A comprehensive examination of current studies regarding alcohol consumption and its association with the rare but alarming disease.
Alcohol-related liver cirrhosis is relatively uncommon in the general population, impacting three individuals per thousand. Nonetheless, liver disease mortality rates in the UK have surged by 400% since 1970, with a nearly fivefold increase in cases among those younger than 65 years.1 The likelihood of developing liver disease heightens as alcohol intake exceeds approximately 30g/day, with a 7.1 times greater risk at 50g/day escalating to a 26-fold risk at 100g/day.2
Hepatic steatosis, commonly referred to as fatty liver, can occur in over 90% of individuals with previously healthy livers within just two weeks of excessive alcohol consumption. Continuing to drink heavily can incite inflammation in the liver (steatohepatitis), leading to liver fibrosis in 20–40% of heavy drinkers.3 In an effort to recover, the liver generates scar tissue, and over time, it can develop into a network of scars with patches of healthy liver tissue interspersed (cirrhosis). A meta-analysis focused on high-risk groups revealed that approximately half of the patients consumed at least 110g of alcohol daily, with the occurrence of cirrhosis in alcohol-problem demographics ranging from 7% to 16% after 8–12 years.4 The observation that only a small percentage of individuals with high-risk alcohol consumption actually develop cirrhosis suggests that there are additional protective or risk factors at play. The variability in individual susceptibility to liver damage from alcohol is significant and is influenced by factors such as gender, genetic predisposition, drinking patterns, preexisting health conditions that heighten risk, and lifestyle choices that either mitigate or exacerbate risk factors.5
Women exhibit a greater vulnerability to the damaging effects of alcohol on the liver compared to men, largely due to their lower total body water volume. For men, the formula for calculating body water is weight (in pounds) multiplied by 0.31, which gives the body water in liters. In contrast, for women, the calculation is weight (pounds) multiplied by 1.21 to find body water in liters. Thus, with identical alcohol consumption relative to body weight, women will experience a higher blood alcohol concentration because of their reduced volume of distribution.
Research indicating a genetic factor in the risk of cirrhosis predominantly comes from an extensive study involving 15,924 male twin pairs. The rate of concordance for alcoholic cirrhosis was found to be 14.6% among monozygotic twins, whereas it was 5.4% among dizygotic twins. A genetic risk score (GRS) that utilizes three genetic variants linked to risk was employed to assess groups of individuals with high alcohol consumption (at or above 80g/d for men, or 50g/d for women). The findings revealed that those in high GRS groups were approximately three times more likely to develop cirrhosis when compared to low GRS groups.
Related
The National Institute on Alcohol Abuse and Alcoholism defines binge drinking as consuming five or more alcoholic drinks (14g alcohol) for males and four or more for females within approximately two hours. Rapid consumption of alcohol can lead to intoxication. A study involving adolescent males who were conscripted into military service in Sweden indicated that those who drank alcohol to mitigate hangover effects had a 50% higher risk of severe liver disease. Furthermore, being apprehended for public intoxication doubled this risk. In Finland, a population-based health study found that engaging in monthly binge drinking doubled the risk of liver disease, while regularly binge drinking on weekends tripled this risk. Additionally, research from the UK Biobank highlighted that heavy binge drinking (defined as women consuming 72g/day or more, and men 96g/day or more) resulted in a four-fold increase in the chances of developing alcohol-related cirrhosis. This risk escalated to ten times higher when combined with a significant genetic predisposition. In this same study, individuals with diabetes had an increased risk of binge drinking that grew from double to five-fold.
According to the Dionysos Study, those who consume alcohol outside of designated mealtimes face a three-fold greater risk of developing cirrhosis compared to those who drink primarily during meals, irrespective of the quantity consumed. Similarly, the UK Million Women Study found that approximately half of the participants typically drank with their meals. After accounting for the amount of alcohol consumed, the incidence of cirrhosis was found to be 30% lower among those who suelen drank with meals compared to those who did not, for participants who exclusively consumed wine as well as for all other types of drinkers.
