Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study - PubMed (original) (raw)
doi: 10.1186/1741-7015-10-102.
Ina Rudloff, Malte Bachmann, Friederike Brunner, Lisa Kapper, Natalie Filmann, Oliver Waidmann, Eva Herrmann, Josef Pfeilschifter, Stefan Zeuzem, Albrecht Piiper, Heiko Mühl
Affiliations
- PMID: 22967278
- PMCID: PMC3519550
- DOI: 10.1186/1741-7015-10-102
Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study
Bernd Kronenberger et al. BMC Med. 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.
Figures
Figure 1
Study protocol.
Figure 2
IL-22 serum concentrations are elevated in patients with liver cirrhosis (n = 120) compared with healthy individuals (n = 40). Dots indicate IL-22 serum levels in individual patients. The straight horizontal line indicates the mean. The dotted horizontal line indicates the upper limit of normal for IL-22 of 18 pg/ml. Error bars indicate the standard deviation. Comparison between the two groups was performed using the Mann Whitney U-test.
Figure 3
Changes of IL-22 in the course of liver disease. Dots indicate serum IL-22 levels in individual patients at baseline (BL) and follow-up (FU), respectively. Corresponding IL-22 serum levels in individual patients at BL and FU are connected. IL-22 serum levels were analyzed in follow-up (FU) sera that were a minimum of 30 days apart from baseline (BL). The dotted horizontal line indicates the upper limit of normal for IL-22 of 18 pg/ml. Comparison between BL and FU was performed with the Wilcoxon matched pairs test.
Figure 4
Immunohistochemical detection of IL-22 in the liver. IL-22 positive cells were non-hepatocytic cells. IL-22 positive cells were detected in cirrhotic livers with different etiologies. HCV, chronic hepatitis C (A); AC, alcoholic cirrhosis (B); arrows indicate typical IL-22 positive cells which were different from hepatocytes. The inset shows a magnification of IL-22 positive cells.
Figure 5
Survival of patients with normal and elevated IL-22 serum levels. Kaplan-Meier curve for survival of patients with normal (IL-22 ≤18 pg/ml, black line) and elevated IL-22 levels (IL-22 >18 pg/ml, grey line). Survival was significantly higher in patients with normal vs. elevated IL-22 serum levels according to the log rank test (P = 0.003). The number of patients at risk is shown in the table below the plot.
Figure 6
Liver-related complications in patients with liver cirrhosis according to IL-22 serum levels. Columns show the percentage of patients with elevated serum IL-22 above 18 pg/ml with (+) or without (-) liver related complications, ascites, hepatorenal syndrome (HRS), spontaneous bacterial peritonitis (SBP) at time of IL-22 quantification. Groups were compared by the Fisher test.
Figure 7
Correlation between MELD score and IL-22 serum levels in patients with liver cirrhosis. The correlation coefficient was calculated by the Spearman test.
References
- European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397–417. - PubMed
- Dumoutier L, Louahed J, Renauld JC. Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol. 2000;164:1814–1819. - PubMed
- Sonnenberg GF, Fouser LA, Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol. 2011;12:383–390. - PubMed
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