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