Impairment In Cirrhotic Patients Research Articles

Extracellular Vesicles From Hyperammonemic Rats Induce Neuroinflammation in Cerebellum of Normal Rats: Role of Increased TNFα Content.

Hyperammonemia plays a main role in the neurological impairment in cirrhotic patients with hepatic encephalopathy. Rats with chronic hyperammonemia reproduce the motor incoordination of patients with minimal hepatic encephalopathy, which is due to enhanced GABAergic neurotransmission in cerebellum as a consequence of neuroinflammation. Extracellular vesicles (EVs) could play a key role in the transmission of peripheral alterations to the brain to induce neuroinflammation and neurological impairment in hyperammonemia and hepatic encephalopathy. EVs from plasma of hyperammonemic rats (HA-EVs) injected to normal rats induce neuroinflammation and motor incoordination, but the underlying mechanisms remain unclear. The aim of this work was to advance in the understanding of these mechanisms. To do this we used an ex vivo system. Cerebellar slices from normal rats were treated ex vivo with HA-EVs. The aims were: 1) assess if HA-EVs induce microglia and astrocytes activation and neuroinflammation in cerebellar slices of normal rats, 2) assess if this is associated with activation of the TNFR1-NF-kB-glutaminase-GAT3 pathway, 3) assess if the TNFR1-CCL2-BDNF-TrkB pathway is activated by HA-EVs and 4) assess if the increased TNFα levels in HA-EVs are responsible for the above effects and if they are prevented by blocking the action of TNFα. Our results show that ex vivo treatment of cerebellar slices from control rats with extracellular vesicles from hyperammonemic rats induce glial activation, neuroinflammation and enhance GABAergic neurotransmission, reproducing the effects induced by hyperammonemia in vivo. Moreover, we identify in detail key underlying mechanisms. HA-EVs induce the activation of both the TNFR1-CCL2-BDNF-TrkB-KCC2 pathway and the TNFR1-NF-kB-glutaminase-GAT3 pathway. Activation of these pathways enhances GABAergic neurotransmission in cerebellum, which is responsible for the induction of motor incoordination by HA-EVs. The data also show that the increased levels of TNFα in HA-EVs are responsible for the above effects and that the activation of both pathways is prevented by blocking the action of TNFα. This opens new therapeutic options to improve motor incoordination in hyperammonemia and also in cirrhotic patients with hepatic encephalopathy and likely in other pathologies in which altered cargo of extracellular vesicles contribute to the propagation of the pathology.

Aberrant stability of brain functional architecture in cirrhotic patients with minimal hepatic encephalopathy.

To investigate the stability changes of brain functional architecture and the relationship between stability change and cognitive impairment in cirrhotic patients. Fifty-one cirrhotic patients (21 with minimal hepatic encephalopathy (MHE) and 30 without MHE (NHE)) and 29 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and neurocognitive assessment using the Psychometric Hepatic Encephalopathy Score (PHES). Voxel-wise functional connectivity density (FCD) was calculated as the sum of connectivity strength between one voxel and others within the entire brain. The sliding window correlation approach was subsequently utilized to calculate the FCD dynamics over time. Functional stability (FS) is measured as the concordance of dynamic FCD. From HCs to the NHE and MHE groups, a stepwise reduction of FS was found in the right supramarginal gyrus (RSMG), right middle cingulate cortex, left superior frontal gyrus, and bilateral posterior cingulate cortex (BPCC), whereas a progressive increment of FS was observed in the left middle occipital gyrus (LMOG) and right temporal pole (RTP). The mean FS values in RSMG/LMOG/RTP (r = 0.470 and P = 0.001; r = -0.458 and P = 0.001; and r = -0.384 and P = 0.005, respectively) showed a correlation with PHES in cirrhotic patients. The FS index in RSMG/LMOG/BPCC/RTP showed moderate discrimination potential between the NHE and MHE groups. Changes in FS may be linked to neuropathological bias of cognitive impairment in cirrhotic patients and could serve as potential biomarkers for MHE diagnosis and monitoring the progression of hepatic encephalopathy.

A multi-omic study for uncovering molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment in rats.

