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PATIENTS WITH ALCOHOL-RELATED CIRRHOSIS WHO RECOMPENSATE ON FOLLOW-UP PRESENT A DISTINCTIVE METABOLIC PROFILE WITH DIFFERENTIAL CONCENTRATIONS OF LIPID AND AMINO-ACID METABOLITES

Helena Hernandez - Evole 1, Jordi Gratacós-Ginés 1, Emma Avitabile 1, Juanjo Lozano 2, Martina Perez-Guasch 1, Julia Sidorova 2, Alex Guillamon Thiery 3, Adrià Juanola 1, Anna Soria 1, Isabel Graupera 1, Ana Belén Rubio 1, Marta Cervera 1, Marta Carol 1, Nuria Fabrellas 1, Pere Ginès 1,4, Elisa Pose 4,1

Affiliations

1 Hospital Clinic, Barcelona, Spain

2 Centro de Investigación Biomédica en Red, Madrid, Spain

3 Universitat de Barcelona, Barcelona, Spain

4 Consorci Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain

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Abstract

Introduction

Decompensated alcohol-related cirrhosis (ArC) is a major cause of liver-related morbidity and mortality. There is a significant proportion of patients with ArC who achieve recompensation, defined as the absence of ascites or encephalopathy and no active treatment for either. Thus, recompensation is a relevant event in clinical practice. However, the factors and metabolic pathways involved in the resolution of clinical decompensation are poorly understood.

Aims & Methods

We aimed to assess the metabolomic profile associated with recompensated ArC. Patients with ArC were recruited from a prospective cohort followed between 2016 and 2020 in a referral hepatology unit (n=63). According to the evolution event at the end of follow-up, they were classified into 4 groups: group 0 patients compensated at baseline and during follow-up; group 1 patients who achieved recompensation; group 2 patients decompensated throughout the study period; group 3 patients who died in the 3 first months since inclusion. Demographic, clinical, and analytic parameters were retrieved from chart review together with evolution events. Plasma samples were analyzed at baseline to identify a metabolic signature using high-performance liquid chromatography-tandem mass spectroscopy. A principal component analysis of the implicated pathways was done using the Metaboanalyst platform.

Results

63 patients with ArC were included: 18 in group 0, 15 in group 1, 15 in group 2 and 15 in group 3. All four groups were similar in terms of age and sex. Baseline MELD score was 8, 17, 16 and 27, respectively. In relation to abstinence during follow-up, 61% of patients in group 1, 47% in group 2 and 20% in group 3 achieved alcohol abstinence (p=0.04).
Median follow-up time was similar when comparing group 1 and 2 (3.5 years and 3.3 years), which were the groups of interest (recompensated vs. decompensated). Each group displayed a distinct metabolic signature. By comparing groups 1 and 2, differences among 32 metabolites were detected: 20 lipids were at a higher concentration in recompensated individuals, which included polyunsaturated fatty acids (docosahenoic and docosapanthenoic acid 2 times greater (p<0.05)) and acylchcoline metabolism compounds; 7 amino acids, as phenyl-lactate (three times less in the recompensated group (p=0.04)) and 5 vitamins.

	Group 0 N=18	Group 1 N=15	Group 2 N=15	Group 3 N=15	p
Age (years)	52 (43-58)	55 (38-59)	48 (39-54)	56 (50-63)	0.354
Sex, women (%)	6 (33)	3 (20)	1 (7)	5 (22)	0.309
Baseline MELD score	8 (7-11)	17 (13-23)	26 (19-33)	26 (19-33)	0.000
Final MELD score	6 (6-8)	9 (8-11)	31 (23-38)	31 (23-39)	0.000
Abstinence (%)	13 (72)	10 (71)	2 (29)	2 (29)	0.022
Follow-up (days)	1462 (549-1846)	1273 (442-2142)	45 (13-104)	45 (13-104)	0.000

Conclusion

Patients who achieved recompensation at the end of follow-up exhibited a distinct metabolomic profile, regarding the metabolism of polyunsaturated fatty acids, acylcarnitines and amino acids. It is likely that these metabolic pathways may play a role in resolution of decompensations in patients with ArC.

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

PP 07 Liver & biliary (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD≤2), n/N (%)	Primary efficacy analysis set (NRI)^c LTE efficacy analysis set (NRI)^d Observed case analysis set^e	34.7 (61/176) 43.0 (61/142) 73.5 (61/83)	19.4 (12/62) 25.5 (12/47) 41.4 (12/29)
AP, abdominal pain; CDAI, Crohn's Disease Activity Index; LTE, long-term extension; NRI, nonresponder imputation; PRO-2, patient reported outcome components of the CDAI [abdominal pain and stool frequency]; SES-CD, Simple Endoscopic Score for Crohn’s Disease; SF, stool frequency ^aIncludes patients randomized to the following guselkumab induction/maintenance regimens: 200 mg IV →100 mg SC q8w; 600 mg IV →200 mg SC q4w; 1200 mg IV →200 mg SC q4w ^bPatients randomized to ustekinumab ^cPrimary efficacy analysis set consists of randomized patients who received ≥1 dose of study medication, with NRI for patients with treatment failure or missing data, including those who did not enter the LTE ^dLTE efficacy analysis set consists of randomized patients who entered the LTE and received ≥1 dose of study medication in the LTE, with NRI for patients with treatment failure or missing data ^eObserved case analysis set consists of randomized patients who entered the LTE, received ≥1 dose of study medication in the LTE, and had available data at the outcome visit. Patients who received dose adjustment were excluded

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