Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China

Abstract

Background: Noninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed.

Aim: To develop a precise noninvasive test to stage liver fibrosis and cirrhosis.

Methods: With liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (10⁹/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis.

Results: Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively.

Conclusion: The AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.

Keywords: Chronic hepatitis B; Cirrhosis; Fibrosis; Liver; Novel noninvasive marker; Prediction.

Figure 1

Selection principles of study population. HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma.

Figure 2

Box plots of [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)]/platelet (10⁹/L) (A), alkaline phosphatase + gamma-glutamyl transpeptidase (B), platelet (C), gamma-glutamyl transpeptidase to platelet ratio (D), aspartate aminotransferase-to-platelet ratio index (E), and age × aspartate transaminase/platelet × alanine aminotransferase (F) according to the METAVIR fibrosis stage in the training cohort. AGPR: [Alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)]/platelet (10⁹/L); ALP + γ-GT: Alkaline phosphatase + gamma-glutamyl transpeptidase; PLT: Platelet; GPR: Gamma-glutamyl transpeptidase to platelet ratio; APRI: Aspartate aminotransferase-to-platelet ratio index; FIB-4: Age × aspartate transaminase/platelet × alanine aminotransferase.

Figure 3

The receiver operating characteristic analysis of [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)]/platelet (10⁹/L), amma-glutamyl transpeptidase to platelet ratio, aspartate aminotransferase-to-platelet ratio index and age × aspartate transaminase/platelet × alanine aminotransferase in the training (A) and validation cohorts (B). AGPR: [Alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)]/platelet (10⁹/L); GPR: Gamma-glutamyl transpeptidase to platelet ratio; APRI: Aspartate aminotransferase-to-platelet ratio index; FIB-4: Age × aspartate transaminase/platelet × alanine aminotransferase; AUC: Area under the curve.