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

BARCELONA . SPAIN
60 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 61
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
Early non-invasive screening of people at high risk to progress to or with advanced ALD will also improve
therapeutic options. First, non-addicted patients at high genetic risk for fibrosis progression due to PNPLA3
variant mutation can be identified at early stages. These patients can be easily motivated to completely
abstain from alcohol being aware of their increased liver stiffness. Second, newly identified patients with
asymptomatic cirrhosis can be screened for complications (varices, HCC) and earlier enrolled in transplant
programs. Third, the role of alcohol consumption and its negative effect on other liver disease namely HCV
or NAFLD can be identified and addressed earlier.
GENERAL CLINICAL DIAGNOSIS OF ALD
Most patients with moderate forms of ALD are asymptomatic and it can be only detected by appropriate
sreening methods. Some patients can show signs suggestive of harmful alcohol drinking such as bilateral
parotid gland hypertrophy, muscle wasting, malnutrition, Dupuytren’s sign and signs of symmetric
peripheral neuropathy. In patients with cirrhosis, most physical findings are not specific of the etiology.
However, some signs such gynecomastia and extensive spider angiomas may be more frequently seen
in those with alcohol as the main cause of liver disease. The diagnosis of ALD is frequently suspected
upon documentation of excess alcohol consumption > 30 g/d and the presence of clinical and/or biological
abnormalities suggestive of liver injury. However, screening of ALD is difficult as significant proportions
of patients with histological features of ALD do not show any clinical symptoms. Liver disease is shown
by physical examination, laboratory, imaging or elastography findings. In contrast to the poorly sensitive
physical examination, initial stages of ALD such as AFL or ASH can be diagnosed e.g. by ultrasound or
laboratory tests. Routine blood tests such as MCV, GGT, AST and ALT can indicate early ALD, endstage
ALD is suspected by decreased liver function tests and thrombocytopenia. While elevated transaminases
are indicative of ongoing hepatocellular inflammation or destruction, GGT is not related to liver function per
se and requires careful discrimination from cholestatic and biliary liver disease or others.
DIAGNOSIS OF ALD BY BLOOD TESTS
Routine blood tests such as mean corpuscular volume (MCV), GGT, AST and ALT can indicate early ALD
whereas advanced ALD is suspected if there is decreased albumin, prolonged prothombin time, increased
bilirubin level or thrombocytopenia.
Although no single laboratory marker definitely establishes chronic alcohol consumption, carbohydrate
deficient transferrin (CDT) and GGT are the most frequently used markers to detect previous alcohol
consumption [2]. Indeed, the sensitivity for detection of daily ethanol consumption >50 g of CDT (69%)
and GGT (73%) are higher than those of AST (50%), ALT (35%), and MCV (52%) [3]. The specificity of
CDT was 92%, compared with 75%, 82%, 86%, and 85% for GGT, AST, ALT, and MCV, respectively [3].
As the measurement of GGT is easy and inexpensive, it remains the most frequently used marker for early
detection of chronic alcohol misuse [4]. GGT is typically 4 times higher in ALD patients as compared to
other liver diseases [5] and can reach up to 4000 U/ml in some individuals. However, GGT looses its alcohol
specificity in more advanced stages. AST is typically elevated to a level of 2-6 times the upper limits of
normal in severe alcoholic hepatitis while AST levels of more than 300 IU/L are rarely seen. In about 70% of
patients, the AST/ALT ratio is higher than two, which is especially relevant for patients without cirrhosis [6].
Combination of these routine blood test further increases the accuracy to diagnose ALD. A sensitivity and
specificity > 90% has been demonstrated for a combination of GGT, MCV, IgA, CDT, and AST/ALT ratio [7].
NON INVASIVE TESTS TO ESTIMATE LIVER FIBROSIS (FIG. 2).
Hepatic Imaging techniques
Imaging techniques such as ultrasonography, MRI and CT may allow the detection of fatty liver, help exclude
other causes of chronic liver disease and contribute to the assessment of advanced liver disease and its
complications independent of the etiology [8]. However, imaging studies do not have a role in establishing
alcohol as the specific etiology of liver disease. The major role of imaging techniques is to exclude other
causes of abnormal liver tests in a patient who abuses alcohol, such as obstructive cholestasis, or infiltrative
and neoplastic diseases of the liver. With respect to fibrosis assessment, all imaging techniques have to rely
on so called definite morphological signs of cirrhosis such as nodular aspects of the liver or recanalization of
the umbilical vein. Despite sometimes high diagnostic accuracy for the detection of alcoholic liver cirrhosis
(ALC) under study conditions, imaging techniques are especially limited in the daily routine in diagnosing
compensated liver cirrhosis (sensitivity