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. Old evidence regarding a possible safe and eventually beneficial effect of alcohol intake in NAFLD have however been extensively challenged by data suggesting a detrimental effects of alcohol on other organs and tissues, namely the cardiovascular system and cancer risk. Current guidelines support alcohol abstinence for individuals with NAFLD.
Author, Year | Type of Study/Patients | Alcohol Assessment | Outcome Measures | Results | ||||||||||
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Suzuki, 2007 [5] | Cross sectional and prospective community-based study. 1177 male subjects with annual check-up. 326 subjects without elevated ALT with had a 5-year F-UP | Questionnaire. Alcohol graded as none, light, moderate, excessive | Raised ALT | Light (70–140 g/week: OR 0.6; 95% CI 0.4–1.0) and moderate (140–208 g/week: OR 0.5; 95% CI 0.3–0.9) alcohol consumption was negatively associated with raised ALT in the older and younger groups, respectively, vs. subjects with none or minimal intake. At F-UP, moderate intake was associated with decreased incidence of raised ALT (adjusted HR 0.4; 95% CI 0.1–0.9) | ||||||||||
Gunji, 2009 [6] | Cross-sectional, community-based study. 5599 Japanese men with regular medical survey | Questionnaire. Alcohol graded in g/week | US-detected fatty liver | Both light (40–140 g/week) and moderate (140–280 g/week) alcohol intake independently reduced the risk of fatty liver (OR 0.82; 95% CI 0.68–0.99 and OR 0.75; 0.61–0.93) | ||||||||||
Dixon, 2001 [15] | [18] |
Cross sectional cohort study. 105 patients with liver disease submitted to bariatric surgery | Medical consultation, questionnaire | Presence of biopsy-proven NASH | Moderate alcohol consumption was associated with a decreased risk of NASH (OR, 0.35; 95% CI, 0.12–1.00). | |||||||||
Dunn, 2008 [16] | [19] |
Cross sectional, community-based study of 7211 NHANES III participants not consuming alcohol and 945 wine drinkers | Questionnaire. Modest consumption: defined <100 g/week | Raised ALT (both laboratory range and updated definition) [60] | [31] |
Irrespective of the reference cut-point, modest wine consumption was associated with 50% reduced risk of elevated ALT (OR 0.51; 95% CI 0.33–0.79 with updated normal ranges); no effect was demonstrated for beer or liquor drinking, whereas mixed drinking was protective. | ||||||||
Gunji, 2009 [6] | Cross-sectional, community-based study. 5599 Japanese men with regular medical survey | Questionnaire. Alcohol graded in g/week | US-detected fatty liver | Both light (40–140 g/week) and moderate (140–280 g/week) alcohol intake independently reduced the risk of fatty liver (OR 0.82; 95% CI 0.68–0.99 and OR 0.75; 0.61–0.93) | ||||||||||
Yamada, 2010 [17] | [20] |
Cross-sectional + longitudinal study (5444 men, 4980 women on regular check-ups. F-UP, 6 years | Frequency and amount of drinking in g/week | US-detected fatty liver | Occasional, daily moderate (1 U/day) or heavy (≥ 2 U/day) drinking was negatively associated with liver fat. On follow-up, moderate drinking maintained a negative association with fatty liver in men (OR 0.72, 95% CI 0.58–0.89), not in women | |||||||||
Hiramine, 2011 [18] | [21] |
Cross-sectional cohort (9886 males on regular health check-ups) | Questionnaire. Classified as none, light (≤ 20 g/day), moderate (20–59), heavy | US-detected fatty liver | Fatty liver was positively associated with obesity and negatively alcohol intake (light, OR 0.71, 95% CI 0.59–0.86; moderate, OR 0.55, CI 0.45–0.67; heavy, OR 0.44, CI 0.32–0.62). The frequency of alcohol consumption was more relevant than total amount. | |||||||||
Moriya, 2011 [19] | [22] |
Cross sectional, community-based study. 4957 men and 2155 women, median age 49, free of known liver disease | Lifestyle data derived from questionnaire (g/day) | US-detected NAFLD. Raised ALT by updated reference [60] | [31] |
