Polymorphonuclear neutrophils are a source of hepatocyte growth factor in patients with severe alcoholic hepatitis

Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in liver regeneration. Plasma HGF levels correlate with survival and hepatocyte proliferation in alcoholic hepatitis (AH). As AH is accompanied by inflammation, neutrophilia and polymorphonuclear neutrophil (PMN) infiltration of the liver, we postulated that PMN could be a source of HGF in such patients.

We studied 25 patients with severe AH in comparison with 20 alcoholic cirrhotic patients without AH and 20 healthy controls; the impact of a 28-day course of corticosteroids was evaluated in patients with AH.

On day 0, HGF plasma and homogenized liver tissue levels were markedly increased in AH patients as compared to controls. The role of PMN in HGF production during AH was confirmed by a significantly higher ex-vivo HGF production capacity of lipopolysaccharide-stimulated blood PMN from AH patients relative to both control groups. Formyl-Methionyl-Leucyl-Phenylalanine-induced PMN release of HGF (degranulation conditions) was also higher in AH patients. In this setting, we found that HGF release by PMN ex vivo correlated strongly with HGF plasma levels, and that the degree of hepatic PMN correlated strongly with hepatic HGF levels. HGF plasma levels and ex-vivo HGF release by PMN were unaffected by steroid therapy.

These findings suggest that, by releasing HGF, PMN could participate in liver regeneration during severe alcoholic hepatitis.