Growth Differentiation Factor 15: An Emerging Diagnostic Biomarker of Liver Fibrosis in Chronic Hepatitis C Patients

Abstract

Background Chronic liver disease and cirrhosis are a major health concern worldwide being the sixth leading cause of all-cause mortality in people aged 25–64 years. Assessment of liver fibrosis is necessary to determine disease severity and prognosis at the time of presentation to determine suitable treatment. The gold standard method of diagnosis is liver biopsy; however, this procedure is invasive; thus, multiple laboratory and radiologic tests are used to help determine the degree of fibrosis. Growth differentiation factor 15 (GDF-15) is a pleiotropic cytokine involved in regulating inflammatory and apoptotic pathways. It plays a role in cardiovascular disease, inflammation, body weight regulation and cancer. It is suggested that GDF-15 plays an important role in pathogenesis of liver fibrosis. Aim of the Work In this study we aimed to evaluate efficiency of growth differentiation factor 15 in diagnosing liver fibrosis. Patients and Methods The study was a case- control study conducted on 55 chronic HCV patients recruited from Hepatitis C virus Clinic at Faculty of Medicine Ain Shams Research Institute (MARSI), and 30 healthy subjects age and sex matched. The patients were classified into three subgroups according to the degree of liver fibrosis assessed by fibro-scan. Serum concentration of GDF-15 was determined by enzyme-linked immunosorbent assay (ELISA). Results Results of our study revealed a highly significant statistical rise in GDF-15 levels among studied chronic HCV patients with liver fibrosis when compared to the control group (p < 0.01). Furthermore, there was a significant positive correlation between the degree of fibrosis assessed by fibro-scan and GDF-15 serum levels. Levels of GDF-15 were significantly higher in patients with mild degree of fibrosis (patients’ subgroup І when compared with the controls’ group (p < 0.01) suggesting the role of this marker in early detection of liver fibrosis. A statistically significant increase in serum GDF-15 levels was noticed among patients with advanced fibrosis “subgroup ІІІ” compared to those with mild fibrosis “subgroup І” (p < 0.05). The diagnostic sensitivity and specificity of GDF-15 were 96.7%, 98.2%, respectively at a cutoff value of 150 ng/L for discrimination between patients’ and controls’ groups. Conclusion Growth differentiation factor 15 could be a potential marker of liver fibrosis especially in early detection as its levels were significantly higher in patients’ group with liver fibrosis than controls’ group and there was a significant positive correlation between the degree of liver fibrosis and GDF-15 serum levels.