Associations of Serum Total Bilirubin with Survival Outcomes in Patients with Cancer Cachexia: A Retrospective, Multicenter Cohort Study

Abstract Background: Cancer cachexia is a systemic paraneoplastic phenomenon involving multiple organs, including the liver. Total bilirubin (TBIL) is an easily obtained blood biomarker that reflects liver homeostasis. This work evaluated the prognostic value of serum TBIL in patients with cancer cachexia.Methods: This study included 2,282 patients from a multicenter research database who were diagnosed with cancer cachexia between June 2012 and December 2019. The hazard ratio (HR) for all-cause mortality was analyzed using Cox proportional hazards regression models. The association of serum TBIL with all-cause mortality was modeled with restricted cubic splines. The optimal cutoff value for TBIL was calculated with maximally selected rank statistics.Results: Among the participants, there were 1,327 (58.2%) males and 955 (41.8%) females. The mean patient age was 60.4±1.5 years. The 12-month all-cause mortality rate for patients with cancer cachexia was 29.5% (95% CI: 27.6%-31.3%), resulting in a rate of 209.58 events per 1000 patient-years. An inverted L-shaped association between TBIL and all-cause mortality was observed. The cutoff point for TBIL for the prediction of the time to mortality was < 21.7 µmol/L. A high TBIL level but not the direct bilirubin (DBIL) or indirect bilirubin (IBIL) level was identified as an independent prognostic factor (HR, 1.60, 95% CI, 1.32-1.93). For patients with digestive system tumors, a high serum TBIL level (≥21.7 µmol/L) was significantly associated with mortality. Conclusion: High TBIL levels are associated with increased all-cause mortality in patients and might be a promising prognostic indicator in patients with cancer cachexia.