Patients with liver cirrhosis may develop covert or minimal hepatic encephalopathy (MHE). Hyperammonemia (HA) and peripheral inflammation play synergistic roles in inducing the cognitive and motor alterations in MHE. The cerebellum is one of the main cerebral regions affected in MHE. Rats with chronic HA show some motor and cognitive alterations reproducing neurological impairment in cirrhotic patients with MHE. Neuroinflammation and altered neurotransmission and signal transduction in the cerebellum from hyperammonemic (HA) rats are associated with motor and cognitive dysfunction, but underlying mechanisms are not completely known. The aim of this work was to use a multi-omic approach to study molecular alterations in the cerebellum from hyperammonemic rats to uncover new molecular mechanisms associated with hyperammonemia-induced cerebellar function impairment. We analyzed metabolomic, transcriptomic, and proteomic data from the same cerebellums from control and HA rats and performed a multi-omic integrative analysis of signaling pathway enrichment with the PaintOmics tool. The histaminergic system, corticotropin-releasing hormone, cyclic GMP-protein kinase G pathway, and intercellular communication in the cerebellar immune system were some of the most relevant enriched pathways in HA rats. In summary, this is a good approach to find altered pathways, which helps to describe the molecular mechanisms involved in the alteration of brain function in rats with chronic HA and to propose possible therapeutic targets to improve MHE symptoms.

Cirrhotic Cardiomyopathy-A Veiled Threat.

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction in patients with liver cirrhosis without preexisting cardiac disease. According to the definition established by the World Congress of Gasteroenterology in 2005, the diagnosis of CCM includes criteria reflecting systolic dysfunction, impaired diastolic relaxation, and electrophysiological disturbances. Because of minimal or even absent clinical symptoms and echocardiographic signs at rest according to the 2005 criteria, CCM diagnosis is often missed or delayed in most clinically stable cirrhotic patients. However, cardiac dysfunction progresses in time and contributes to the pathogenesis of hepatorenal syndrome and increased morbidity and mortality after liver transplantation, surgery, or other invasive procedures in cirrhotic patients. Therefore, a comprehensive cardiovascular assessment using newer techniques for echocardiographic evaluation of systolic and diastolic function, allowing the diagnosis of CCM in the early stage of subclinical cardiovascular dysfunction, should be included in the screening process of liver transplant candidates and patients with cirrhosis in general. The present review aims to summarize the most important pathophysiological aspects of CCM, the usefulness of contemporary cardiovascular imaging techniques and parameters in the diagnosis of CCM, the current therapeutic options, and the importance of early diagnosis of cardiovascular impairment in cirrhotic patients.

Mini-dose albumin can reduce renal impairment in cirrhotic patients with spontaneous bacterial peritonitis

Mini-dose albumin can reduce renal impairment in cirrhotic patients with spontaneous bacterial peritonitis

Effect of terlipressin on renal function in cirrhotic patients with acute upper gastrointestinal bleeding.

BackgroundRenal dysfunction is a serious morbidity in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB). Terlipressin is the first-line treatment choice for acute variceal bleeding and hepatorenal syndrome (HRS). This study aimed to assess the effect of terlipressin on renal function in patients with liver cirrhosis and AUGIB.MethodsWe retrospectively reviewed 40 cirrhotic patients with AUGIB treated with terlipressin by an attending physician between January 2016 and June 2018. We analyzed the change of renal function parameters, including cystatin C (CysC) and creatinine (Cr), during the use of terlipressin and after terlipressin was stopped. We also identified the factors associated with renal function improvement in patients without active bleeding during the use of terlipressin.ResultsDuring the use of terlipressin, CysC value was significantly reduced (1.3±0.8 vs. 1.1±0.7, P=0.001); Cr value was reduced, but the reduction was not statistically significant (68.8±24 vs. 65.5±23, P=0.817); the rate of CysC reduction was significantly higher in patients treated with terlipressin than those treated with somatostatin/octreotide (73.1% vs. 0%, P=0.005); the rate of Cr reduction was not significantly different between patients treated with terlipressin and somatostatin/octreotide (61.5% vs. 20%, P=0.148); no factor associated with CysC reduction was identified; higher hemoglobin, red blood cell, and platelet and lower prothrombin time and international normalized ratio at baseline were significantly associated with Cr reduction. After terlipressin was stopped, neither CysC nor Cr value was significantly reduced (P=0.852 and P=0.296).ConclusionsTerlipressin may be beneficial on preventing renal function impairment in cirrhotic patients with AUGIB.

