Metabolic syndrome is associated with poor response to rifaximin in minimal hepatic encephalopathy

Abstract

Patients with cirrhosis may show minimal hepatic encephalopathy (MHE), for which rifaximin is effective. Metabolic syndrome may be associated with cognitive impairment. Our aims were to evaluate the influence of metabolic syndrome features on response to rifaximin for neurological and inflammatory alterations in MHE. A prospective cohort study was conducted in 63 cirrhotic patients and 30 controls from two tertiary centres recruited between 2015 and 2019. Metabolic syndrome was defined according to the Adult Treatment Panel-III. Patients were classified into 31 without and 32 with MHE according to the Psychometric Hepatic Encephalopathy Score (PHES). All participants performed specific psychometric tests, and inflammatory parameters were studied. Patients with MHE received rifaximin (400 mg/8 h). Response was evaluated by PHES at 3 and 6 months. Response according to metabolic syndrome manifestations was compared. The response rate was 66%. Older age (p = 0.012) and all metabolic syndrome diseases (p < 0.05) were associated with non-response, plus an increase in risk as the number of manifestations rose (p < 0.001). Patients with metabolic manifestations exhibited worse processing speed (p = 0.011), working memory (p = 0.005), visual coordination (p = 0.013) and lower proportion of activated CD4+ lymphocytes (p = 0.039) at baseline, as well as worse concentration (p = 0.030), bimanual coordination (p = 0.004) and higher levels of intermediate monocytes (p = 0.026), CX3CL1 (p < 0.05), IL-17 (p = 0.022), AHR (p = 0.010) and IgG (p < 0.05) at 3 and/or 6 months of rifaximin. Patients with clinical signs of metabolic syndrome have poor response to rifaximin for MHE, with a higher proportion of neurological alterations associated with a pro-inflammatory environment.

Diabetes mellitus – risk factor and potential future target for hepatic encephalopathy in patients with liver cirrhosis?

“…Here, metformin intake was associated with a lower risk of OHE during follow-up. However, these findings are in contrast to a recently published study indicating that metformin is associated with a reduced responsiveness to rifaximin (Ballester et al 2022 ). In the future, prospective and randomized trials are needed to investigate these associations in more detail.…”

“…In addition to studies indicating DM as a potential target for reducing the risk of HE, there is also preliminary evidence suggesting potentially harmful effects of DM on established HE treatments. Recently, a bicentric prospective cohort study including 63 patients with cirrhosis investigated the association of the metabolic syndrome on the response to rifaximin in patients with MHE (Ballester et al 2022 ). The study found that older age, NAFLD, all metabolic syndrome-associated diseases including DM and metformin intake were associated with a reduced responsiveness to rifaximin (Ballester et al 2022 ).…”

“…Recently, a bicentric prospective cohort study including 63 patients with cirrhosis investigated the association of the metabolic syndrome on the response to rifaximin in patients with MHE (Ballester et al 2022 ). The study found that older age, NAFLD, all metabolic syndrome-associated diseases including DM and metformin intake were associated with a reduced responsiveness to rifaximin (Ballester et al 2022 ). However, the results of this study have to be interpreted in the context of its design.…”

Rifaximin plus lactulose versus lactulose alone for reducing the risk of HE recurrence

“…Diabetes is a common condition in cirrhosis and can affect HE therapy efficacy. 5 , 10 However, the current results indicate that the efficacy of rifaximin plus lactulose for reducing the risk of OHE recurrence is not affected by comorbid diabetes; however, hemoglobin A1c levels were not collected during the trials. Rifaximin plus lactulose therapy should be considered for adults with cirrhosis and a history of OHE, including those with comorbid diabetes or ascites and those being discharged from an inpatient setting after a recurrent OHE episode.…”

Neurofilament Light Chain Protein in Plasma and Extracellular Vesicles Is Associated with Minimal Hepatic Encephalopathy and Responses to Rifaximin Treatment in Cirrhotic Patients

“…Healthy volunteers also undertook the PHES to rule out any kind of cognitive impairment. The other psychometric tests performed to study specific cognitive and motor alterations were the same as in [37]. Overall, 31 of 40 MHE patients were treated with rifaximin (1.2 g/day, in three doses of 400 mg every 8 h) for 6 months.…”