Complement 5a is an indicator of significant fibrosis and earlier cirrhosis in patients chronically infected with hepatitis B virus

Abstract

Purpose: To investigate the association between serum complement 5a (C5a) concentration and liver fibrosis and cirrhosis in a large cohort of patients chronically infected with hepatitis B virus (HBV).

Methods: Five hundred and eight patients with chronic HBV infection undergoing liver biopsy were included. Serum concentrations of C5a was measured by Luminex screening system. Ishak histological system was obtained.

Results: C5a levels were negatively associated with liver fibrosis stages and significantly declined in patients with severe fibrosis and cirrhosis (P < 0.001). Multiple analysis showed C5a, AST, laminin, Co-IV, platelet count, albumin, HBsAg associated with liver fibrosis independently. Based on the markers above, we created two scores, Fib-model for significant fibrosis and Cirrh-model for earlier cirrhosis. Fib-model was performing better to differentiate from significant fibrosis, with an AUROC of 0.82 (95 % CI 0.78, 0.86), in comparison to existed models APRI, FIB-4 and Forns' index with AUROCs of 0.71 (95 % CI 0.66, 0.76), 0.72 (95 % CI 0.67, 0.77), 0.77 (95 % CI 0.72, 0.81), respectively. Although, Cirrh-model showed AUROC of 0.85 (95 % CI 0.80, 0.91) for evaluation of earlier cirrhosis, superior to APRI, and Forns' index, C5a + FIB-4 performed best with an AUROC of 0.94 (95 % CI 0.90, 0.97).

Conclusion: In patients with chronic HBV infection, serum C5a concentration significantly decreased in severe fibrosis stages and earlier cirrhosis. Fib-model and C5a + FIB-4 performed better than existed models for assessment of significant fibrosis and earlier cirrhosis, respectively.

Keywords: Cirrhosis; Complement 5a; Hepatitis B; Liver fibrosis.

Fig. 1

Association between complement 5a concentration and liver fibrosis. Dotplots for complement 5a according to fibrosis stage showing mean values and interquartile ranges (IQRs). a Complement 5a in total patients; b complement 5a in patients with ALT ≤ 2 × ULN. P < 0.001 for all fibrosis stags. ***p < 0.001, **p < 0.01, *p < 0.05

Fig. 2

Receiver operating characteristics (ROC) analysis showing the predictive value of non-invasive models for significant fibrosis and cirrhosis. a Area under the ROC curves (AUC) for Fibmodel, ARPI, FIB-4, and Forns’ index in the diagnosis of significant fibrosis (F ≥ 3): AUC Fibmodel = 0.82 (0.78, 0.86), APRI = 0.71 (0.66, 0.76), FIB-4 = 0.72 (0.67, 0.77), Forns’ index = 0.77 (0.72, 0.81). (Marker 1: cut off at 0.67). b Area under the ROC curves (AUC) for Fib-model, ARPI, FIB-4, Forns’ index and C5a + FIB-4 in the diagnosis of cirrhosis (F ≥ 5): AUC Fib-model = 0.79 (0.72, 0.85), APRI = 0.74 (0.67, 0.82), FIB-4 = 0.85 (0.77, 0.94), Forns’ index = 0.78 (0.71, 0.86), C5a + FIB-4 = 0.94 (0.90, 0.97).(Marker 2: cut off at −2.625)