Noninvasive diagnosis of significant liver inflammation in patients with chronic hepatitis B in the indeterminate phase

Virulence. 2023 Dec;14(1):2268497. doi: 10.1080/21505594.2023.2268497. Epub 2023 Nov 8.

Abstract

The presence of significant liver inflammation is an important indication for antiviral treatment in patients with chronic hepatitis B (CHB) in the indeterminate phase. We aimed to establish a non-invasive nomogram to predict significant liver inflammation in these patients. A total of 195 CHB patients in the indeterminate phase were randomly split into training and validation sets. The least absolute shrinkage and selection operator and logistic regression were applied to identify risk factors and establish a predictive model. A calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve were applied to assess the performance of the nomogram. The median age was 42.0 y and 59.5% of the patients were male. Alkaline phosphatase, γ-glutamyl transpeptidase, and prothrombin time were independent predictors for significant liver inflammation and selected to establish the AGP-nomogram. The calibration plot demonstrated that the predicted results matched the actual values. The DCA showed a high net benefit when the threshold probability was 25-83% in the training set and 31-100% in the validation set. The areas under ROC curves of AGP-nomogram in predicting significant inflammation were significantly higher than ALT in the training set (0.744 vs. 0.642, P = 0.049) and validation set (0.766 vs. 0.660, P = 0.047). The ability of AGP-nomogram in predicting advanced inflammation was also superior to ALT. The AGP-nomogram can accurately identify significant inflammation in CHB patients in the indeterminate phase, and its application may reduce the need for liver biopsy and help identify candidates for antiviral treatment.Abbreviations: AASLD: American Association for the Study of Liver Diseases; ALB: albumin; ALP: alkaline phosphatase; ALT: alanine aminotransferase; APRI: aspartate aminotransferase-to-platelet ratio index; AST: aspartate aminotransferase; AUROC: area under the receiver operating characteristic curve; CHB: chronic hepatitis B; CI: confidence interval; DCA: decision curve analysis; FIB-4: fibrosis index based on the four factors; GLB: globulin; GGT: γ-glutamyl transpeptidase; HBcAb: hepatitis B core antibody; HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HIV: human immunodeficiency virus; INR: international-normalized ratio; IQR: interquartile range; LASSO: least absolute shrinkage and selection operator; LB: liver biopsy; LR: Likelihood ratio; NAFLD: non-alcoholic fatty liver disease; NPV: negative predictive value; PLT: platelets; PPV: positive predictive value; PT: prothrombin time; ROC: receiver operating characteristic; TB: total bilirubin; TE: transient elastography; ULN: upper limit of normal.

Keywords: Chronic hepatitis B; diagnosis; indeterminate phase; inflammation; nomogram.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkaline Phosphatase / therapeutic use
  • Antiviral Agents / therapeutic use
  • Aspartate Aminotransferases / therapeutic use
  • Biomarkers
  • Carcinoma, Hepatocellular* / complications
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Female
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Inflammation / complications
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Neoplasms* / complications
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Male
  • Retrospective Studies
  • gamma-Glutamyltransferase / therapeutic use

Substances

  • gamma-Glutamyltransferase
  • Alkaline Phosphatase
  • Antiviral Agents
  • Aspartate Aminotransferases
  • Biomarkers

Grants and funding

The study was supported by the Nanjing Medical Science and Technique Development Foundation [QRX17121, YKK21067, JQX21002], Natural Science Foundation of Jiangsu Province [BK20211004], National Natural Science Fund [81970545; 82170609; 82300719], Natural Science Foundation of Shandong Province (Major Project) [ZR2020KH006] and Jin’nan Science and Technology Development Project [2020190790], and Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University [2021-LCYJ-PY-43 and 2022-LCYJ-MS-07].