Critique 043: Frequent moderate drinking of alcohol is associated with a lower risk of fatty liver disease – 23 May 2011

Hiramine Y, Imamura Y, Uto H, Koriyama C, Horiuchi M, Oketani M, Hosoyamada K, Kusano K, Ido A, Tsubouchi H.   Alcohol drinking patterns and the risk of fatty liver in Japanese men.  J Gastroenterol 2011 46:519–528.  DOI 10.1007/s00535-010-0336-z.

Authors’ Abstract

Background  Alcohol is considered to be a major cause of fatty liver (FL).  In contrast, however, recent investigations have suggested that moderate alcohol consumption is protective against FL.  To clarify the role of alcohol consumption in FL development, we examined the association between drinking patterns and FL prevalence.

Methods  We enrolled 9,886 male participants at regular medical health checks.  Each subject’s history of alcohol consumption was determined by questionnaire.  The subjects were classified according to alcohol consumption as non-, light, moderate, and heavy drinkers (0,<20, 20 – 59, and ≥60 g/day, respectively).  FL was defined by ultrasonography.  Independent predictors of FL were determined by logistic regression analysis.

Results  The prevalence of FL displayed a ‘‘U-shaped curve’’ across the categories of daily alcohol consumption (non-, 44.7%; light, 39.3%; moderate, 35.9%; heavy drinkers, 40.1%; P<0.001).  The prevalence of FL was associated positively with body mass index and other obesity-related diseases and inversely with alcohol consumption (light, odds ratio [OR] 0.71, 95% confidence interval [CI] 0.59–0.86; moderate, OR 0.55, CI 0.45–0.67; heavy, OR 0.44, CI 0.32–0.62) as determined by multivariate analysis after adjusting for potential confounding variables.  In addition, examination of drinking patterns (frequency and volume) revealed that the prevalence of FL was inversely associated with the frequency of alcohol consumption (≥21 days/month: OR 0.62, CI 0.53–0.71) but not with the volume of alcohol consumed.

Conclusions  Our observations suggest that alcohol consumption plays a protective role against FL in men, and consistent alcohol consumption may contribute to this favorable effect.

Forum Comments

Background:  Excessive alcohol consumption is a leading cause of cirrhosis and other serious types of liver disease.  On the other hand, the most common liver disease in many populations, fatty liver disease, is associated primarily with obesity and other features of the metabolic syndrome.  And recent reports have consistently shown that moderate alcohol intake may not only not increase the risk, but may actually decrease the risk of this common disease. 

Suzuki et al1 reported a cross-sectional analysis of alcohol intake and an abnormal liver function test (hypertransaminasemia) suggesting fatty liver disease among approximately 1,200 Japanese male workers.  There was an increase in risk of abnormal liver function associated with obesity.  However, for “moderate drinkers” (defined as 140 to 279 grams of alcohol per week, or about 12-23 drinks/week), there was a significant 60% reduction in such abnormal liver function tests (HR = 0.4).  These investigators then followed 326 subjects without a history of fatty liver or hypertransaminasemia up to 5 years.  During follow up, moderate consumption (versus none or minimal intake) was associated with decreased incidence of hypertransaminasemia, with an adjusted hazard ratio of 0.4 [0.1–0.9], P = 0.02).

In the United States, Dunn et al2 evaluated data from Third National Health and Nutrition Examination Survey participants who either reported no alcohol consumption or preferentially drinking wine with total alcohol consumption up to 10 g per day.  Suspected non-alcoholic fatty liver disease (NAFLD) was based on unexplained serum alanine aminotransferase (ALT) elevation.  After multivariable adjustment, the authors found that moderate drinkers (defined as up to 10 g of alcohol per day in this study) of any type of alcoholic beverage was not associated with an increase in NAFLD.  Further, they found that the consumption of up to 10 g of alcohol per day from wine was associated with a marked lowering of the prevalence of such liver disease; the adjusted odds ratio was 0.15 (95% confidence interval, 0.05-0.49) for modest wine drinkers in comparison with non-drinkers.  More recent studies from Japan3,4 have reached the same conclusions. 

While mechanisms of such protection are not clear, Szabo5 described experimental studies in mice showing that moderate amounts of alcohol were associated with decreased inflammation in liver cells, rather than the increase in inflammation associated with chronic heavy alcohol intake.  Other studies have suggested a variety of inflammatory pathways affected by alcohol, and Sierksma et al6 and others7,8 have found that alcohol increases adiponectin levels and affects other factors associated with a lower risk of liver steatosis.

Comments on the present study:  Both the frequency (days per month) and amount (grams of alcohol per day) were assessed.  There were 11.4% non-drinkers (three-quarters of whom were lifetime abstainers), 45.9% were classified as light drinkers (averaging approximately < 20 g/d), 39.1% as moderate drinkers (20-59 g/d), and 3.5% as heavy drinkers (≥ 60 g/d).  The analyses were done appropriately, with adjustment for the usual factors associated with liver disease (BMI, smoking, diabetes, etc.).  In the analyses, never drinkers were evaluated separately from former drinkers.  A high percentage of the subjects (38.6%) had ultrasonic evidence of fatty liver.   

