Modest Drinkers Research Articles

Complete alcohol abstinence increases the risk of NAFLD but not severity. A population analysis with transient elastography

Background & Aims As the global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise, ubiquity of alcohol use has also prompted discussion regarding the potential interactions between the two. This study aims to examine the effects of modest alcohol consumption on the prevalence and complications of NAFLD in a multi-ethnic population. Methods This study analyses the 2017–2018 cycles of NHANES that examined liver fibrosis and steatosis with vibration controlled transient elastography. A coarsened exact matching was conducted to reduce confounding. Logistic regression was done with a multivariate model to assess the relationship between alcohol consumption (modest drinkers and non-drinkers) and risk of NAFLD and its complications. Results 2,067 individuals were found to have NAFLD and 284 NAFLD patients had a total history of alcohol abstinence. After coarsened exact matching, the prevalence of NAFLD was 49% (CI: 0.41 − 0.58) in non-drinkers and 33% (CI: 0.26 − 0.41) in modest drinkers. Non-drinkers had twice the odds of NAFLD compared to modest drinkers (OR: 1.99, CI: 1.22 − 3.22, p<.01) after adjustment for confounders. There were no significant differences in the odds of significant fibrosis, advance fibrosis, cirrhosis, cardiovascular disease and stroke between non-drinkers and modest drinkers. The odds of malignancy in non-drinkers were almost significantly less than modest drinkers (OR: 0.28, CI:0.08 − 1.02, p=.053). Conclusion Interestingly, modest alcohol consumption is associated with decreased odds of NAFLD. Further investigations are required to examine the relationship between alcohol consumption and NAFLD and subsequently the potential impact on NAFLD management.

The effects of modest drinking on life expectancy and mortality risks: a population-based cohort study.

Modest drinking has been repeatedly discussed in scientific papers as protective against certain diseases, such as cardiovascular diseases, but in most cases, alcohol worsens health conditions, especially when consumed at high risk levels. The complexity of the risk relationship between alcohol and health conditions has confused clinicians as to whether it should be recommended. The study aims to balance the risks and benefits of modest drinking. This retrospective cohort study of 430,016 adults recruited from a standard health-screening program since 1994, with 11,031 deaths identified as of 2008. Drinking distinguished “modest drinker” (no more than one drink a day) from “regular drinker”. Mortality risks including all-cause mortality and diseases-specific mortality with hazard ratio (HR) were calculated by adjusting for 15 confounders. Life table was used for life expectancy. Risk predictors were subjected to Cox proportional hazards regression analysis to identify significant predictors in multivariate models and life expectancy analysis. Nearly one out of 4 males (23%) was a modest drinker, who gained 0.94 year (95% CI 0.65–1.23 year) in life over non-drinker and had 8% reduction in adjusted all-cause mortality (HR 0.92, 95% CI 0.86–0.97). In contrast, regular drinkers had 43% increase in overall mortality (HR 1.43, CI 1.35–1.52) and shortened life by 6.9 years (95% CI 6.6–7.1 years). As most drinkers also smoked, 59% in modest and 75% in regular, the combined effect shortened life by 2.0 years (95% CI 1.6–2.4 years) in modest drinker and 10.3 years (95% CI 9.8–10.7 years) in regular drinker. Cancer were increased in modest drinkers for oral (HR 2.35, CI 1.38–4.01) and esophageal (HR 3.83, CI 1.90–7.73) cancer. The gain of one year by modest drinkers was erased by a two to fourfold increase in oral and esophageal cancer and that drinking beyond modest amount led to a large loss of life expectancy. Given that drinkers are prone to cross the line of drinking, clinicians should balance the risks and benefits of drinking, as well as the understanding of whether the patient is at risk for addiction.

Modest alcohol intake not associated with significant hepatic steatosis or more severe liver disease among patients with diabetes mellitus.

The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear. This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤21units/week in men and ≤14units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter>263dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement≥9.6kPa using M probe or ≥9.3kPa using XL probe. Patients with liver stiffness measurement≥8.0kPa were offered liver biopsy. Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease. Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.

