Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.

OBJECTIVE To study the interaction of alcohol consumption with body mass index (BMI) in the development of hepatic steatosis and mortality. PARTICIPANTS AND METHODS We conducted a retrospective cohort study of 18,506 participants without fatty liver disease or cirrhosis at enrollment in the Mayo Clinic Biobank from April 9, 2009, through March 31, 2016. Participants were classified by self-reported alcohol consumption status (nondrinkers, moderate drinkers [0 to 2 drinks per day], and heavy drinkers [>2 drinks per day]). The primary outcome of interest was the incidence of hepatic steatosis, identified by International Classification of Diseases, Ninth Revision code and confirmed with imaging. The secondary outcome of interest was all-cause mortality. Multivariate Cox regression analysis determined the impact of alcohol consumption stratified by BMI on outcomes compared with nondrinkers. RESULTS The cohort (mean ± SD age, 55.8±16.9 years; 63.8% female; mean ± SD BMI, 28.8±6.1 kg/m2) of 18,506 participants included 3657 (19.8%) nondrinkers, 14,236 (76.9%) moderate drinkers, and 613 (3.3%) heavy drinkers at enrollment. After a median follow-up of 5.8 years (interquartile range, 3.8 to 7.2 years), 684 participants had development of hepatic steatosis and 968 died. In moderate drinkers, the risk of hepatic steatosis development was high in the obese group (adjusted hazard ratio [AHR], 1.31; 95% CI, 1.03 to 1.67), insignificant in the overweight group (AHR, 0.86; 95% CI, 0.58 to 1.26), and decreased in the normal-BMI group (AHR, 0.48; 95% CI, 0.26 to 0.90). Heavy drinkers had an increased risk of hepatic steatosis irrespective of BMI. Moderate alcohol use was associated with decreased mortality in the normal-weight (AHR, 0.44; 95% CI, 0.34 to 0.58) and overweight (AHR, 0.70; 95% CI, 0.56 to 0.88) groups but not in the obese group (AHR, 0.80; 95% CI, 0.64 to 1.00). CONCLUSION In obese individuals, even moderate alcohol use is associated with the development of hepatic steatosis. Moderate alcohol consumption is associated with lower mortality in normal-BMI and overweight individuals but not in those who are obese.

BACKGROUND & AIMS The new classification for steatotic liver disease (SLD) identifies three phenotypes based on alcohol consumption. We aimed to evaluate the associations between alcohol intake and liver-related events (LREs) across different drinking categories and whether genetic predisposition influences these associations. METHODS We analyzed data from 301,673 UK Biobank participants. Alcohol consumption was self-reported and categorized by weekly intake as mild (<140 g females, <210 g males), moderate (140 to 350 g females, 210 to 420 g males), and heavy (>350 g females, >420 g males). A polygenic risk score based on 5 well-known single nucleotide polymorphisms associated with hepatic steatosis was calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. The analysis was validated in 47,252 participants from China Kadoorie Biobank. RESULTS During a median follow-up of 12.8 years, 1,742 incident cases of LREs were documented. The multivariable-adjusted HRs per standard deviation increment in alcohol intake for LREs were 0.95 (95% CI: 0.89, 1.02) among mild drinkers, 1.23 (1.10, 1.37) among moderate drinkers, and 1.18 (1.14, 1.22) among heavy drinkers. The associations appeared stronger in those with high genetic risk. Compared with adults with low genetic risk and mild alcohol consumption, those with high genetic risk and heavy alcohol consumption had higher risks of LREs (HR: 6.50; 95% CI: 5.26, 8.04; P for interaction < 0.001). Similar findings were observed in China Kadoorie Biobank. CONCLUSIONS Associations between alcohol intake and LREs vary across different drinking categories. Individuals with a higher genetic risk for SLD appear more susceptible to alcohol.

<h4>Background and aim</h4>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains controversial regarding the impact of moderate alcohol consumption on disease progression and clinical outcomes. This systematic review aimed to evaluate the effects of moderate alcohol intake (up to 30 g/day for men and 20 g/day for women) on the development and progression of Steatotic Liver Disease (SLD), including outcomes such as histopathological progression, hepatocellular carcinoma (HCC), cardiovascular disease, and mortality.<h4>Methods</h4>The review followed PRISMA guidelines and included longitudinal cohort studies identified through PubMed, Scopus, Web of Science, Embase, and LILACS. Nine studies were selected for qualitative analysis, and seven were included in the meta-analysis. Effect measures, Hazard Ratios (HR) and Odds Ratios (OR), were pooled using Cochrane RevMan, and study quality was assessed with the Newcastle-Ottawa Scale.<h4>Prospero</h4>CRD420261277466.<h4>Results</h4>The meta-analysis showed no statistically significant association between moderate alcohol consumption and fibrosis progression (HR: 1.63 [95% CI: 0.96-2.77]; OR: 1.44 [95% CI: 0.56-3.72]). However, a statistically significant protective association was observed for all-cause mortality (HR: 0.73 [95% CI: 0.62-0.86]). High heterogeneity was noted across studies (I² = 56.9-86.2%). Excessive alcohol consumption remained a strong risk factor for adverse outcomes, and the incidence of HCC significantly increased among patients with advanced fibrosis, even with light alcohol intake.<h4>Conclusions</h4>Even moderate alcohol consumption may contribute to the progression of severe hepatic outcomes in SLD. These findings support clinical recommendations for total abstinence, particularly in patients with established fibrosis, to prevent progression to cirrhosis and hepatocellular carcinoma.

