Value of fibrosis markers for staging liver fibrosis in patients with precirrhotic alcoholic liver disease.
BACKGROUND
Our aim was to identify markers predictive of fibrosis in alcoholic liver disease (ALD). Percutaneous liver biopsy is the recommended standard for histologic assessment of liver fibrosis. Seven serum markers (tissue inhibitor of matrix metalloproteinase 1 [TIMP1], tenascin, collagen VI, amino-terminal propeptide of type III collagen [PIIINP], matrix metalloproteinases [MMP2], laminin, and hyaluronic acid [HA]) representing various aspects of collagen and extracellular matrix deposition and degradation, have been proposed as noninvasive surrogates for liver biopsy. Moreover, a diagnostic algorithm including 3 serum markers (TIMP1, PIIINP, HA) and age has been proposed to accurately detect fibrosis with acceptable levels of sensitivity/specificity in a chronic hepatitis C subgroup.


METHODS
To determine variability of these markers in liver fibrosis with different etiologies, we conducted an evaluation of their correlative properties in a subgroup of patients (n = 247) with biopsy confirmed liver fibrosis resulting from long-term heavy alcohol consumption. Patients were participants in a recently completed VA multicenter clinical trial followed over 2 years with liver biopsy at baseline and 24 months, and with markers assessed every 3 months.


RESULTS
Among the markers measured in this alcoholic subgroup all except collagen VI displayed significant correlation with degrees of fibrosis. Three markers, TIMP1, PIIINP and HA adjusted for age, emerged as the most promising predictors of the degree of fibrosis in a population of alcoholics. However, there was little change over time as related to change in fibrosis. The lower than expected accuracy of these markers based on receiver operating curves (ROC) also showed their limited use in this etiologic subgroup.


CONCLUSIONS
In alcoholic patients, various markers have limited value in predicting and diagnosing the stages of fibrosis compared to liver biopsy. Thus, further prospective studies are required to better define the usefulness of each marker or their combination which are possibly affected by alcohol metabolism.
Lieber
Charles S
CS
James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468, USA. liebercs@aol.com
Weiss
David G
DG
Paronetto
Fiorenzo
F
D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007797:Laminin / Q000097:blood; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood* / Q000473:pathology* / Q000517:prevention & control; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010713:Phosphatidylcholines / Q000627:therapeutic use; D010919:Placebos; D011347:Procollagen / Q000097:blood; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019063:Tenascin / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D015415:Biomarkers; D007797:Laminin; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010919:Placebos; D011347:Procollagen; D019063:Tenascin; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; C005152:lipostabil; D006820:Hyaluronic Acid; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2