Moderate Alcohol Intake in Non-Alcoholic Fatty Liver Disease: To Drink or Not to Drink?

Nonalcoholic fatty liver disease (NAFLD) is defined by hepatic steatosis in the presence of alcohol intake within safe limits, defined by guidelines of scientific associations (usually 20 g or 2 units/day in women, 30 g or 3 units in men). The diagnosis is usually followed by medical counseling of total abstinence, in order to prevent disease progression. This policy has been challenged by epidemiological studies, suggesting that the risk of liver disease and disease progression is lower in modest drinkers than in total abstainers. We revised the literature on the effects of modest alcohol intake on disease burden. Epidemiological data may suffer from several potential biases (recall bias for retrospective analyses, difficulties in the calculation of g/day), limiting their validity. Prospective data suggest that NAFLD patients with regular alcohol intake, although within the safe thresholds, are at higher risk of liver disease progression, including hepatocellular carcinoma; a detrimental effect of modest alcohol drinking is similarly observed in liver disease of viral etiology. Alcohol intake is also a risk factor for extrahepatic cancers, particularly breast, oral, and pharyngeal cancers, with gender difference and no floor effect, which outweigh the possible beneficial effects on cardiovascular system, also derived from retrospective studies. Finally, the negative effects of the calorie content of alcohol on dietary restriction and weight loss, the pivotal intervention to reduce NAFLD burden, should be considered. In summary, the policy of counseling NAFLD patients for alcohol abstinence should be maintained.

Abstract 12: Day-to-Day Modest Drinking Rather Than Occasional Binge Drinking May Raise Risk of Ischemic Stroke

Introduction: Although it has been reported that amount of alcohol consumption has J-shaped association with ischemic stroke, it is yet to be concluded whether difference in drinking pattern affects the relationship. Given that drinking pattern may vary even among individuals with similar drinking amount, it is necessary to further assess the association between drinking pattern and ischemic stroke. Methods: The National Health Insurance Service-National Sample Cohort is a large-sized, standardized population cohort in Korea, which consists of randomly selected 2% of Koreans considering demographic characteristics. Drinking pattern was defined in 5 categories by frequency and quantity per occasion. Participants who reported to have rarely or never drunken alcohol were classified as abstainers. Those who drank less than 5 days per week were defined as social drinkers or episodic heavy drinkers, depending on whether the amount of alcohol consumed at one occasion exceeded a bottle of Soju (60g of alcohol). In the same way, participants drinking 5 days or more a week were classified as daily modest drinkers or daily heavy drinkers. We analyzed the relationship between drinking pattern and ischemic stroke occurrence. Results: A total of 286,256 eligible participants (mean age, 45 years; 148,985 men [52.0%]) were analyzed. Median follow-up period was 9.0 years. As reported in previous studies, social drinking had protective effect for ischemic stroke (HR, 0.88; 95% CI, 0.81-0.96). In participants who drink more, however, the drinking pattern influenced the results. Drinking modest amount of alcohol everyday significantly elevated the risk of ischemic stroke (HR, 1.16; 95% CI, 1.01-1.33), whereas episodic heavy drinking did not (HR, 0.90; 95% CI, 0.76-1.07). Conclusions: Risk of ischemic stroke may be influenced by drinking pattern. Particularly, daily modest drinkers may be at higher risk for ischemic stroke compared with intermittent excessive drinkers.

