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To the Editor:

Dr. Dunn and colleagues1 are to be congratulated on the first description of protective effects of modest wine drinking on the prevalence of nonalcoholic fatty liver disease (NAFLD), which was suspected on the basis of unexplained increases in serum alanine aminotransferase (ALT) following the exclusion of other causes accounting for ALT elevation, in a large sample of participants reflecting the general population in the United States. In their excellent cross-sectional study recruiting 7,211 nondrinkers, 945 modest wine drinkers, 2,237 modest beer drinkers, 688 modest liquor drinkers, and 673 modest mixed drinkers, modest wine drinking (up to 10 g alcohol per day) was associated with reduced prevalence of suspected NAFLD. The adjusted odds ratio was 0.15 when laboratory cut-off point (ALT > 43 U/L) was applied, and the odds ratio was 0.51 based on the gender-specific healthy subject cut-off point (ALT > 30 U/L for men; ALT > 19 U/L for women). Unlike previous studies that assessed the relationship between modest alcohol drinking and chronic liver damage, the validity of the study is characterized by the exclusion of nondrinkers predisposed to alcoholic liver damage for the analysis. To adjust for potential confounders, multiple logistic regression analysis was repeated three times. In the first multivariate analysis, age, gender, race, income, education, neighborhood population density, caffeine consumption, and physical activity were entered. In addition to the above factors, body mass index, waist:hip ratio, systolic and diastolic blood pressure, high-density lipoprotein (HDL) level, and diabetes status were included in the second model. The authors added triglyceride level and quantitative insulin sensitivity as the variable to the third analysis. I would like to ask the authors what was the most important predictor for the prevalence of NAFLD among the variables including wine drinking in the final multivariate analysis.

Apart from being an indicator of NAFLD, moderate ALT elevation is linked to metabolic syndrome, coronary artery disease, and stroke.2 Furthermore, serum concentration of ALT, even if one to two times the upper limit of normal, was associated with increased mortality in a U.S. community.3 In the study, the authors revealed that log-transformed ALT level was significantly lower in modest wine drinkers than in nondrinkers, but there were no significant interactions between wine drinking and age, race, gender, or body mass index. I would like to ask the authors whether modest wine drinking was correlated with serum HDL or triglyceride levels that are components of the metabolic syndrome and risk factors of atherosclerosis leading to ischemic heart disease and stroke.

In the article, the authors do not mention possible mechanisms underlying the association of modest wine drinking with decreased prevalence of NAFLD. In a recent clinical study including 100 patients with histologically verified NAFLD extending from simple steatosis to advanced nonalcoholic steatohepatitis (NASH),4 intrahepatic messenger RNA expression levels of C-reactive protein (CRP) in NASH were significantly higher than in steatosis, and messenger RNA expression of CRP was positively correlated with the severity of fibrosis in NASH patients. These findings suggest that NAFLD possesses an aspect of chronic inflammatory disease as does metabolic syndrome or atherosclerosis. In a recent crossover study evaluating the anti-inflammatory effects of low-dose intake of white and red wine (20 g alcohol per day during 4 weeks) in 35 healthy women,5 serum HDL level increased whereas serum CRP and the ability of monocytes to adhere to endothelial cells decreased after either type of wine. I speculate that part of the protection against NAFLD by light drinking of wine is attributed to the anti-inflammatory effects of polyphenol, alcohol, or both.

It appears to be confirmed that modest alcohol consumption decreases cardiovascular morbidity and mortality.6 An updated meta-analysis of 34 prospective studies has shown that alcohol drinking up to 20 g/day is inversely associated with total mortality in women.7 From the practical viewpoint, however, the only easy rules are that heavy drinkers would be better off reducing their drinking or abstaining, and that all persons, whether modest to moderate drinkers or abstainers, should be warned to avoid heavy drinking. Finally, I would like to ask the authors whether physicians should advise lifelong nondrinkers who seem not to be susceptible to alcohol-related disease but are at risk for NAFLD to start drinking for health.

References

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  • 1
    Dunn W, Xu R, Schwimmer JB. Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease. HEPATOLOGY 2008; 47: 19471954.
  • 2
    Vento S, Nobili V. Aminotransferases as predictors of mortality. Lancet 2008; 371: 18221823.
  • 3
    Lee TH, Kim WR, Benson JT, Themeau TM, Melton LJ. Serum aminotransferase activity and mortality risk in a United States community. HEPATOLOGY 2008; 47: 880887.
  • 4
    Yoneda M, Mawatari H, Fujita K, Iida H, Yonemitsu K, Kato S, et al. High-sensitivity C-reactive protein in an independent clinical feature of non alcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastoenterol 2007; 42: 573582.
  • 5
    Sacanella E, Vazquoz-Agell M, Mena MP, Antanez E, Fernandez-Sola J, Nicolas JM, et al. Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial. Am J Clin Nutr 2007; 86: 14631469.
  • 6
    Klatsky AI. Should patients with heart disease drink alcohol? JAMA 2001; 285: 20042006.
  • 7
    Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women. Arch Intern Med 2006; 166: 24372445.

Tetsuji Fujita M.D.*, * Department of Surgery, Jikei University School of Medicine, Tokyo, Japan.