CONNECTIVE TISSUE GROWTH FACTOR (CTGF) AS A PROMOTER IN THE DEVELOPMENT OF FIBROSIS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS

Introduction and Objectives

Primary biliary cholangitis (PBC), an immune-mediated disease, is characterized by destroying the intrahepatic bile ducts, leading to progressive damage to the biliary tree, cholestasis, and development of progressive fibrosis leading to cirrhosis with all its complications. The development of fibrosis is multifactorial and includes connective tissue growth factor (CTGF). in a mouse model of cholestasis by bile duct ligation, the hepatic and serum increase in CTGF associated with the progression of fibrosis was demonstrated. Our goal was to determine the relationship between CTGF levels and their association with the development of fibrosis in patients with PBC.

Material and methods

Prospective, cross-sectional, and analytical study, including patients with PBC. The degree of fibrosis was determined by transient elastography (Fibroscan). Serum concentrations of FCTC-8pg/ml were quantified, for statistical analysis, the SPSS version 25.0 software was used; the medians (Q3, Q1) of CTGF, alkaline phosphatase, gamma-glutamyl-transpeptidase, and degree of fibrosis were compared with the Mann-Whitney U test with significantly less than 0.05.

Results

We included 30 patients, 29 women (96.6%) and 1 man (3.4%), with a mean age of 55.5±12.4 years. Overexpression of CTGF protein was shown in 28 subjects (93.3%). Regarding the degree of fibrosis, all patients were categorized into one of two stages: Significant fibrosis (F2) and cirrhosis (F4). The F2 group had 11 patients with a median and standard deviation for CTGF of 915.9 and 522.9, respectively; The F4 group had 19 patients who showed a median: 945.7 (1313.85-738.32); p:0.025. In relation to the differences between fibrosis levels and markers of alkaline phosphatase cholestasis, the median and interquartile ranges F2: 79 (180.60) F4: 169(266-5.84) p: 0.066; GGT: F2: 1.51(7.7-1,04); F4: 1.2(2-1.92) p:0.746 In (Figure 1) The difference in medians of patients with different degrees of fibrosis and different concentration of CTGF is shown, confirming the association between peptide and the development and progression of fibrosis.

Discussion

According to the results obtained in patients with CBP and chronic cholestasis, the increase in CTGF showed significant differences between the degree of fibrosis and its levels; this could perhaps be interpreted as if it were an important factor for the development and progression of liver fibrosis, taking into account the antecedent of the initial study in mice with bile duct ligation and secondary cholestasis, where this factor was overexpressed at the hepatic and serum level in subjects with advanced fibrosis. It will be important to add more samples to this work and compare it with healthy controls to have better evidence.

Conclusions

Connective tissue growth factor (CTGF) probably participates directly in the processes of synthesis of extracellular matrix and therefore in the progression of fibrosis in subjects with primary biliary cholangitis, which makes it a possibility of a therapeutic target to develop in future studies.

The authors declare that there is no conflict of interest.

(Figure 1) The difference in medians of patients with different degrees of fibrosis and different concentration of CTGF is shown, confirming the association between peptide and the development and progression of fibrosis.