A case-control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is a great health burden. Neuregulin 4 (Nrg4) is a recently identified secret factor that may be associated with NAFLD.

Aim: To investigate the association between serum Nrg4 level and NAFLD by conducting a case-control study.

Method: A total of 174 subjects were included. 87 NAFLD subjects and 87 age- and sex-matched non-NAFLD controls were identified by hepatic ultrasound examination. Anthropometric and biochemical data were measured and recorded. Serum Nrg4 level was evaluated by using enzyme-linked immunosorbent assay. SPSS software was used for statistical analyses.

Results: Compared to the controls, subjects with NAFLD presented with reduced level of serum Nrg4 (0.40 (0.27, 0.55) vs. 0.50 (0.30, 0.81)ng/mL (median (interquartile range)), P=0.029). By multivariate logistic regression analysis, reduced serum levels of Nrg4 were associated with higher NAFLD odds (OR=0.251, 95% confidence interval=0.081-0.779, P=0.017). By dividing the distribution of serum Nrg4 level into quartiles, there was borderline statistical difference of NAFLD prevalence among the four groups (P=0.058). There was no significant difference of serum Nrg4 levels in subjects according to the grades of fatty liver by ultrasound (P=0.080). No statistical difference of serum Nrg4 level was observed between obese and non-obese subjects (P=0.932).

Conclusion: Decreased serum Nrg4 level is prevalent in NAFLD subjects compared to non-NAFLD controls, and is an independent risk factor associated with NAFLD, indicating that Nrg4 might have a protective role in the development of NAFLD.