An appraisal of the histopathological assessment of liver fibrosis
Authors: R A Standish
Journal: Gut (2006)

SUMMARY One of the most important aspects of the histopathological assessment of liver biopsies in the setting of chronic liver disease is determination of the degree of fibrosis and architectural change. Most of the work in this regard has been concerned with chronic viral hepatitis. This article attempts to assess critically our current and historical biopsy practice, from subjective fibrosis scoring systems to biopsy sample size; and the appropriate use of the data that scoring systems generate in the research and clinical setting. An understanding of the limitations of each of the components of the fibrosis assessment process can help to devise appropriate protocols to ensure that the information obtained is optimised, and its degree of reliability appreciated. It is only from this starting point that recently promulgated antifibrotic medications and ''non-invasive'' liver fibrosis assessment techniques can be evaluated properly. chronic liver disease. Histological assessment of fibrosis is regarded as the ''gold standard'' in this respect. Clinical manifestations of liver disease and liver dysfunction accompany architectural changes of the liver parenchyma that are a result of advanced stages of liver fibrosis. Previously, it was thought that liver fibrosis and end stage liver disease (cirrhosis) were irreversible, and therefore crude determinations of liver fibrosis were acceptable because the therapeutic impact of this assessment was relatively minor. Recent work suggests that liver fibrosis may be modified by treatment 1-4 and so critical re-evaluation of the histopathological methods used to assess liver fibrosis is necessary. Liver biopsy assessment of fibrosis is not only the end point for the development of antifibrotic treatments but also forms the benchmark for validation of serum ''surrogate markers'' of liver fibrosis and other non-invasive techniques that purport to measure liver fibrosis and stage of liver disease. There are several important issues which make interpretation of the current literature difficult. c Firstly, the bulk of the literature published recently regarding the adequacy of liver biopsies is based on studies of chronic viral hepatitis. This literature suggests that the majority of liver biopsy samples are too small to be representative and therefore are inadequate for a reliable assessment of histological stage or grade. c Secondly, that the histopathological scoring of the stage of liver disease is largely an assessment of architectural change and not a measurement of amount or degree of fibrosis. c Thirdly, that stage scores are often mistaken for measurements, and inappropriate statistical techniques are then applied. c Lastly, although recognised but often forgotten, that the scores generated are prone to considerable intraobserver and interobserver error. Thus histopathological liver fibrosis assessment has become a tarnished ''gold standard'' and it needs to be improved. Progress will depend on recognition of the problem, a better understanding of the need for an adequate sample, and a much better understanding of the nature of ''staging scores''—including the use of more appropriate statistical tools and strategies to minimise observer variation. For proper quantification of liver collagen, image analysis (IA) of appropriately stained liver sections or biochemical assay might be necessary. SCORING SYSTEMS AND VARIABILITY Before going on to address the important issue of biopsy size and adequacy, we would like first to consider analysis of the biopsy. Currently, most centres carry out descriptive reporting when assessing diagnostic biopsies from an individual patient. However, in the trial and research setting, evaluation of biopsies is carried out using subjective scoring systems that produce shorthand values for various categories of inflammation (grade), and fibrosis and architectural 569