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

Abstract

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.Nutrients 2019, 11, 3048 2 of 23 equals mortality in alcohol users) for an average alcohol consumption of approximately 25-30 g in women and 40 g in men [4].All NAFLD studies explicitly report the exclusion of subjects with alcohol intake at risk, defined according to pre-specified criteria, and most clinicians suggest total abstinence from alcohol as therapeutic measure for prevention NAFLD and/or disease progression. More than a decade ago a few epidemiological studies reported an inverse association between moderate alcohol consumption (within presumably safe limits) and the prevalence of NAFLD in the population [5,6], pointing to a favorable effect of moderate alcohol use extending from the cardiovascular system to the setting of metabolic liver disease. This raised a lot of debate on the correct dietary and lifestyle treatment of NAFLD, which has not settled yet. Do we need to counsel our NAFLD patients for total alcohol abstinence to prevent disease progression?This narrative review is intended to summarize the evidence linking moderate alcohol intake with NAFLD, starting from difficulties in the correct assessment of alcohol intake. The conclusions are based on the experience of authors and the general effects of alcohol on the liver and outside the liver, in the hope to generate a common health policy among healthcare professionals. Literature Search

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

“…Although the effect of active smoking on NAFLD development remained controversial [ 222 ] a recent systematic review and meta-analysis from 20 observational studies revealed a slight but significant association between active and passive smoking and NAFLD [ 223 ]. The link between a modest alcohol consumption with NAFLD development is described in a very recent review [ 224 ].…”

Stratification of patients in NASH clinical trials: A pitfall for trial success

“…Alcohol intake is an exclusion criterion for NAFLD clinical trials (>20 g and >30 g per day in men and women, respectively), although its baseline assessment is suboptimal, and the benefits or harms of its intake are controversial. 19 Irrespective of baseline parameters, patients receiving placebo show significant histologic, radiologic, and biochemical responses. 8 This means that patients change their behaviour after enrolment (Hawthorne effect), indirectly reflecting the impact of lifestyle on response rates (not only on the placebo but also on the experimental group).…”

Management of non-alcoholic fatty liver disease

“…Changes in body weight and physical activity should be recorded and included in the final analysis to avoid potential biases. Quantification of alcohol intake is also challenging, with consistent variability in drinking patterns within NAFLD thresholds, which is likely to influence the results 183. Finally, gene polymorphisms associated with NASH ( PNPLA3 I148M and TM6SF2 E167K ) are likely to affect trial response.…”