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Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre-disposition pending between fiction and reality.

Gressner OA, Weiskirchen R, Gressner AM - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: Many of them, however, proved to be disappointing with regard to sensitivity and specificity.The translation of genetic pre-disposition biomarkers into clinical practice has not yet started, but some polymorphisms indicate a link to progression and outcome of fibrogenesis.Parallel to serum markers non-invasive physical techniques, for example, transient elastography, are developed, which can be combined with serum tests and profiling of serum proteins and glycans.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Central Laboratory, RWTH-University Hospital, Aachen, Germany. agressner@ukaachen.de

ABSTRACT
Fibrosis is a frequent, life-threatening complication of most chronic liver diseases. Despite major achievements in the understanding of its pathogenesis, the translation of this knowledge into clinical practice is still limited. In particular, non-invasive and reliable (serum-) biomarkers indicating the activity of fibrogenesis are scarce. Class I biomarkers are defined as serum components having a direct relation to the mechanism of fibrogenesis, either as secreted matrix-related components of activated hepatic stellate cells and fibroblasts or as mediators of extracellular matrix (ECM) synthesis or turnover. They reflect primarily the activity of the fibrogenic process. Many of them, however, proved to be disappointing with regard to sensitivity and specificity. Up to now hyaluronan turned out to be the relative best type I serum marker. Class II biomarkers comprise in general rather simple standard laboratory tests, which are grouped into panels. They fulfil most criteria for detection and staging of fibrosis and to a lesser extent grading of fibrogenic activity. More than 20 scores are currently available, among which Fibrotest is the most popular one. However, the diagnostic use of many of these scores is still limited and standardization of the assays is only partially realized. Combining of panel markers in sequential algorithms might increase their diagnostic validity. The translation of genetic pre-disposition biomarkers into clinical practice has not yet started, but some polymorphisms indicate a link to progression and outcome of fibrogenesis. Parallel to serum markers non-invasive physical techniques, for example, transient elastography, are developed, which can be combined with serum tests and profiling of serum proteins and glycans.

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Receiver-operating-characteristic (ROC) curves of the diagnostic power of serum CTGF and of the CTGF/platelet ratio for fibrosis and cirrhosis, respectively. AUC, area under the curve. Data compiled from ref. [55].
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fig04: Receiver-operating-characteristic (ROC) curves of the diagnostic power of serum CTGF and of the CTGF/platelet ratio for fibrosis and cirrhosis, respectively. AUC, area under the curve. Data compiled from ref. [55].

Mentions: Preliminary studies point to CTGF/CCN2 in serum as an innovative class I biomarker of fibrogenesis [55]. This 38 kD protein is synthesized not only in HSC, but also in hepatocytes where the expression and secretion is strongly dependent on TGF-β[32]. Accordingly, CTGF expression in fibrotic liver tissue is up-regulated and its concentration in serum or plasma elevated if fibrogenesis is going on. There is a correlation between CTGF levels and fibrogenesis, because the levels decrease in fully developed, end-stage cirrhosis, compared to fibrosis. The area under the curve (AUCs) for fibrosis versus control and cirrhosis versus control were calculated to be 0.955 and 0.887, respectively, the sensitivities 100% and 84%, respectively, the specificities 89% and 85%, respectively (Fig. 4) [55]. These criteria suggest CTGF as a potentially valuable class I biomarker of active fibrogenesis.


Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre-disposition pending between fiction and reality.

Gressner OA, Weiskirchen R, Gressner AM - J. Cell. Mol. Med. (2007 Sep-Oct)

Receiver-operating-characteristic (ROC) curves of the diagnostic power of serum CTGF and of the CTGF/platelet ratio for fibrosis and cirrhosis, respectively. AUC, area under the curve. Data compiled from ref. [55].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401271&req=5

fig04: Receiver-operating-characteristic (ROC) curves of the diagnostic power of serum CTGF and of the CTGF/platelet ratio for fibrosis and cirrhosis, respectively. AUC, area under the curve. Data compiled from ref. [55].
Mentions: Preliminary studies point to CTGF/CCN2 in serum as an innovative class I biomarker of fibrogenesis [55]. This 38 kD protein is synthesized not only in HSC, but also in hepatocytes where the expression and secretion is strongly dependent on TGF-β[32]. Accordingly, CTGF expression in fibrotic liver tissue is up-regulated and its concentration in serum or plasma elevated if fibrogenesis is going on. There is a correlation between CTGF levels and fibrogenesis, because the levels decrease in fully developed, end-stage cirrhosis, compared to fibrosis. The area under the curve (AUCs) for fibrosis versus control and cirrhosis versus control were calculated to be 0.955 and 0.887, respectively, the sensitivities 100% and 84%, respectively, the specificities 89% and 85%, respectively (Fig. 4) [55]. These criteria suggest CTGF as a potentially valuable class I biomarker of active fibrogenesis.

Bottom Line: Many of them, however, proved to be disappointing with regard to sensitivity and specificity.The translation of genetic pre-disposition biomarkers into clinical practice has not yet started, but some polymorphisms indicate a link to progression and outcome of fibrogenesis.Parallel to serum markers non-invasive physical techniques, for example, transient elastography, are developed, which can be combined with serum tests and profiling of serum proteins and glycans.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Central Laboratory, RWTH-University Hospital, Aachen, Germany. agressner@ukaachen.de

ABSTRACT
Fibrosis is a frequent, life-threatening complication of most chronic liver diseases. Despite major achievements in the understanding of its pathogenesis, the translation of this knowledge into clinical practice is still limited. In particular, non-invasive and reliable (serum-) biomarkers indicating the activity of fibrogenesis are scarce. Class I biomarkers are defined as serum components having a direct relation to the mechanism of fibrogenesis, either as secreted matrix-related components of activated hepatic stellate cells and fibroblasts or as mediators of extracellular matrix (ECM) synthesis or turnover. They reflect primarily the activity of the fibrogenic process. Many of them, however, proved to be disappointing with regard to sensitivity and specificity. Up to now hyaluronan turned out to be the relative best type I serum marker. Class II biomarkers comprise in general rather simple standard laboratory tests, which are grouped into panels. They fulfil most criteria for detection and staging of fibrosis and to a lesser extent grading of fibrogenic activity. More than 20 scores are currently available, among which Fibrotest is the most popular one. However, the diagnostic use of many of these scores is still limited and standardization of the assays is only partially realized. Combining of panel markers in sequential algorithms might increase their diagnostic validity. The translation of genetic pre-disposition biomarkers into clinical practice has not yet started, but some polymorphisms indicate a link to progression and outcome of fibrogenesis. Parallel to serum markers non-invasive physical techniques, for example, transient elastography, are developed, which can be combined with serum tests and profiling of serum proteins and glycans.

Show MeSH
Related in: MedlinePlus