Autonomic and diastolic dysfunction association with quality of life impairment in cirrhotic patients

Background and study aimsCirrhosis is a multisystem disorder characterized by hyperdynamic circulation which can progress to multiple organ dysfunctions. Recent studies have demonstrated autonomic dysfunction and cirrhotic cardiomyopathy including diastolic dysfunction, systolic dysfunction with electrophysiologic abnormalities in patients with cirrhosis. Due to the long and complicated course of the disease, health related quality of life is affected. We aimed to evaluate the frequency of diastolic dysfunction and autonomic dysfunction in cirrhosis, and the effects on health-related quality of life. Patients and methodsHundred cirrhotic patients were enrolled in the study. According to the Child-Pugh classification 35 patients were of Child A, 36 of Child B and 29 of Child C. The proportion of autonomic dysfunction was 52%, and diastolic dysfunction 51%. Autonomic dysfunction was diagnosed using bedside maneuvers and tests; diastolic dysfunction was diagnosed using the E/A ratio in echocardiographic findings. Health-related quality of life measurements was obtained from an SF-36 questionnaire. ResultsPatients with advanced Child-Pugh classifications were found to have significantly lower health-related quality of life values (p < 0.05). Likewise, health-related quality of life values were observed to be significantly lower in patients with autonomic dysfunction (p < 0.05). No significant difference was found in health related quality of life measurements between patients with and without diastolic dysfunction. ConclusionOur study showed that autonomic dysfunction and diastolic dysfunction are found in patients with cirrhosis. Further studies are needed to assess the effects of autonomic dysfunction and diastolic dysfunction on health-related quality of life.

Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). MHE is considered as a preclinical stage of HE and is part of a wide spectrum of typical neurocognitive alterations characteristic of patients with liver cirrhosis, particularly involving the areas of attention, alertness, response inhibition, and executive functions. MHE can be detected by testing the patients’ psychometric performance, attention, working memory, psychomotor speed, and visuospatial ability, as well as by means of electrophysiological and other functional brain measures. MHE is very frequent, affecting from 20% up to 80% of patients tested, depending of the diagnostic tools used. Although subclinical, MHE is considered to be clinically relevant. In fact, MHE has been related to the patients’ falls, fitness to drive, and working ability. As a consequence, MHE affects the patients and caregivers lives by altering their quality of life and even their socioeconomic status. Recently sarcopenia, a very common condition in patients with advanced liver disease, has been shown to be strictly related to both minimal and overt HE. Aim of this review is to summarize the most recently published evidences about the emerging relationship between sarcopenia and cognitive impairment in cirrhotic patients and provide suggestions for future research.

Right heart impairement in cirrhotic patients

Right ventricular dysfunction in cirrhotic patients is not well described, we suggest that cirrhosis will result in an increase of pulmonary resistance and the post-charge of RV, we aim to assess ventricle function in cirrhotic patients and the correlation between the severity of cirrhosis and the RV dysfunction. We assessed echocardiographic RV systolic function in 80 patients with cirrhosis. We compared compensated ( n = 39) and uncompensated patients ( n = 41) to controls ( n = 80). The severity of cirrhotic disease was assessed by Child and Mild scores. RV was significantly enlarged in cirrhotic patients compared to controls and in uncompensated patients compared to compensated patients (RV diastolic area = 16.7 ± 5 cm 2 , 14.5 ± 4 cm 2 , P = 0.01). The TAPSE and the S wave were significantly lower in cirrhotic patients ( P = 0.007) compared to controls but there were no difference between the sub-groups. Longitudinal peak systolic speckle tracking of lateral RV wall was significantly decreased in cirrhotic patients ( P < 0.001). There was no correlation between the different parameters of the RV and Child as well as Mild scores. The present study illustrated RV systolic function impairment in cirrhotic patients. The lack of correlation between the right ventricle dysfunction and the severity of cirrhosis suggest a complex mechanism. Right ventricular dysfunction in cirrhotic patients is not well described, we suggest that cirrhosis will result in an increase of pulmonary resistance and the post-charge of RV, we aim to assess ventricle function in cirrhotic patients and the correlation between the severity of cirrhosis and the RV dysfunction. We assessed echocardiographic RV systolic function in 80 patients with cirrhosis. We compared compensated ( n = 39) and uncompensated patients ( n = 41) to controls ( n = 80). The severity of cirrhotic disease was assessed by Child and Mild scores. RV was significantly enlarged in cirrhotic patients compared to controls and in uncompensated patients compared to compensated patients (RV diastolic area = 16.7 ± 5 cm 2 , 14.5 ± 4 cm 2 , P = 0.01). The TAPSE and the S wave were significantly lower in cirrhotic patients ( P = 0.007) compared to controls but there were no difference between the sub-groups. Longitudinal peak systolic speckle tracking of lateral RV wall was significantly decreased in cirrhotic patients ( P < 0.001). There was no correlation between the different parameters of the RV and Child as well as Mild scores. The present study illustrated RV systolic function impairment in cirrhotic patients. The lack of correlation between the right ventricle dysfunction and the severity of cirrhosis suggest a complex mechanism.