The prevalence of fatty liver was significantly lower in drinkers than in nondrinkers (28% vs. 40% in men and 10% vs. 16% in women (p < 0.001 for both). NAFLD prevalence was inversely associated with both amount and frequency of alcohol intake. | ||||||||
Gunji, 2012 [20] | [23] |
Cross-sectional, community-based study. 1138 Japanese men with regular check-up, age ≥ 40 | Questionnaires | CT-detected NAFLD | Alcohol consumption was associated with a reduced risk of liver fat, independently of features of metabolic syndrome, physical activity ad raised liver enzymes. | |||||||||
Hamaguchi, 2012 [21] | [24] |
Cross-sectional community-based study. 8571 Japanese men and women, aged 18–88; mean BMI, 22.6 kg/m2 | Questionnaires. Alcohol intake categorized into 4 grades | Fatty liver by ultrasounds | For both men and women, light and moderate alcohol intake was inversely associated with fatty liver (Men: OR 0.69, 95% CI 0.60–0.79 and OR 0.72, 95% CI 0.63–0.83; Women: OR 0.54, 95% CI 0.34–0.88 and OR 0.43,95% CI 0.21–0.88). | |||||||||
Dunn, 2012 [22] | [25] |
Cross-sectional cohort study. 251 lifetime modest drinkers; 331 non-drinkers (NIH NASH CRN) | AUDIT test. Alcohol intake <140 g/week: extensive analysis of drinking pattern | Liver biopsy | Modest drinking within safe limits reduced the odds of NASH (OR 0.56, 95% CI 0.39–0.84), fibrosis (OR 0.56; 95% CI 0.41–0.77) and ballooning (OR 0.66, 95% CI 0.48–0.92) vs. lifetime non-drinking habits | |||||||||
Kwon, 2013 [23] | [26] |
Cross-sectional cohort study. 77 patients with biopsy-assessed NAFLD, alcohol intake < 40 g/day | Lifetime retrospective alcohol intake by questionnaire | Liver biopsy | Increasing age (OR 1.07, 95% CI 1.01–1.14) was associated with more severe liver disease, whereas lifetime alcohol intake ≥ 24 g-years was associated with less severe disease (OR 0.26, 95% CI 0.07–0.97). | |||||||||
Moriya, 2015 [24] | [27] |
Prospective analysis of several community-based cohorts (3773 men and 1524 women); F-UP, NS | Questionnaire | US-assessed NAFLD incidence | In both men and women, modest alcohol intake was associated with negative odds of NAFLD. In men, NAFLD was also reduced by alcohol intake in the range ≥280 g/week, after adjustment for confounders (OR 0.68; 95% CI 0.58–0.79) | |||||||||
Hagstrom, 2017 [25] | [28] |
Cross-sectional, cohort study. 120 subjects with biopsy-proven NAFLD | Questionnaires for lifetime alcohol intake. PEth for recent alcohol | Liver biopsy | Alcohol intake up to 13 U/week was associated with reduced risk of fibrosis (OR 0.86 per U/week, 95% CI 0.76–0.97). High PTth was associated with a higher risk of fibrosis (OR 2.77, 95% CI 1.01–7.59) | |||||||||
Mitchell, 2018 [26] | [29] |
Cross-sectional, cohort study. 187 NAFLD patients (24% with advanced fibrosis) | Questionnaires for previous and actual alcohol intake and binge drinking | Liver biopsy | Modest consumption was associated with a decreased risk of advanced fibrosis (OR 0.33, 95% CI 0.14–0.78). The association was not confirmed in binge drinking. Exclusive wine, not beer drinking, was negatively associated with advanced fibrosis (OR 0.20, 95% CI 0.06–0.69), compared to lifetime abstinence. | |||||||||
Hajifathalian, 2018 [27] | [30] |
Prospective, community-based study of 4568 NHANES participants. F-UP, 70 months | Questionnaire for amount and type of alcohol drinking | Hepatic Steatosis Index [61] | [33] |
Modest alcohol consumption was associated with decreased overall mortality (HR 0.64, 95% CI 0.42–0.97 for a drinking pattern of 0.5–1.5 U/day). However, in NAFLD alcohol consumption ≥ 1.5 U/day had a harmful effect on mortality (HR 1.45, 95% CI 1.01–2.10), after adjustment for confounders. |
Abbreviations: ALT—alanine aminotransferase; AUDIT—Alcohol Use Disorder Identification Test; BMI—body mass index; CI—confidence interval; CT—computed tomography; F-UP—follow-up; HR—hazard ratio; NS—not specified; NHANES—National Health and Nutrition Examination Survey; NIH NASH CRN—National Institute of Health NASH Clinical Research Network; OR—odds ratio; PEth—phosphatidyl ethanol; US—ultrasonography.