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

BARCELONA . SPAIN
42 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 43
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
Figure 1
MECHANISMS OF ALCOHOL-INDUCED LIVER FIBROSIS
Fabio Marra
Florence, Italy
E-mail: f.marra@dmi.unifi.it
Figure 2
Figure 3
KEY POINTS
• Alcoholic liver disease has a broad spectrum of clinical-histological pictures, and fibrosis
occurs only in a proportion of patients with alcohol abuse unless the patient presents with
overt signs of cirrhosis it is not easy to predict the presence of fibrosis based on clinical and
laboratory findings.
• The pathogenesis of fibrosis in ALD is regulated by mechanisms unique to these conditions
and by others common to the development of fibrosis in other chronic liver diseases.
• Direct effects of chronic alcohol abuse that promote fibrogenesis include generation of
acetaldehyde, induction of oxidative stress, alterations of innate immunity and increased gut
permeability.
• The fibrogenic process in ALD is an example of extensive cross-talk among liver resident and
infiltrating cells, with paracrine and autocrine effects leading to injury, apoptosis, inflammation.
CLINICAL ASPECTS OF FIBROSIS IN ALCOHOLIC LIVER DISEASE (ALD)
ALD ranges between simple steatosis, alcoholic steatohepatitis (ASH), progressive fibrosis, cirrhosis and
hepatocellular carcinoma. Moreover, patients with underlying ALD may experience episodes of alcoholic
hepatitis (AH) that are associated with high mortality rate in its severe forms. Patients with mild ALD are
usually asymptomatic or show unspecific symptoms such as fatigue or mild abdominal pain. Because
alcohol abuse can lead to severe organ damage in the brain, peripheral nervous system, skin, heart, kidney
and pancreas, patients may develop a variety of liver-unrelated symptoms. Patients with advanced fibrosis
and cirrhosis may show typical exploratory findings, yet physical examination can be normal in patients
with early cirrhosis. Decompensated cirrhotic patients may show signs of jaundice, ascites, asterixis, and
variceal bleeding. In alcoholic patients, Dupuytren’s contractures, parotid gland enlargement and peripheral
neuropathy can also be noted. The presence of an AH, which is usually associated with impairment of liver
function and clinical decompensation, can be suspected based on clinical and biochemical data, yet a
definitive diagnosis needs histological confirmation.
The diagnosis of the existence and degree of liver fibrosis in patients with alcohol abuse is based in
both noninvasive and invasive methods. Patients with mild to moderate fibrosis show mild increase of
aminotransferases, especially AST, and elevated GGT. Advanced fibrosis with portal hypertension leads to
decreased platelet count and eventually liver failure develops with elevated bilirubin levels and decrease
albumin serum levels and prothrombin time. The use of serum markers of fibrosis (Fibrotest, ELF panel)
has been shown to estimate the presence and degree of liver fibrosis. Imaging techniques such as
ultrasonography detect steatosis and advanced fibrosis, but they fail to distinguish between steatosis and
ASH and are not reliable to diagnosis mild fibrosis. The measurement of liver stiffness by elastography is
also useful to evaluate the degree of fibrosis, yet its results can be influenced by the amount of steatosis
and inflammation.
The indications of liver biopsy in patients with ALD are under debate. It is particularly indicated in patients
with unclear diagnosis or in those with aggressive disease. In addition to confirming the diagnosis, liver
biopsy is also useful for ruling out other unsuspected causes of liver disease, better characterizing the
extent of the damage, providing prognosis, confirm active alcohol intake and guiding therapeutic decisionmaking.
Another indication is the diagnosis of superimposed AH, since there are no reliable noninvasive