The decrease of serum levels of human neutrophil alpha-defensins parallels with the surgery-induced amelioration of NASH in obesity

Background: Innate immune system participates actively into inflammatory processes, with immune cells and liver secreting a number of immune peptides. Among them, both soluble CD14 receptor (sCD14) and human neutrophil alpha-defensins (HNDs) may represent serum markers of necro-inflammation in obese patients with non-alcoholic fatty liver disease. Methods: To verify this hypothesis, we investigated changes in circulating levels of sCD14 and HNDs in 11 severely obese young women following surgery-induced weight loss (bilio-pancreatic diversion). Patients were evaluated before surgery and 2 years later, with NAS score evaluated on liver biopsies and whole body glucose uptake (M value) by euglycemic hyperinsulinemic clamp. Results: NAS score improved in nine patients [median NAS score in the whole sample, 6 (5-6) vs. 3 (3-4), p∈=∈0.016]. Serum concentrations of HNDs decreased significantly in all (p∈=∈0.016), whilst sCD14 increased only in the nine women who showed the amelioration of the NAS score [2.4 (1.7-2.6) vs. 2.6 (2.3-3.3) μg/ml, p∈=∈0.001]. NAS score and HNDs correlated significantly both before (r ∈=∈0.671, p∈=∈0.02) and after weight loss (r ∈=∈0.683, p∈=∈0.029), NAS score and sCD14 only before surgery (r ∈=∈0.605, p∈=∈0.04). The M value increased in all patients [2.67 (1.99-3.01) vs. 6.89 (6.35-7.32) mg kg min; p∈=∈0.01], but independently of NAS score changes. Conclusions: Changes in levels of HNDs and sCD14 accompany those in hepatic necro-inflammation due to surgical-induced weight loss. Further studies are needed to verify any causative role of these peptides in non-alcoholic steatohepatitis. © 2010 Springer Science + Business Media, LLC.