Systematic Worldwide Review on the Performance of Non-Invasive Exhalation-Based Methods for the Diagnosis of Liver Fibrosis.

Liver fibrosis is a chronic disease diagnosed through invasive methods that can worsen patients' health. Moreover, this disease is diagnosed in terminal stages, when the damage is already widespread and irreversible, which makes it necessary to have minimally invasive diagnostic methods with high performance. The aim was to compare research on non-invasive methods, respiratory footprint, and volatile organic compounds for the diagnosis of liver fibrosis through patient exhalation. Following the PRISMA guidelines, systematic searches were conducted in 13 databases. We could identify 17,454 documents between 2009 and 2022. Inclusion criteria comprised original investigations using Gas Chromatography-Mass Spectrometry (GC-MS), Ion Mobility-Mass Spectrometer (IMR-MS), and e-nose for liver fibrosis diagnosis. We considered the precision, specificity, and sensitivity of each test and the methodological quality of each study according to the PEDro guideline. Seven investigations were included. Four (57%) studies used GC-MS, and two (28.6%) used e-nose. The most commonly used gold standard was liver biopsy, and all studies were of European origin, with only adult populations. Three (42%) studies had a specificity >90%, and five (71.4%) had a sensitivity between 85 and 100%. Isoprene is the most significant and distinguishable biomarker for liver fibrosis diagnosis. Five (71.4%) studies had high methodological quality. GC-MS is the most used technique for detecting liver fibrosis, and isoprene is the most frequent volatile organic compound (VOC) found in the exhalation of patients with liver fibrosis. More studies are needed in areas with high risk and prevalence of hepatic fibrosis.