P4687 - Targeted Breath Biopsy® Profiling of Induced Biomarkers Unveils a Metabolic Adaptation in Cirrhosis Toward Alcohol Production

Giuseppe Ferrandino, PhD¹, Federico Ricciardi, PhD¹, Antonio Murgia, PhD¹, Menisha Manhota, PhD¹, Daniela Fonseca, MSc¹, Louise Nicholson-Scott, MS¹, Chloe Fitzpatrick, MS¹, Olga Gandelman, PhD¹, Max Allsworth, PhD¹, Billy Boyle, MS¹, Agnieszka Smolinska, PhD¹, Huw Davies, PhD¹, Alexandra Ginesta Frings, MD², Jorge Contreras, MD³, Victor Gabrielli, MS⁴, Claudia Asenjo-Lobos, MS⁵, Francisca Bascur, BSc⁵, Viviana Barrientos, MS⁶, Nataly Clavo, MS⁴, Melissa Jerez, MS⁷, Luis Méndez, MD^2
1Owlstone Medical, Cambridge, England, United Kingdom; ²Unidad de Gastroenterología y Endoscopía, Clínica Alemana, Facultad de Medicina Clínica Alemana, Universidad de Desarrollo, Santiago 7650568, Chile. Unidad de Endoscopia, Hospital Padre Hurtado, Santiago 8880465, Chile., Santiago, Region Metropolitana, Chile; ³Unidad de Gastroenterología y Endoscopía, Clínica Alemana, Facultad de Medicina Clínica Alemana, Universidad de Desarrollo, Santiago 7650568, Chile, Santiago, Region Metropolitana, Chile; ⁴Unidad de Endoscopia, Hospital Padre Hurtado, Santiago, Region Metropolitana, Chile; ⁵Centro de Estudios Clínicos, Instituto de Ciencias e Innovación en Medicina (ICIM), Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7610315, Chile., Santiago, Region Metropolitana, Chile; ⁶Unidad de Endoscopia, Hospital Padre Hurtado,, Santiago, Region Metropolitana, Chile; ⁷Nursing School, Universidad de Las Américas, Santiago, Region Metropolitana, Chile

Introduction: Subjects with chronic liver disease showed higher circulating ethanol levels after fasting or carbohydrates ingestion. However, clinical functional data about the capability of the injured liver to cope with alcohols remain limited. In this study we used exhaled breath analysis to explore the conversion of an alcohol to the corresponding ketone, and a ketone to the corresponding alcohol, to establish the suitability of potential metabolic alterations and identify subjects with cirrhosis using a non-invasive breath test

Methods: We selected 2-butanol, and 2-pentanone (the substrates) as an alcohol and a ketone based on their safe human consumption, reported hepatic metabolism, and presence in breath. Hepatic metabolism was confirmed by treating human suspension hepatocytes with 10 ng/µl of 2-butanol, and 2-pentanone to measure their conversion to respectively 2-butanone, and 2-pentanol (the bioproducts) by using headspace analysis coupled with gas-chromatography mass-spectrometry (GC-MS). Clinical metabolism was evaluated by analysing the breath profile of 14 subjects with cirrhosis and 15 controls before and at different timepoints (10 - 120 minutes) after ingestion of 2-butanol (100 mg) and 2-pentanone (100 mg), using Breath Biopsy® OMNI

Results: Bioproducts were present in primary hepatocytes treated with the substrates and absent in control conditions omitting primary hepatocytes or substrates. After an overnight fasting all the participants showed breath levels of investigated compounds with no differences between healthy and cirrhosis groups (p > 0.05). After ingestion of the substrates, all the subjects showed a > 100-fold increase of investigated compounds within 10 minutes. Subjects with cirrhosis showed higher levels of 2-butanol and 2-pentanol (p < 0.05) compared to controls between 20- and 90-minutes post-administration. An exploratory classification model built on these breath-induced biomarkers at 20 minutes showed an area under the ROC curve of 0.85

Discussion: 2-butanol and 2-pentanone are metabolized to the corresponding ketone and alcohol in primary hepatocytes. Cirrhosis subjects showed higher breath levels of secondary alcohols independently from administration of the alcohol or the corresponding ketone, suggesting hepatic function is more balanced toward alcohol production compared to controls. This metabolic adaptation may contribute to higher circulating ethanol levels in subjects with chronic liver disease and be exploited in a breath test for cirrhosis detection



Disclosures:


Giuseppe Ferrandino, PhD¹, Federico Ricciardi, PhD¹, Antonio Murgia, PhD¹, Menisha Manhota, PhD¹, Daniela Fonseca, MSc¹, Louise Nicholson-Scott, MS¹, Chloe Fitzpatrick, MS¹, Olga Gandelman, PhD¹, Max Allsworth, PhD¹, Billy Boyle, MS¹, Agnieszka Smolinska, PhD¹, Huw Davies, PhD¹, Alexandra Ginesta Frings, MD², Jorge Contreras, MD³, Victor Gabrielli, MS⁴, Claudia Asenjo-Lobos, MS⁵, Francisca Bascur, BSc⁵, Viviana Barrientos, MS⁶, Nataly Clavo, MS⁴, Melissa Jerez, MS⁷, Luis Méndez, MD². P4687 - Targeted Breath Biopsy® Profiling of Induced Biomarkers Unveils a Metabolic Adaptation in Cirrhosis Toward Alcohol Production, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.