Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Hannu Koistinen,Sonja Boyd,Riitta Koistinen,Johanna Arola,Kristina Hotakainen,Martti Färkkilä,Anna Lempiäinen,Kalle Jokelainen,Ulf-Håkan Stenman

doi:10.3390/livers1040025

Hannu Koistinen, Sonja Boyd + Show 7 more

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https://doi.org/10.3390/livers1040025

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Journal: Livers	Publication Date: Dec 15, 2021
Citations: 1	License type: CC BY 4.0

Affiliation: Helsinki University Hospital, University of Helsinki

Abstract

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease, which is associated with an increased risk of cholangiocarcinoma (CCA). Novel markers, to complement or replace CA19-9, are urgently needed for the screening of PSC-associated biliary neoplasia. Previous studies have suggested that serum trypsinogen-2 and human chorionic gonadotropin β-subunit (hCGβ) may serve as such markers. Using highly specific in-house immunoassays, we studied trypsin(ogen)-2 and -3, SPINK1 and hCGβ in bile samples of 214 patients, referred for endoscopic retrograde cholangiography. We found that biliary trypsinogen-2 was decreased (p = 0.027) and hCGβ was elevated (p < 0.001) in PSC patients who were diagnosed 1.6 years (median, range 0.1–8.8 years) later with CCA or in whom biliary dysplasia was observed at least twice in brush cytology (n = 11) as compared to PSC patients without CCA or repeated dysplasia (n = 171). The other studied markers did not show significant differences between these groups. Our results warrant further evaluation of hCGβ as a predictive marker for PSC-associated biliary neoplasia.

Highlights

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease leading to strictures of bile ducts causing cholestasis and biliary cirrhosis [1]
There is a great need for novel biomarkers in PSC to predict the development of biliary neoplasia
Trypsin(ogen)-2 and human chorionic gonadotropin β-subunit (hCGβ) have previously been found to be elevated in the serum of patients with CCA, irrespective of the concomitant PSC, and they distinguish

Summary

Introduction

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease leading to strictures of bile ducts causing cholestasis and biliary cirrhosis [1]. PSC is associated with a markedly increased risk of cholangiocarcinoma (CCA), the lifetime risk being up to 20%. CCA is preceded by biliary dysplasia, which is a highly significant predictor of later development of CCA [3]. CCA is the most common reason for death among patients with PSC [4]. Treatment options for CCA are limited, especially when diagnosed at later stages [2]. An early diagnosis of both PSC and CCA is important but challenging, as 27–50% of CCA cases are diagnosed simultaneously at the time of PSC or within the first year after diagnosis of PSC [4,5]. Serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) are routinely used for the screening of CCA, but neither of them is a sensitive or specific marker for biliary neoplasia [1]

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