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A comparative study of cirrhosis sub-staging using the Laennec system, Beijing classification, and morphometry

Abstract

There is constant remodeling in a cirrhotic liver resulting in cirrhosis being spatially heterogeneous. The Laennec system, and, more recently the Beijing classification, have been used to sub-classify various degrees of cirrhosis. It is unknown how these two schemes compare with each other, how they are impacted by geographic variation, and how they correlate with clinical outcomes. Five needle biopsies were obtained from 20 explanted cirrhotic HCV livers at the time of transplantation. Collagen proportionate area (CPA) was measured by computerized quantitative morphometry. The Laennec system (4A-4C indicating increasing degrees of cirrhosis) and Beijing classification (P—progressive, R—regressive, I—indeterminate) were assessed and then correlated with CPA. Geographical variation using CPAs was calculated by the coefficient of variation (CoV). CPA of Laennec 4C cirrhosis was higher than 4A (p = 0.00008) or 4B (p = 0.0002). The CPA of the P pattern was greater than the R (p = 0.002) or I patterns (p = 0.037). The mean CoV of the five CPAs was 47.3 ± 4.5%, suggesting a significant degree of geographic variation. There was 100% overlap between the Beijing R pattern and Laennec 4A, and 80% overlap between the P pattern and Laennec 4C. Patients’ platelet counts of P pattern were lower than R pattern (p = 0.008) or I pattern (p = 0.024), while Laennec 4C was lower than 4A (p = 0.036) and 4B patients (p = 0.7). There was no correlation between CPA, Laennec stage, or Beijing classification and MELD score, liver weights, total bilirubin, or albumin levels. The Laennec system and the Beijing classification are highly correlated with CPA in cirrhosis. This study confirms that there is a significant degree of geographic variation in terms of fibrosis content and cirrhosis morphology throughout the liver.

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Fig. 1: Collagen-proportionate area (CPA) measurement by computerized morphometrical quantification.
Fig. 2: The CPA correlates significantly with Laennec stages.
Fig. 3: The CPA correlates with the fibrosis grade according to the Beijing classification.
Fig. 4: The effect of geographic variation and fibrosis remodeling on cirrhosis substaging using the Laennec grading system and the Beijing classification.
Fig. 5: The correlation between the Beijing classification and clinical parameters.
Fig. 6: The correlation between the Laennec grading system and clinical parameters.
Fig. 7: Sustained virologic response (SVR) tends to have lower collagen-proportionate area (CPA) values.

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Acknowledgements

This study was funded in part with a grant from Merck Pharmaceutical Company. We thank Brandy Haydel for her invaluable assistance in obtaining the pathology specimens. The study was sponsored in part by Merck Pharmaceuticals.

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X Zhang—paper preparation, performance of morphometry, and statistical analysis. TD Schiano—concept of the study, principal investigator and funding, and preparation, writing, and final approval of the paper. E Doyle—procurement of materials, laboratory data. A Branch—study concept, final approval of the paper. S Florman—patients, clinical input, and concept of study. MI Fiel—concept of study, histopathological analysis, writing, and final approval of the paper.

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Correspondence to M. Isabel Fiel.

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Each patient gave consent to participate in the study. The study was approved by the Institutional Review Board.

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Zhang, X., Schiano, T.D., Doyle, E. et al. A comparative study of cirrhosis sub-staging using the Laennec system, Beijing classification, and morphometry. Mod Pathol 34, 2175–2182 (2021). https://doi.org/10.1038/s41379-021-00881-z

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