barcelona . spain - European Association for the Study of the Liver

BARCELONA . SPAIN
86 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 87
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
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EXTRAHEPATIC INVOLVEMENT IN PATIENTS WITH CHRONIC
ALCOHOL LIVER DISEASE
Joaquim Fernández-Solà
Barcelona, Spain
E-mail: jfernand@clinic.ub.es
KEY POINTS
• ALD does not involve just the liver, but is a real systemic disease. Systemic damage parallels
in degree and timing that of ALD.
• Extrahepatic involvement, mainly neurological, cardiovascular and nutritional, should be
regularly assessed in patients with ALD.
• There is a clear relationship between the degree of hepatic and systemic toxics effects of
alcohol. The greater the liver damage, the greater systemic damage expected.
• To improve global health status of the subjects with ALD a multidisciplinary management
approach is necessary.
INTRODUCTION
The purpose of this presentation is to consider some aspects that make Alcohol Liver Diseases (ALD)
as a real systemic disease with a clear extrahepatic involvement, in which a multidisciplinary approach
is necessary. The pathogenic effects that induce liver damage and disease may also generate additional
systemic organ damage through common pathogenic mechanisms. Similarly, liver is frequently involved
in most systemic diseases either of infectious, toxic, metabolic, inflammatory, autoimmune or neoplastic
origin.
When liver disease develops in the setting of alcohol misuse (ALD), the noxious pathogenic effects locally
generated in the liver also involve other organs such as heart and vascular system, bone and skeletal
muscle, central and peripheral nervous system, and disrupts the nutritional status, endocrine and immune
functions of the individual. Therefore, ALD usually develops in the setting of a multisystemic scenario. In
fact, there is a clear relationship between the degree of hepatic and systemic toxic effects of alcohol. The
final result of all these interactions determinates the global health status of the subject.
Ethanol has a widespread toxic and sensitizing effect on the human body with different threshold pathological
range and also with clear organ specificity according to the nature of target cells. The WHO report (2006)
recognizes more than 60 diseases related to excessive alcohol consumption. Its hydrophilic and lypophilic
properties confer a global body diffusion potential. Ethanol is a potent enzymatic inductor and its metabolites
(acetaldehyde-acetate, FAEEs) are very active. In addition, ethanol is a pro- inflammatory agent increasing
cytokine production.
Individual susceptibility to EtOH depends on different factors, some of them specific (type of cell, enzymatic
or metabolic factors) and others of non-specific nature (genetic, gender and environmental factors). In
addition, ethanol has different synchronic and synergic effects with other pathogenic factors (toxics,
nutrition, viruses) increasing its final damaging tissue effect.
Liver is the major site of EtOH metabolism in the body and receive this direct noxious effect. However, other
organs shared most mechanisms causing ALD. The products generated by the liver (oxidative radicals,
acetaldehyde and acetate, protein adducts, cytokines, circulating antibodies) may also induce significant
oxidative and inflammatory damage to other organs. This damage parallels in degree and timing that of
ALD. In general, ethanol increases the lesion and decreases the cell protection mechanisms increasing