Issue Highlights

Issue Highlights

Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis

Cross-sectional studies of patients with nonalcoholic fatty liver disease (NAFLD) have reported a lower prevalence of severe disease among modest drinkers compared with nondrinkers. We collected data from adult participants in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network to evaluate the longitudinal association between modest use of alcohol and histology findings in patients with NAFLD, using paired liver biopsies collected more than 1 year apart. We studied NASH Clinical Research Network participants 21 years or older, not receiving pharmacologic therapy, from whom 2 or more liver biopsies and data on alcohol use within 2 years of the initial biopsy were available. Alcohol consumption was evaluated at study entry using the Alcohol Use Disorders Identification Test and Skinner Lifetime Drinking History questionnaires. At each follow-up visit participants were asked about alcohol use frequency, number of drinks on a typical day, and frequency of heavy drinking. The association between baseline drinking status and changes in fibrosis stage, NASH histology, and the NAFLD Activity Score and its individual components were evaluated by analysis of covariance. The association between change in drinking status and change in histology was evaluated using adjusted logistic regression. Of 285 participants (82% white, 70% female, mean age, 47 y) meeting entry criteria, 168 (59%) were modest alcohol users (≤2 drinks/d) and the remaining 117 were abstinent. At baseline, a higher proportion of modest alcohol users were white (86% vs 76% nonwhite) (P= .04) and a lower proportion of modest alcohol users were diagnosed with definite NASH (57% vs 74% without NASH; P= .01). During a mean follow-up period of 47 months between biopsies, nondrinkers had a greater mean reduction in steatosis grade (reduction, 0.49) than modest drinkers (reduction, 0.30; P= .04) and a greater reduction in mean level of aspartate transaminase (reduction, 7 U/L vs an increase of 2 U/L in modest drinkers; P= .04). Modest drinkers had significantly lower odds of NASH resolution compared with nondrinkers (adjusted odds ratio, 0.32; 95% CI, 0.11-0.92; P= .04) on adjusted analysis. In a longitudinal analysis of liver biopsies from patients with NAFLD not receiving pharmacologic therapy, modest alcohol use was associated with less improvement in steatosis and level of aspartate transaminase, as well as lower odds of NASH resolution, compared with no use of alcohol.

Bacterial endotoxin and non-alcoholic fatty liver disease in the general population: a prospective cohort study.

Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth. To test the hypothesis that endotoxemia is associated with non-alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia. Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton-magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays. Two hundred and sixty-three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin-18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin-A levels than nondrinkers. Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies.

P0981 : Adaptation of hepatic mitochondrial function in obese humans with or without non-alcoholic steatohepatitis

Background and Aims: Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth. We aimed to test the hypothesis that endotoxaemia is associated with fatty liver in the general population and to study dietary factors associated with endotoxaemia. Methods: Community adult subjects were randomly selected from the Hong Kong Government’s census database and underwent proton-magnetic resonance spectroscopy and transient elastography to assess hepatic steatosis and fibrosis, respectively. Intrahepatic triglyceride content (IHTG) of 5% was the cutoff to define fatty liver. Endotoxaemia was assessed using the Limulus Amebocyte Lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays. Dietary pattern was recorded by a 7-day food-frequency questionnaire. Results: 920 subjects were included (42% male, age 48±11, 23% body mass index ≥25kg/m and 5% diabetes). 263 (29%) had fatty liver; 60 (7%) had raised serum cytokeratin-18 fragment level (CK-18) suggestive of NASH; 27 of 887 (3%) subjects with reliable liver stiffness measurement had advanced fibrosis or cirrhosis. Compared with those without fatty liver, subjects with fatty liver had higher LBP (13.4±3.2mg/ml vs 11.4±2.7mg/ml; P < 0.001) and EndoCab IgG (228±247 GMU/ml vs 188±137 GMU/ml; P = 0.013) levels. Endotoxin markers also correlated positively with aminotransferases, IHTG, CK-18, insulin resistance and dyslipidaemia. Endotoxaemia was not associated with increased liver stiffness. Fetuin-A, the ligand linking fatty acid and Toll-like receptor 4, correlated with IHTG, insulin resistance and dyslipidaemia but did not have consistent association with endotoxaemia markers. Although total energy consumption and individual macronutrients were not associated with endotoxaemia, current drinkers (median alcohol consumption 20g/week [interquartile range 10–70 g]) had lower endotoxin, EndoCab IgG and fetuin-A levels than non-drinkers. Conclusions: Endotoxaemia is associated with fatty liver and possibly NASH in the general population. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of fatty liver and NASH in modest drinkers in previous observational studies. This study was supported by a grant from the Health and Medical Research Fund sponsored by the Hong Kong SAR Government [Ref CUHK-11120621]. P0981 ADAPTATION OF HEPATIC MITOCHONDRIAL FUNCTION IN OBESE HUMANS WITH OR WITHOUT NON-ALCOHOLIC STEATOHEPATITIS C. Koliaki, J. Szendroedi, K. Kaul, T. Jelenik, P. Nowotny, F. Jankowiak, C. Herder, M. Carstensen, M. Krausch, W. Trudo Knoefel, M. Schlensak, M. Roden. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Dusseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Dusseldorf, Germany; Department of Endocrinology and Diabetology, Heinrich Heine University, Dusseldorf, Germany; Institute of Pathology, Heinrich Heine University, Dusseldorf, Germany; Department of General, Visceral and Pediatric Surgery, Heinrich Heine University, Dusseldorf, Germany; General Surgery Department, St. Martinus Hospital, Dusseldorf, Germany, Dusseldorf, Germany E-mail: ckoliaki@yahoo.com

