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
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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