Association between Circulating Growth Differentiation Factor 15 and Cirrhotic Primary Biliary Cholangitis.

Zhanyi Li,Qiwan Mo,Xiangyong Li,Yutian Chong,Fangji Yang,Yuankai Wu,Yu Liu,Fernando G Romeiro

doi:10.1155/2020/5162541

Abstract

Primary biliary cholangitis (PBC) is a common condition that usually shows a progressive course towards cirrhosis without adequate treatment. Growth differentiation factor 15 (GDF15) plays multiple roles in various pathological conditions. The overall role of circulating GDF15 in cirrhotic PBC requires further investigation. Twenty patients with cirrhotic PBC, 26 with non-cirrhotic PBC, and 10 healthy subjects were enrolled between 2014 and 2018, and the serum levels of GDF15 were measured via enzyme immunoassay. The correlations between serum GDF15, weight, biochemical parameters, and the prognosis were analysed. Serum levels of GDF15 were significantly higher in cirrhotic PBC patients than in non-cirrhotic PBC patients or healthy controls (p = 0.009 and p < 0.001, respectively). The circulating GDF15 levels strongly correlated with weight changes (r = −0.541, p = 0.0138), albumin (r = −0.775, p < 0.0001), direct bilirubin (r = −0.786, p < 0.0001), total bile acids (r = 0.585, p = 0.007), and C-reactive protein (r = 0.718, p = 0.0005). Moreover, circulating GDF15 levels strongly correlated with the Mayo risk score (r = 0.685, p = 0.0009) and Model for End-stage Liver Disease score (r = 0.687, p = 0.0008). Determined by the area under the receiver operating characteristic curves, the overall diagnostic accuracies of GDF15 were as follows: cirrhosis = 0.725 (>3646.55 pg/mL, sensitivity: 70.0%, specificity: 69.2%), decompensated cirrhosis = 0.956 (>4073.30 pg/mL, sensitivity: 84.62%, specificity: 100%), and cirrhotic biochemical non-responders = 0.835 (>3479.20 pg/mL, sensitivity: 71.43%, specificity: 92.31%). GDF15 may be a useful and integrated biochemical marker to evaluate not only the disease severity and prognosis but also the nutrition and response to treatment of cirrhotic PBC patients, and its overall performance is satisfactory. Therapy targeting GDF15 is likely to benefit cirrhotic PBC patients and is worth further research.

Highlights

Primary biliary cholangitis (PBC) is an immune-mediated inflammatory cholestatic liver disease characterized by nonsuppurative destructive cholangitis and interlobular bile duct destruction
Our findings are in accord with those of previous studies which suggested that serum Growth differentiation factor 15 (GDF15) levels were elevated in patients with chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B or C virus infection [28, 29] and supplement those of previous studies
These findings provide evidence that GDF15 can predict liver fibrosis, severity response to ursodeoxycholic acid (UDCA) treatment, and malnutrition in chronic liver disease

Summary

Introduction

Primary biliary cholangitis (PBC) is an immune-mediated inflammatory cholestatic liver disease characterized by nonsuppurative destructive cholangitis and interlobular bile duct destruction. It is a chronic progressive condition leading to end-stage liver disease including liver cirrhosis (LC) and hepatocellular carcinoma and their associated complications that commonly require liver transplantation [1,2,3]. It has been reported that without effective therapy, the median time of progression to extensive liver fibrosis is 2 years with about one-third of the patients remaining in early-stage disease over a follow-up period of 4 years [4,5,6]. The VCTE is recommended as the initial assessment for significant liver fibrosis and cirrhosis, and it is a quick, portable

Objectives

Methods

Results

Discussion

Conclusion