Modest alcohol consumption and carotid plaques or carotid artery stenosis in men with non-alcoholic fatty liver disease

BackgroundFavorable association between modest alcohol consumption and cardiovascular disease had been reported in general population, however, whether observed benefit extend to men with established fatty liver disease remains unknown. MethodsCross-sectional study of 10,581 consecutive male participants aged 30 years or older undergoing abdominal ultrasonography and carotid artery ultrasonography were screened. Non-alcoholic fatty liver disease (NAFLD) was diagnosed with ultrasonography and exclusion of secondary causes for fat accumulation or other causes of chronic liver disease. Modest alcohol use was defined as consumption of less than 20 g of alcohol per day. ResultsThere were total 2280 men diagnosed with fatty liver, and the mean age was 51.8 years old. Among them, 1797 were modest alcohol drinkers. The prevalence of carotid plaques (55.3% vs. 43.4%, p < 0.001) and carotid artery stenosis (11.0% vs. 5.5%, p < 0.001) was higher in non-drinkers than modest drinkers. Modest alcohol consumption had the independent inverse association with carotid plaques [odd ratio (OR): 0.74, 95% confidence interval (CI): 0.60–0.92] and carotid artery stenosis (OR: 0.62, 95% CI: 0.43–0.90), adjusted for age, smoking and metabolic syndrome. ConclusionsModest alcohol consumption had a favorable association with carotid plaque or CAS in men with NAFLD.

Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor. Although modest alcohol consumption may reduce the risk for cardiovascular mortality, whether patients with NAFLD should be allowed modest alcohol consumption remains an important unaddressed issue. We aimed to evaluate the association between modest alcohol drinking and non-alcoholic steatohepatitis (NASH), among subjects with NAFLD. In a cross-sectional analysis of adult participants in the NIH NASH Clinical Research Network, only modest or non-drinkers were included: participants identified as (1) drinking >20 g/day, (2) binge drinkers, or (3) non-drinkers with previous alcohol consumption were excluded. The odds of having a histological diagnosis of NASH and other histological features of NAFLD were analyzed using multiple ordinal logistic regression. The analysis included 251 lifetime non-drinkers and 331 modest drinkers. Modest drinkers compared to non-drinkers had lower odds of having a diagnosis of NASH (summary odds ratio 0.56, 95% CI 0.39-0.84, p=0.002). The odds of NASH decreased as the frequency of alcohol consumption increased within the range of modest consumption. Modest drinkers also had significantly lower odds for fibrosis (OR 0.56 95% CI 0.41-0.77) and ballooning hepatocellular injury (OR 0.66 95% CI 0.48-0.92) than lifetime non-drinkers. In a large, well-characterized population with biopsy-proven NAFLD, modest alcohol consumption was associated with lesser degree of severity as determined by lower odds of the key features that comprise a diagnosis of steatohepatitis, as well as fibrosis. These findings demonstrate the need for prospective studies and a coordinated consensus on alcohol consumption recommendations in NAFLD.

Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography

ObjectiveKnowledge of the epidemiology of non-alcoholic fatty liver disease (NAFLD) is incomplete because liver biopsy cannot be performed on the general population to assess disease severity. New non-invasive tests allow...

Genetic variation in alcohol dehydrogenase 1C and the beneficial effect of alcohol intake on coronary heart disease risk in the Second Northwick Park Heart Study

Alcohol dehydrogenase 1C ( ADH1C or ADH3) genotype reportedly modifies the association between alcohol consumption and coronary heart disease (CHD) risk, as well as influencing plasma high-density lipoprotein (HDL) levels [Hines LM, Stampfer MJ, Ma J, et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001;344:549–55]. This relationship has been examined in a sample of middle-aged (50–61 years) men (total of 2773 with 220 CHD events), participating in the prospective Second Northwick Park Heart Study (NPHS II). Alcohol consumption was assessed by questionnaire as the number of units consumed in the previous week. Drinkers experienced lower CHD risk than abstainers [hazard ratio (HR) 0.73 (95% confidence intervals (CI) 0.53, 0.99; p = 0.04)] and had significantly higher HDL and apolipoprotein (apo)AI concentrations (both p < 0.0001) and a lower fibrinogen ( p = 0.02). Overall, there was no effect of ADHC1 γ1 > γ2 genotype on plasma levels of HDL, apoAI or fibrinogen or on CHD risk. To consider whether the effect of alcohol consumption on risk was modulated by genotype, the men were divided into abstainers, modest drinkers (1–3 units/week) and those who consumed more than 3 units/week. Significant alcohol:genotype interaction on CHD risk was observed ( p = 0.02), with γ2 homozygotes, who were modest drinkers, displaying 78% CHD risk reduction compared to γ1 homozygotes (HR = 0.22, 95% CI 0.05–0.94). There was, however, no association between genotype and apoAI, HDL or fibrinogen and this was not altered when alcohol intake was considered. These findings confirm that the cardiovascular benefit of modest alcohol consumption. ADH1C genotype modifies the relationship between alcohol consumption and CHD risk but at lower levels than previously reported.

Cancer Prevention in Primary Care: Reducing alcohol intake

Alcohol is second in importance only to smoking as a proved cause of cancer. The risk associated with excessive alcohol consumption can be reduced by adopting national and local population based policies. The population approach is aimed at reducing the level of consumption across the whole population, which contains many modest drinkers. Underlying this approach is the fact that a larger proportion of the total morbidity and mortality attributed to alcohol in a population occurs in modest drinkers, even though individually they are at lower risk. This approach should be complemented by risk reduction initiatives in primary care, focused on high risk individuals. Several studies have shown the efficacy of brief interventions by general practitioners in patients with excessive alcohol consumption. Brief interventions, taking 5 to 10 minutes, use simple assessments to identify those at risk and provide information and advice. Evidence exists that general practitioners underuse opportunities to identify and advise patients about excessive drinking.

The Effect of Fructose on Alcohol Metabolism

The blood level of alcohol reflects the tissue levels throughout the body, and in a general way indicates the degree of impairment of the individual with drunkenness. The blood level is most importantly determined by the size of the person and the amount of alcohol ingested, for it is distributed throughout the total body water. The removal of alcohol is remarkably constant in a given person, although severe alcoholics have a substantially higher rate of removal than abstinent persons or modest drinkers.¹ The proneness of the heavy drinker to head trauma, automobile accidents, and unusual infections, and the frequency with which detailed mental and neurological evaluations are needed in a somewhat intoxicated and often very uncooperative subject, are within the experience of every physician. The desirability of a rapid means to bring about sobriety to facilitate these evaluations and provide better care for the alcoholic is apparent. Most adults