The risk of alcohol-associated liver disease depends on how much a person drinks, how they drink it, and who they are. More than 90% of heavy drinkers accumulate fat in the liver (steatosis), but only 10–35% develop steatohepatitis with fibrosis, and fewer still progress to cirrhosis, so these three dimensions decide both whether injury begins and how far it progresses.
Burden of disease
Alcohol use is considered the seventh leading risk factor for premature death and disability worldwide. Between 2007 and 2016, mortality caused by hepatitis C virus (HCV)-related disease continued to fall as new drugs became available, while mortality due to alcohol-associated liver disease (ALD) rose. In developed countries such as the United States, the most common cause of cirrhosis is ALD, followed by HCV. The mortality rate of patients with ALD is 9 times higher than that of patients with fatty liver alone. Worldwide, total alcohol consumption in 2016 averaged about 6.4 litres of pure alcohol per person aged 15 and over, roughly 14 grams per person per day.
How much and how
Studies show that the minimum amount of alcohol that raises the risk of liver disease is higher in men than in women. For women it is 20–40 g, or about 1.5–3 standard drinks, per day for 10–12 years; for men it is 40–80 g, or about 3–6 standard drinks, per day for 10–12 years. A standard drink, or alcoholic unit, contains 14 grams of alcohol, although the European standard measure is 10 g. Studies in Europe and the United States show that people who develop cirrhosis and other alcohol-caused liver disease take in 15 standard drinks per day on average.
For people without liver disease, guidance caps safe drinking at no more than one standard drink in 24 hours for women and two for men. For anyone who already has ALD or another liver disease, there is no safe level, and they should abstain.
Binge drinking is a pattern of drinking that brings the blood alcohol concentration to 0.08 g/dL or more, which typically happens after 5 or more drinks for a man or 4 or more for a woman within about 2 hours. Binge drinking is associated with a higher incidence of cardiovascular events, neurocognitive impairment, and a higher risk of alcohol dependence.
Who progresses
Among heavy drinkers, the factors that decide who develops advanced disease are called disease modifier factors. They fall into three groups.
The first is the pattern of drinking: daily drinking and drinking while fasting carry more risk than the same amount taken with food, and binge drinking adds risk.
The second is the person. Women are more prone to ALD, and progress faster, than men, even at comparable intake. Part of the reason is first-pass metabolism: women have less gastric alcohol dehydrogenase, the enzyme that breaks down some alcohol in the stomach before it reaches the circulation, and a lower proportion of body water, so the same drink produces a higher blood alcohol concentration. Genetic variation matters too — variants in PNPLA3, TM6SF2 and MBOAT7 increase the risk of alcohol-associated cirrhosis and hepatitis, while a variant in HSD17B13 is protective.
The third is the rest of the liver’s health. Obesity, smoking, and coexisting liver disease such as chronic viral hepatitis, hemochromatosis or fatty liver disease all raise the risk that drinking will cause advanced fibrosis. Coffee consumption, by contrast, appears to protect against cirrhosis from many causes, including ALD.