Background: Higher choline/betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival. Methods: 866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Both LCSS (T3 vs. T1: HR=0.69, 95% CI: 0.51-0.94; P-trend <0.05) and OS (T3 vs. T1: HR=0.73, 95% CI: 0.54-0.99; P-trend <0.05) were better with sex-specific tertiles of serum choline levels. The associations were not significantly modified across strata of selected prognostic factors, except in the different C-reactive protein (CRP) levels, the favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS. Conclusions: This study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our finding might open new prospect in understanding the benefits of choline on HCC survival. Registration: The Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT 03297255.
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