Association between immunologic markers and cirrhosis in individuals with chronic hepatitis B

Background: Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Methods: We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. Results: After multivariable adjustment, HGF (Q4v1OR:3.74;p-trend=0.0001), SLAMF1 (Q4v1OR:4.07;p-trend=0.0001), CSF1 (Q4v1OR:3.00;p-trend=0.002), uPA (Q4v1OR:3.36;p-trend=0.002), IL-8 (Q4v1OR:2.83;p-trend=0.004), and OPG (Q4v1OR:2.44;p-trend=0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. Conclusion: This is the first prospective study to assess immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis.