The cytokines of fibrogenesis in patients with chronic hepatitis C and nonalcoholic fatty liver disease

Abstract

Introduction. The progression of fibrosis has been linked to various factors, including nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), increased body weight, infection with hepatitis B and C viruses and HIV infection. The cytokines are involved in the process of regulation in the development of inflammatory reactions of liver tissue, apoptosis and necrosis of liver cells, development of cholestasis and fibrosis. The aim of the study. To establish the relationship between the levels of a fibrogenic and angiogenetic cytokines, including angiogpoietin-2 (Ang-2), transforming growth factor β1 (TGF-β1), leptin and adiponectin with the degree of fibrosis and stage of fatty liver infiltration in patients with chronic hepatitis C (HCV), with increased body weight and concomitant nonalcoholic fatty liver disease (NAFLD). Materials and methods. 82 patients with CHC where examined, of which 56 (68.3%) were diagnosed with NAFLD and increased body weight. All participants were examined for HCV RNA, body mass index (BMI), angiogpoietin-2 (Ang-2), transforming growth factor-β1 (TGF- β1), leptin and adiponectin. The degree of liver fibrosis was determined by the noninvasive FibroMax method. Patients were divided into groups: 1 group (n=23) CHC + increased body weight + liver steatosis, 2 group (n=33) – CHC + increased body weight + nonalcoholic steatohepatitis (NASH), 3rd group (n=26) – HCV+ normal body weight. Results. Out of 82 patients, progressive liver fibrosis (F3-4) had 31 patients (37.8%), moderate fibrosis (F1-2) – 25 patients (30.5%), minimal fibrosis (F0-1) – 11patients (13.4%), and 15 patients (18.3%) had no fibrosis (F0). Progressive liver fibrosis F3-4 is more common in patients with CHC combined with NASH. It was also found that patients with CHC+NASH significantly more often than patients of the groups 1 and 3 had liver steatosis S 2-3 (45.5% compared with 30.4% and 3.9% of patients; p<0.05). Serum levels of Ang-2 were significantly higher (p<0.05) in patients with CHC + NASH with a BMI of 24.9 kg/m2 and progressive degrees of fibrosis (F3-4), than in patients with a degree of fibrosis up to F2 and normal body weight. The concentration of leptin in patients with HCV +NAFLD was increased by 4.2 times, and in patients with CHC with simple steatosis – by 2.9 times, compared to the control group. At the same time, serum adiponectin level in patients of groups 2 and 1 was reduced by 2.5 times and 1.4 times compared with patients of group 3. A positive correlation of leptin and Ang-2 values (r=0.49; p<0.05) with the degree of fatty infiltration of the liver was revealed, while a similar relationship of the ratio adiponectin/leptin ratio was negative (r=-0.34; p<0.05). As blood leptin levels increased and the adiponectin/leptin ratio decreased, the degree of liver steatosis increased, corresponding to higher levels of Ang-2. Conclusions. Dysregulatory changes in angiopoietin-2 and transforming growth factor-β1 are registered in patients with CHC+NAFLD and increased body weight, which correlate positively with the stage of fatty infiltration and the degree of liver fibrosis, that could be an important as biomarkers of angiogenesis and fibrogenesis.