Tumor Necrosis Factor-α as a Predictor for the Development of Nonalcoholic Fatty Liver Disease: A 4-Year Follow-Up Study

Background: Tumor necrosis factor (TNF)-alpha is associated with insulin resistance and systemic inflammatory responses. The aim of this study was to investigate the relationship between TNF-alpha and the development of nonalcoholic fatty liver disease (NAFLD) in a longitudinal study. Methods: Three hundred and sixty-three apparently healthy subjects (mean age, 40.5 +/- 6.1 years; male, 57.6%) without NAFLD were enrolled in 2003. Anthropometric and laboratory measurements were performed. The participants were grouped into tertiles according to their serum TNF-alpha levels from samples taken in 2003. At a 4-year follow-up, we compared the odds ratios (ORs) of the development of NAFLD according to the tertiles of TNF-alpha levels measured in 2003. Results: At the 4-year follow-up, the cumulative incidence of NAFLD was 29.2% (106/363). The group that developed NAFLD had higher levels of TNF-alpha than those in the group without NAFLD (3.65 +/- 1.79 pg/mL vs. 3.15 +/- 1.78 pg/mL; P=0.016). When the 2003 serum TNF-alpha levels were categorized into tertiles: incidence of NAFLD observed in 2007 was significantly higher with increasing tertiles (22.6%, 35.8%, and 41.5%, respectively; P<0.05). The risk of developing NAFLD was significantly greater in the highest tertile of TNF-alpha than in the lowest tertile after adjusting for age, smoking, and BMI (OR, 2.20; 95% confidence interval, 1.12 to 4.01; P<0.05). Conclusion: Higher serum TNF-alpha levels in subjects without NAFLD were associated with the development of NAFLD. The results of study might suggest a pathologic role of inflammation in NAFLD.