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  • Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals

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Letter
Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals
  1. Silvia Sookoian1,2,3,
  2. Gustavo O Castaño2,3,
  3. Carlos J Pirola4
  1. 1 Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires—National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
  2. 2 Research Council in Health, Ciudad Autónoma de Buenos Aires, Argentina
  3. 3 Liver Unit, Medicine and Surgery Department, Hospital Abel Zubizarreta, Ciudad Autónoma de Buenos Aires, Argentina
  4. 4 Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires—National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
  1. Correspondence to Dr Silvia Sookoian, Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires—National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires 1427, Argentina; ssookoian{at}lanari.fmed.uba.ar

https://doi.org/10.1136/gutjnl-2013-305718

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    Epidemiological studies suggested that the prevalence and the disease severity of non-alcoholic fatty liver disease (NAFLD) are lower for people who drink modest amounts of alcohol than those who are abstainers. Nevertheless, the evidence is still inconclusive because some recently published studies1 showed that modest alcohol consumption (MAC) increases hepatic fat without increasing the risk of advanced fibrosis.

    Remarkably, we found in our population that MAC has a beneficial effect in preventing not only NAFLD but the main features of the metabolic syndrome, including body mass index (BMI), blood pressure, homeostatic model assessment-insulin resistance and C-reactive protein levels. Accordingly, NAFLD and non-alcoholic steatohepatitis (NASH) prevalence, liver enzymes and inflammatory markers were lower in subjects who took modest amounts of alcohol than those who are abstainers (table 1).

    View this table:
    Table 1

    Clinical and biochemical characteristics of the Argentinean population according to drinking status: non-drinkers versus modest drinkers

    Hence, we propose to take advantage of meta-analysis to estimate from published data the effect of MAC on the odds of having NAFLD to give a quantitative assessment of this relationship. The drinkers were classified into two groups: non-drinkers, persons who drinks 0 g/day of alcohol, and light or modest drinkers, persons who drinks less than 40 g/day of alcohol; all the studies accomplished the inclusion criteria.

    Thus, we addressed two different relevant clinical questions.

    Is MAC associated with lower prevalence of NAFLD?

    Data regarding MAC and NAFLD were extracted from eight heterogeneous (I2=80.7, p<0.0001) studies1–8 that were meta-analysed along with our own data; the analysis included 43 175 adult individuals (30 791 non-drinkers and 12 384 modest drinkers). The analysis showed that MAC was associated with a significant protection from the odds of having NAFLD in both fixed (OR 0.688, 95% CI 0.646% to 0.733%, p<10−8) and random models (OR 0.684, 95% CI 0.580% to 0.806%, p<10−5) (figure 1). This beneficial effect seems to be independent of covariates such as BMI (meta-regression analysis showed that this association was independent of BMI (slope=0.01, p<0.44), but is much influenced by sex. Of note, among women (n=12 459), the protective effect of MAC on NAFLD was surprisingly higher (about 53%) compared with men (about 30%).

    Figure 1
    Figure 1

    Summary estimates for OR (effect); the corresponding 95% CI (lower and upper) and significance (p value) were calculated by fixed and random effects meta-analysis for non-alcoholic fatty liver disease (as dichotomous variable) between non-drinkers and modest drinkers. The first author of the study and the year of publication are shown after the study name; b stands for female data; Popul indicates design features. GP, general population; HB, hospital-based. In the graph, numbers indicate OR, filled squares stand for the effect of individual studies and filled diamonds express combined fixed and random effects. The symbol size is proportional to the number of individuals involved in each study.

    Is MAC associated with lower prevalence of NASH among those with NAFLD?

    MAC was found to have a significant protective effect on the development of NASH in both fixed and random models (OR 0.501, 95% CI 0.340% to 0.740%, p<0.0005) without any evidence of heterogeneity (p=NS, I2=0); the data are from 822 patients (550 non-drinkers and 272 modest drinkers) diagnosed by liver biopsy in our population and two additional studies.2–9

    In conclusion, quantitative evidence showed that MAC is associated with a significant protective effect of about 31% on the risk of having NAFLD. Even more remarkable, MAC was associated with an average protective effect of about 50% on the risk of developing an advanced disease stage.

    Future research agenda still remains open, looking for answers from cohort prospective studies elucidating the exact role of MAC on the natural history of NAFLD. A note of caution should be added because a previous study showed that NASH patients who report any regular alcohol consumption are 3.6 times more likely to develop liver cancer than abstainers.10

    In addition, further exploration in future epidemiological studies should answer the question of whether different kinds of beverages are equally beneficial or able to protect against NAFLD.

    Meanwhile, the deleterious effects of excess drinking must always be highlighted to NAFLD patients, but they might be allowed to drink low amounts of alcohol, including a narrow window between maximum protection and harm, which is not the same in men and women.

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    Footnotes

    • Contributors SSdesigned the study, collected data, analysed data, collected patients’ data, performed liver biopsy and wrote the manuscript. GC collected patients’ data and performed LB. CJP designed the study, collected data, analysed data and wrote the manuscript.

    • Funding This study was supported in part by grants UBACYT CM04 (Universidad de Buenos Aires), PICT 2008-1521 and 2010-0441 (Agencia Nacional de Promoción Científica y Tecnológica).

    • Competing interests SS and CJP belong to Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET).

    • Patient consent Obtained.

    • Ethics approval Ethical Committee of the Hospital Zubizarreta. GCBA.

    • Provenance and peer review Not commissioned; externally peer reviewed.