Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C
Fontana, Robert John; Goodman, Zachary D.; Dienstag, Jules L.; Bonkovsky, Herbert L.; Naishadham, Deepa; Sterling, Richard K.; Su, Grace L.; Ghosh, Mita; Wright, Elizabeth C.
2008-03
Citation
Fontana, Robert J.; Goodman, Zachary D.; Dienstag, Jules L.; Bonkovsky, Herbert L.; Naishadham, Deepa; Sterling, Richard K.; Su, Grace L.; Ghosh, Mita; Wright, Elizabeth C. (2008). "Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C Potential conflict of interest: Financial relationships of the authors with Hoffmann-La Roche Inc., are as follows: R.J. Fontana is on the speaker's bureau; R.K. Sterling is a consultant and on the speaker's bureau; Authors with no financial relationships related to this project are: Z.D. Goodman, J.L. Dienstag, D. Naishadham, Grace Su, Mita Ghosh, H.L. Bonkovsky, and E.C. Wright. ." Hepatology 47(3): 789-798. <http://hdl.handle.net/2027.42/58027>
Abstract
This study determined the utility of a panel of serum fibrosis markers along with routine laboratory tests in estimating the likelihood of histological cirrhosis in a cohort of prior nonresponders with chronic hepatitis C. The relationship between serum markers and quantitative hepatic collagen content was also determined. Liver biopsy samples from 513 subjects enrolled in the HALT-C trial were assigned Ishak fibrosis scores. The collagen content of 386 sirius-red stained, nonfragmented biopsy samples was quantified using computerized morphometry. Serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), amino-terminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA), and YKL-40 levels were determined using commercially available assays.Sixty-two percent of patients had noncirrhotic fibrosis (Ishak stage 2-4) whereas 38% had cirrhosis (Ishak stage 5,6). Multivariate analysis identified a 3-variable model (HA, TIMP-1, and platelet count) that had an area under the receiver operating curve (AUROC) of 0.81 for estimating the presence of cirrhosis. This model was significantly better than that derived from the cirrhosis discriminant score (AUROC 0.70), the AST-to-platelet ratio (AUROC 0.73), and a prior model developed in HALT-C patients (AUROC 0.79). Multivariate analysis demonstrated that the serum fibrosis markers correlated substantially better with Ishak fibrosis scores than with the log hepatic collagen content (AUROC 0.84 versus 0.72). Conclusion: A 3-variable model consisting of serum HA, TIMP-1, and platelet count was better than other published models in identifying cirrhosis in HALT-C Trial subjects. The stronger correlation of the serum markers with Ishak scores suggests that serum fibrosis markers reflect the pattern of fibrosis more closely than the quantity of hepatic collagen. (H EPATOLOGY 2008.)Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0270-9139 1527-3350
Other DOIs
PMID
18175357
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18175357&dopt=citationMetadata
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