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(o) = 0.671, p = 0.02) and after weight loss (r(o) = 0.683, p = 0.029), NAS score and sCD14 only before surgery (r(o) = 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 (FFM)(-1)min(-1); 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.