Association between Complement C3 and Prevalence of Fatty Liver Disease in an Adult Population: A Cross-Sectional Study from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study

Yang Xia,Yuntang Wu,Li Liu,Ming Zhou,Honglin Zhao,Chun-Jen Liu,Shaomei Sun,Kaijun Niu,Hongbin Shi,Qiyu Jia,Xing Liu,Kun Song,Chunlei Li,Xing Wang,Qing Zhang,Hongmei Wu,Chongjin Wang,Huanmin Du,Xiaoyan Guo

doi:10.1371/journal.pone.0122026

Abstract

Activation of the innate immune system plays a key role in the development of fatty liver disease (FLD). The complement system is a major humoral component of the innate immune response and complement C3 plays a central role, implying that C3 may be a powerful predictor or therapeutic target for FLD. However, few studies have assessed the association between C3 and FLD in a large population. Here we use a cross-sectional study to investigate the link between serum C3 levels and FLD. Participants were recruited from Tianjin Medical University’s General Hospital-Health Management Centre. Serum C3 was measured using immunoturbidimetry method and FLD was diagnosed by liver ultrasonography. Multiple logistic regression analysis was used to examine the association between quartiles of C3 and FLD prevalence. The overall prevalence of nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) were 37.3% and 10.1%, respectively. After adjusting for covariates, the odds ratio of having NAFLD or AFLD (only in males) in the fourth quartile of C3 compared with the first quartile was 4.13 times greater (95% confidence interval, 2.97-5.77) (trend P values < 0.0001) and 2.09 times greater (95% confidence interval, 1.08-4.18) (trend P values = 0.02). This is the first study to demonstrate that serum C3 levels are independently associated with a higher prevalence of NAFLD and AFLD (only in males) in an adult population. Further studies are needed to establish a causal link and determine the precise role of C3 in FLD.

Highlights

Fatty liver diseases (FLD) is the most common liver dysfunction worldwide and can be categorized as nonalcoholic FLD (NAFLD) or alcoholic FLD (AFLD) according to etiology [1, 2]
The results of one such study using liver biopsy strongly indicate that complement is altered in liver damage [12]. Another case-control study mentioned that C3 serum levels were higher in NAFLD patients [13] and one crosssectional study concluded that C3a levels paralleled the degree of liver injury [14]
These results suggest that complement C3 may be a useful predictor or therapeutic target for the treatment or prevention of FLD

Summary

Introduction

Fatty liver diseases (FLD) is the most common liver dysfunction worldwide and can be categorized as nonalcoholic FLD (NAFLD) or alcoholic FLD (AFLD) according to etiology [1, 2]. The results of one such study using liver biopsy strongly indicate that complement is altered in liver damage [12]. Another case-control study mentioned that C3 serum levels were higher in NAFLD patients [13] and one crosssectional study concluded that C3a levels paralleled the degree of liver injury [14]. One study found that FLD and concomitant liver dysfunction (represented by alanine aminotransferase (ALT) levels), led to enhanced production of complement C3 [15]. Together, these results suggest that complement C3 may be a useful predictor or therapeutic target for the treatment or prevention of FLD. Few studies have shown a direct correction between C3 levels and FLD in an adult population

Methods

Results

Conclusion