Assessment of Interleukin-6 Levels in Patients with Liver Cirrhosis and its Correlation with Disease Severity and Mortality.

Abstract

Context: Interleukin-6 (IL-6) is a pleiotropic cytokine that has an important function in the regulation of immunity, inflammation, hematopoiesis, and cancer biosynthesis. Liver cirrhosis is an advanced stage of liver fibrosis, and inflammatory cytokines play a key role in the activation of numerous cells involved in the pathogenesis of fibrosis.

Aims: The aims of this study were to assess serum IL-6 levels in patients with liver cirrhosis, and to study the correlation of IL-6 levels with the disease severity and mortality at 1 month in these patients.

Settings and design: This prospective observational study was conducted in the Medicine department of a tertiary care teaching hospital.

Subjects and methods: The study was conducted on 50 patients with liver cirrhosis aged 20-60 years. Serum IL-6 levels were measured by the chemiluminescence method in all the patients at the time of presentation. The relationships between IL-6 levels and the disease severity, in terms of Child-Turcotte-Pugh (CTP) score and class, and between IL-6 levels and mortality at 1 month, were analyzed.

Statistical analysis used: The continuous variables were expressed as mean and standard deviation, whereas the categorical variables were summarized as frequencies and percentages (%). Non-normally distributed variables were expressed as the median and interquartile range (IQR). The Mann-Whitney U-test was employed for the comparison of two continuous variables and the Kruskal-Wallis test was employed for comparing 3 or more continuous variables. Spearman's correlation coefficient (r) was employed to check the correlation between two continuous variables. Logistic regression analysis was used to identify independent predictors of disease outcome. P <0.05 was considered statistically significant.

Results: Most patients were males (82%), and the maximum number of patients were in the age groups of 35-44 (32%) and 45-54 years (34%). Most of them had decompensated cirrhosis (CTP class B: 42% and CTP class C: 40%). On follow-up, 84% of patients were alive at 1 month, whereas 16% expired. Mean IL-6 levels of the study population were 38.39 ± 39.36 pg/mL. IL-6 levels showed a positive correlation with grade of ascites (P = 0.0001), grade of encephalopathy (P = 0.0001), CTP class (P = 0.0001), CTP score (r = 0.863), international normalized ratio (r = 0.356), serum bilirubin (r = 0.432), and a negative correlation with serum albumin (r = -0.344). IL-6 levels were significantly higher in patients who expired in comparison to those who were alive at 1 month (mean: 109.87 ± 45.57 pg/mL, median [IQR]: 120.13 [73.87-145.60] pg/mL vs. 24.77 ± 17.60 pg/mL, 22.55 [11.87-35.50] pg/mL, P = 0.0001). IL-6 was found to be a significant predictor of disease outcome (odds ratio = 1.084, 95% confidence interval = 0.99-1.19).

Conclusions: IL-6 levels were found to be significantly associated with the severity of liver cirrhosis. It also correlated with the disease outcome; higher levels were found in patients who expired during the follow-up period. Thus, IL-6 may be a reliable and independent predictor of disease severity and outcome in patients with liver cirrhosis.