The Impact of G6PD Deficiency on Liver Damage and Disease Progression in Hepatocellular Carcinoma: A Cross-Sectional Study in Thailand

Background. Glucose 6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, producing reduced nicotinamide adenine dinucleotide phosphate (NADPH) to support redox homeostasis and cancer cell proliferation. While G6PD deficiency has been linked to reduced cancer risk, its impact on hepatocellular carcinoma (HCC) remains unclear. Objectives. This study investigates the prevalence of G6PD deficiency in HCC patients and its association with clinical parameters across disease stages. Methods. A cross-sectional study analyzed G6PD activity and clinical data from 174 HCC patients, 100 hepatitis B virus (HBV)-infected patients, and 154 healthy controls. Peripheral blood G6PD activity was measured, and clinical parameters were compared between early- and advanced-stage HCC patients with and without G6PD deficiency. Results. The prevalence of G6PD deficiency was comparable across HCC patients (6.9%), HBV-infected patients (6.0%), and healthy controls (6.5%) (p=0.965), with no difference between early (6.7%) and advanced-stage HCC (7.0%). Median G6PD activity was significantly higher in HCC patients (7.9±2.1 U/g Hb) compared to healthy controls (7.1±2.5 U/g Hb) (p=0.048). Advanced-stage HCC patients exhibited elevated G6PD activity (8.1±2.5 U/g Hb), largely due to anemia. G6PD-deficient HCC patients, particularly in advanced-stage, had elevated liver damage markers, including alkaline phosphatase (ALP) (125.0±68.8 U/L), serum glutamic oxaloacetic transaminase (SGOT) (69.5±78.0 U/L), and alpha-fetoprotein (AFP) levels (258.8±1,010.1 ng/mL). Conclusion. G6PD deficiency does not appear to reduce HCC susceptibility but is associated with increased liver damage in advanced-stage patients. These findings highlight the potential importance of G6PD in liver cancer progression and the need for further research into its therapeutic implications.