Serum sIL-2R predicts significant histological disease in indeterminate phase chronic hepatitis B

The indeterminate (IM) phase of chronic hepatitis B (CHB) lies between immune clearance and inactivity. We evaluated liver histology to guide treatment decisions.

Treatment-naïve patients were enrolled from 33 Chinese centers (2018-2020). Serum soluble interleukin-2 receptor (sIL-2R) was measured via chemiluminescence. IM patients were stratified by hepatitis B e antigen (HBeAg) status and alanine aminotransferase (ALT) levels. Histopathology was analyzed, and a diagnostic nomogram constructed.

Among 211 IM patients, 74.9% had significant histological disease, with a higher rate in HBeAg(+) than HBeAg(-) patients (90.5% vs 68.2%, P = 0.0012). Serum sIL-2R independently predicted histological injury in IM patients (middle tertile: OR = 2.29, P = 0.034; highest tertile: OR = 3.69, P = 0.004). A nomogram integrating sIL-2R, AST, and ALB showed good and consistent discriminative ability, with an area under the curve of 0.743 in the training set and 0.747 in the validation set. In 56 treated CHB patients, sIL-2R significantly declined after 78 weeks of entecavir (448.0-382.5 U/ml, P = 0.038), correlating with ALT reduction (r = 0.327, P = 0.025). Public data linked high hepatic IL2RA to immune activation and impaired function.

sIL-2R effectively identifies significant histological disease in IM patients. The derived nomogram aids risk stratification, while dynamic sIL-2R monitoring reflects therapeutic response, supporting its clinical utility.