Liquid biopsy for non-invasive assessment of liver injury in hepatitis B patients

Figure 1 Correlations of blood biomarkers with severity of hepatocyte inflammation in 263 chronic hepatitis B patients. The scatter plots show that there are statistically significant correlations between the severity of hepatocyte inflammation and levels of serum biomarkers. A: Alanine aminotransferase; B: Bilirubin; C: Plasma DNA; D: Hepatitis B virus DNA. ALT: Alanine aminotransferase; HBV: Hepatitis B virus.

Figure 2 The receiver operator characteristic curves of using four blood biomarkers to assess hepatocellular injury severity in 263 chronic hepatitis B patients. The areas under the curves (AUCs) of using serum alanine aminotransferase (ALT, black), bilirubin (yellow), plasma DNA (orange), serum aspartate aminotransferase (green), albumin (purple), and hepatitis B virus DNA (gray) to distinguish between patients with mild-moderate and marked-severe inflammation were 0.8059, 0.7910, 0.7921, 0.6530, 0.4877, and 0.4952, respectively. After the combination of serum ALT, bilirubin, and plasma DNA (blue), there was a statistically significant increase of AUC (0.9564). ALT: Alanine aminotransferase; HBV: Hepatitis B virus; AST: Aspartate aminotransferase; AUC: Area under the curve.

Figure 3 Quantitative analysis of serum alanine aminotransferase and plasma DNA of 263 chronic hepatitis B patients to assess hepatocellular injury severity. A: The scatter plot of serum alanine aminotransferase (ALT) and plasma DNA levels of chronic hepatitis B patients with mild-moderate (blue dots) or marked-severe (red dots) inflammation. Most (84.0%) of the patients with high serum ALT levels (> 100.0 U/L) had marked-severe hepatocyte injury, while the other patients with marked-severe hepatocyte injury and low serum ALT levels (≤ 100.0 U/L) can be distinguished from patients with mild-moderate hepatocyte injury by plasma DNA quantification (e.g., Case 85); B: The hematoxylin and eosin stained microscopic image (× 400) of hepatic tissue of the case 85 showed severe piecemeal necrosis (marked portal inflammation) (Grade 3). ALT: alanine aminotransferase.

Figure 4 Pattern diagram of liquid biopsy with serum alanine aminotransferase, bilirubin, and plasma DNA for assessment of hepatocellular injury in hepatitis B patients. Serum alanine aminotransferase levels in patients with severe hepatocellular injury may not be very high and plasma DNA combined with serum bilirubin may be a good complementary biomarker for these patients. ALT: Alanine aminotransferase.