Serum microRNA-125b correlates with hepatitis B viral replication and liver necroinflammation

Abstract

MicroRNAs (miRNAs) were recently reported to play an important role in hepatitis B virus (HBV) infection and related diseases. We evaluated the correlation between serum miRNA-125b, viral replication and liver necroinflammation in Chinese patients with chronic hepatitis B (CHB) infection. Serum miRNA-125b levels in samples from 211 CHB patients were determined by RT-PCR. Liver biopsies were collected from 138 patients. Serum miRNA-125b, miRNA-122 and miRNA-124 levels were determined. Correlations between serum miRNA-125b, viral replication and liver necroinflammation were analysed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum miRNA-125b to grade liver necroinflammation (G). HepG2.2.15 cells were transfected with miRNA-125b mimics. Intracellular viral core DNA was extracted and analysed by Southern blot. We found that serum miRNA-125b was positively correlated with the serum HBV DNA level. HBV replication capacity increased after transfection with miRNA-125b mimics. Patients with CHB with moderate-to-severe liver necroinflammation (G ≥2) showed significantly higher (p <0.001) serum miRNA-125b levels than those with G <2. In patients with alanine transaminase levels less than twice the upper limit of normal, serum miRNA-125b combined with miRNA-124 yielded an area under the ROC curve of 0.816, with 70.4% sensitivity and 84.9% specificity to discriminate the grade of liver necroinflammation (G ≥2). Hence, we concluded that miRNA-125b may enhance HBV replication. Serum miRNA-125b correlates with viral load. Serum miRNA-125b alone or combined with miRNA-124 has the potential to discriminate grades of liver necroinflammation, particularly in Chinese patients with CHB who have normal or mildly increased alanine transaminase levels.

Keywords: Chronic hepatitis B; hepatitis B virus; liver necroinflammation prediction; microRNA-125b; viral replication.