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I
mplications
of
alcoholic
cirrhosis
in
atherosclerosis
of
autopsied
patients
R
ev
A
ssoc
M
ed
B
ras
2017; 63(4):336-340
339
D
iscussion
Our analysis led to the confirmation of the hypothesis that
cirrhotic patients have a higher degree of atherosclerosis
and aortic fibrosis than non-cirrhotic ones. Furthermore,
we observed that liver fibrosis increases with BMI and the
intensity of atherosclerosis. This shows a possible link
between the two diseases, and the worsening of liver disea-
se could influence the formation of atherosclerotic plaques.
There is increasing evidence that atherosclerosis starts
to develop early in life, progressing to more advanced
stages since young adulthood.
15
We also noted a higher
degree of atherosclerosis and aortic fibrosis in patients
with alcoholic liver cirrhosis. A possible explanation for
this would be that the vitamins involved in homocysteine
metabolismmight be reduced in chronic alcoholism, thus
leading to the accumulation of homocysteine, primary
indicator of atherogenesis.
7
Furthermore, it has been
discussed that increased levels of homocysteine in patients
with alcoholic liver disease also have consequences to the
liver, triggering endoplasmic stress
16
and inhibiting the
production of adiponectin, a hormone that induces li-
polysis,
17
stimulates fatty acid oxidation
18
and inhibits
the production of hepatic glucose.
19
Adipose tissue plays a crucial role in the regulation
of fatty acid homeostasis in the entire body. The idea of
a dynamic adipose tissue as an endocrine organ is being
increasingly recognized, which is very important for the
regulation of metabolism in health and disease condi-
tions. Adipocytes secrete proteins called adipokines, such
as adiponectin, resistin, Il-6, TNF-alpha, and leptin;
20,21
and overweight individuals have altered secretion of
adipokines, increasing the production of TNF-alpha and
IL-6 by macrophages, which fuels inflammatory pro-
cesses.
22
Lifestyle is a significant factor in the development
of hepatic steatosis, since it can promote weight gain,
ultimately leading to obesity, generating an increase in
inflammatory cytokines and insulin resistance that can,
in turn, lead to inflammation of visceral fat and increased
accumulation of fat in the liver. This cycle of responses
of the organism to obesity and the development of he-
patic steatosis trigger chronic inflammation (increased
C-reactive protein, interleukin 6 and tumor necrosis
factor alpha), hypercoagulation, hyperlipidemia (in-
creased levels of triglycerides, decreased HDL-cholester-
ol levels and possible increased LDL), which increases
the risk of heart disease.
23
This information corroborates
our findings, where patients with higher BMI showed a
higher degree of cirrhosis and atherosclerosis.
Analysis in the aortas showed that older patients pre-
sented more intense macroscopic atherosclerosis. This
may be due to progression of the disease; in more advanced
stages, there is the formation of fibrous connective tissue,
associated with a lipid core, called fibroatheroma.
24
Regarding fibrosis in the liver of cirrhotic patients,
the high incidence may have been a result of repeated use
of alcohol.
3
Triglyceride storage in the form of VLDL is a
physiological mechanism that prevents the accumulation
of neutral fats in the liver, since VLDL is carried away
from the organ. However, excess ethanol causes changes
in the triglyceride storage mechanism, and this causes
severe cellular stress, resulting in the accumulation of
neutral fats in hepatocytes, which can later lead to fibro-
sis and cirrhosis.
25
A
cknowledgments
This study was conducted with grants from Conselho
Nacional de Desenvolvimento Científico e Tecnológico
(CNPq), Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior (Capes), Fundação de Amparo à Pesquisa
do Estado de Minas Gerais (Fapemig) and Fundação de
Ensino e Pesquisa de Uberaba (Funepu).
R
esumo
Implicações da doença hepática alcoólica na aterosclero-
se de pacientes autopsiados
Introdução:
O alcoolismo é um grande problema de
saúde pública, de elevado custo social e que afeta vários
aspectos da atividade humana. Hepatopatia é uma das
primeiras consequências do abuso de álcool, podendo
ocorrer esteatose, cirrose hepática e hepatite. Outros ór-
gãos, porém, também são afetados, ocorrendo alterações
patológicas, como pancreatite, cardiomiopatias, dislipi-
demias e aterosclerose.
Objetivo:
Identificar a ocorrência e a intensidade de ate-
rosclerose em alcoolistas com cirrose hepática, observan-
do alterações macro e microscópicas do depósito lipídico
e de fibras colágenas e fígado. Verificar a associação de
depósito lipídico e de fibras colágenas com gênero, idade
e índice de massa corporal (IMC). Relacionar alcoolismo,
cirrose hepática e aterosclerose.
Método:
Foi realizado estudo com base em laudos de
autópsias de pacientes com cirrose hepática alcoólica,
sendo estudados aortas e fígados para verificar a ocorrên-
cia e a intensidade de aterosclerose, bem como a quanti-
dade de colágeno encontrada.
Resultados:
A aterosclerose microscópica foi maior em
jovens (lesão inicial) e em pacientes com cirrose hepática
alcoólica. A análise macroscópica da aterosclerose nas aor-