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Open Access Research article

Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study

Bernd Kronenberger1*, Ina Rudloff2, Malte Bachmann2, Friederike Brunner1, Lisa Kapper1, Natalie Filmann3, Oliver Waidmann1, Eva Herrmann3, Josef Pfeilschifter2, Stefan Zeuzem1, Albrecht Piiper1 and Heiko Mühl2

Author Affiliations

1 Medizinische Klinik 1, Klinikum der J.W. Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany

2 Pharmazentrum Frankfurt, Klinikum der J.W. Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany

3 Institut für Biostatistik und mathematische Modellierung, Klinikum der J.W. Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany

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BMC Medicine 2012, 10:102  doi:10.1186/1741-7015-10-102

Published: 11 September 2012

Abstract

Background

Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far.

Methods

This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications.

Results

A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 ± 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P < 0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P < 0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular (≤18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with reduced overall survival were high CRP (≥2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258, CI (0.077 to 0.862)), model of end stage liver disease (MELD) score ≥20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 0.955, CI (0.922 to 0.989)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)).

Conclusions

In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.

Keywords:
Interleukin-22; Liver cirrhosis; Liver-related complications; Hepatitis; Alcoholic liver disease; MELD