Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage: A prospective case control study

Abstract

Background: Biliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually. Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality, it is important to identify factors and mechanisms involved in its development.

Aim: To determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status.

Methods: This was a prospective case control study performed in a tertiary center in Zagreb, Croatia. Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled. After excluding patients who developed procedure related complications or were lost in the follow-up, out of initial 73 patients, 55 patients were included in the analysis, including 34 with benign and 21 with malignant disease. Meanwhile, 40 non-jaundiced controls were also included. Appetite, nutritional status, and serum ghrelin, cholecystokinin (CCK), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were determined at admission, 48 h and 28 d after internal biliary drainage. Chi square test was used for categorical variables. Continuous variables were analysed for normality by Kolmogorov-Smirnov test and relevant non-parametric (Mann-Whitney, Kruskal-Wallis, and Friedman) or parametric (t-test and analysis of variance) tests were used.

Results: Patients with obstructive jaundice were significantly malnourished compared to controls, regardless of disease etiology. Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice. Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α, but had no correlation with CCK concentrations. After internal biliary drainage, a significant improvement of nutritional status was observed although serum concentrations of ghrelin, IL-6, and TNF-α remained significantly elevated even 28 d after the procedure. CCK levels in patients without malnutrition remained elevated 28 d after the procedure, but in patients with malnutrition, CCK levels decreased to levels comparable with those in the control group. We have not established any correlation between appetite and serum levels of ghrelin, CCK, IL-6, and TNF-α before and after biliary drainage.

Conclusion: Possible abnormalities in ghrelin and CCK regulation may be associated with the development of malnutrition during the inflammatory response in patients with biliary obstruction.

Keywords: Biliary obstruction; Cholecystokinin; Ghrelin; Malnutrition.

Figure 1

Study enrollment flowchart.

Figure 2

Appetite regulating hormone dynamics in biliary obstruction. A: Ghrelin levels during and after resolution of biliary obstruction compared to those of the control group; B: Cholecystokinin levels during and after resolution of biliary obstruction compared to those of the control group. CCK: Cholecystokinin.

Figure 3

Differences in inflammatory marker changes depending on nutritional risk. A: Interleukin 6 levels during and after biliary obstruction depending on nutritional status; B: Tumor necrosis factor α levels during and after biliary obstruction depending on nutritional status. TNF-α: Tumor necrosis factor α; NRS: Nutritional risk screening.