Preference for wine
In the Copenhagen City Heart Study, it was found that wine drinkers (who consumed more than 51% of their total alcohol intake as wine) had a risk of developing cirrhosis that was one third lower than those who did not drink wine at all, for a given total alcohol intake level.13 This protective aspect of wine consumption was further supported by the Danish Cancer, Diet, and Health study. When comparing those who drank fewer than 14 drinks (12g alcohol) per week, men consuming 14–28 drinks per week had a 7.5-fold higher risk of alcoholic cirrhosis if they did not drink wine at all (<1% wine), a 3.1-fold higher risk if they consumed some wine (1–15%), and just a 1.7-fold higher risk if they primarily drank wine (50–100%).14
According to a study conducted in Norway, drinking a pint of beer (16.8g alcohol) doubled the risk of dying from alcoholic liver disease, while a shot of liquor (12.8g alcohol) raised the risk by 2.6 times. In contrast, consuming a glass of wine (16.8g alcohol) decreased the risk by one third. Individuals who tend to prefer wine and consume lower amounts of alcohol generally display more health-conscious dietary habits, a healthier lifestyle, higher socioeconomic standing, and greater levels of physical activity compared to those who abstain from alcohol entirely. These variables pose challenges when conducting adjustments in observational studies.15
Non-alcoholic fatty liver disease (NAFLD)
The liver fat content of force-fed ducks and geese (which can reach 44%) exemplifies that alcohol is not a necessary factor for the development of fatty liver. In recent years, there has been a significant rise in obesity and metabolic syndrome risk factors throughout the general population. NAFLD primarily results from consuming excess calories without high levels of alcohol intake—commonly, a daily threshold of <10g for women and <20g for men is considered. In Europe, NAFLD affects about 25–30% of individuals, yet this percentage escalates to 65% among those who are overweight, 80–90% in individuals with central obesity, and 79% in those with type-2 diabetes. A considerable number of people now experience NAFLD alongside alcohol consumption, with either factor potentially heightening the liver's vulnerability to the damaging effects of the other. However, the specific amount of alcohol consumption deemed harmful for individuals with fatty liver disease remains uncertain. While some research indicates that moderate alcohol consumption may provide protective benefits, other findings report increased risks associated even with low to moderate intake.2
Obesity
In Europe, about 20 to 25% of individuals are classified as obese. A meta-analysis reviewing nine cohort studies revealed that the risk of developing chronic liver disease triples for those who are obese compared to those with normal weight who consume alcohol in line with recommended guidelines. Additionally, those drinking above these limits have a risk elevated by 2.7 times. When both obesity and excessive alcohol consumption are present, the risk increases dramatically to 5.4 times. Notably, individuals with significant abdominal obesity who consume just one alcoholic drink daily face a similar risk of developing liver disease as non-obese men who have four drinks a day.
Metabolic syndrome
Metabolic syndrome refers to a collection of conditions that elevate your chances of heart disease and type-2 diabetes. It is characterized by the presence of at least three metabolic risk factors: elevated blood pressure, elevated blood sugar levels (indicating insulin resistance), abdominal obesity (often described as an “apple shape”), high triglycerides, and reduced levels of HDL cholesterol (the good cholesterol). In moderate drinkers (consuming 10–20g/d for women and 10–30g/d for men) and heavy drinkers (20–50g/d for women and 30–50g/d for men), the presence of metabolic syndrome heightens the ten-year cumulative risk of advanced liver disease from 0.3% to 1.4% among moderate drinkers, and from 0.8% to 2.4% among heavy drinkers.
Cigarette Smoking
The Copenhagen City Heart Study revealed significant hazard ratios for alcoholic liver cirrhosis, reporting figures of 3.9 for women and 1.6 for men who smoked more than 10 grams of tobacco daily, compared to those who never smoked. This was after making adjustments for age, alcohol consumption, education level, and body mass index. It was estimated that around 26% of alcoholic cirrhosis cases in women and 8% in men within this study could be linked to smoking.
Exercise
Findings from randomized studies suggest that both high-intensity and moderate-intensity exercises, matched for energy expenditure, effectively reduce intrahepatic fat and the risk of Non-Alcoholic Fatty Liver Disease (NAFLD), regardless of changes in body weight or abdominal fat. A specific randomized study involving 220 obese individuals diagnosed with NAFLD demonstrated that a year-long exercise program led to improvements in liver fat accumulation, reduction in abdominal obesity, and lower blood pressure, lasting for up to a year following the intervention.
Coffee
Recent research, specifically the Italian Study on Liver Cirrhosis Determinants, has focused on the link between lifelong consumption of caffeine and alcohol. The findings indicate a significant negative correlation between coffee intake and the risk of developing liver cirrhosis, with no equivalent connection found for other caffeinated drinks. New evidence suggests that this protective effect is not influenced by factors such as education, smoking habits, or diet. The prevailing theory is that the non-caffeine components in coffee may offer a protective benefit to liver cells. A thorough review has highlighted this evidence, concluding that coffee consumption could lead to as much as a 40% reduction in the risk of alcoholic cirrhosis with an increase of two cups per day.
