Reply to: “Modest alcohol consumption and non-alcoholic steatohepatitis”
Authors: Winston Dunn, Jeffrey B. Schwimmer
Journal: Journal of Hepatology (2012)

Modest alcohol consumption and non-alcoholic steatohepatitisJournal of HepatologyVol. 57Issue 6PreviewWe read with great interest the article by Dunn et al., published in March 2012 [1]. This cross-sectional study reported some interesting observations on the relationship between modest alcohol consumption and non-alcoholic steatohepatitis (NASH). However, the study has some limitations. Full-Text PDF Open AccessModest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD)Journal of HepatologyVol. 57Issue 2PreviewNon-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. Full-Text PDF We studied the association of modest alcohol consumption and steatohepatitis in a large sample of well-characterized study participants with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from referral centers across the United States. Modest alcohol consumption was associated with significantly lower odds of non-alcoholic steatohepatitis (NASH). Feng et al. raise questions about diabetes and soft drink consumption as potential confounders. The first question about diabetes speaks to one possible mechanism by which alcohol could lower the odds for NASH. Diabetes has consistently been shown to be a major risk factor for steatohepatitis. In order to be considered a confounder, a factor must be associated with both the exposure and outcome, but cannot be in the causal pathway. Therefore, our main analysis did not include the diagnosis of diabetes as a confounder because diabetes is thought to be in the causal pathway. We did, however, perform a series of sensitivity analyses to address such issues. Sensitivity analysis #4 adjusted for the diagnosis of diabetes and showed that the odds ratio between modest alcohol and NASH was attenuated from 0.52 (95% CI 0.36–0.76) to 0.58 (95% CI 0.41–0.84). Thus as evidenced by this small attenuation, the effect of modest alcohol on steatohepatitis may in part be manifested through reduced prevalence of diabetes, but this is not likely to be the major explanation for the lower odds of steatohepatitis. While we adjusted for an extensive list of social, demographic and lifestyle covariates, the possibility remains for any epidemiology study that the exposure of interest is a surrogate marker of other unmeasured factors. The second question posed by Feng et al. was whether non-drinkers may consume greater amounts of soft drinks, especially those containing fructose. Thus, soft drink consumption could be one of the unmeasured factors, because previous data has suggested an association between fructose consumption and an increased risk for NAFLD [1Abid A. Taha O. Nseir W. Farah R. Grosovski M. Assy N. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome.J Hepatol. 2009; 51: 918-924Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar, 2Nseir W. Nassar F. Assy N. Soft drinks consumption and nonalcoholic fatty liver disease.World J Gastroenterol. 2010; 16: 2579-2588Crossref PubMed Scopus (147) Google Scholar] and NASH. We performed a literature search, but were unable to find published studies comparing soft drink consumption between non-drinkers and modest drinkers. Thus it is unclear whether the amount of soft drink consumption was different between our two groups. However, in our main analysis we did adjust for total calories per day and percent calories from carbohydrates. Neither of these adjustments attenuated the association between modest alcohol and lower odds of having NASH. Beyond issues of mechanism and statistical analyses, the question of whether or not to permit adult patients with NAFLD to drink alcohol in modest amounts remains controversial. As opposed to being harmful, many studies now support the belief that modest alcohol consumption in adults with NAFLD could be beneficial. However, to date no studies can definitively support nor refute this contention. Therefore, hepatologists are not unified on this issue and thus fall into one of three camps: (1) those that continue to recommend strict avoidance; (2) those that counsel their patients that heavy drinking is bad, but that there is not enough evidence to know whether modest alcohol is good or bad, and (3) those that have taken to proactively recommending one alcoholic beverage a few times per week. In order to move past the controversy and know how to best counsel our patients will require collaborations to further build the evidence than can support a clinical consensus. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Supported in part by NIH U01DK061734. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.