Discussion
In the current sample of European men and women, we demonstrated a dose–response relationship between average daily alcohol consumption and hepatic steatosis and an association between binge drinking with hepatic steatosis in men. In addition, our analyses revealed that being overweight or obese increased the effect of average daily alcohol consumption and binge drinking on hepatic steatosis in men and women.
We revealed a clear dose–response relationship between the average daily alcohol consumption and hepatic steatosis in the male study population suggesting a detrimental influence of alcohol consumption on hepatic steatosis in men. This finding is in striking contrast to results from previous cross-sectional studies that demonstrated inverse associations between alcohol consumption and hepatic steatosis and hypothesised a protective effect of moderate alcohol consumption on hepatic steatosis. However, the latter results were mostly based on data from Japanese males who underwent medical health check-ups. As discussed by Hiramine et al., ethnicity and lifestyle factors including drinking style, type of alcohol and dietary habits might be factors explaining the contrasting results of previous studies. Future research should address these issues. Regarding the pathogenesis of hepatic steatosis, it has been highlighted that the role of gender as risk factor remains unclear and that also ethnic differences in the prevalence of hepatic steatosis are not explained. It might be assumed that hepatic steatosis may be affected by yet unidentified genetic or environmental factors.
In the present study, average daily alcohol consumption was not associated with hepatic steatosis in women. This lack of significance might be explained by the very low number of women who drink heavily. Therefore, more studies of women with high levels of alcohol intake are necessary to further explore the association between alcohol consumption and hepatic steatosis. Moreover, we have demonstrated that women with hepatic steatosis were more often physically inactive and more likely to be in obesity class II as defined as a BMI >35 kg/m than men with hepatic steatosis which might lead to the assumption that obesity played a greater role in the development of hepatic steatosis in women than alcohol consumption.
We performed sensitivity analyses to validate self-reported alcohol consumption using CDT. CDT has been demonstrated to be a reliable marker for alcohol consumption with a high diagnostic specificity. A daily alcohol consumption of more than 50–80 g for at least 1 week results in an increased CDT plasma concentration. Our analyses revealed a significant association between CDT values of 10.1% and hepatic steatosis in the male study population, while the association between CDT and hepatic steatosis in the female study population was nonsignificant. This finding confirms the observed association between alcohol consumption as assessed by self-report and hepatic steatosis. The lack of association between CDT and hepatic steatosis in the female study population gives support to our hypothesis that the quantity of alcohol consumption in women in the present study was too low to detect potential harmful effects on hepatic steatosis. The present finding also leads to the assumption that the quantity of alcohol consumption in women was too low to result in increased CDT values. Furthermore, it has been demonstrated that female gender and elevated BMI reduce the diagnostic sensitivity of %CDT using the HPLC method.
We demonstrated an association between binge drinking and hepatic steatosis in men. This finding also suggests that excessive, irregular drinking might have an impact on hepatic steatosis. In view of the increasing prevalence of binge drinking in western countries, in particular among young adults, further studies are needed to focus on this issue. In the present study, binge drinking was not associated with hepatic steatosis in women. Presumably, the number of binge drinking females was too low in the present study. Alternatively, participants may have underreported binge drinking episodes to provide socially desirable responses in the face-to-face interviews.
We further demonstrated that increasing BMI amplified the effect of average daily alcohol consumption in men, whereas ORs of having hepatic steatosis were the highest in individuals with a BMI of ≥30 kg/m over all levels of alcohol consumption. In women, only obesity enhanced the effect of average daily alcohol consumption on the likelihood of having hepatic steatosis. Thereby, the findings of the present study are consistent with results from previous surveys demonstrating that alcohol consumption along with being overweight or obese increased the risk of having elevated liver enzymes. In the Italian Dionysos study, the risk of having hepatic steatosis, as indicated by liver ultrasound, was higher among obese, heavy drinking individuals than among heavy drinking and normal weight individuals and among obese and moderate drinking individuals. Along with these findings, the results of the present study indicate that the co-occurrence of being overweight or obese and having a high average daily alcohol consumption has a much greater impact on hepatic steatosis than the presence of each of the single risk factors alone. Similar results have been observed concerning the combined effect of binge drinking and BMI on hepatic steatosis. Among male and female binge drinkers, the chance for hepatic steatosis increased with increasing BMI giving further support for our conclusion that the impact of alcohol consumption on hepatic steatosis is strengthened by overweight and obesity.
Our study has several strengths and potential limitations that should be considered. Major strengths of the study include the population-based design, the large sample size, the CDT measurement as a biomarker for alcohol consumption, and the ultrasound examinations to detect hepatic steatosis. In addition, data were collected according to a standardised protocol and certified staff maintained strict quality standards. Limitations may include the inability to perform liver biopsy in a large population-based study like SHIP due to ethical concerns, given that liver biopsy is the best diagnostic approach to detect hepatic steatosis.
To conclude, in European men and women, being overweight or obese aggravates the effect of alcohol consumption on hepatic steatosis. In view of the results regarding the dose–response relationship between average daily alcohol consumption and hepatic steatosis, further studies are needed to explain the reported inconsistent findings of current research.