BACKGROUND: Alcohol use increases the risk of many conditions in addition to liver disease; patients with alcohol-related liver disease (ALD) are therefore at risk from both extra-hepatic and hepatic disease. AIMS: This review synthesises information about non-liver-related mortality in persons with ALD. METHODS: A systematic literature review was performed to identify studies describing non-liver outcomes in ALD. Information about overall non-liver mortality was extracted from included studies and sub-categorised into major causes: cardiovascular disease (CVD), non-liver cancer and infection. Single-proportion meta-analysis was done to calculate incidence rates (events/1000 patient-years) and relative risks (RR) compared with control populations.
RESULTS: Thirty-seven studies describing 50 302 individuals with 155 820 patient-years of follow-up were included. Diabetes, CVD and obesity were highly prevalent amongst included patients (5.4%, 10.4% and 20.8% respectively). Outcomes varied across the spectrum of ALD: in alcohol-related fatty liver the rate of non-liver mortality was 43.4/1000 patient-years, whereas in alcoholic hepatitis the rate of non-liver mortality was 22.5/1000 patient-years. The risk of all studied outcomes was higher in ALD compared with control populations: The RR of death from CVD was 2.4 (1.6-3.8), from non-hepatic cancer 2.2 (1.6-2.9) and from infection 8.2 (4.7-14.3). CONCLUSION: Persons with ALD are at high risk of death from non-liver causes such as cardiovascular disease and non-hepatic cancer.
OBJECTIVE: This study aimed to shed light on contradictory associations of alcohol intake with waist circumference (WC) and body mass index (BMI) by examining 5-yr changes in alcohol intake in relation to 5-yr WC and BMI changes. METHODS: This prospective study included 4,355 participants (1,974 men and 2,381 women) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study at baseline (1985-1986) and followed over 25 years (2010-2011). Longitudinal random effects linear regression models were used to test whether changes in drinking (defined categorically) as starting to drink, increasing, decreasing, stable drinking or stopping drinking (versus stable non-drinking) over a series of 5-yr periods were associated with corresponding 5-yr WC and BMI changes. Associations with 5-yr changes (defined categorically as starting, stable or stopping) in drinking level (i.e., light/moderate and excessive) and 5-yr changes (defined categorically as increasing, no change, or decreasing) by beverage type (i.e., beer, wine and liquor/mixed drinks) were also examined.
RESULTS: In men, compared to stable non-drinking, decreasing total alcohol intake was associated with lower 5-yr WC (beta:-0.62 cm; 95% CI: -1.09, -0.14 cm) and BMI gains (beta:-0.20 kg/m2; 95% CI: -0.30, -0.03 kg/m2) and stopping excessive drinking was associated with lower 5-yr WC gains (beta:-0.77 cm; 95% CI: -1.51, -0.03 cm). In women, compared to those with stable non-drinking habits, starting light/moderate drinking was associated with lower 5-yr WC (beta: -0.78 cm; 95% CI: -1.29, -0.26 cm) and BMI gains (beta:-0.42 kg/m2; 95% CI: -0.64, -0.20 kg/m2). Increasing wine intake was associated with a lower 5-yr BMI gain (beta:-0.27 kg/m2; 95% CI: -0.51, -0.03 kg/m2). Decreasing liquor/mixed drink (beta:-0.33 kg/m2; 95% CI: -0.56, -0.09 kg/m2) intake was associated with lower 5-yr WC (beta:-0.88 cm; 95% CI: -1.43, -0.34 cm) and BMI (beta:-0.33 kg/m2; 95% CI: -0.56, -0.09 kg/m2) gains. CONCLUSIONS: Associations of alcohol intake with obesity measures are complex. In women, wine and liquor/mixed drink intakes had contrasting associations with WC and BMI change. In men, decreasing weekly alcoholic beverage intake with an emphasis on stopping excessive consumption may be beneficial in managing WC and BMI gains.
Previous studies have reported conflicting results on the clinical impact of alcohol consumption on the glomerular filtration rate (GFR). This retrospective cohort study aimed to assess the dose-dependent association between alcohol consumption and the slope of the estimated GFR (eGFR) in 304,929 participants aged 40-74 years who underwent annual health checkups in Japan between April 2008 and March 2011. The association between the baseline alcohol consumption and eGFR slope during the median observational period of 1.9 years was assessed using linear mixed-effects models with the random intercept and random slope of time adjusting for clinically relevant factors. In men, rare drinkers and daily drinkers with alcohol consumptions of >/=60 g/day had a significantly larger decline in eGFR than occasional drinkers (difference in multivariable-adjusted eGFR slope with 95% confidence interval (mL/min/1.73 m(2)/year) of rare, occasional, and daily drinkers with /=60 g/day: -0.33 [-0.57, -0.09], 0.00 [reference], -0.06 [-0.39, 0.26], -0.16 [-0.43, 0.12], -0.08 [-0.47, 0.30], and -0.79 [-1.40, -0.17], respectively).
In women, only rare drinkers were associated with lower eGFR slopes than occasional drinkers. In conclusion, alcohol consumption was associated with the eGFR slope in an inverse U-shaped fashion in men but not in women.
While the detrimental effects of binge drinking are well recognized, low-to-moderate alcohol consumption may be beneficial to health, although the underlying mechanism(s) remains elusive. In this opinion article, we will examine the effects of low dose alcohol consumption from the perspective of epigenetic modulation. Biochemically, alcohol is metabolized into acetate and subsequently to acetyl-coA, which can modulate histone acetylation levels. While elevated levels of acetyl-CoA are detrimental for longevity, we argue that diminished acetyl-CoA also negatively affects fatty acid biosynthesis and histone acetylation, which play a critical role in gene expression and, ultimately, health span. Since mitochondrial function and glucose metabolism, which provide the main source of nucleocytoplasmic acetyl-CoA, are compromised with age, alcohol-derived acetate could be an alternative source of acetyl-CoA to compensate. Hence, the health benefits of low ethanol consumption may be more pronounced after midlife, since mitochondrial function and/or glucose metabolism are diminished in this phase of the life course.
Indeed, various clinical alcohol consumption studies concur with this notion, and have shown that a low dose of regular alcohol intake after midlife brings about various health and survival benefits. The requirement for regular alcohol intake may also reflect the transient nature of ethanol-induced histone acetylation. Conversely, ethanol may also stimulate carcinogenesis by inhibiting DNA methylation, as it was shown to reduce various pathways leading to DNA and histone methylation. However, unlike acetylation, where ethanol directly increases the substrate for acetylation, this effect was only observed in the high alcohol exposure cohort. While alcohol-derived acetate may be beneficial for health after midlife, various detrimental effects of alcohol consumption remain, and hence, we do not advocate excessive drinking to increase acetate. This opinion article establishes a possible role of ethanol-derived acetate in achieving homeostasis and sustaining an organism's health span.