Serum laminin and type IV collagen are accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis.
OBJECTIVE
Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver biopsy. Extracellular matrix serum markers have been proposed as non-invasive diagnostic tools in alcoholic liver disease. The aim of this study was to determine the accuracy of 5 extracellular matrix serum markers, i.e. laminin (Lam), N-terminal peptide of type III procollagen (PIIINP), type I (CI), type III (CIII) and type IV (CIV) collagens in identifying patients with severe histologic alcoholic hepatitis from among those with cirrhosis and suspected alcoholic hepatitis.


METHODS
We studied 80 consecutive patients with alcoholic cirrhosis and clinical suspicion of alcoholic hepatitis referred for transvenous liver biopsy. Clinical severity of alcoholic hepatitis was assessed according to Maddrey's score. Histological severity was scored using the sum of the 3 following items: polynuclear infiltration (0-3); hepatocytes alterations (0-3); Mallory bodies (0-2). According to this score, patients were divided into 3 groups: mild (1-3), moderate (4-6), and severe (7-8) alcoholic hepatitis. Serum levels of the 5 extracellular matrix serum markers were measured at the time of biopsy using radioimmunoassays. Diagnostic value for histologically severe alcoholic hepatitis of the 5 extracellular matrix serum markers was assessed using receiver operating characteristic curves.


RESULTS
Histological alcoholic hepatitis was present in 67 patients (mean alcoholic hepatitis score: 3.4+/-2.3). Maddrey's score was 66% sensitive and 69% specific for the diagnosis of severe histologic alcoholic hepatitis. The serum Lam and CIV concentrations were the most accurate in identifying correctly patients with severe histologic alcoholic hepatitis. At a cut-off of 4.1 UI/ml, Lam was 90% sensitive and 77% specific, whereas at a cut-off of 150 ng/ml, CIV was 89% sensitive and 77% specific. Combination of markers did not result in improved diagnostic value.


CONCLUSIONS
In patients with cirrhosis, determination of serum Lam or CIV could represent a simple and accurate non-invasive method for identification of patients with histologically severe alcoholic hepatitis eligible for corticosteroid treatment.
Castera
L
L
Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier, Bondy, France.
Hartmann
D J
DJ
Chapel
F
F
Guettier
C
C
Mall
F
F
Lons
T
T
Richardet
J P
JP
Grimbert
S
S
Morassi
O
O
Beaugrand
M
M
Trinchet
J C
JC
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006519:Hepatitis, Alcoholic / Q000097:blood* / Q000150:complications* / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000097:blood*; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012720:Severity of Illness Index
D015415:Biomarkers; D007797:Laminin; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D003094:Collagen