Liver cirrhosis due to alcohol is a rare disease in general populations, affecting three people in a thousand. Liver-disease mortality rates in the UK, however, have increased 400% since 1970, and in people younger than 65 years, have risen by almost five-times.1 The risk of liver disease increases as alcohol consumption rises beyond about 30g/day, with a 7.1-fold relative risk at 50g/day rising to a 26-fold relative risk at 100g/day.2
Hepatic steatosis (fatty liver) may be found in ≥90% of people with previously normal livers after only two weeks of heavy alcohol ingestion. Continued heavy drinking may cause the liver to become inflamed (steatohepatitis), with further progression to liver fibrosis in 20–40% of heavy drinkers.3 In response, the liver tries to heal itself, producing scar tissue, and the liver can become a mesh of scars with small islands of “good” liver in between (cirrhosis). A meta-analysis of high-risk populations found that roughly half of the patients consumed ≥110g alcohol per day, and the incidence of cirrhosis in the alcohol-problem groups ranged from 7–16% after 8–12 years.4 The fact that only a minority of people with high-risk alcohol intake develop cirrhosis indicates that additional protective/risk factors are involved. Individual differences in susceptibility to liver toxicity from alcohol are wide and depend on gender, genetic factors, drinking habits, health issues that increase the risk, and lifestyle factors associated with risk or protection.5
Gender
Women are more susceptible to the hepatotoxic effects of alcohol than men due to a smaller volume of total body water: for men, weight (in pounds) x 0.31 = body water (in liters); for women, weight (pounds) x 1.21 = body water (liters). With the same intake of alcohol (gram/kg bodyweight), a woman’s lower volume of distribution will result in a higher blood alcohol concentration.
Genetic factors
Evidence supporting a genetic component to cirrhosis risk comes mainly from a large study of 15,924 male twin pairs. The concordance rate for alcoholic cirrhosis was 14.6% in monozygotic twins and 5.4% in dizygotic twins.6 A genetic risk score (GRS) based on three genetic risk variants was used to score groups of people with high-risk alcohol intake (≥80g/d for men, or ≥50g/d for women), and the risk of cirrhosis was about three times higher among groups with a high GRS in comparison with groups with a low GRS.7
Related
Drinking habits and liver cirrhosis
The National Institute on Alcohol Abuse and Alcoholism (USA) defines binge-drinking episodes as consumption of ≥5 drinks (14g alcohol) (male) or ≥4 drinks (female) in the space of about two hours. Drinking too much too fast leads to getting drunk, and a study of adolescent men conscribed to military service in Sweden found a 50% increased risk for severe liver disease in men who reported drinking alcohol to alleviate a hangover, while a report of having been apprehended for being drunk doubled the risk.8 In a Finnish population-based health study, monthly binge drinking doubled the risk of liver disease, while a regular weekend binge trebled the risk.9 A UK Biobank study found heavy binges (women ≥72g/day, men ≥96g/day) conferred a four-fold higher risk for alcohol-related cirrhosis, while heavy binge drinking combined with a high genetic predisposition risk score was associated with a tenfold higher risk. In the UK Biobank study, diabetes status increased the risk of binge drinking from double, to five-fold.10
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In the Dionysos Study, the risk of developing cirrhosis was three-fold higher for drinkers who drank alcohol outside mealtimes compared with those who drank only at mealtimes, independently of the amount ingested.11 In the prospective UK Million Women Study, about half of the participants reported usually drinking with meals and, after adjusting for amount consumed, cirrhosis incidence was 30% lower for usually drinking with meals than not, in wine-only drinkers as well as all other drinkers.12
Preference for wine
In the Copenhagen City Heart Study, the risk of developing cirrhosis in wine drinkers (more than 51% wine of total alcohol intake) was one third of the risk of those drinking no wine for any given level of total alcohol intake.13 The protective effect of wine preference was confirmed by the Danish Cancer, Diet, and Health study; compared to drinking <14 drinks (12g alcohol)/week, the risk of alcoholic cirrhosis in men drinking 14–28 drinks/week, was 7.5-fold in drinkers of no wine (<1% wine), 3.1-fold in drinkers of some wine (1–15%), and 1.7-fold in drinkers of mostly wine (50–100%).14
In a Norwegian study, a pint of beer (16.8g alcohol) doubled the risk of alcoholic liver mortality; a shot of liquor (12.8g alcohol) increased the risk 2.6-fold, while a glass of wine (16.8g alcohol) reduced the risk by one third. Individuals with low alcohol use and wine preference tend to exhibit healthier dietary habits, healthier lifestyle, higher socioeconomic status, and increased physical activity compared to complete abstainers. These factors are difficult to adjust for fully in observational studies.15
Health issues that increase the risk of liver cirrhosis
Non-alcoholic fatty liver disease (NAFLD)
