FOR THE METAVIR COOPERATIVE STUDY GROUP histological classification of chronic hepatitis, and several Histological activity reflects the global assessment of propositions have recently been made by different groups of basic necroinflammatory lesions and is a criterion of mapathologists. [4][5][6][7] A consensual proposition was to separately jor importance in chronic hepatitis C. The aim of this assess, using scoring systems, the degree of liver fibrosis and study was to propose and test the accuracy of a simple that of activity. 4,6 Liver fibrosis is simple to precisely define algorithm that generates a single activity score based and thus to reproducibly score. 8 In contrast, the grading of on basic pathological features. A panel of 10 pathologists activity, which integrates the different basic necroinflammareviewed 363 chronic hepatitis C liver biopsies and tory lesions, is more difficult to assess; morever, it is of imporgraded the activity of hepatitis according to their own tance in the decision of whether or not to treat patients in experience (reference activity). Then, a consensual algomany therapeutic trials. Although not proven, inflammation rithm on the grading of activity was established by the and liver cell necrosis are the hallmarks of active disease 10 experts in a panel discussion. Finally, stepwise disthat may predict evolution toward fibrosis and cirrhosis. criminant analysis was performed to define which basic Several approaches have been proposed to assess histologifeatures had been intuitively used in the reference activcal activity. One of them is the semiquantitative scoring sysity (statistical activity). To test the accuracy of the algotem of Knodell et al., in which fibrosis and portal, periportal, rithm, concordance between the activity defined by the and lobular necrotic and inflammatory components are asalgorithm and the reference activity was assessed. It was sessed separately and their coding values added. 10 The global compared with concordance between the activity descore appears accurate because it varies over large ranges, fined by the statistical model and the reference activity.but its value may be limited by poor reproducibility, because The algorithm proposed by the panel for the grading of each feature has its own observer variation. 8 Another possible activity included piecemeal necrosis and lobular necroapproach is to consider that periportal and intralobular nesis. Concordance between reference activity and activity croinflammatory lesions are related to the same pathogenic defined by the algorithm was substantial (305 cases, 84%, mechanism and that they must be globally assessed. As prek Å .75). Discriminant analysis showed that piecemeal viously reported, assessment of activity must be separated necrosis, lobular necrosis, and portal inflammation were from staging of fibrosis.4 independently used to grade the activity. Concordance The aim of this study was to propose a simple algorithm between reference activity and activity defined by the that generates a single sco...

No abstract

Link to publication on Research at Birmingham portal General rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law.• Users may freely distribute the URL that is used to identify this publication.• Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research.• User may use extracts from the document in line with the concept of 'fair dealing' under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version. Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.

Fibrosis is a common endpoint of clinical trials in chronic hepatitis C, and liver biopsy remains the gold standard for fibrosis evaluation. However, variability in the distribution of fibrosis within the liver is a potential limitation. Our aim was to assess the heterogeneity of liver fibrosis and its influence on the accuracy of assessment of fibrosis with liver biopsy. Surgical samples of livers from patients with chronic hepatitis C were studied. Measurement of fibrosis was performed on the whole section by using both image analysis and METAVIR score (reference value). From the digitized image of the whole section, virtual biopsy specimens of increasing length were produced. Fibrosis was assessed independently on each individual virtual biopsy specimen. Results were compared with the reference value according to the length of the biopsy specimen. By using image analysis, the coefficient of variation of fibrosis measurement with 15-mm long biopsy specimens was 55%; and for biopsy specimens of 25-mm length it was 45%. By using the METAVIR scoring system, 65% of biopsies 15 mm in length were categorized correctly according to the reference value. This increased to 75% for a 25-mm liver biopsy specimen without any substantial benefit for longer biopsy specimens. Sampling variability of fibrosis is a significant limitation in the assessment of fibrosis with liver biopsy. In conclusion, this study suggests that a length of at least 25 mm is necessary to evaluate fibrosis accurately with a semiquantitative score. Sampling variability becomes a major limitation when using more accurate methods such as automated image analysis.

No abstract

Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. • Users may freely distribute the URL that is used to identify this publication. • Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. • User may use extracts from the document in line with the concept of 'fair dealing' under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.

A post-hoc analysis of data from trial of patients with NASH showed that elafibranor (120 mg/d for 1 year) resolved NASH without fibrosis worsening, based on a modified definition, in the intention-to-treat analysis and in patients with moderate or severe NASH. However, the predefined end point was not met in the intention to treat population. Elafibranor was well tolerated and improved patients' cardiometabolic risk profile. ClinicalTrials.gov number: NCT01694849.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and being overweight is a significant risk factor. The aim was to build an algorithm along with a scoring system for histopathologic classification of liver lesions that covers the entire spectrum of lesions in morbidly obese patients. A cohort of 679 obese patients undergoing liver biopsy at the time of bariatric surgery was studied. An algorithm for segregating lesions into normal liver, NAFLD, or nonalcoholic steatohepatitis (NASH) was built based on semiquantitative evaluation of steatosis, hepatocellular ballooning, and lobular inflammation. For each case, the SAF score was created including the semiquantitative scoring of steatosis (S), activity (A), and fibrosis (F). Based on the algorithm, 230 obese patients (34%) were categorized as NASH, 291 (43%) as NAFLD without NASH, and 158 (23%) as not NAFLD. The activity score (ballooning 1 lobular inflammation) enabled discriminating NASH because all patients with NASH had A ! 2, whereas no patients with A < 2 had NASH. This score was closely correlated with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P < 0.0001, analysis of variance [ANOVA]). Comparison of transaminase levels between patients with normal liver and pure steatosis did not reveal significant differences, thus lending support to the proposal not to include steatosis in the activity score but to report it separately in the SAF score. In the validation series, the interobserver agreement for the diagnosis of NASH was excellent (j 5 0.80) between liver pathologists. There was no discrepancy between the initial diagnosis and the diagnosis proposed using the algorithm. Conclusion: We propose a simple but robust algorithm for categorizing liver lesions in NAFLD patients. Because liver lesions in obese patients may display a continuous spectrum of histologic lesions, we suggest describing liver lesions using the SAF score.