As expected, fatty liver was associated with increased BMI, more frequent abnormalities in all liver function tests, and greater prevalence of hypertension, dyslipidemia, and diabetes.  The most striking finding was an inverse association between the frequency of alcohol consumption and the risk of fatty liver (p<0.001).  In unadjusted analyses, the amount of alcohol per day showed the opposite effect, a positive relation with fatty liver, but no clear association was seen with multivariable analysis.  Obesity was inversely associated with frequency of drinking (p=0.03) and positively associated with amount of alcohol consumed per day (p<0.001). 

All Forum reviewers thought that this was a well-done paper.  As one said, “This is another interesting paper based on a well performed study.  And, once more, evidence that light to moderate alcohol consumption is good for health.  The effects of obesity, however, are not.”  As another Forum reviewer stated: “The importance of drinking pattern (small amounts on a frequent basis) has been shown once again in relation to body weight and central adiposity.  A convincing demonstration of the inverse association between a regular drinking pattern and central adiposity has been shown by Tolstrup et al in Denmark9,10 and by Dorn et al11 in the Western New York Health Study.

The limitations of this study are described by the authors.  They did not exclude subjects who may have had other types of liver disease (which occur less frequently than fatty liver disease in most populations).  Further, the investigators had no data on genetic polymorphisms that may relate to liver disease, and the associations with fatty liver of different types of alcoholic beverages were not assessed.

Forum summary:  In a large study of men in Japan, the presence of fatty liver disease by ultrasonography showed an inverse association with the frequency of alcohol consumption; there was some suggestion of an increase in fatty liver disease with higher volume of alcohol consumed per day.  Moderate drinkers had lower levels of obesity than did non-drinkers, and both obesity and metabolic abnormalities were positively associated with fatty liver disease. 

These findings support the results of a number of other recent studies showing that moderate drinking does not increase the risk of this common type of liver disease; instead, it is associated with a lower risk of its occurrence.  We agree with the implications of these studies as stated by the authors: “These results suggest that lifestyle modifications aimed at fighting central obesity and metabolic abnormalities should be the most important recommendations for the management of fatty liver.  In addition, it seems unlikely that the risk of fatty liver can be reduced by the discontinuation and/or reduction of alcohol consumption alone.”

References from Forum review

1.  Suzuki A, Angulo P, St. Sauver J, Muto A, Okada T, Lindor K.  Light to moderate alcohol consumption is associated with lower frequency of hypertransaminasemia.  Am J Gastroenterol 2007;102:1912-1919.

2.  Dunn W, Xu R, Schwimmer JB.  Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease.  Hepatology 2008;47:1947-1954.

3.  Gunji T, Matsuhashi N, Sato H, Fujibayashi K, Okumura M, Sasabe N, et al.  Light and moderate alcohol consumption significantly reduces the prevalence of fatty liver in the Japanese male population.  Am J Gastroenterol 2009;104:2189-2195.

4.  Yamada T, Fukatsu M, Suzuki S, Yoshida T, Tokudome S, Joh T.  Alcohol drinking may not be a major risk factor for fatty liver in Japanese undergoing a health checkup.  Dig Dis Sci 2010;55:176-182.

5.  Szabo G.  Moderate drinking, inflammation, and liver disease.  Ann Epidemiol 2007;17(Suppl):S49-S54.

6.  Sierksma A, Patel H, Ouchi N, Kihara S, Funahasi T, Heine RJ, et al.  Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-a, and insulin sensitivity.  Diabetes Care 2004;27:184-189.

7.  Sazci A, Akpinar G, Aygun C, Ergul E, Senturk O, Hulagu S.  Association of apolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis.  Dig Dis Sci 2008;53:3218-3224.

8.  Fujita K, Nozaki Y, Wada K, Yoneda M, Fujimoto Y, Fujitake M, et al.  Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis.  Hepatology 2009;50:772-780.

9.  Tolstrup JS, Heitmann BL, Tjonneland A, Overvad K, Sorensen TI, Gronbaek M.  The relation between drinking pattern and body mass index, waist and hip circumference.  Int J Obes (Lond) 2005;29:490-497.

10.  Tolstrup JS, Halkjaer J, Heitmann BL, Tjønneland AM, Overvad K, Sørensen TI, Grønbaek MN.  Alcohol drinking frequency in relation to subsequent changes in waist circumference.  Am J Clin Nutr 2008;87:957-963.

11.  Dorn JM, Hovey K, Muti P, Freudenheim JL, Russell M, Nochajski TH, Trevisan M.  Alcohol drinking patterns differentially affect central adiposity as measured by abdominal height in women and men.  J Nutr 2003;133:2655-2662.

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Comments on the present paper were provided by the following members of the International Scientific Forum on Alcohol Research:

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway.

Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia.

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA.

Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis, USA.