Inflammation But Not Biliary Obstruction Is Associated With Carbohydrate Antigen 19-9 Levels in Patients With Primary Sclerosing Cholangitis

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Abstract

BACKGROUND & AIMS:

Assays that measure the serum level of carbohydrate antigen 19-9 (CA19-9) are used to screen patients with primary sclerosing cholangitis (PSC) for malignancies. However, in patients with PSC, cholestasis, and bacterial cholangitis, the CA19-9 level can be affected by variants in the fucosyltransferases 2 and 3 genes (FUT2andFUT3), which regulate the production of CA19-9. We investigated how these genotypes affect cancer screening in these patients.

METHODS:

We performed a retrospective analysis of data from 209 patients with PSC (19 patients with biliary malignancy, 23 patients with cholestasis and bacterial cholangitis) treated at the University Hospital Heidelberg from 1987 through 2014. We collected data on the maximum serum level of CA19-9; laboratory measures of cholestasis or inflammation; the presence of dominant stenosis, cholestasis, and bacterial cholangitis; andFUT2andFUT3genotypes. Patients were assigned to intermediate (n = 161) or high (n = 48) CA19-9 biosynthesis groups, based onFUT2andFUT3genotypes. Patients incapable of CA19-9 biosynthesis, based on genetic features, were excluded.

RESULTS:

The median level of CA19-9 was 31.1 U/mL in cancer-free patients. The CA19-9 level correlated with the level of C-reactive protein (P< .001); high CA19-9 biosynthesis correlated with high leukocyte counts (P= .037), but not intermediate CA19-9 biosynthesis. There was no correlation between the level of CA19-9 and laboratory markers of cholestasis. The level of CA19-9 was the lowest in patients without biliary obstruction, cholestasis, or bacterial cholangitis (7.8 U/mL), followed by patients with only obstruction (28.0 U/mL), and then patients with cholestasis and bacterial cholangitis (77.0 U/mL and 205.4 U/mL in patients without or with concomitant obstruction, respectively). The greatest increase in CA19-9 as a result of cholestasis and bacterial cholangitis was observed in patients in the high CA19-9 biosynthesis group.

CONCLUSIONS:

In patients with PSC, cholestasis has little effect on the level of CA19-9, but cholestasis and bacterial cholangitis increase the level. Their effects on CA19-9 level depend on theFUT2andFUT3genotype. These findings support the analysis ofFUT2andFUT3genotype during follow-up evaluation of patients with PSC.

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