Use of Nakanuma staging and cytokeratin 7 staining for diagnosing recurrent primary biliary cholangitis after living‐donor liver transplantation

Abstract

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). Liverrelated 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.

The ursodeoxycholic acid response score predicts pathological features in primary biliary cholangitis

“…44 The associations between the POR and the CK7 grading of the ductular reaction or fibrosis at pretreatment in our study were different from those in the original study by Carbone et al 24 Extension of the CK7-positive bile ductules was employed for evaluation in the original study; however, we evaluated the CK7 grading of the ductular reaction by using the semiquantitative scoring system, which is often used in clinical and basic science research. 29,45 This difference in the evaluation method and the pathological heterogeneity may influence our results. Secondly, while the American Association for the Study of Liver Diseases practice guidance 13 and the European Association for the Study of the Liver clinical practice guidelines 14 recommend UDCA at a dose of 13-15 mg/kg/day, the standard dose of UDCA for PBC recommended by the clinical practice guidelines in Japan is 600 mg/day.…”

Posttransplant immune-mediated cholangiopathies

“…As in de novo PBC, progressive fibrosis is observed in rPBC. It has been shown that the scoring and grading systems used for de novo PBC, and especially the popular Nakanuma staging system, can be applied in rPBC to evaluate disease progression and prognosis [26 ▪ ].…”

Early histopathologic changes in primary biliary cholangitis: does ‘minimal change’ primary biliary cholangitis exist? A pathologist’s view

“…Subsequent studies have suggested that the Nakanuma system is more practical because it predicts adverse prognosis of PBC patients [75,76] and may also help to predict treatment responses [77]. Moreover, as a recent study suggested, the Nakanuma staging system and K 7 grading correlate well with recurrent PBC and disease progression after living-donor liver transplantation [78]. Bile ducts loss and K 7 score may be used as markers for progressive recurrent PBC [78].…”

“…Moreover, as a recent study suggested, the Nakanuma staging system and K 7 grading correlate well with recurrent PBC and disease progression after living-donor liver transplantation [78]. Bile ducts loss and K 7 score may be used as markers for progressive recurrent PBC [78]. Also, a study by Warnes et al concluded that sinusoidal fibrosis is the major histologic parameter providing independent prognostic value [79].…”