Application and Validation of a New Histologic Staging and Grading System for Primary Biliary Cirrhosis

Harada, Kenichi; Hsu, Maylee; Ikeda, Hiroko; Zeniya, Mikio; Nakanuma, Yasuni

doi:10.1097/mcg.0b013e31827234e4

Cited by 38 publications

(34 citation statements)

References 23 publications

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“…Serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) levels were quantified by an immunoassay using a commercially available kit (HISCL M2BPGi; Sysmex, Kobe, Japan). Histological stage and grade were semiquantified using Nakanuma's classification system . In this classification system, histological grades were divided into two categories: chronic cholangitis activity and hepatitis activity (HA) grades.…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy

Amano

Ikeda

Hayashida

et al. 2020

Hepatology Research

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Aim Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis. Methods A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched‐chain amino acids and tyrosine, and branched‐chain amino acid‐to‐tyrosine ratio were determined. The hazard ratios of factors associated with liver‐related events were analyzed by Cox proportional hazard analysis. Results Of the 75 patients enrolled, 12 showed a decrease in serum branched‐chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched‐chain amino acid‐to‐tyrosine ratio decreased in 16 patients. During a median 5.6‐year follow up, liver‐related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 μmol/L was identified as a cut‐off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3–101.5, P < 0.001). Kaplan–Meier analysis showed that the 5‐year cumulative incidences of event occurrence in patients with high and low serum tyrosine concentration were 56.5% and 5.5%, respectively (P < 0.001). The 10‐year survival probabilities also showed significant differences between patients with high and low serum tyrosine concentration (44.9% vs. 92.0%, P < 0.001). Conclusion Elevation of serum tyrosine concentration indicates a high risk of liver‐related events in primary biliary cholangitis patients receiving urusodeoxycholic acid therapy.

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Section: Methodsmentioning

confidence: 99%

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy

Amano

Ikeda

Hayashida

et al. 2020

Hepatology Research

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“…Biopsy specimens were processed according to routine protocols. Tissue sections were stained with hematoxylin–eosin and Azan Mallory, followed by evaluations for Scheuer and Nakanuma classifications . According to the Scheuer staging system, patients were classified into four stages: stages 1 and 2, early disease; and stages 3 and 4, advanced disease.…”

Section: Methodsmentioning

confidence: 99%

“…The proposed staging system by Nakanuma et al . is useful in separately assessing the degree of liver fibrosis and BDL for the histological staging of PBC …”

Section: Introductionmentioning

confidence: 99%

Liver fibrosis progression predicts survival in patients with primary biliary cirrhosis

Namisaki

Moriya

Noguchi

et al. 2016

Hepatology Research

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Aim:The prognosis and natural history of primary biliary cirrhosis (PBC) has improved, and the clinical end-point for PBC needs to be discovered. We aimed to identify surrogate markers for predicting long-term prognosis in patients with PBC.Methods: A total of 106 patients were divided into 53 responders and 53 non-responders based on the median rate (69%) of decrease in γ-glutamyl transpeptidase levels at 1 year after initiating ursodeoxycholic acid therapy. We aimed to identify the differences between ursodeoxycholic acid responders and non-responders. Correlation of patient survival with histologic parameters based on Scheuer and Nakanuma staging systems was investigated. The Nakanuma system comprises grading for liver fibrosis and bile duct loss (BDL).

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“…Activated NKT cells may prompt BEC death, leading to the development of PBC[140]. A novel hepatic histological grading system for PBC, proposed by Japanese scholars, includes the degree of chronic cholangitis activity (CA 0-3), which is associated with clinic-laboratory characteristics of cholangitis, and hepatitides activity (HA 0-3), which is related to the progression of cirrhosis-related conditions[141]. French scholars proposed another novel histological scoring system for PBC, which covers assessment of hepatic fibrosis, leukomonocyte interface hepatitides, and absence of biliary ducts[142].…”

Section: Histopathological Featuresmentioning

confidence: 99%

Recent advances in the diagnosis and treatment of primary biliary cholangitis

Huang¹

2016

WJH

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Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients.

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Application and Validation of a New Histologic Staging and Grading System for Primary Biliary Cirrhosis

Abstract: Background:We proposed a new grading and staging system for primary biliary cirrhosis (PBC),

Cited by 38 publications

References 23 publications

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy

Liver fibrosis progression predicts survival in patients with primary biliary cirrhosis

Recent advances in the diagnosis and treatment of primary biliary cholangitis

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