Admission direct bilirubin and direct bilirubin-to-lymphocyte ratio as exploratory markers of early severity and in-hospital functional status in acute ischemic stroke.

Authors

Yingxia Li, Ruixing Zhang, Yang Luo, Youquan Gu

Published in

Frontiers in stroke. Volume 5. Pages 1800285. Epub Aug 07, 2026.

Abstract

To investigate the correlation between direct bilirubin (DBIL), direct bilirubin-lymphocyte ratio (DBLR), and the severity of acute ischemic stroke (AIS), and to evaluate their potential as auxiliary biomarkers for early severity assessment and short-term in-hospital functional outcome of AIS.
A retrospective study was conducted to enroll 234 patients with AIS who presented within 24 h of admission to The First Hospital of Lanzhou University as the AIS Group, and 180 healthy individuals who underwent a health checkup at the same time were randomly selected as the Control Group. The patients' general information, National Institute of Health Stroke Scale (NIHSS) scores, and laboratory indicators at admission were collected with DBLR calculated as DBIL divided by lymphocyte (LYM) count. The AIS Group was divided into Mild Group (NIHSS ≤ 6, n = 91), Moderate Group (6 < NIHSS < 15, n = 82), and Severe Group (NIHSS ≥ 15, n = 61) according to the NIHSS scores at admission. The AIS Group was further divided into Good early functional outcome Group (mRS < 3, n = 133) and Poor early functional outcome Group (mRS ≥ 3, n = 101) according to the Modified Rankin Scale (mRS) scores at 7 ± 2 days of treatment. The differences in past medical history, general clinical data, and laboratory indicators between the AIS Group and the Control Group were compared, and the differences in laboratory indicators between the different subgroups were analyzed respectively.
Compared to the Control Group; the AIS Group exhibited significantly higher direct bilirubin (DBIL) levels and a lower lymphocyte (LYM) count (P < 0.05). Both the Moderate and Severe Groups presented elevated direct bilirubin (DBIL) levels (P < 0.001), indirect bilirubin (IBIL) levels (P = 0.021), and direct bilirubin ratio (DBLR) (P < 0.001). Notably, DBIL (r = 0.269, P < 0.001) and DBLR (r = 0.321, P < 0.001) were positively correlated with the extent of neurological deficit, while LYM count (r = -0.274, P < 0.001) exhibited a negative correlation with neurological deficit severity. At the time of admission, DBIL and DBLR were identified as risk factors for neurological deficits. This study performed receiver operating characteristic (ROC) curve analysis on DBLR and DBIL among patients with severe strokes. The area under the curve (AUC) for DBLR was 0.612, with an optimal diagnostic threshold of 2.82, yielding a sensitivity of 47.2% and a specificity of 79.4% (P = 0.005, 95% CI: 0.537-0.686). For DBIL, the AUC was 0.596, the optimal diagnostic threshold was 2.85, with a sensitivity of 72.7% and a specificity of 43.5% (P = 0.017, 95% CI: 0.521-0.671), and the difference was statistically significant (P < 0.05). In comparison to the Good early functional outcome Group, the Poor early functional outcome Group showed higher DBIL and DBLR levels, along with a lower LYM count. Moreover, DBIL and DBLR were positively correlated with the Modified Rankin Scale (mRS) scores at 7 ± 2 days. The AUC for DBLR was 0.650, with an optimal diagnostic threshold of 2.86, a sensitivity of 69.8%, and a specificity of 58.5% (P < 0.001, 95% CI: 0.581-0.719). The AUC for DBIL was 0.582, with an optimal diagnostic threshold of 2.55, a sensitivity of 80.8%, and a specificity of 36.6% (P = 0.031, 95% CI: 0.509-0.654), with a statistically significant difference (P < 0.05). Additionally, elevated continuous DBLR was independently associated with poor early functional outcome, and the exploratory cutoff of DBLR > 2.86 indicated a higher risk of poor short-term functional status.
Admission levels of DBIL and DBLR are significantly correlated with the degree of neurological impairment and short-term (7 ± 2 days) in-hospital functional status in AIS patients, where higher values indicate more severe acute neurological deficits and poorer early outcomes. Elevated DBLR is independently associated with poor short-term functional status, and the exploratory cutoff of DBLR > 2.86 (OR = 5.169, 95% CI: 1.623-16.461, P = 0.005) may assist in early risk stratification. However, their independent predictive ability is limited (all AUCs < 0.7). Therefore, these biomarkers should only be used as auxiliary tools in combination with clinical scores such as the NIHSS, and their clinical value should not be overinterpreted.

PMID:
42630218
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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