Diagnosis of fibrosis in liver biopsy

1. Diagnosis of fibrosis in liver biopsy Wagdi Elkashef, PhD. Pathology Department, Gastro-enterology Center, Mansoura Univercity

2. The degree of liver fibrosis is one of the main diagnostic and prognostic assessments in chronic liver disease. • Recent studies suggest that liver fibrosis can be modified by treatment. • Re-evaluation of the histo-pathological methods used to measure liver fibrosis is required.

3. All scoring systems assess the extent and location of fibrosis and changes in liver tissue architecture. All systems use a single numerical scale, where 0 (zero) represents the absence of fibrosis and the highest number indicates cirrhosis. • Different systems use different score intermediate stages. The numbers reflect not measurements, but mainly qualitative concepts.

4. The most currently used scoring systems are: METAVIR scoring system and modified HAI (Ishak) scoring system. • Staging fibrosis is an assessment of both the extent of fibrosis and architectural disorganization. • These semi-quantitative scores have been used effectively for years in both clinical trials and for individual evaluation.

7. F2 F1 F3 F4

8. Examination of liver biopsy using the semi-quantitative scoring systems is associated with some difficulties. • The fibrosis in many diseases is heterogeneous and biopsy size is significantly affecting the accuracy of fibrosis assessment. • Inter observer variation is another limitation of fibrosis assessment in liver biopsy that is related to the difference between pathologist’s interpretations of the biopsy.

9. The level of experience (specialization, duration, and location of practice) has significant influence on inter observer variations and agreement can be improved by experienced pathologist or consensus reading.

10. Histological scores are categorical data and not numbers. Any statistical analysis must be carried out according to this fact. • Diagnostic evaluation of longitudinal changes of disease stage in individual patients should be performed by direct comparison and review of all biopsies, and not by comparison of recorded scores.

12. The histopathological diagnosis of cirrhosis (and assignment of ‘‘Ishak stage 6’’), and the measured amount of fibrosis are entirely different assessments.

13. Despite these limitations, liver biopsy delivers important information that none of the non-invasive markers provide. • Beside the stage of fibrosis liver biopsy also determine the activity of chronic hepatitis and may help to reveal associated diseases that may affect the progression of the disease and response to treatment.

14. Recently attempts to utilize the existing semi-quantitative methods of liver fibrosis assessment to develop real quantitative ones with significant reduction in variability and subjectivity are made. • Morphometric assessment of fibrosis may be more sensitive than semi-quantitative methods to identify changes in fibrosis after therapy.

15. However, variability in collagen proportionate area (CPA) scores between selected microscopic fileldrepresent the main limitation of morphometric assessment. • Use of (CPA) by digital image analysis (Mosaic pictures generated from automated sequential digitalized images) provides more objective data for statistical analysis.

17. Recommendations: • A liver biopsy may be indicated in the case of co-morbidities such as metabolic syndrome and should not be performed when the clinical diagnosis is obvious (cirrhosis). Also liver biopsy may be necessary to differentiate between F2 and F3 stages suggested by non-invasive techniques.

18. Recommendations: • The biopsy should be examined by an experienced liver pathologist because it decreases the source of variability in the histological interpretation.

19. Recommendations: • Combination of semi-quantitative and morphometric assessment of fibrosis in liver biopsy should be considered for assessment of fibrosis in research purposes (2 B).

20. THANK YOU