Published online Sep 21, 2023. doi: 10.3748/wjg.v29.i35.5166
Peer-review started: July 2, 2023
First decision: July 14, 2023
Revised: July 22, 2023
Accepted: August 31, 2023
Article in press: August 31, 2023
Published online: September 21, 2023
In clinical practice, a considerable proportion of chronic hepatitis B (CHB) patients (27.8%-55%) fall into the “grey zone (GZ)” or “indeterminate phase”. Additionally, there is still debate regarding how best to treat these GZ patients and the advantages of antiviral therapy. Moreover, an issue that complicates the management of CHB is the disagreement regarding the appropriate treatment threshold for alanine aminotransferase (ALT) levels.
To explore the impact of varying the threshold of ALT levels in identifying significant hepatic injury (SHI) among GZ patients.
Our research evaluated the clinical and histological characteristics and additionally explored the impact of adjusting the threshold of ALT in identifying significant liver injury among GZ patients.
This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy. Significant hepatic injury was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2). Kruskal-Wallis tests and Pearson’s chi-squared tests were applied to compare variables that were significantly different between groups.
The study showed that 50.22% of the patients with HBV infection fell into the GZ category, and more than half of the patients (63.7%) in the GZ category exhibited SHI. The areas under the receiver operating characteristic curves of Aspartate aminotransferase-to-platelet ratio index, fibrosis score based on four factors, and gamma-glutamyl transpeptidase-to-platelet ratio in predicting SHI were 0.717, 0.713, and 0.727, respectively, in the HBeAg-positive GZ phases and 0.717, 0.645, and 0.692, respectively, in the HBeAg-negative GZ phases. Lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria can more accurately identify patients with significant liver damage in the GZ phases. When we lowered the ALT treatment threshold to the new criteria, the same outcome was revealed.
This study showed that 50.22% of CHB patients were in the GZ, and over half of GZ patients (63.7%) had SHI. Lowering ALT thresholds can more accurately identify patients with significant liver damage at an earlier stage and reduce the need for some unnecessary liver biopsies. Furthermore, age may not be a limitation for initiating antiviral therapy in patients with CHB who have normal ALT levels.
Further investigation is needed to determine the assessment and treatment strategy for CHB patients in the GZ phases.