EASL Clinical Practice Guidelines

Burden of ALD

Burden of alcohol-related disease and injury

Alcohol consumption is responsible for 3.8% of global mortality and 4.6% of disability-adjusted life-years (DALYs) lost due to premature death [4]. The attributable burden in Europe, with 6.5% of all deaths and 11.6% of DALYs attributable to alcohol, is the highest proportion of total ill health and premature deaths due to alcohol of all WHO regions [[4], [5]]. Europe shows particularly large sex differences in burden: the deaths attributable to alcohol being 11.0% and 1.8% for men and women, respectively. The young account for a disproportionate amount of this disease burden, with an alcohol-associated mortality over 10% and 25% of female and male youth, respectively [6].

Burden of ALD in Europe

The burden of compensated alcohol cirrhosis among the general population and heavy drinkers is not well known. The development of non-invasive methods to detect significant liver fibrosis (e.g., elastography, serum markers) should help in elucidating this issue. A recent study in France indicates that alcohol abuse accounts for up to one third of liver fibrosis cases [7]. The best comparative proxy for the burden of ALD is mortality from liver cirrhosis as a whole, although as discussed later this has its limitations. Mortality rates from liver cirrhosis vary considerably between European countries [8]with a 15-fold variation between the highest and lowest national rates [9]. However, Europe is essentially divided into two, with Eastern European states tending to have higher rates than the others [8].

Time trends in liver cirrhosis mortality over the past 30 years show very heterogeneous patterns between countries. About half the countries of Europe, including Austria, France, Germany, Italy, Portugal, and Spain as well as two Eastern European countries (Hungary and Romania) have experienced sharp declines in liver cirrhosis mortality [9], whereas the Western countries of Finland, Ireland, and the United Kingdom [10], as well as a larger number of Eastern European countries including Estonia [11], Lithuania, Poland, and Russia have increasing rates. In terms of alcohol-related hospital admissions, for example, parallel to the upward trend in liver cirrhosis mortality, general hospital admissions [12], and admissions to intensive care units with ALD have risen sharply in the United Kingdom [13].

Limitations to estimate the burden of ALD

The extent of international variation and trends in ALD is difficult to determine. Mortality data from liver disease is available for most countries, and to this extent liver cirrhosis mortality is frequently used as the indicator of choice. However, it is not possible to reliably separate out alcoholic from non-alcoholic cirrhosis mortality. In an undetermined proportion of deaths in which alcohol is the key factor, the certifying doctor may choose not to explicitly mention alcohol on the death certificate [14]. The extent of this bias is unknown, but it is likely to vary by country, sex, age, and era. For this reason, emphasis is usually given to analyzing mortality from liver cirrhosis regardless of whether it is specified as alcoholic or not [15]. These factors, taken together, mean that at the present time our best estimates about the international variation in the burden of ALD, based on mortality from liver cirrhosis as a whole, need to be interpreted with caution. There is a clear need to perform large-scale epidemiological studies to determine the prevalence of compensated ALD in the general population and the weight of ALD as a cause of cirrhosis.

Types of alcohol and patterns of consumption

European countries vary considerably in terms of per capita alcohol consumption, predominant beverage type, and the extent to which drinkers imbibe substantial quantities on single occasions (binge drinking) [6]. In order to propose a consensual definition, the National Institute of Alcohol Abuse and Alcoholism defines binge drinking episodes as consumption of five or more drinks (male) or four or more drinks (female) in the space of about 2 h [16]. These differences in type and pattern of consumption tend to fall along an East–West divide [17]. While per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates across countries [18], there remains uncertainty about whether these other dimensions of drinking behavior in a population are related to risk [[19], [20]]. There are several aspects to this. Firstly, does beverage type matter above and beyond volume of ethanol consumed [21]? Secondly, does drinking to intoxication (sometimes referred to as binge drinking) confer a particular risk? Thirdly, what is the contribution to the burden of ALD induced by the consumption of substances that may contain hepatotoxic substances in addition to ethanol [[20], [22],[23]]? This latter class of drink includes fruit brandies, which are frequently consumed in Hungary, for example [24] as well as home brewed alcohols that are drunk in Russia [25] and other parts of the former Soviet Union [26].

Risk threshold of alcohol consumption for liver cirrhosis

An important aspect of public health policy concerning alcohol has been the attempt to establish a safe threshold for consumption. This revolves primarily around the extent to which moderate alcohol consumption is cardioprotective [[27],[28]]. This positive effect of alcohol, if real, can then offset the large array of negative health consequences of even moderate alcohol consumption. For many individual diseases such as liver cirrhosis; however, there is no a priori reason to believe a threshold effect exists, as risk appears to increase steeply with the amount of alcohol consumed. In a meta-analysis of daily consumption levels in relation to cirrhosis, patients taking 25 g of ethanol a day were at higher risk of cirrhosis than non-drinkers [29]. A more recent meta-analysis found increased risks of mortality from liver cirrhosis among men and women drinking 12–24 g of ethanol per day [30]. Indeed, among women, a significant increase was also seen for those drinking up to 12 g/day. These levels of consumption (<25 g/day) are appreciably lower than most public health recommendations for overall safe levels of consumption. The human evidence to date therefore suggests that if a threshold exists, it is very low, and may in fact be difficult to detect because of limitations in measuring consumption below 10–12 g per day.

It should be noted that neither meta-analysis was able to distinguish between the effects of daily consumption from the effects of “binge” drinking. To this extent little is known about thresholds as applied to “binge” drinking. Further clinical and experimental studies are required to define the role of “binge” in the pathogenesis of ALD and the underlying mechanisms. Finally, risk of cirrhosis is almost certainly related to the length of time over which an individual has drunk regularly and not simply to the usual amount consumed.


Conversely, there is some clinical evidence that cessation of drinking at any point in the natural history of the disease reduces the risks of disease progression and occurrence of complications from cirrhosis.

Public health implications

Even though there remain uncertainties about the precise burden of and trends in ALD in Europe, there is no doubt that in many countries it is very substantial and or increasing. While improvements in treatment are essential, developing population-based policies to reduce levels of harmful and hazardous consumption are a priority. More broadly, there is increasing recognition of the heavy social, health, and economic burdens imposed by heavy alcohol drinking and the policies to reduce harm caused by alcohol, need to be urgently implemented [31]. Several meta-analyses have evaluated the efficacy and cost efficacy of different policy targeted areas [32]. The most cost-effective policies are those that reduce availability of alcohol, either through the pricing policies or the hours and places of sale, as well as implementation of minimum age purchase laws.

Statements

  1. Alcohol abuse is a major cause of preventable liver disease worldwide.
  2. Per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates across countries. Any evidence based policy in Europe need to implement preventive measures aimed at reducing alcohol consumption at the population level.
  3. The binge drinking pattern is becoming increasingly prevalent, mainly among young individuals, but its impact on liver disease is unknown.

Recommendations

Suggestions for future studies

  1. Large epidemiological studies using non-invasive methods should establish the prevalence of all forms of alcoholic liver disease in the general population.
  2. Studies evaluating the short and long-term impact of binge drinking in the development and severity of ALD are particularly needed.