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

Kakuda, Yuko; Harada, Kenichi; Sawada-Kitamura, Seiko; Ikeda, Hiroko; Sato, Yasunori; Sasaki, Motoko; Okafuji, Hirofumi; Mizukoshi, Eishiro; Terasaki, Shuichi; Ohta, Hiroyuki; Kasashima, Satomi; Kawashima, Atsuhiro; Kaizaki, Yasuharu; Kaneko, Shuichi; Nakanuma, Yasuni

doi:10.1016/j.humpath.2012.09.017

Cited by 69 publications

(57 citation statements)

References 18 publications

(10 reference statements)

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“…showed a significant prognostic value of Nakanuma components fibrosis and CBP deposition, as well as Nakanuma and Ludwig staging systems as a whole for the development of cirrhosis related conditions before ursodeoxycholic acid (UDCA) treatment. [24] In a retrospective cohort of 58 PBC patients Chan et al confirmed the Nakanuma system as a prognostic factor for liver related events, while the Ludwig system was not. [27] It must be stated that, despite that PSC and PBC are both cholangiopathies, sharing biochemical, clinical and a some morphological features, considerable differences exist in both disease entities [15].…”

Section: Discussionmentioning

confidence: 98%

Applicability and prognostic value of histologic scoring systems in primary sclerosing cholangitis

Vries

Verheij

Hübscher

et al. 2015

Journal of Hepatology

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Section: Discussionmentioning

confidence: 98%

Applicability and prognostic value of histologic scoring systems in primary sclerosing cholangitis

Vries

Verheij

Hübscher

et al. 2015

Journal of Hepatology

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“…Kakuda et al [19] reported that the new PBC staging and grading system reflected liver dysfunction prior to specific treatment. In the present study, however, the expression of IgG and IgM did not appear to reflect clinicolaboratory features following intervention or specific treatment.…”

Section: Discussionmentioning

confidence: 99%

The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases

Abe

Takahashi

Nozawa³

et al. 2014

Med Mol Morphol

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Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) present with distinct clinical features. The term "PBC-AIH overlap syndrome (OS)" has been adopted to describe the condition characterized by occurrence of both PBC and AIH, although this clinical entity is difficult to define. This study aimed to assess the utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of AIH, PBC, and OS. Immunohistochemistry was performed with anti-human IgG, IgM, and CD138 to detect specific plasma cells in the liver. Predominant IgG staining was observed in AIH (85.7 %), while equivocal (46.1 %) or predominant (38.5 %) IgM staining was observed in PBC. In OS, equivocal (20 %) or predominant (80 %) IgG staining was observed. The IgM/IgG ratio was significantly higher in PBC than in AIH or OS (P < 0.005). Histological findings revealed significantly higher IgM expression in PBC at cholangitis activity grades 2-3 compared to those at cholangitis activity grades 0-1. In contrast, a significantly higher IgG expression was observed in PBC at hepatitis activity and fibrosis grades 2-3 compared to those at hepatitis activity and fibrosis grades 0-1. Taken together, periportal plasmacytic infiltrates with variable immunohistochemistry patterns of IgG and IgM expression characterized different autoimmune liver diseases.

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“…Primary biliary cirrhosis (PBC) is characterized by nonsuppurative cholangitis and autoimmune-mediated destruction of the small or medium-sized bile ducts (8). Inflammation causes cholestasis and the liver develops cirrhosis (9). AIH is treated with immunosuppressive drugs, such as prednisolone or azathioprine (10,11), while PBC is treated with ursodeoxycholic acid (10).…”

Section: Introductionmentioning

confidence: 99%

Anti-mitochondrial M2 antibody-positive autoimmune hepatitis

Tomizawa

Shinozaki

Fugo

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Anti-mitochondrial M2 antibody (AMA-M2) is specific to primary biliary cirrhosis (PBC), but can also be found in certain patients with autoimmune hepatitis (AIH). Effective methods of differentiating between PBC and AIH are required, as their clinical course and management are different. Titers of AMA-M2 were analyzed before and after follow-up in patients with PBC or AIH. Patients who underwent liver biopsy and were diagnosed with either AIH (10 patients) or PBC (3 patients) were enrolled in the study. The AMA-M2 antibody titers of these patients were analyzed upon hospital admission. AMA-M2 reacted with the pyruvate dehydrogenase complex-E2, branched-chain 2-oxo acid dehydrogenase complex and 2-oxoglutaric acid dehydrogenase complex in the assay utilized for this study. The cut-off value for AMA-M2 was 5. Six AIH patients were AMA-M2(-) and 4 were AMA-M2(+). The titer for the AIH patients who were AMA-M2(+) was 24.8±14.8, compared with 324±174 in the patients with PBC (P= 0.0138). Three AMA-M2(+) AIH patients were followed-up after liver biopsy. The AMA-M2 levels had decreased in all 3 patients, becoming undetectable in 2 of them. In conclusion, certain patients with AIH in this study were found to be AMA-M2(+), but the titers were significantly lower than those in the patients with PBC. At follow-up, the AIH patients exhibited decreased AMA-M2 titers. IntroductionAutoimmune hepatitis (AIH) is caused by an immune attack on the hepatocytes (1). Patients with AIH are positive for auto-antibodies, such as anti-nuclear, anti-smooth muscle and liver-kidney microsomal type 1 antibodies (2). Chronic inflammation in the liver can progress to liver cirrhosis (3). One major problem of AIH is that an acute presentation or exacerbation of the disease can progress to liver failure (4,5). Furthermore, patients with AIH can be susceptible to hepatocellular carcinoma (6); therefore, patients should be followed-up for exacerbation and hepatocellular carcinoma (7). Primary biliary cirrhosis (PBC) is characterized by nonsuppurative cholangitis and autoimmune-mediated destruction of the small or medium-sized bile ducts (8). Inflammation causes cholestasis and the liver develops cirrhosis (9). AIH is treated with immunosuppressive drugs, such as prednisolone or azathioprine (10,11), while PBC is treated with ursodeoxycholic acid (10). It is important to differentiate AIH from PBC due to the differences in the clinical course and management of the two diseases.Anti-mitochondrial antibody (AMA) can be tested via indirect immunofluorescence (12). In this technique, unfixed sections of the kidney and stomach of Wistar rats are used. AMA is used for the diagnosis of PBC (13), as 90-95% of patients with PBC are positive for AMA (14); however, the use of AMA as a differential test is problematic, as 5% of patients with AIH are positive for AMA (15), and the interpretation of a positive AMA result in AIH is difficult.The auto-antigens of AMA have been identified as pyruvate dehydrogenase complex-E2 (PDC-E2), branched-chain 2-oxo...

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

Cited by 69 publications

References 18 publications

Applicability and prognostic value of histologic scoring systems in primary sclerosing cholangitis

Applicability and prognostic value of histologic scoring systems in primary sclerosing cholangitis

The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases

Anti-mitochondrial M2 antibody-positive autoimmune hepatitis

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