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
The clinical and histological features of chronic hepatitis B (CHB) patients who fall into the "grey zone (GZ)" and do not fit into conventional natural phases are unclear.
To explore the impact of varying the threshold of alanine aminotransferase (ALT) levels 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. The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines. GZ CHB patients were classified into four groups: GZ-A (HBeAg positive, normal ALT levels, and HBV DNA ≤ 107 IU/mL), GZ-B (HBeAg positive, elevated ALT levels, and HBV DNA < 104 or > 107 IU/mL), GZ-C (HBeAg negative, normal ALT levels, and HBV DNA ≥ 2000 IU/mL), and GZ-D (HBeAg negative, elevated ALT levels, and HBV DNA ≤ 2000 IU/mL). Significant hepatic injury (SHI) was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2).
The results showed that 50.22% of patients were classified as GZ, and 63.7% of GZ patients developed SHI. The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria (35 U/L for men and 25 U/L for women) can more accurately identify patients with significant liver damage in the GZ phases. In total, the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 64.86% [(221 + 294)/794]. When we lowered the ALT treatment threshold to the new criteria (30 U/L for men and 19 U/L for women), the same outcome was revealed, and the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 75.44% [(401 + 198)/794]. Additionally, the proportion of SHI was 49.1% in patients under 30 years old and increased to 55.3% in patients over 30 years old (P = 0.136).
These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.
Core Tip: In clinical practice, 27.8%-55% of chronic hepatitis B patients fall into the “grey zone” or “indeterminate phase” that does not meet the diagnostic criteria of the traditional stages. Additionally, there is still debate regarding how best to treat these grey zone (GZ) patients and the advantages of antiviral therapy. Hence, we evaluated the clinical and histological characteristics, and additionally explored the impact of adjusting the threshold of alanine aminotransferase (ALT) in identifying significant liver injury among GZ patients. Based on these data, lowering ALT thresholds can more accurately identify patients with significant hepatic injury at an earlier stage and reduce the need for unnecessary liver biopsies.