Hepatic Fibrosis -- Role of Hepatic Stellate Cell Activation

Scott L. Friedman, MD

Disclosures
In This Article

Diagnosis and Assessment of Hepatic Fibrosis

Accurate assessment of the extent of fibrosis is essential in guiding management and predicting prognosis in patients with chronic liver injury. Histologic assessment of a liver biopsy specimen remains the gold standard for quantifying fibrosis, with increasing interest in the use of noninvasive markers to allow more frequent sampling and avoid the risks of percutaneous biopsy.

Histologic and Morphometric Methods

Several semiquantitative morphologic methods have been described that evaluate ECM in biopsy specimens stained with either hematoxylin and eosin (H & E) or connective tissue stains (such as Masson's trichrome, reticulin silver impregnation, or van Gieson). Even these methods are not perfect, however, and can be prone to sampling error if the fibrosis is patchy. Semiquantitative methods include the Knodell-Ishak score,[50] the French METAVIR system,[51] and others (see [52] for review). Immunohistochemical and in situ mRNA hybridization methods for identifying specific matrix components can be employed for experimental studies, but are no better than standard methods for routine clinical use.

Noninvasive Methods

There has been considerable effort aimed at identifying serum markers as noninvasive measures of hepatic fibrosis (see [52] for review). Although the accuracy and predictive value of these markers are improving, they cannot yet supplant direct analysis of liver. Thus far, no single test has emerged as the perfect marker of fibrosis, although it remains possible that a "battery" of tests used collectively may prove useful. A recent multicenter effort to employ such a battery of serum markers has shown promise in distinguishing minimal from advanced fibrosis.[53]

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