Alcohol consumption can cause, beyond addiction, roughly 200 different diseases and at least fourteen types of cancer. In 2016 the WHO estimated that 29% of alcohol-related deaths were mainly due to oncological diseases, liver cirrhosis (20%), and cardiovascular disorders (19%). The aim of this review was to focus on the absorption and metabolism of ethanol and discuss the main conditions caused by alcohol consumption (i.e., liver and cardiovascular diseases, and tumors). This narrative review is based on a detailed analysis of the scientific literature published before January 31, 2024 (PubMed, Web of Science, Scopus, Google Scholar). Approximately 90% of the absorbed alcohol reaches the liver where it is metabolized to acetaldehyde, a highly reactive and toxic compound. The excessive use of alcohol causes damage to several organs and systems, mainly the liver (e.g., steatosis, steato-hepatitis, fibrosis, and cirrhosis), cardiovascular system (cardiomyopathy, arrythmias, arterial hypertension, and stroke), and significantly contribute to the onset of neoplastic lesions to various organs including the esophagus, liver and breast. Even moderate drinking appears not to reduce mortality risk. Alcohol intake is one of the main risk factors for several pathological conditions and social problems, thus drastically impacting on public health. Proper awareness of the high risk related to alcohol consumption is of crucial importance to reduce the harm to public health.

It is well known that heavy drinking increases the risk of alcohol-related liver disease (ALD). Female gender, hepatitis C or B, obesity, and other cofactors increase susceptibility to ALD, so “safe” levels of alcohol consumption in regard to ALD vary among individuals. Inflammation is one mechanism by which alcohol causes liver damage. Increasing evidence suggests that in contrast to the proinflammatory activation by chronic excessive alcohol consumption, acute moderate alcohol administration has anti-inflammatory effects. Long-term alcohol administration results in increased baseline nuclear regulatory factor κB (NF-κB) activation in the livers of mice; in contrast, acute alcohol administration in mice attenuates lipopolysaccharide (LPS)-induced NF-κB activation in the liver and serum tumor necrosis factor alpha (TNFα) induction. Consistent with this notion, peripheral blood monocytes from patients with alcoholic hepatitis spontaneously produce increased amounts of TNFα and respond to ex vivo LPS stimulation with increased TNFα levels, while acute moderate alcohol consumption in normal volunteers results in the attenuation of TNFα production by various stimulants and attenuates monocyte production of other proinflammatory cytokines. To date, no evidence for a beneficial role of the anti-inflammatory effect of acute moderate alcohol consumption on the liver has been demonstrated, but this may contribute to the effect of alcohol on other organ systems.

Alcoholism is the continued drinking of alcohol despite the problems it causes. Some definitions require evidence of dependence and withdrawal. Problematic Alcoholism is the continued drinking of alcohol despite the problems it causes. Some definitions require evidence of dependence and withdrawal. Problematic alcohol use has been mentioned in the earliest historical records. The World Health Organization (WHO) estimated there were 283 million people with alcohol use disorders worldwide as of 2016. The term alcoholism was first coined in 1852, but al In 2023, the World Health Organization stated that no level of alcohol consumption is safe, and even low or moderate consumption may cause harms to someone's health, including an increased risk of many cancers. Having more than one drink a day for women or two drinks for men increases the risk of heart disease, high blood pressure, atrial fibrillation, and stroke. Risk is greater with binge drinking, which may also result in violence or accidents. Globally, about 3.3 million deaths (5.9% of all deaths) are believed to be due to alcohol each year. Alcoholism reduces a person's life expectancy by around ten years and alcohol use is the third leading cause of early death in the United States. Long-term alcohol misuse can cause a number of physical symptoms, including cirrhosis of the liver, pancreatitis, epilepsy, polyneuropathy, alcoholic dementia, heart disease, nutritional deficiencies, peptic ulcers and sexual dysfunction, and can eventually be fatal. Other physical effects include an increased risk of developing cardiovascular disease, malabsorption, alcoholic liver disease, and several cancers such as breast cancer and head and neck cancer. Damage to the central nervous system and peripheral nervous system can occur from sustained alcohol consumption. A wide range of immunologic defects can result and there may be a generalized skeletal fragility, in addition to a recognized tendency to accidental injury, resulting in a propensity for bone fractures. Women develop long-term complications of alcohol dependence more rapidly than do men; women also have a higher mortality rate from alcoholism than men. Examples of long-term complications include brain, heart, and liver damage and an increased risk of breast cancer. Additionally, heavy drinking over time has been found to have a negative effect on reproductive functioning in women. This results in reproductive dysfunction such as anovulation, decreased ovarian mass, problems or irregularity of the menstrual cycle, and early menopause. Alcoholic ketoacidosis can occur in individuals who chronically misuse alcohol and have a recent history of binge drinking. The amount of alcohol that can be biologically processed…