barcelona . spain - European Association for the Study of the Liver
barcelona . spain - European Association for the Study of the Liver
barcelona . spain - European Association for the Study of the Liver
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BARCELONA . SPAIN<br />
12 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 13<br />
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012<br />
PREVALENCE AND TRENDS IN ALCOHOL CONSUMPTION AND ALCOHOLIC LIVER DISEASE<br />
The trends in alcohol consumption and alcohol-related harm vary significantly among different countries<br />
and areas <strong>of</strong> Europe as well as according to policies and interventions in each country. In fact, in <strong>the</strong> period<br />
1990‒2006, <strong>the</strong>re have been substantial fluctuations with decrease, increase and <strong>the</strong>n stabilization. There<br />
is evidence <strong>of</strong> a very marked disparity in alcohol consumption trends among different countries, with a<br />
predominance <strong>of</strong> Eastern <strong>European</strong> countries experiencing an increase. Also, <strong>the</strong> financial crisis in <strong>the</strong><br />
<strong>European</strong> Union is probably going to result in an increase in alcohol-related harm. In fact, already a more<br />
than three per cent increase in unemployment is associated with as much as a 28 per cent increase in<br />
deaths from alcohol use disorders (3).<br />
It is difficult to estimate <strong>the</strong> true prevalence <strong>of</strong> alcoholic liver disease in <strong>the</strong> population. A population based<br />
study in France, using transient elastography as a screening tool, found that alcohol was <strong>the</strong> probable<br />
cause <strong>of</strong> one third <strong>of</strong> <strong>the</strong> cases <strong>of</strong> excess fibrosis (4). However, we really need fur<strong>the</strong>r studies combining<br />
serum markers, ultrasound and elastography to better define <strong>the</strong> real prevalence <strong>of</strong> compensated and<br />
decompensated alcoholic liver disease. Fur<strong>the</strong>r studies also need more detailed alcohol drinking pattern,<br />
since that may have implications on <strong>the</strong> risk <strong>of</strong> liver disease. In fact, it is still unclear if <strong>the</strong> risk is different<br />
when alcohol consumption concentrates on one or two days <strong>of</strong> <strong>the</strong> week, or if it distributes homogeneously<br />
during <strong>the</strong> week. Also, <strong>the</strong> effect <strong>of</strong> binge drinking (by definition more than 5 drinks <strong>for</strong> men, and more than<br />
4 drinks <strong>for</strong> women in two hours) on <strong>the</strong> risk <strong>of</strong> progression to more advanced <strong>for</strong>ms <strong>of</strong> ALD is yet ill-defined.<br />
Since binge drinking is steeply increasing, mostly in young people, and in some countries, <strong>the</strong> in<strong>for</strong>mation<br />
would be <strong>of</strong> great importance.<br />
<strong>Liver</strong> cirrhosis mortality remains <strong>the</strong> best tool to evaluate <strong>the</strong> burden and trends <strong>of</strong> alcoholic liver disease,<br />
although it is still subject to important bias, including differences in death certificates accuracy according to<br />
different countries, and <strong>the</strong> reluctance to include alcohol in <strong>the</strong> death certificate due to legal implications.<br />
During <strong>the</strong> last 30 years, mortality due to liver cirrhosis followed a pattern similar to alcohol consumption,<br />
with a large disparity between countries. In fact, it was well shown that per capita alcohol consumption is<br />
strongly correlated with liver cirrhosis mortality rates across countries.<br />
There have been sharp declines in liver cirrhosis mortality in about half <strong>the</strong> countries in Europe, mostly<br />
Western <strong>European</strong> countries, such as Austria, France, Germany, Italy, Portugal and Spain, but also in<br />
Eastern countries such as Hungary and Romania. On <strong>the</strong> opposite, impressive increases in liver mortality<br />
cirrhosis are seen in Eastern countries, such as Russia, Lithuania, Estonia and Polonia, but also in some<br />
Western countries such as United Kingdom and Ireland and Finland (Figure 3). It is <strong>of</strong> interest that <strong>the</strong>se<br />
differences are more evident in <strong>the</strong> group older than 45 years. Also, incidence <strong>of</strong> ALD is 2 to 3 times higher<br />
in males than females, although frequency between males and females tend to correlate in every country<br />
and <strong>for</strong> each level <strong>of</strong> consumption (5).<br />
Data from <strong>the</strong> <strong>European</strong> <strong>Liver</strong> Transplantation Registry showed that alcohol represents one third <strong>of</strong><br />
<strong>the</strong> causes <strong>of</strong> cirrhosis leading to liver transplantation and is <strong>the</strong> second cause <strong>for</strong> liver transplantation<br />
(Figure 4). These numbers underscore <strong>the</strong> importance <strong>of</strong> alcohol as a cause <strong>of</strong> liver disease, although still<br />
underestimating it, since alcoholics are probably less transplanted than o<strong>the</strong>r patients. Also, and according<br />
to <strong>the</strong> same study, <strong>the</strong>re has been a recent increase in <strong>the</strong> number <strong>of</strong> patients transplanted due to alcoholic<br />
liver disease (6).<br />
Ano<strong>the</strong>r important issue is <strong>the</strong> recent change in <strong>the</strong> pattern <strong>of</strong> alcohol consumption, and how is it going to<br />
affect <strong>the</strong> risk <strong>of</strong> liver disease. In fact, recent years have shown an increase in <strong>the</strong> binge drinking pattern,<br />
particularly in young people, and <strong>the</strong>re is evidence that binge-drinking can cause liver cirrhosis, with <strong>the</strong><br />
risk increasing with <strong>the</strong> number <strong>of</strong> binge episodes (7). This evidence comes from experimental as well<br />
as epidemiological studies. Besides from <strong>the</strong> effect on <strong>the</strong> liver, binge has also been associated with an<br />
increased risk <strong>of</strong> atrial fibrillation and ventricular arrhythmias, myocardial infarction, as well as haemorrhagic<br />
and ischaemic strokes.<br />
Besides from <strong>the</strong> effect on <strong>the</strong> liver, it is increasingly recognized that alcohol has a very important role<br />
in several o<strong>the</strong>r diseases, such as cardiovascular diseases, showing a very strong risk association with<br />
hypertension, hemorrhagic stroke and cancer. Indeed, alcohol metabolism produces acetaldehyde,<br />
strongly involved in alcohol-associated carcinogenesis; in addition, ethanol itself stimulates carcinogenesis<br />
by inhibiting DNA methylation and by interacting with retinoid metabolism. The importance <strong>of</strong> alcohol as<br />
a risk <strong>for</strong> cancer, namely <strong>of</strong> <strong>the</strong> oral cavity, pharynx, esophagus, liver, colon, rectum, larynx and female<br />
breast have been well recognized. According to <strong>the</strong> WHO estimates <strong>for</strong> global burden <strong>of</strong> disease, more<br />
than 389,000 cases <strong>of</strong> cancer were attributable to alcohol drinking worldwide, thus representing 3.6% <strong>of</strong><br />
all cancers, (5.2% in men, and 1.7% in women). Similar results were found by <strong>the</strong> International Agency <strong>for</strong><br />
Research on Cancer, that alcohol is a risk factor <strong>for</strong> upper aerodigestive tract cancer (oral cavity, pharynx,<br />
hypopharynx, larynx, and esophagus), liver cancer, colorectal cancer, and breast cancer. In fact, it was<br />
only recently that <strong>the</strong> increased risk <strong>for</strong> breast cancer, even <strong>for</strong> very low consumptions, was highlighted and<br />
documented, with breast cancer comprising 60% <strong>of</strong> alcohol-attributable cancers, in women. It is also <strong>of</strong> note<br />
that alcohol consumption and smoking has a synergistic effect on <strong>the</strong> risk <strong>of</strong> some <strong>of</strong> <strong>the</strong>se cancers. Alcoholassociated<br />
changes in behavior, is also a major cause <strong>of</strong> intentional and unintentional injuries, ei<strong>the</strong>r to <strong>the</strong><br />
drinker or to o<strong>the</strong>rs. It is also an important cause <strong>of</strong> pr<strong>of</strong>essional absenteeism and low per<strong>for</strong>mance, as<br />
well as family violence and disruption. Alcohol is also a potent teratogen and a cause <strong>of</strong> neurological and<br />
