In Hepatology research : the official journal of the Japan Society of Hepatology
BACKGROUND & AIMS : Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that obstructs the bile ducts and causes liver cirrhosis and cholangiocarcinoma. Efficient surrogate markers are required to measure disease progression. The cytokeratin 7 (K7) load in a liver specimen is an independent prognostic indicator that can be measured from digitalized slides using artificial intelligence (AI)-based models.
METHODS : A K7-AI model 2.0 was built to measure the hepatocellular K7 load area of the parenchyma, portal tracts, and biliary epithelium. K7-stained PSC liver biopsy specimens (n = 295) were analyzed. A compound endpoint (liver transplantation, liver-related death, and cholangiocarcinoma) was applied in Kaplan-Meier survival analysis to measure AUC values and positive likelihood ratios for each histological variable detected by the model.
RESULTS : The K7-AI model 2.0 was a better prognostic tool than plasma alkaline phosphatase-ALP, fibrosis stage evaluated by Nakanuma classification, or K7 score evaluated by a pathologist based on the AUC values of measured variables. A combination of parameters, such as portal tract volume and area of K7-positive hepatocytes analyzed by the model, produced an AUC of 0.81 for predicting the compound endpoint. Portal tract volume measured by the model correlated with the histological fibrosis stage.
CONCLUSIONS : The K7-staining of histological liver specimens in PSC provides significant information on disease outcomes through objective and reproducible data, including variables that cannot be measured by a human pathologist. The K7-AI model 2.0 could serve as a prognostic tool for clinical endpoints and as a surrogate marker in drug trials. This article is protected by copyright. All rights reserved.
Nelli Sjöblom, Sonja Boyd, Anniina Manninen, Sami Blom, Anna Knuuttila, Martti Färkkilä, Johanna Arola
2022-Dec-09
artificial intelligence, ductular reaction, liver histology, primary sclerosing cholangitis, surrogate marker
