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IL-22 levels predictive of survival in patients with advanced cirrhosis

Patients with elevated systemic levels of interleukin-22 had reduced survival time compared to those with normal levels in a recent study.

In a prospective cohort study, researchers evaluated the interleukin-22 (IL-22) levels of 120 patients with cirrhosis and 40 healthy controls. Incidences of death related to cirrhosis were observed over a mean follow-up of 196 ± 165 days, and potential associations between IL-22 levels and liver-related complications were assessed.

Upon inclusion, 71% of participants had complications related to cirrhosis. More cirrhotic patients had detectable levels of systemic IL-22 than healthy patients (74.1% with levels higher than 2.6 pg/ml compared with 10%, P<.0001), and 57 participants had elevated IL-22 levels (more than 18 pg/ml).

Among 29 participants with available follow-up IL-22 sera, mean levels increased over the course of the study from 33.3 ± 49.2 pg/ml to 61.3 ± 82.2 pg/ml (P=.0192). No difference was observed in IL-22 levels according to the cause of cirrhosis, but patients with alcoholic cirrhosis (P<.001) or cirrhosis related to chronic HBV (P=.009) or HCV (P<.001) all had higher serum IL-22 levels than controls.

Twenty-three percent of patients died over the course of the study, with all deaths attributed to cirrhosis and related complications. Participants with elevated systemic IL-22 levels survived for a shorter amount of time overall than those with normal IL-22 (mean survival=321.3 days compared with 526.4, P=.003).

Elevated IL-22 was found to be independently predictive of reduced survival via multivariate analysis (adjusted HR=0.218, 0.072-0.662). CRP of 2.9 mg/dl or higher (HR=0.314, P=.005), higher serum creatinine levels (HR=0.453, P=.05), complications related to the liver (HR=0.258, P=.028), a MELD score of 20 or higher (HR=0.364, P=.017) and advanced age (HR=0.955, P=.011) were significantly associated with reduced survival time via univariate but not multivariate analysis.

“We demonstrate herein that elevated systemic IL-22 levels are predictive for reduced survival in patients with liver cirrhosis independent of age, presence of liver-related complications, CRP, creatinine and the MELD score,” the researchers concluded. “… Overproduction of IL-22 in liver cirrhosis may serve protective functions as indicated by murine models of disease; however, IL-22 beyond a certain threshold may also be pathogenic.”