As the 44% liver fat content of nondrinking, force-fed ducks and geese demonstrate, alcohol is not a sine qua non for development of a fatty liver. In recent years, there has been a dramatic increase in the prevalence of obesity and metabolic syndrome risk-factors within the general population. NAFLD is driven by excess caloric intake in the absence of excessive alcohol consumption—typically, a threshold of <10g/day for women and <20g/day for men is adopted. In Europe NAFLD is reported in 25–30% of subjects, but the prevalence of NAFLD increases up to 65% in overweight subjects, 80–90% in subjects with central obesity, and 79% in patients with type-2 diabetes. NAFLD now coexists with alcohol consumption in a substantial proportion of the population, with each exposure potentially sensitizing the liver to the injurious effects of the other. The amount of alcohol consumption that would be detrimental for patients with fatty liver disease is not well known, however. Indeed, while some studies have suggested protective effects of moderate alcohol use, others reported increased risks of even low to moderate use.2
Obesity
In Europe, 20–25% of the population is obese. Compared to normal-weight participants drinking within the recommended limits, a meta-analysis of nine cohort studies found the relative risk of chronic liver disease associated with obesity increased three-fold, the risk of drinking above recommended limits was increased 2.7-fold, and the combination of obesity and consumption of alcohol above limits increased the risk 5.4-fold.16 In the presence of marked abdominal obesity, one daily drink yielded a similar relative risk for incident liver disease as four daily drinks in non-obese men.17
Metabolic syndrome
Metabolic syndrome is a cluster of conditions that increases your risk of heart disease and type-2 diabetes. The syndrome is defined by the presence of ≥3 metabolic risk factors: increased blood pressure, high blood sugar (insulin resistance), abdominal obesity (“having an apple shape”), high blood triglycerides, and low HDL-C level (good cholesterol). Among moderate drinkers (10–20g/d for women, 10–30g/d for men) or heavy drinkers (20–50g/d for women, 30–50g/d for men), concomitant metabolic syndrome increased the ten-year cumulative risk for advanced liver disease from 0.3%, to 1.4% in moderate drinkers, and from 0.8%, to 2.4% in heavy drinkers.18
Lifestyle factors: risk or protection
Cigarette smoking
The Copenhagen City Heart Study found alcoholic liver cirrhosis hazard ratios of 3.9 for women and 1.6 for men smoking >10g of tobacco/day compared with never-smokers, after adjusting for age, alcohol intake, education, and body-mass index. It was estimated that approximately 26% of alcoholic cirrhosis cases among women and 8% of cases among men were attributable to smoking among the participants in this study.19
Exercise
The results from randomized studies indicate that energy-matched high-intensity and moderate-intensity exercise is effective at decreasing intrahepatic fat and NAFLD risk, and not contingent upon reductions in abdominal adiposity or body weight.20 A randomized study of 220 obese people with NAFLD found that a 12-month exercise intervention induced reductions in hepatic fat accumulation, abdominal obesity, and blood pressure for up to one year after the active intervention.21
Coffee
The Italian Study on Liver Cirrhosis Determinants, which measured the consumption of caffeine-containing beverages and alcohol-containing beverages for the entire life of each included subject, found a strong negative association between coffee consumption and the risk of liver cirrhosis and no such evidence for other beverages containing caffeine.22 New findings included evidence that the observed protective effect is not caused by a confounding effect of education, smoking habits, and dietary patterns. The most likely hypothesis is that non-caffeine coffee fractions have a protective effect on liver cells. An excellent review has examined this evidence in great detail, with the conclusion that the protective effect of coffee is real and amounts to as much as a 40% reduction of the risk of alcoholic cirrhosis for a daily increase of two cups.23
Conclusion
The information about factors that increase or diminish your risk of alcoholic liver disease should be instrumental in your consideration of whether you are in a good place to enjoy your glasses of wine with minimal risk of liver cirrhosis—a terrifying disease. The safe levels of alcohol consumption proposed by the European Association for the Study of the Liver are 30g/day and 20g/day of alcohol in men and women respectively. The level at which any potentially beneficial effect derived from the consumption of alcohol shifts to become clearly harmful, however, is neither consistent nor clearly defined with sufficient accuracy in patients that have coexistent features of metabolic syndrome like obesity or type-2 diabetes.2 The presence of steatosis seems to amplify alcoholic liver toxicity, and there is no clear safe limit of alcohol intake in individuals with a fatty liver; the absolute risk, however, from maximum one daily glass of wine with your meal, seems small.17
NOTES
1. R Williams et al., “Addressing liver disease in the UK: A blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis,” The Lancet 384 (2014), pp.1953–97.
