Elsevier

Human Pathology

Volume 44, Issue 6, June 2013, Pages 1107-1117
Human Pathology

Original contribution
Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems,☆☆

https://doi.org/10.1016/j.humpath.2012.09.017Get rights and content

Summary

Recently, our research team proposed a new histologic staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histologic heterogeneity. The present study aimed to confirm the usefulness of the new evaluation system. A total of 152 liver biopsy specimens and clinical data (including outcomes in patients with PBC before treatment with ursodeoxycholic acid) were analyzed with respect to the new system. Staging was evaluated on the basis of 3 histologic components (fibrosis, bile duct loss, and deposition of orcein-positive granules), and grading was assessed on the basis of chronic cholangitis activity and hepatitis activity. Concurrently, the classical systems, that is, the Scheuer and Ludwig staging systems, were also assessed and compared with our new system. PBC cases showed different distributions in each stage of the 3 systems. The new staging and grading system reflected liver dysfunctions before specific treatment. This was on a par with the results obtained using the classical systems. Development of cirrhosis-related conditions correlated well with the new staging system compared with the 2 classical staging systems, and in particular, the amount of deposition of orcein-positive granules could reflect development of cirrhosis-related conditions (scores 0-1 versus scores 2-3 groups, P < .0001). In conclusion, the new PBC staging system was demonstrated to reflect clinicolaboratory features, and its progression was associated with the development of cirrhosis-related conditions.

Introduction

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown cause. Histologically, interlobular bile ducts are selectively affected, presenting chronic nonsuppurative destructive cholangitis (CNSDC). After cholangiopathy, the affected bile ducts finally disappear, causing cholestatic liver failure and cirrhosis [1], [2].

Several histologic staging systems for PBC have been proposed since the 1960s, including those by Scheuer [3], Rubin et al [4], and Ludwig et al [5]. In the staging systems devised by Scheuer and Ludwig et al, PBC is classified into 4 stages according to a single histologic feature (eg, CNSDC and fibrosis), similar to the system used for chronic hepatitis. These classical systems have been used widely, but the staging process is subjective. Moreover, the histologic features of PBC are heterogeneously distributed in the entire liver; therefore, sampling errors are often encountered in the same liver biopsy specimens. In the staging system devised by Rubin et al [4], the cirrhotic stage is described clearly but the distinctions among the 3 precirrhotic stages are not.

Recently, we proposed a new grading and staging system for PBC that takes into account the histologic findings of cholangitis and hepatitis activities for grading as well as those of fibrosis, bile duct loss, and chronic cholestasis for staging [6]. Furthermore, we have proposed a revised and more practical version of this new grading and staging system for liver biopsy [7], [8], [9]. In the present study, we attempted to evaluate our new staging and grading system by examining relationships with clinicolaboratory features including outcomes in 152 patients with PBC.

Section snippets

Patient selection and tissue preparations

A total of 152 patients were enrolled in this study. They were histologically diagnosed as having PBC on the basis of liver biopsies (144 needle biopsies and 8 wedge biopsies). All patients received no specific treatments such as ursodeoxycholic acid (UDCA) at the time of biopsy and were serologically negative for hepatitis B surface antigen or hepatitis C antibody. These 152 cases were selected consecutively from the files of Kanazawa University Hospital and Department of Human Pathology,

Distribution of histologic grades, scores, and stages

The main clinical profile and laboratory data of 152 patients with PBC are shown in Table 3. The distribution of grades of cholangitis activity (CA) and HA and scores of the 3 lesions for staging (fibrosis, bile duct loss, and deposition of orcein-positive granules) are shown in Fig. 2A to E. As for necroinflammatory activity, CA3 was the most frequent and CA0, CA1, and CA2 were relatively infrequent. In contrast, HA1 was the most frequent, followed by HA0, HA2, and HA3, indicating that the

Discussion

Recently, we proposed a new histologic evaluation system for liver biopsies of PBC to avoid sampling errors and to evaluate necroinflammatory activities. In the present study, we applied this new system to the liver biopsies of 152 patients with PBC. We found different distributions of cases among the 3 systems. In particular, a considerable number of stage 1 cases of the Scheuer/Ludwig systems were reclassified as stage 2 or 3 in the new system because of bile duct loss and/or deposition of

Acknowledgments

The authors thank Dr Takeshi Urabe (Department of Gastroenterology, Public Central Hospital of Matto Ishikawa, Hakusan, Japan), Dr Yasutsugu Mizuno (Department of Internal Medicine, Nomi Hospital, Nomi, Japan), Dr Hisanori Oiwake (Department of Internal Medicine, Suzu General Hospital, Suzu, Japan), Dr Ryuhei Nishino (Department of Internal Medicine, Hakui Public Hospital, Hakui, Japan), and Dr Hideki Osaka (Yawata Medical Center, Komatsu, Japan) for generously donating clinical samples. They

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    Citation Excerpt :

    Evidence showing the presence of autoreactive cells within the liver is well grounded, and self-antigens have been revealed, most frequently referring to the E2-domain of the pyruvate dehydrogenase complex (PDC-E2) (Lleo et al., 2010). On histology, PBC is characterized by lymphocytic inflammation around portal tracts and biliary epithelial cells; these infiltrates are mainly composed of autoreactive CD4+ and CD8+ T-cells that are reacting to PDC-E2 (Kakuda et al., 2013). Immunosuppressive medications (e.g. Budesonide) have shown some beneficial effect on liver enzymes in PBC (Hirschfield et al., 2020), but their benefit-risk ratio is considered unfavourable and are typically reserved to cases when also features of Autoimmune Hepatitis are concomitantly present (European Association for the Study of the Liver, 2017).

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Conflict of interest: The authors declare that they do not have anything to disclose with regard to funding or conflict of interest with respect to this manuscript.

☆☆

Financial support: This work was supported partially by the Research Program of Intractable Disease provided by the Ministry of Health, Labor, and Welfare of Japan and Grants-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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