Neurological Impairment in Cirrhotic Patients Admitted to ICU: Hepatic Versus Drug-Induced Encephalopathy

Neurological Impairment in Cirrhotic Patients Admitted to ICU: Hepatic Versus Drug-Induced Encephalopathy

Is cognitive impairment in cirrhotic patients due to increased peroxynitrite and oxidative stress?

Cirrhotic patients may suffer minimal hepatic encephalopathy (MHE), with mild cognitive impairment. 3-Nitro-tyrosine levels are a good biomarker for diagnosis of the cognitive impairment and MHE in cirrhotic patients. This suggests that oxidative stress could be involved in the induction of cognitive and motor alterations in MHE. We have observed that patients with MHE show increased oxidative stress in blood compared with cirrhotic patients without MHE, with increased lipid peroxidation, DNA oxidation, protein carbonylation, 3-nitrotyrosine, oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio, and GSH levels. The activities of antioxidant enzymes are enhanced in erythrocytes and mononuclear cells from patients with and without MHE compared with control subjects. Only glutathione peroxidase activity was increased in MHE patients compared with patients without MHE. Oxidative stress markers in blood, especially GSSG/GSH ratio, GSH, malondialdehyde, and 3-nitrotyrosine, correlate with deficits in attention and motor coordination. The increase in antioxidant activities in patients would be an adaptive mechanism to cope with enhanced oxidative stress, although it is not effective enough to normalize it. Our observations lead to the hypothesis that oxidative stress and increased peroxynitrite formation would mediate the synergistic effects of hyperammonemia and inflammation on cognitive and motor impairment in MHE.

Ammonia-induced senescence in cultured rat astrocytes and in human cerebral cortex in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis and is due to a low-grade cerebral edema associated with oxidative/nitrosative stress. Recent reports suggest that cognitive impairment in cirrhotic patients may not resolve completely after an attack of manifest HE. As astrocyte dysfunction is central to the pathogenesis of HE and astrocytes are critically involved in synaptic plasticity, we tested for sustained impairment of astrocyte function by analyzing expression levels of senescence biomarkers in ammonia-treated cultured rat astrocytes and in postmortem brain samples from cirrhotic patients with or without HE. NH4 Cl time- and dose-dependently inhibited proliferation of cultured astrocytes by up to 45% (5 mmol/L, 72 h) and strongly increased senescence-associated β-galactosidase activity. Inhibition of astrocyte proliferation by ammonia was mediated by a l-methionine sulfoximine-, oxidative stress-, and p38(MAPK) -dependent activation of p53 associated with enhanced transcription of cell cycle inhibitory genes GADD45α and p21. Mitochondria and the nucleus were identified as sources of oxygen radical formation after prolonged NH4 Cl exposure. Concurrently, NH4 Cl (5 mmol/L) treatment inhibited both epidermal growth factor- and brain-derived neurotrophic factor (BDNF)-induced proliferation as well as BDNF-mediated astrocyte morphology changes through downregulation of the respective growth factor receptors epidermal growth factor receptor and truncated tyrosine receptor kinase B. Increased mRNA expression levels of senescence-associated genes were also found in post mortem brain samples from patients with liver cirrhosis with HE, but not in those without HE. The data suggest that ammonia toxicity and HE are associated with premature astrocyte senescence, which may impair neurotransmission and contribute to persistence of cognitive disturbances after resolution of episodes of overt HE.

Mo1022 Effect of Body Mass Index (BMI) on Functional Status of Patients With Cirrhosis Based on the Six-Minute Walk Test (6mwt)

