Impact of altitude on hemoglobin dynamics and prognosis in patients with advanced hepatocellular carcinoma receiving antiangiogenic TKIs: A propensity score matched study

Abstract

Purpose: Antiangiogenic tyrosine kinase inhibitors (TKIs) are associated with elevated hemoglobin [Hb] levels, potentially influencing prognosis in advanced hepatocellular carcinoma (HCC) patients. However, the impact of altitude on Hb dynamics and its prognostic significance remains underexplored. This study aimed to assess altitude-related Hb changes and their relationship with treatment outcomes in patients following TKI treatment.

Methods: In this retrospective cohort study, medical data from two institutions in Tibet and Beijing were analyzed. Between 2016 and 2022, 128 advanced HCC patients treated with antiangiogenic TKIs were divided into high- and low-altitude groups based on their city of residence. Hematological parameters were retrieved at baseline and every 3 months for 9 months post-treatment initiation. Propensity score matching (PSM) was used to adjust for demographic and baseline differences. Hb percentage changes from baseline (no increase, increase < 15%, increase ≥ 15%) were evaluated at each time point as predictors of time to treatment failure (TTTF) using the Cox proportional hazards model.

Results: After PSM, Hb trajectories differed between the altitude groups. The high-altitude patients exhibited progressive increases, while the low-altitude patients experienced a transient rise followed by a decline. We found no significant TTTF differences between the matched altitude groups (P = 0.33). However, in the high-altitude unmatched cohort, a ≥ 15% increase in Hb at 9 months was linked to a significantly lower risk of treatment failure (HR = 0.22 [95% CI = 0.06-0.83]; P = 0.03). Patients with increases < 15% showed a numerical trend toward prolonged TTTF (HR = 0.30 [0.08-1.15]).

Conclusion: Antiangiogenic TKIs induce altitude-dependent Hb changes, with sustained increases at high altitudes and transient reversibility at low altitudes. A ≥ 15% increase in Hb at 9 months after TKI therapy may serve as a potential biomarker for identifying high-altitude populations likely to benefit more from TKI therapy. Future studies should validate these findings in larger cohorts.

Keywords: Altitude; Antiangiogenic drugs; Hemoglobin; Hepatocellular carcinoma.