Interferon lambda 4 genotype and pathway in alcoholic hepatitis

Single nucleotide polymorphisms within the interferon lambda 4 (IFNL4) gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is also the case during acute liver disease, alcoholic hepatitis. We, therefore, related variants within the IFNL4 gene to the clinical course of acute alcoholic hepatitis, and characterized the activation state of the IFN lambda system in these patients.

In this pilot study, 58 patients with alcoholic hepatitis were genotyped for the rs368234815IFNL4 single nucleotide polymorphism (deltaG, deltaG/TT: IFN lambda 4 positive, TT/TT: IFN lambda 4 negative). The genotypes were related to mortality, infection and inflammation and expression of the IFNL receptor 1 and IFN inducible genes were measured in liver and peripheral leukocytes.

Amongst the alcoholic hepatitis patients who died, the IFN negative patients live longer after diagnosis, and also the IFN negative patients tended to have an overall short-term survival benefit compared to IFN lambda positive patients (p = .058). The IFN lambda 4 negative patients at diagnosis had fewer circulating monocytes and lower plasma soluble CD163. The patients with alcoholic hepatitis had reduced expression of the IFNL receptor 1in both liver and blood compared with healthy controls. In blood, the expression of IFN stimulated genes was lower than in healthy controls and most so in the patients, who died.

The IFN lambda 4 pathway seems involved in the acute disease processes of alcoholic hepatitis and patients without IFN lambda expression seem to have a short-term survival benefit.