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Background: Previously, we reported that microRNA-181b (miR-181b) activates hepatic stellate cells partly through the phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/Akt pathway. Aims: The main objective of this study was to ascertain whether serum miR-181b expression is correlated with that of liver hepatitis B virus (HBV) DNA and disease progression in chronic hepatitis B (CHB) patients. Methods: Serum miR-181b and liver HBV DNA levels were quantified in 64 CHB patients with real-time PCR. Liver fibrosis and necroinflammation were graded according to the Ishak scoring system. Results: Serum miR-181b levels were evaluated in the CHB group, compared with healthy controls. Expression in patients with HBsAg (+) was higher than that in patients with HBsAg (−). Notably, serum miR-181b and liver HBV DNA levels were significantly correlated ( P < 0.05). Serum miR-181 levels were higher in patients with serum HBV DNA > 10 IU/ml ( P = 0.017), histologic activity index (HAI) >8 ( P = 0.001) and fibrosis score >4 ( P < 0.0001). Liver HBV DNA levels were higher in patients with abnormal alanine aminotransferase (ALT) values ( P = 0.004), serum HBV DNA levels > 10 IU/ml ( P = 0.034) and fibrosis score >4 ( P = 0.006). Using multivariate logistic regression analysis, serum miR-181b was identified as an independent predictor of disease progression (OR 4.172, 95 % CI 1.838-9.473, P = 0.009 for HAI >8; OR 5.387, 95 % CI 2.067-14.036, P = 0.001 for fibrosis score >4). Conclusions: Serum miR-181b is correlated with liver and serum HBV DNA levels as well as disease progression in CHB. [ABSTRACT FROM AUTHOR]