psychiatric disturbances.<br />
ECONOMIC BURDEN<br />
It was estimated that <strong>the</strong> total tangible costs <strong>of</strong> alcohol to <strong>the</strong> EU in 2003 were about €125 billion (€79bn-<br />
€220bn), equivalent to 1.3% (0.9–2.4%) <strong>of</strong> gross domestic product (GDP). Actual spending on alcoholrelated<br />
problems accounts <strong>for</strong> €66 billion <strong>of</strong> this, while potential production not realized due to absenteeism,<br />
unemployment and premature mortality accounts <strong>for</strong> a fur<strong>the</strong>r €59 billion. This amount largely exceeds<br />
<strong>the</strong> reported contribution <strong>of</strong> around 9 billion euros to <strong>the</strong> goods account balance <strong>for</strong> <strong>the</strong> EU. Fur<strong>the</strong>rmore,<br />
it seems to contribute to health inequalities between and within <strong>European</strong> Member States, due to more<br />
frequent risky alcohol use in lower socioeconomic groups and also to greater mortality from directly alcoholrelated<br />
conditions (8).<br />
HOW TO DEAL WITH THE PROBLEM<br />
Since alcohol is indeed a major health risk factor and simultaneously a heavy economic burden, it becomes<br />
obvious that measures need to be taken to change/reduce <strong>the</strong> pattern <strong>of</strong> consumption. One <strong>the</strong> major<br />
problems regarding control <strong>of</strong> alcohol consumption is that drinking alcohol can be harmless and is very<br />
strongly rooted in our Society. In fact, it is not constantly harmful as <strong>for</strong> example tobacco smoking, and this<br />
duality results in difficulty in delineating measures to reduce consumption and to implement <strong>the</strong>m.<br />
One <strong>of</strong> <strong>the</strong> first controversies is what <strong>the</strong> safe-drinking limit is In what regards <strong>the</strong> threshold <strong>for</strong> liver<br />
cirrhosis, Rehm et al. found in a recent meta-analysis, an increased risk <strong>of</strong> mortality from liver cirrhosis<br />
among men and women drinking 12-24g/ethanol per day (9), and a large epidemiological study on Italy,<br />
found that <strong>the</strong>re was an increased risk <strong>of</strong> cirrhosis in those drinking 30 g/ethanol per day. More difficult and<br />
controversial is to find a threshold in <strong>the</strong> case <strong>of</strong> binge-drinking (7). It is possible that <strong>for</strong> some diseases<br />
<strong>the</strong>re is not a safe limit. For example, in breast cancer, a recent meta-analysis that included 98 studies<br />
reported a 10% increase in breast cancer risk per 10 g <strong>of</strong> alcohol con¬sumed per day, with no definition <strong>of</strong><br />
a safe threshold.<br />
Alcohol policies and <strong>the</strong>ir effectiveness<br />
Several policy targeted areas have been developed, including in<strong>for</strong>mation and education, health<br />
sector response, community programmes, drink driving policies, availability <strong>of</strong> alcohol, marketing <strong>of</strong><br />
alcohol beverages, pricing policies, harm reduction, and reducing <strong>the</strong> effect <strong>of</strong> illegal produced alcohol.<br />
Regarding interventions on in<strong>for</strong>mation and education, <strong>the</strong>y are not expensive, but systematic reviews <strong>of</strong><br />
this programmes showed that <strong>the</strong>y do not particularly affect consumption levels or health outcomes (10),<br />
although <strong>the</strong>y are important to convey awareness and knowledge <strong>of</strong> <strong>the</strong> problem. O<strong>the</strong>r policies, like drinkdriving,<br />
seem to be quite effective, mostly if <strong>the</strong>y are efficiently implemented and rigorously en<strong>for</strong>ced (10).<br />
Also, brief interventions to those at-risk seem to be useful.<br />
One <strong>of</strong> <strong>the</strong> most effective measures is reducing availability <strong>of</strong> alcohol, ei<strong>the</strong>r through <strong>the</strong> pricing policies<br />
or <strong>the</strong> hours and places <strong>of</strong> sale and minimum purchase age laws (8). In fact, laws that set a minimum age<br />
<strong>for</strong> <strong>the</strong> purchase <strong>of</strong> alcohol show clear reduction in drink-driving casualties and o<strong>the</strong>r alcohol-related harm.