Preventing and Reversing Fibrosis in Autoimmune Hepatitis
Preventing and Reversing Fibrosis in Autoimmune Hepatitis
The emerging opportunities to prevent, stabilise or reverse hepatic fibrosis have mandated improvements in the methods for grading and monitoring changes in the extracellular matrix of the liver. Liver tissue examination remains the gold standard for the assessment of hepatic fibrosis in autoimmune hepatitis, but its accuracy is limited by sampling error and interpretative variations. Early studies in patients with autoimmune hepatitis demonstrated that multiple tissue samples obtained at the same time from different sites disclosed cirrhosis in all specimens in only 33% of instances. Furthermore, intra-observer consistency in making the same diagnosis in the same tissue sample varied from 50% to 78%.
Similar results were obtained in patients with diverse liver diseases who underwent multiple tissue samples during the same procedure. Cirrhosis was present in all specimens in only 50% of instances, and reliance on the needle biopsy procedure to determine the appearance or disappearance of hepatic fibrosis was challenged. Autopsy studies indicated that cirrhosis could be detected in at least one of three biopsy specimens in all patients with cirrhosis, but concerns about the histological variability between samples and the confident documentation of fibrotic change were not alleviated.
The accuracy of the liver biopsy assessment of hepatic fibrosis in autoimmune hepatitis has been improved by the routine use of reticulum and trichrome stains of the liver tissue, clarification of the optimal sample size for evaluating fibrosis and the strict application of codified guidelines for staging fibrosis. The reticulum and trichrome stains facilitate the distinction between fibrosis and stromal collapse and the recognition of regenerative nodules. The ideal tissue specimen for grading liver inflammation and staging fibrosis has six to eight portal tracts, and it is ≥2.5 cm in length and ≥1.4 mm in diameter. Scoring systems for staging hepatic fibrosis have also been validated and codified.
The Ishak scoring system is able to evaluate mild changes of fibrosis that are unevenly distributed in the liver tissue, and it has been associated with an 84% agreement among three independent pathologists for staging fibrosis. These attributes have justified its preference for assessing changes in hepatic fibrosis in patients with autoimmune hepatitis. The METAVIR scoring system has also had a high concordance among observers for grading liver inflammation and staging fibrosis, but its design, validation and application have focused on chronic hepatitis C. The liver biopsy assessment remains the gold standard for assessing hepatic fibrosis in autoimmune hepatitis because high quality liver biopsy specimens can be obtained and the processing and interpretation of the tissue sample have been codified.
Staging of Hepatic Fibrosis by Liver Tissue Examination
The emerging opportunities to prevent, stabilise or reverse hepatic fibrosis have mandated improvements in the methods for grading and monitoring changes in the extracellular matrix of the liver. Liver tissue examination remains the gold standard for the assessment of hepatic fibrosis in autoimmune hepatitis, but its accuracy is limited by sampling error and interpretative variations. Early studies in patients with autoimmune hepatitis demonstrated that multiple tissue samples obtained at the same time from different sites disclosed cirrhosis in all specimens in only 33% of instances. Furthermore, intra-observer consistency in making the same diagnosis in the same tissue sample varied from 50% to 78%.
Similar results were obtained in patients with diverse liver diseases who underwent multiple tissue samples during the same procedure. Cirrhosis was present in all specimens in only 50% of instances, and reliance on the needle biopsy procedure to determine the appearance or disappearance of hepatic fibrosis was challenged. Autopsy studies indicated that cirrhosis could be detected in at least one of three biopsy specimens in all patients with cirrhosis, but concerns about the histological variability between samples and the confident documentation of fibrotic change were not alleviated.
The accuracy of the liver biopsy assessment of hepatic fibrosis in autoimmune hepatitis has been improved by the routine use of reticulum and trichrome stains of the liver tissue, clarification of the optimal sample size for evaluating fibrosis and the strict application of codified guidelines for staging fibrosis. The reticulum and trichrome stains facilitate the distinction between fibrosis and stromal collapse and the recognition of regenerative nodules. The ideal tissue specimen for grading liver inflammation and staging fibrosis has six to eight portal tracts, and it is ≥2.5 cm in length and ≥1.4 mm in diameter. Scoring systems for staging hepatic fibrosis have also been validated and codified.
The Ishak scoring system is able to evaluate mild changes of fibrosis that are unevenly distributed in the liver tissue, and it has been associated with an 84% agreement among three independent pathologists for staging fibrosis. These attributes have justified its preference for assessing changes in hepatic fibrosis in patients with autoimmune hepatitis. The METAVIR scoring system has also had a high concordance among observers for grading liver inflammation and staging fibrosis, but its design, validation and application have focused on chronic hepatitis C. The liver biopsy assessment remains the gold standard for assessing hepatic fibrosis in autoimmune hepatitis because high quality liver biopsy specimens can be obtained and the processing and interpretation of the tissue sample have been codified.
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