Serological Markers of Intestinal Barrier Function and Inflammation as Potential Predictors of Recurrent Primary...

The impairment of intestinal barrier function is implicated in primary sclerosing cholangitis, but the clinical evidence is scarce. Therefore, we performed a cross-sectional study to evaluate serological markers of inflammation and intestinal permeability (Reg3a, iFABP, Zonulin, Calprotectin) in patients after liver transplantation (LT) for PSC. The cohort included 26 subjects with PSC recurrence (rPSC), 87 subjects without PSC recurrence (non-rPSC), and a unique control group consisting of post-LT patients (n = 113) transplanted due to alcohol cirrhosis. Generalized Linear Models were calculated to assess the association between serological markers of intestinal barrier function or inflammation (IP_Models) and PSC diagnosis per se (IP_Model_1), non-rPSC (IP_Model_2) or rPSC incidence (IP_Model_3) and compared with models (ST_Models) based on validated PSC markers (ALP, GGT, bilirubin). The increased probability of PSC occurrence (IP_Model_1, p < 0.001, AIC = 182) was associated with higher serum Reg3a concentration, while a negative association was found for iFABP, BMI, and age. The probability of non-recurrence (IP_Model_2, p < 0.001, AIC = 167) was associated with lower Reg3a concentration, older age, and BMI. The performance of IP_Models_1,2 and ST_models_1,2 was comparable. rPSC prediction was less precise by both models (IP_Model_3 p = 0.063, AIC = 92; ST_Model_3 p < 0.001, AIC = 108). rPSC incidence was positively associated with fecal calprotectin and serum zonulin concentrations, while it was independent of Reg3a, iFABP, age or BMI. In conclusion, this pilot study suggests that impaired intestinal permeability is associated with the pathophysiology of rPSC. Our data could serve as a basis for testing in a larger independent validation cohort and, if confirmed, help to explain the mechanisms underlying the pathophysiology of PSC and the recurrence of this disease after transplantation.