Collagens of the third and fourth types in various forms of alcoholic liver disease

Abstract

The aim of the study was to determine the clinical and diagnostic significance of collagens of the third type (Col3) and the fourth type (Col4) in various forms of alcoholic liver disease (ALD). Materials and methods. 98 patients with ALD were examined: 13 (13.3%) with liver steatosis (LS), 15 (15.3%) with steatohepatitis (SH), 56 (57.1%) with liver cirrhosis (LC), 14 (14.3%) with severe alcoholic hepatitis against the background of liver cirrhosis (SAH-LC). Among the examined there were 59 (60.2%) men and 39 (39.80%) women, the average age was 53.48±11.45 years. The content of fibrogenesis proteins in the blood serum - type III collagen (Col3) and type IV collagen (Col4) was determined by enzyme immunoassay (test systems “Kit For Collagen Type III (Col3)” and “Kit For Collagen Type IV (Col4)”, “Cloud-Clone Corp”, USA), a marker of hepatocyte apoptosis - fragments of cytokeratin-18 (FCK-18) (“Biotech” test system, Sweden), cytokines - IL-1β, IL-4, IL-6, IL- 8, TNF-α (“Vector-Best”, Russia). Results. The level of Col3 in healthy individuals was 6.12±0.73 ng/ml and Col4-9.45±0.32 ng/ml. In all forms of ALD, the content of both types of collagen exceeded that in healthy individuals: Col3 in LS was 6.52±0.94 ng/ml (p<0.05), in SH it was 12.50±3.18 ng/ml (p<0.05), in LC - 20.96±4.93 ng/ml (p<0.05), in SAH-LC - 26.90±3.87 ng/ml (p<0.05); Col4-10.14±0.66 ng/ml, 13.87±1.15 ng/ml, 79.56±33.10 ng/ml and 107.12±39.09 ng/ml, respectively. Col3 positively correlated with ALT (r=0.27, p=0.02) and alkaline phosphatase (r=0.28, p=0.04). Col4 correlated with bilirubin (r=0.74), AST (r=0.65), glutamyl transpeptidase (r=0.58), cytokeratin-18 (r=0.56), sedimentation rate of erythrocytes (r=0.61), C-reactive protein (r=0.59), IL -6 (r= 0.51) and leukocytes (r=0.45) (all p<0.001). Conclusion. Col4 demonstrated greater diagnostic and clinical significance in alcoholic liver disease compared to Col3. The level of Col4 increased by an average of 8 times with the progression of the disease from liver steatosis to cirrhosis, and Col3 - only by 3 times. There were more diverse and stronger associations between Col4 and markers of hepatocellular damage and inflammation than between Col3 and these indicators. The maximum rise in the levels of both types of collagen found in SAH-LC confirmed the important role of this form of liver disease in the development of fibrosis, and hence in the further decompensation of liver cirrhosis.