Selective improvement by rifaximin of changes in the immunophenotype in patients who improve minimal hepatic encephalopathy

• Published in: Journal of translational medicine Vol. 17; no. 1; p. 293
• Main Authors: Mangas-Losada, Alba, García-García, Raquel, Leone, Paola, Ballester, María Pilar, Cabrera-Pastor, Andrea, Urios, Amparo, Gallego, Juan-José, Martínez-Pretel, Juan-José, Giménez-Garzó, Carla, Revert, Fernando, Escudero-García, Desamparados, Tosca, Joan, Ríos, María Pilar, Montón, Cristina, Durbán, Lucia, Aparicio, Luis, Montoliu, Carmina, Felipo, Vicente
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 28.08.2019; BioMed Central; BMC
• Subjects: Antibiotics; Autoimmunity; Care and treatment; CCL20 protein; CD14 antigen; CD16 antigen; CD28 antigen; CD4 antigen; CD69 antigen; Cell activation; Cognitive ability; Cytokines; Data analysis; Diagnosis; Encephalopathy; Flow cytometry; Hepatic encephalopathy; Immune system; Immunoglobulin G; Immunophenotype; Inflammation; Interleukin 6; Liver; Liver cirrhosis; Liver diseases; Liver encephalopathy; Lymphocyte typing; Lymphocytes; Lymphocytes T; Measurement methods; Microbiota; Minimal hepatic encephalopathy; Monocytes; Quantitative psychology; Rifaximin; T cells; T lymphocytes activation; Testing; Transcription factors; Spain; Minimal hepatic encephalopathy; Rifaximin; Immunophenotype; T lymphocytes activation
• DOI: 10.1186/s12967-019-2046-5
• ISSN: 1479-5876

Minimal hepatic encephalopathy (MHE) in cirrhotic patients is associated with specific changes in parameters of the immune system reflecting a more pro-inflammatory environment than in patients without MHE. The aims of this work were to assess the effects of rifaximin treatment of cirrhotic patients with MHE on: (1) MHE; (2) intermediate (CD14 CD16 ) pro-inflammatory monocytes; (3) expression of early activation marker CD69 in T lymphocytes; (4) autoreactive CD4 CD28 T lymphocytes; (5) differentiation of CD4 T lymphocytes to Th follicular and Th22; (6) serum IgG levels; and (7) levels of some pro-inflammatory cytokines. These parameters were measured by immunophenotyping and cytokine profile analysis in 30 controls without liver disease, 30 cirrhotic patients without MHE and 22 patients with MHE. Patients with MHE were treated with rifaximin and the same parameters were measured at 3 and 6 months of treatment. We assessed if changes in these parameters are different in patients who improve MHE (responders) and those who remain in MHE (non-responders). Rifaximin improved MHE in 59% of patients with MHE. In these responder patients rifaximin normalized all alterations in the immune system measured while in non-responders it normalizes only IL-6, CCL20, and differentiation of T lymphocytes to Th22. Non-responder patients do not show increased expression of CD69 before treatment. Rifaximin normalizes changes in the immune system in patients who improve MHE but not in non-responders. Some alterations before treatment are different in responders and non-responders. Understanding these differences may identify predictors of the response of MHE to rifaximin.