Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis

Abstract

We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation.

Figure 1. Flow diagram depicting the participants’ selection process.

Figure 2

Correlation between serum HBsAg levels and serum HBV DNA levels in all patients (A) treated patients (B) and untreated patients (C); correlation between serum HBeAg and serum HBV DNA levels in total patients (D), treated patients (E) and untreated patients (F). The correlation coefficients (r) between HBsAg and HBV DNA were calculated using Spearman’s correlation; the relationship between serum HBeAg and serum HBV DNA was identified using Kruskal-Wallis test.

Figure 3. Distribution of liver necroinflammation among 200 chronic hepatitis B patients.

(A) Distribution of liver necroinflammation in treated and untreated group; (B) Distribution of liver necroinflammation in groups with ALT ≤ 40 U/L and ALT 40–80 U/L. P values were calculated by the Fisher’s exact test.

Figure 4. ROC curve for determining the predictive power of the prediction model including AST, TBIL, TBA, PT, APRI and serum HBV-DNA.

PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR−, negative likelihood ratio.