Cell death biomarker M65 is a useful indicator of liver inflammation and fibrosis in chronic hepatitis B: A cross-sectional study of diagnostic accuracy

Abstract

Cell death markers, M65 and M30, have been suggested to be sensitive markers of liver inflammation and fibrosis in nonalcoholic fatty liver disease and chronic hepatitis C. Our aim was to investigate whether these markers were useful in diagnosing liver inflammation and fibrosis in chronic hepatitis B (CHB).We examined 186 patients with CHB; 18 sex- and age-matched healthy subjects were controls. The blood samples were collected from CHB patients within 1 week before or after liver biopsy. According to METAVIR score system, liver inflammation was graded from A0 to A3, and fibrosis from F0 to F4.Serum M65 and M30 levels were in parallel with the grades of liver inflammation. M65, not M30, increased significantly in patients with severe inflammation and normal alanine aminotransferase. M65 is one of the independent predictors of severe liver inflammation (≥A2). The levels of M65 and M30 levels significantly increased in parallel with the degree of inflammation in F1 patients, whereas they showed no statistical difference between different stages of fibrosis in A1 patients.Serum M65 is a useful indicator of liver inflammation in CHB patients. Serum M65, not M30, is valuable in the grading of liver fibrosis.

Figure 1

The serum levels of M65 and M30 in different grades of liver inflammation. (A) Serum M65 in A3 group was much higher than that in control group, A1 group and A2 groups. (B) Serum M30 was much higher in A3 group than that in the control and A2 group. Compared with A1 group, serum M65 (C) and M30 (D) were higher in ≥A2 group. A1 = patients with liver inflammation of grade 1, A2 = patients with liver inflammation of grade 2, A3 = patients with liver inflammation of grade 3. The top and bottom of each box are the 25th and 75th percentiles. The line through the box is the median and the error bars are the 5th and 95th percentiles.

Figure 2

Model of prediction of significant liver inflammation in chronic hepatitis B. The area under the receiver-operating characteristic curve showed the performance of M65 and HBV DNA for predicting severe liver inflammation (A ≥2). Y = 0.001 × M65(U/L) − 0.261 ^× lg HBV DNA − 0.732, area under receiver-operating characteristic curve = 0.683. The cut-off point at −1.2 predicts A ≥2 with a sensitivity of 59.5%, and a specificity of 73.2%, respectively.

Figure 3

The serum levels of M65 and M30 in different stages of liver fibrosis. (A) Serum M65 in F2 and cF3 groups was higher than that in control and F1 group. (B and D) There was no difference of serum M30 levels between different fibrosis stages. (C) Serum M65 was higher in ≥F2 group than that in F1 group. F1 = patients with liver fibrosis stage 1; F2 = patients with liver fibrosis stage 2; cF3 (combined F3)  = patients with liver fibrosis stage 3 and 4. The top and bottom of each box are the 25th and 75th percentiles. The line through the box is the median and the error bars are the 5th and 95th percentiles.

Figure 4

The levels of serum M65 and M30 in A1 or F1. (A and B) No difference of serum M65 and M30 was found between A1F1 and A1F ≥1 group. (C and D) Serum M65 and M30 were higher in A ≥2F1. A1F1 = patients with liver inflammation of grade 1 and liver fibrosis of stage1, A ≥2F1 = patients with liver inflammation of grade 2 and liver fibrosis of stage1, A1F ≥2 = patients with liver inflammation of grade 1 and liver fibrosis of stage 2. The top and bottom of each box are the 25th and 75th percentiles. The line through the box is the median and the error bars are the 5th and 95th percentiles.