Exploring Liver Mitochondrial Function by ¹³C-Stable Isotope Breath Tests: Implications in Clinical Biochemistry

The liver is at the crossroad of key metabolic processes, which include detoxification, glycolipidic storage and export, and protein synthesis. The gut-liver axis, moreover, provides hepatocytes with a series of bacterial products and metabolites, which contribute to maintain liver function in health and disease. Breath tests (BTs) are developed as diagnostic tools for indirect, rapid, noninvasive assessment of several metabolic processes in the liver. BTs monitor the appearance of CO₂ in breath as a marker of a specific substrate metabolized in the liver, typically within microsomes, cytosol, or mitochondria. The noninvasiveness of BTs originates from the use of the, nonradioactive, naturally occurring stable isotope ¹³C marking a specific substrate which is metabolized in the liver, leading to the appearance of ¹³CO₂ in expired air. Some substrates (ketoisocaproic acid, methionine, and octanoic acid) provide information about dynamic liver mitochondrial function in health and disease. In humans, the application of ¹³C-breath tests ranges from nonalcoholic and alcoholic liver diseases to liver cirrhosis, hepatocarcinoma, preoperative and postoperative assessment of liver function, and drug-induced liver damage. ¹³C-BTs are an indirect, cost-effective, and easy method to evaluate dynamic liver function and gastric kinetics in health and disease, with ongoing studies focusing on further applications in clinical medicine.