Limits...
Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy.

Rai R, Ahuja CK, Agrawal S, Kalra N, Duseja A, Khandelwal N, Chawla Y, Dhiman RK - Clin Transl Gastroenterol (2015)

Bottom Line: MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group.MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment.IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

ABSTRACT

Objectives: Decreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-α in its pathogenesis.

Methods: Twenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-α estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG).

Results: Ammonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions.

Conclusions: This study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE.

No MeSH data available.


Related in: MedlinePlus

Flow of the patients into the study. MHE, minimal hepatic encephalopathy; MRI, magnetic imaging resonance; NMHE, no minimal hepatic encephalopathy; PHES, psychometric hepatic encephalopathy score.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4816249&req=5

fig1: Flow of the patients into the study. MHE, minimal hepatic encephalopathy; MRI, magnetic imaging resonance; NMHE, no minimal hepatic encephalopathy; PHES, psychometric hepatic encephalopathy score.

Mentions: Between April 2012 and June 2013, 150 patients diagnosed to have cirrhosis of liver attending the outpatient liver clinic as well as those admitted under Hepatology services, PGIMER, Chandigarh were screened. Twenty-three patients (15.3%) who met the eligibility criteria were included in the study. Reasons that 127 patients (84.7%) were excluded from the study were: history of alcohol intake in the past 6 weeks (33 patients), hepatocellular carcinoma (13 patients), chronic kidney disease (4 patients), psychiatric/neurological disease (3 patients), need for long-term antibiotic use (6 patients), interferon treatment for hepatitis C virus (5 patients), spontaneous spleno-renal shunt (1patient), recent gastrointestinal bleed <6 weeks (4 patients), serum sodium <135 mEq/dl (23 patients), illiterate (10 patients), significant co-morbidities (3 patients), refusal to give consent for MRI brain or follow-up (25 patients), and unfit for MRI (4 patients). Several patients were excluded for more than one reason. After exclusion, 23 patients included in the study were screened with PHES: 14 (60.9%) patients were found to have MHE and 9 (39.1%) constituted the NMHE group. Patients found to have MHE were treated with rifaximin and lactulose as per protocol. During a follow-up of 8 weeks, 1 patient was lost to follow-up and 1 died (owing to spontaneous bacterial peritonitis resulting in sepsis and renal failure) in the NMHE group, while 1 patient was lost to follow-up and 6 died (1 owing to refractory gastrointestinal bleed, 2 owing to development of overt HE followed by sepsis and 3 owing to community-acquired infections resulting in sepsis and multi-organ failure) in the MHE group. Rest of the patients, 7 in each group, completed the study. Figure 1 shows flow of participants into the study. The clinical and demographic characteristics of patients enrolled in the study are shown in Table 1. There was no statistically significant difference between patients completing and those not completing the study (Supplementary Table S1).


Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy.

Rai R, Ahuja CK, Agrawal S, Kalra N, Duseja A, Khandelwal N, Chawla Y, Dhiman RK - Clin Transl Gastroenterol (2015)

Flow of the patients into the study. MHE, minimal hepatic encephalopathy; MRI, magnetic imaging resonance; NMHE, no minimal hepatic encephalopathy; PHES, psychometric hepatic encephalopathy score.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4816249&req=5

fig1: Flow of the patients into the study. MHE, minimal hepatic encephalopathy; MRI, magnetic imaging resonance; NMHE, no minimal hepatic encephalopathy; PHES, psychometric hepatic encephalopathy score.
Mentions: Between April 2012 and June 2013, 150 patients diagnosed to have cirrhosis of liver attending the outpatient liver clinic as well as those admitted under Hepatology services, PGIMER, Chandigarh were screened. Twenty-three patients (15.3%) who met the eligibility criteria were included in the study. Reasons that 127 patients (84.7%) were excluded from the study were: history of alcohol intake in the past 6 weeks (33 patients), hepatocellular carcinoma (13 patients), chronic kidney disease (4 patients), psychiatric/neurological disease (3 patients), need for long-term antibiotic use (6 patients), interferon treatment for hepatitis C virus (5 patients), spontaneous spleno-renal shunt (1patient), recent gastrointestinal bleed <6 weeks (4 patients), serum sodium <135 mEq/dl (23 patients), illiterate (10 patients), significant co-morbidities (3 patients), refusal to give consent for MRI brain or follow-up (25 patients), and unfit for MRI (4 patients). Several patients were excluded for more than one reason. After exclusion, 23 patients included in the study were screened with PHES: 14 (60.9%) patients were found to have MHE and 9 (39.1%) constituted the NMHE group. Patients found to have MHE were treated with rifaximin and lactulose as per protocol. During a follow-up of 8 weeks, 1 patient was lost to follow-up and 1 died (owing to spontaneous bacterial peritonitis resulting in sepsis and renal failure) in the NMHE group, while 1 patient was lost to follow-up and 6 died (1 owing to refractory gastrointestinal bleed, 2 owing to development of overt HE followed by sepsis and 3 owing to community-acquired infections resulting in sepsis and multi-organ failure) in the MHE group. Rest of the patients, 7 in each group, completed the study. Figure 1 shows flow of participants into the study. The clinical and demographic characteristics of patients enrolled in the study are shown in Table 1. There was no statistically significant difference between patients completing and those not completing the study (Supplementary Table S1).

Bottom Line: MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group.MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment.IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

ABSTRACT

Objectives: Decreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-α in its pathogenesis.

Methods: Twenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-α estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG).

Results: Ammonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions.

Conclusions: This study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE.

No MeSH data available.


Related in: MedlinePlus