PREVALENCE, EPIDEMIOLOGY, CHARACTERIZATION AND MECHANISMS OF ACUTE-ON-CHRONIC LIVER FAILURE (ACLF) IN LATIN AMERICA. COMPARISON WITH DATA FROM OTHER REGIONAL STUDIES (EUROPE AND ASIA)
The ACLF-ACLARA study will consist of in a prospective follow-up observational investigation in 1300 patients with cirrhosis hospitalized for AD with and without ACLF in the 57 hospitals from the Latin America CLIF Consortium. Clinical and standard laboratory data and samples for measuring circulating levels of inflammatory inducers and mediators, biomarkers of systemic circulatory dysfunction and oxidative stress, innate immune cell function and cell death, and genotyping (obtained only at admission), transcriptomics and metabolomics will be obtained at admission, 8-10 days after admission and at discharge. The one-year clinical course (survival, liver transplantation and causes of death) will also be recorded. Since the translocation of bacteria and bacterial products are thought to play a major contributory role on systemic inflammation in cirrhosis, additional blood, saliva, and stool samples will be taken for metagenomics assessment.
The aims of the ACLF-ACLARA project are:
- To investigate the characteristics of the ACLF syndrome in Latin America (including clinical course severity and mortality) by sequential assessment of multi-organ failure, specific biomarkers of systemic inflammation and oxidative stress, effective arterial blood volume, immune cell function and cell death, exogenous precipitating factors, and genotyping (assessed only at enrolment), transcriptomics and metabolomics.
- To investigate the relationship between the prevalence of ACLF and of potential specific phenotypes (subtypes) with pathogenic, ethnic, lifestyle and other features related with geographic and environmental variations.
- To perform systems biology modeling analysis for better understanding of ACLF mechanism and identification of new predictive biomarkers and potential therapeutic targets.
- To integrate the Latin-America cohort with other prospective highly harmonizable international cohorts developed with the CANONIC template for comparative assessment.
- To obtain stool and blood samples for future metagenomics assessment.