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

Abstract

Background 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. Methods 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). Results 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. Conclusions 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.

A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease

“…Using the PHES, 12% of NAFLD patients (7 out of 59) were classified as having MCI. This prevalence is lower than in cirrhotic patients, who show MHE prevalence of 31-59% when diagnosed using the PHES [13,21,30,31]. However, it has been reported that the PHES is not sensitive enough and fails to detect the presence of mild cognitive impairment in a substantial proportion of cirrhotic patients.…”

“…MHE reduces the ability to perform daily life tasks and is associated with altered postural control, increased risk of falls, fractures, and hospitalizations, and of progression to overt hepatic encephalopathy, increased costs, and reduced life quality and span [6,[10][11][12]. Early MHE detection may help to reverse or halt progression of MHE [13].…”

Rifaximin Prevents T-Lymphocytes and Macrophages Infiltration in Cerebellum and Restores Motor Incoordination in Rats with Mild Liver Damage

“…Rifaximin is a non-absorbable antibiotic that was approved as treatment for the prevention of HE in the USA in 2010 [59]. Rifaximin reduces the risk of overt HE recurrence and mortality [59] and also improves cognitive and motor function in a large percentage of cirrhotic patients with MHE [23].…”

“…Treatment with rifaximin, a nonpermeable antibiotic, improves cognitive and motor function in a relevant proportion of patients with MHE [22,23], and this is associated with normalization of peripheral IL-17, CCL20, CX3CL1, and IL-15 [23], which promote the infiltration of lymphocytes into the brain. This, together with the above reports, suggests that rifaximin could improve MHE by reducing T lymphocytes infiltration into the brain.…”

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

“…It is postulated that it can regulate the metabolism of intestinal bacteria or stabilize intestinal barrier functions ( Kaji et al, 2017 ; Montagnese et al, 2018 ).Other studies have shown that it has immunomodulatory effects as it reduces inflammation by regulating bacteria. Rifaxmin was shown to improve the immune system in 59% of MHE patients ( Mangas-Losada et al, 2019 ).…”