Understanding the factors that can either enhance or reduce your risk of alcoholic liver disease is crucial when contemplating enjoying wine with minimal chances of developing liver cirrhosis, a serious condition. The European Association for the Study of the Liver suggests safe alcohol consumption levels at 30g/day for men and 20g/day for women. However, the threshold where potential benefits of alcohol consumption turn harmful is not consistent and varies, particularly in individuals with metabolic syndrome features such as obesity or type-2 diabetes. Evidence indicates that steatosis increases the toxic effects of alcohol on the liver, and no definitive safe drinking limit exists for those with fatty liver. Nevertheless, the absolute risk of having one glass of wine daily with meals appears to be minimal.
NOTES
1. R Williams et al. explored the issue of liver disease in the UK, presenting a comprehensive guide aimed at improving healthcare quality and decreasing early deaths linked to lifestyle factors such as excessive alcohol intake, obesity, and viral hepatitis in their article in The Lancet 384 (2014), pages 1953–97.
2. M Boyle, S Masson, and QM Anstee discussed the reciprocal effects of alcohol consumption and metabolic syndrome, highlighting them as contributing factors to the progression of fatty liver disease in their work published in Journal of Hepatology 68:2 (2018), pages 251–67.
3. R Ramkissoon and VH Shah examined the relationship between Alcohol Use Disorder and Alcohol-Associated Liver Disease in their article found in Alcohol Research 42:1 (2022), page 13.
4. G Askgaard, MS Kjær, and JS Tolstrup conducted a systematic review with meta-analysis that addressed various strategies to prevent alcoholic liver cirrhosis in at-risk populations, as presented in the American Journal of Gastroenterology 114:2 (2019), pages 221–32.
5. M Roerecke and colleagues conducted a systematic review titled “Alcohol Consumption and Risk of Liver Cirrhosis,” published in the American Journal of Gastroenterology in 2019, spanning pages 1574 to 1586.
6. Z Hrubec and GS Omenn explored the genetic links to alcoholic cirrhosis and psychosis in their study, “Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: Twin concordances for alcoholism and its biological end points by zygosity among male veterans,” featured in Alcoholism: Clinical and Experimental Research in 1981, on pages 207 to 215.
7. In the Journal of Hepatology article “A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers,” JB Whitfield and others highlighted significant findings in 2022, with details on pages 275 to 282.
8. H Hagström and team investigated the link between risk behaviors and alcohol consumption in their work “Risk Behaviors Associated with Alcohol Consumption Predict Future Severe Liver Disease,” published in Digestive Diseases and Sciences in 2019, covering pages 2014 to 2023.
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, “The Interplay Between Alcohol Consumption and Metabolic Risk Factors for Liver Disease: A Thorough Review of Epidemiological Studies,” Alcoholism: Clinical and Experimental Research 44:2 (2020), pp.384–403.
18. F Åberg et al., “The Joint Impact of Alcohol and Metabolic Disorders in Individuals with Chronic Liver Disease,” Clinical Gastroenterology and Hepatology 18:4 (2020), pp.995–97.
19. MK Dam et al., “Cigarette Smoking and the Risk of Liver Cirrhosis: Findings from a Population-Based Cohort Study,” Scandinavian Journal of Gastroenterology 48:5 (2013), pp.585–91.
20. NC Winn et al., “Similar Energy Loads from Moderate and High-Intensity Exercise Training Reduce the Risk of Nonalcoholic Fatty Liver Disease, Regardless of Alterations in Body Mass or Abdominal Fat: A Randomized Trial,” Metabolism 78 (2018), pp.128–40.
21. H-J Zhang and colleagues conducted a longitudinal study titled “Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study,” published in Diabetes, Obesity and Metabolism, volume 19, issue 2 in 2017, spanning pages 284 to 289.
22. G Corrao and his team explored the association between coffee, caffeine, and the potential risk of liver cirrhosis in their article, published in Annals of Epidemiology, volume 11 in 2001, on pages 458 to 465.
23. OJ Kennedy et al. conducted a systematic review and meta-analysis titled “Coffee consumption and the risk of cirrhosis,” featured in Alimentary Pharmacology & Therapeutics, volume 43, issue 5 in 2016, covering pages 562 to 574.