Low Baseline Plasma L-Glutamine Concentration Identifies Hepatocellular Carcinoma Patients at High Risk of Developing Early Gastrointestinal Adverse Events during Sorafenib Treatment

Gastrointestinal adverse events (GIAEs) are common in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Diarrhea is a prevalent event responsible for treatment interruptions and dosage modifications. Our study evaluates the role of baseline blood L-glutamine (L-Gln) levels in the prediction of gastrointestinal adverse events development early during treatment (eGIAE). Blood L-Gln was measured in 135 patients with advanced HCC prior to starting sorafenib. Any adverse events developed during therapy were registered in a prospective database. We used Mann-Whitney U and Fisher's exact tests to compare quantitative or categorical variables, respectively, Kaplan-Meier method to analyze time to event variables, log-rank test for the survival functions and Cox regression models to estimate hazard ratios (HR). Fifteen per cent of patients developed eGIAE, with diarrhea as the most frequent one. Patients displaying the lowest L-Gln levels presented a significant higher risk of eGIAE, while those with the highest levels were protected from eGIAE and achieved better survival. Our study shows for the first time the association of baseline blood L-Gln levels with eGIAE development in HCC patients during sorafenib treatment. Low L-Gln concentrations might reflect a potentially compromised intestinal barrier that becomes clinically relevant early after treatment start.