2. M Boyle, S Masson, QM Anstee, “The bidirectional impacts of alcohol consumption and the metabolic syndrome: Cofactors for progressive fatty liver disease,” Journal of Hepatology 68:2 (2018), pp.251–67.
3. R Ramkissoon, VH Shah VH, “Alcohol Use Disorder and Alcohol-Associated Liver Disease,” Alcohol Research 42:1 (2022), p.13.
4. G Askgaard, MS Kjær, JS Tolstrup, “Opportunities to Prevent Alcoholic Liver Cirrhosis in High-Risk Populations: A Systematic Review With Meta-Analysis,” American Journal of Gastroenterology 114:2 (2019), pp.221–32.
5. M Roerecke et al., “Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review,” American Journal of Gastroenterology 114 (2019), pp.1574–86.
6. Z Hrubec, GS Omenn, “Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: Twin concordances for alcoholism and its biological end points by zygosity among male veterans,” Alcoholism: Clinical and Experimental Research 5 (1981), pp.207–15.
7. JB Whitfield et al., “A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers,” Journal of Hepatology 76:2 (2022), pp.275–82.
8. H Hagström et al., “Risk Behaviors Associated with Alcohol Consumption Predict Future Severe Liver Disease,” Digestive Diseases and Sciences 64:7 (2019), pp.2014–23.
9. F Åberg et al., “Binge drinking and the risk of liver events: A population-based cohort study,” Liver International 37 (2017), pp.1373–81.
10. C Ding et al., “Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease,” Nature Communications 14:1 (2023), p.8041.
11. S Bellentani et al., “Drinking habits as cofactors of risk for alcohol induced liver damage,” The Dionysos Study Group, Gut 41 (1997), pp.845–50.
12. RF Simpson et al., “Alcohol drinking patterns and liver cirrhosis risk: Analysis of the prospective UK Million Women Study,” Lancet Public Health 4 (2019), e41–48.
13. U Becker, M Grønbæk, D Johansen, TIA Sørensen, “Lower risk for alcohol-induced cirrhosis in wine drinkers,” Hepatology 35 (2002), pp.868–75.
14. G Askgaard et al., “Alcohol drinking pattern and risk of alcoholic liver cirrhosis: A prospective cohort study, Journal of Hepatology 62:5 (2015), pp.1061–67.
15. A Tverdal et al., “Coffee and wine consumption is associated with reduced mortality from alcoholic liver disease: follow-up of 219,279 Norwegian men and women aged 30–67 years,” Annals of Epidemiology 28:11 (2018), pp.753–58.
16. K Glyn-Owen et al., “The combined effect of alcohol and body mass index on risk of chronic liver disease: A systematic review and meta-analysis of cohort studies,” Liver International 41:6 (2021), pp.1216–26.
17. F Åberg, M Färkkilä, V Männistö, “Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies,” Alcoholism: Clinical and Experimental Research 44:2 (2020), pp.384–403.
18. F Åberg F et al., “Combined Effects of Alcohol and Metabolic Disorders in Patients with Chronic Liver Disease,” Clinical Gastroenterology and Hepatology 18:4 (2020), pp.995–97.
19. MK Dam et al., “Smoking and risk of liver cirrhosis: A population-based cohort study,” Scandinavian Journal of Gastroenterology 48:5 (2013), pp.585–91.
20. NC Winn et al., “Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity: A randomized trial,” Metabolism 78 (2018), pp.128–40.
21. H-J Zhang et al., “Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study,” Diabetes, Obesity and Metabolism 19:2 (2017), pp.284–89.
22. G Corrao et al., “Coffee, caffeine, and the risk of liver cirrhosis,” Annals of Epidemiology 11 (2001), pp.458–65.
23. OJ Kennedy et al., “Systematic review with meta-analysis: Coffee consumption and the risk of cirrhosis,” Alimentary Pharmacology & Therapeutics 43:5 (2016), pp.562–74.
