcohol use remains among the top causes of preventable deaths in the U.S. Although there is a recognition of alcohol-related health and social costs, there are no current studies quantifying the medical costs incurred under health plans. This study estimates the direct medical costs attributable to excessive alcohol use using claims records from a large national insurer. The sample consists of adults with commercial insurance and Medicaid between 2008 and 2019. A case-control matched study design is used to compare individuals with a condition considered 100% attributable to alcohol by the Centers for Disease Control and Prevention with similar individuals. Medical care use and costs are examined over a 12-month follow-up. Costs are broken down by healthcare setting and health conditions as defined by the Centers for Disease Control and Prevention's Alcohol-Related Disease Impact diagnoses codes. We find that having a diagnosis attributable to alcohol is associated with higher annual per-person healthcare expenditures in both commercially insured and Medicaid-insured participants by $14,918 (95% CI=$14,540, $15,297) and $4,823 (95% CI=$4,489, $5,158), respectively. We find that 60%‒75% of the additional costs of excessive alcohol use are driven by heart disease and stroke; conditions of the liver, gallbladder, and pancreas; and certain cancers as well as acute conditions that may be attributable to alcohol. The findings suggest that public and private initiatives to target people vulnerable to the harms of excessive alcohol use may potentially help to cut down significant costs on the already strained healthcare system in the U.S.

Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study

BackgroundNew direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan.MethodsWe conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis.ResultsA decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis.ConclusionsElderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.

Using the alcohol use disorders identification test to predict hospital admission for alcohol-related conditions in the Danish general population: a record-linkage study.

Most studies validating the alcohol use disorders identification test (AUDIT) have either assessed its factor structure and/or test-retest reliability or used diagnostic interviews as validators of current alcohol use disorders. The aim of the present study was to determine whether AUDIT and AUDIT-Consumption (AUDIT-C) scores are associated with subsequent risk of hospital admission for alcohol-related disorders and diseases (ARDDs). We used a historical cohort study. Using national registers, survey respondents were tracked from 1 September 2011 to hospitalization for an ARDD, emigration, death, or 31 December 2018, whichever occurred first. Denmark. Respondents (n = 4522) from a Danish national survey conducted in autumn 2011. Outcome was incident ARDD admission recorded in the National Patient Register. Predictors were AUDIT and AUDIT-C scores, and covariates were age, gender, highest level of education and previous psychiatric disorder. During the study period, 56 respondents had a first-time ARDD admission. Respondents who scored above the 8-point AUDIT cut-off and respondents who scored above the 5-point AUDIT-C cut-off had a significantly increased risk of being admitted for an ARDD compared with respondents who scored below the cut-offs, (AUDIT: hazard ratio (HR), 4.72; 95% CI, 2.59-8.60; AUDIT-C: HR, 7.97; 95% CI, 3.66-17.31). Scores above alcohol use disorders identification test (AUDIT) and AUDIT-Consumption (AUDIT-C) cut-offs are associated with an increased risk of long-term alcohol-related hospital admissions. At widely used cut-offs, the AUDIT-C is a better predictor of alcohol-related hospitalizations among members of the general population than the full AUDIT.

Hospital admissions from alcohol-related acute pancreatitis during the COVID-19 pandemic: A single-centre study.

BACKGROUNDThe United Kingdom government introduced lockdown restrictions for the first time on 23 March 2020 due to coronavirus disease 2019 (COVID-19) pandemic. These were partially lifted on 15 June and further eased on 4 July. Changes in social behaviour, including increased alcohol consumption were described at the time. However, there were no data available to consider the impact of these changes on the number of alcohol-related disease admissions, specifically alcohol-related acute pancreatitis (AP). This study evaluated the trend of alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown.AIMTo evaluate the trend in alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown in the United Kingdom.METHODSAll patients admitted with alcohol-related AP from March to September 2016 to 2020 were considered in this study. Patient demographics, their initial presentation with AP, any recurrent admissions, disease severity and length of stay, were evaluated using ANOVA and χ2 and Kruskal–Wallis tests.RESULTSOne hundred and thirty-six patients were included in the study. The highest total number of AP admissions was seen in March–September 2019 and the highest single-month period was in March–May 2020. Admissions for first-time presentations of AP were highest in 2020 compared to other year groups and were significantly higher compared to previous years, for example, 2016 (P < 0.05). Furthermore, the rate of admissions decreased by 38.89% between March–May 2020 and June–September 2020 (P < 0.05), coinciding with the easing of lockdown restrictions. This significant decrease was not observed in the previous year groups during those same time periods. Admissions for recurrent AP were highest in 2019. The median length of hospital stay did not differ between patients from each of the year groups.CONCLUSIONAn increased number of admissions for alcohol-related AP were observed during months when lockdown restrictions were enforced; a fall in figures was noted when restrictions were eased.

New insights into the mechanism of alcohol-mediated organ damage via its impact on immunity, metabolism, and repair pathways: A summary of the 2021 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

On November 19th, 2021, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Chicago Health Sciences Campus in Maywood, Illinois. The 2021 meeting focused on how alcohol misuse is linked to immune system derangements, leading to tissue and organ damage, and how this research can be translated into improving treatment of alcohol-related disease. This meeting was divided into three plenary sessions: the first session focused on how alcohol misuse affects different parts of the immune system, the second session presented research on mechanisms of organ damage from alcohol misuse, and the final session highlighted research on potential therapeutic targets for treating alcohol-mediated tissue damage. Diverse areas of alcohol research were covered during the meeting, from alcohol's effect on pulmonary systems and neuroinflammation to epigenetic changes, senescence markers, and microvesicle particles. These presentations yielded a thoughtful discussion on how the findings can lead to therapeutic treatments for people suffering from alcohol-related diseases.