摘要
BACKGROUND Hepatitis B is a major public health problem in China. Accurate liver injury assessment is essential for clinical evidence-based treatment. Liver biopsy is considered the gold standard method to stage liver disease, but it is not widely used in resource-limited settings. Therefore, non-invasive liquid biopsy tests are needed. AIM To assess liver injury in hepatitis B patients using quantified cell free DNA combined with other serum biomarker as a liquid biopsy-based method. METHODS A cohort of 663 subjects including 313 hepatitis B patients and 350 healthy controls were enrolled. Ultrasound-guided liver biopsies followed by histopathological assessments were performed for the 263 chronic hepatitis B patients to determine the degree of liver injury. Cell-free DNA was quantified using a novel duplex real-time polymerase chain reaction assay. RESULTS Compared with healthy controls, patients with hepatitis B virus (HBV) infection had significantly higher plasma DNA, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and HBV DNA levels (P<0.01). Serum ALT, AST, bilirubin, and plasma DNA levels of patients with markedsevere inflammation were significantly higher than those with mild-moderate inflammation (P<0.01). There was a statistically significant correlation between hepatocyte inflammation severity and serum bilirubin (R^2=0.673, P<0.01) or plasma DNA (R^2=0.597, P<0.01) levels. The areas under the curves of serum ALT, bilirubin, plasma DNA, and their combination to distinguish between patients with mild–moderate and marked-severe inflammation were 0.8059, 0.7910, 0.7921, and 0.9564, respectively. CONCLUSION The combination of plasma DNA, serum ALT, and bilirubin could be a candidate liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients.
BACKGROUND Hepatitis B is a major public health problem in China. Accurate liver injury assessment is essential for clinical evidence-based treatment. Liver biopsy is considered the gold standard method to stage liver disease, but it is not widely used in resource-limited settings. Therefore, non-invasive liquid biopsy tests are needed.AIM To assess liver injury in hepatitis B patients using quantified cell free DNA combined with other serum biomarker as a liquid biopsy-based method.METHODS A cohort of 663 subjects including 313 hepatitis B patients and 350 healthy controls were enrolled. Ultrasound-guided liver biopsies followed by histopathological assessments were performed for the 263 chronic hepatitis B patients to determine the degree of liver injury. Cell-free DNA was quantified using a novel duplex real-time polymerase chain reaction assay.RESULTS Compared with healthy controls, patients with hepatitis B virus(HBV) infection had significantly higher plasma DNA, serum alanine aminotransferase(ALT),aspartate aminotransferase(AST), bilirubin, and HBV DNA levels(P < 0.01).Serum ALT, AST, bilirubin, and plasma DNA levels of patients with markedsevere inflammation were significantly higher than those with mild-moderate inflammation(P < 0.01). There was a statistically significant correlation between hepatocyte inflammation severity and serum bilirubin(R2 = 0.673, P < 0.01) or plasma DNA(R2 = 0.597, P < 0.01) levels. The areas under the curves of serum ALT, bilirubin, plasma DNA, and their combination to distinguish between patients with mild–moderate and marked-severe inflammation were 0.8059,0.7910, 0.7921, and 0.9564, respectively.CONCLUSION The combination of plasma DNA, serum ALT, and bilirubin could be a candidate liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients.
基金
the National Natural Science Foundation of China,No.81672100 and No.81371894
the Key Laboratory for Laboratory Medicine of Jiangsu Province of China,No.ZDXKB2016005
Jiangsu Provincial Commission of Health and Family Planning,No.H201609
