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Use of Nakanuma staging and cytokeratin 7 staining for diagnosing recurrent primary biliary cholangitis after living‐donor liver transplantation
Author(s) -
Yamashiki Noriyo,
Haga Hironori,
Ueda Yoshihide,
Ito Takashi,
Yagi Shintaro,
Kamo Naoko,
Hata Koichiro,
Mori Akira,
Kaido Toshimi,
Okajima Hideaki,
Uemoto Shinji
Publication year - 2020
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13476
Subject(s) - medicine , gastroenterology , liver transplantation , liver biopsy , stage (stratigraphy) , biopsy , cytokeratin , fibrosis , bile duct , transplantation , pathology , immunohistochemistry , paleontology , biology
Aim Diagnosis of primary biliary cholangitis (PBC), which recurs in approximately 30% of liver transplant recipients, is histology‐based, but no staging system has been established for recurrent PBC (rPBC). We used the Nakanuma staging system and cytokeratin 7 (CK7) staining to examine post‐transplant liver biopsy specimens retrospectively and to evaluate histological features of rPBC. Methods From 107 patients who underwent living donor liver transplantation for PBC, 60 recipients with 214 liver biopsies after 1‐year post transplant were enrolled. Fibrosis, bile duct loss (BL), cholangitis activity, hepatitis activity, and CK7‐positive hepatocytes were scored. Nakanuma staging was based on fibrosis and BL scores. We examined the correlation of scores and clinicolaboratory data among rPBC patients. We also evaluated whether chronological change of stage was correlated with liver‐related failure. Results Of 214 biopsies, 52 were protocol biopsy; 162 were episodic. Higher BL, cholangitis activity, and hepatitis activity scores were associated with rPBC diagnosis. At median follow up of 10.0 years (range 1.4–18.7 years), 29 (48%) patients were diagnosed with rPBC at 4.6 years (range 1.3–14.5 years). Liver‐related failure occurred in five rPBC cases; three from rPBC, and two from chronic rejection. At rPBC diagnosis, higher BL and CK7 scores were more frequent in patients who developed liver‐related failure than in other patients ( P = 0.04, P < 0.01, respectively). In failure patients, the Nakanuma stage increased over time, and reached up to stage 4, whereas the Scheuer stage did not reach above stage 3. Conclusions Nakanuma staging is associated with rPBC and disease progression. Scores for BL and CK7 might be early markers for progressive rPBC.