Background & Aims: Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment, however recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment. Methods: Of 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). Among 102 patients included in the study, 86 were men and 16 were women; 67 (65.7%) patients had alcoholic etiology and 35 (34.3%) had non-alcoholic etiology (hepatitis B virus 6 patients, hepatitis C virus 4 patients, cryptogenic 14 patients, miscellaneous 11 patients). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at 3 separate visits (Day 1, Day 3 and between 30 and 60 days, median 34). PHES ≤5 was considered abnormal and diagnostic of minimal HE (MHE). One point improvement in PHES between first and second evaluation was considered as a measure of learning. Results: Thirty-four (33.3%) of patients with cirrhosis of liver had MHE; 20 (40%) with prior episode and 14 (26.9%) without prior episode of OHE had MHE. Patients with previous OHE episode showed learning impairment in PHES on repetition on 3rd day [Day 1, mean -3.70 (95% confidence intervals -4.71 -2.68) versus Day 3, -4.02 (-5.06-2.97); P = 0.084] as compared to patients without prior OHE episode [Day 1, -2.26 (-3.13 -1.40) versus Day 3, -0.44 (-1.24 0.35); P <0.0001] irrespective of having MHE or not. In this study, 57 patients were learners, i.e., 1point improvement in PHES (55.8%) and 45 patients were non-learners (44.2%). Univariate analysis demonstrated that Child-Turcotte-Pugh score, lactulose and/or rifaximin therapy, presence of MHE and previous OHE episode were associated with learning impairment. Multivariate analysis demonstrated that only presence of previous episode of OHE (adjusted odds ratio [95%, confidence interval; 38.398, 9.192 160.4]; p <0.0001) significantly affected learning. Conclusions: This study conclusively demonstrated learning impairment in cirrhotic patients with previous episode of OHEdespite normalmental status. Improvement in PHES on repetition can be used as a measure of learning in future studies.

Persistence of cognitive impairment after resolution of overt hepatic encephalopathy.

Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment; however, recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment. Of the 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at three separate visits (day 1, day 3, and between 30 and 60 days). A one-point improvement in PHES between the first and second evaluation was considered as a measure of learning. Patients with a previous OHE episode showed learning impairment in PHES on repetition on day 3 (P=0.084), whereas patients without a previous OHE episode demonstrated learning effect (P<0.0001) irrespective of whether they had minimal HE (MHE) or not. Univariate analysis demonstrated that Child-Turcotte-Pugh score, lactulose and/or rifaximin therapy, the presence of MHE, and a previous OHE episode were associated with learning impairment. Multivariate analysis demonstrated that only the presence of a previous episode of OHE (adjusted odds ratio 38.398; 95% confidence interval 9.192-160.4; P<0.0001) significantly affected learning. This study conclusively demonstrated learning impairment in cirrhotic patients with a previous episode of OHE despite normal mental status. Improvement in PHES on repetition may be a measure of learning.

Urinary biomarkers of acute kidney injury in patients with liver cirrhosis.

Acute kidney injury (AKI) is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. This study aimed to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients. 160 patients with cirrhosis admitted to the Liver Units at Zagazig University Hospitals were classified into three groups: (I) nonascitic patients, (II) ascitic patients without renal impairment, and (III) ascitic patients with renal impairment. Patients with renal impairment were further divided into four subgroups: [A] prerenal azotemia, [B] chronic kidney disease (CKD), [C] hepatorenal syndrome (HRS), and [D] acute tubular necrosis (ATN). Significant elevation of both urinary NGAL and urinary IL-18 in cirrhotic patients with renal impairment especially in patients with ATN was observed. Urinary NGAL and urinary IL-18 have the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI.

Urinary biomarkers of acute kidney injury in patients with liver cirrhosis.

ABSTRACTBackground and aim:Acute kidney injury is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. The aim of this study was to evaluate Urinary Neutrophils Gelatinase-Associated Lipocalin (NGAL) and Urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients.Patients and methods:160 cirrhotic patients was enrolled in this study divided into 3 main groups according to presence or absence of ascites and renal impairment. Results:Significant elevation of both Urinary NGAL and Urinary IL-18 in cirrhotic patients with renal impairment especially in patients with Acute tubular necrosis (ATN) was observed. AUROC was (0.909) with (sensitivity 95.5 %, specificity 76.1) for Urinary NGAL and AUROC was (0.975), with (sensitivity 95.5 %, specificity 91.3 %) for Urinary IL-18.Conclusion:both Urinary NGAL and Urinary IL-18 can act as urinary biomarkers of acute kidney injury in cirrhotic patient

Increased risk of cognitive impairment in cirrhotic patients with bacterial infections

A causal relationship between infection, systemic inflammation, and hepatic encephalopathy (HE) has been suggested in cirrhosis. No study, however, has specifically examined, in cirrhotic patients with infection, the complete pattern of clinical and subclinical cognitive alterations and its reversibility after resolution. Our investigation was aimed at describing the characteristics of cognitive impairment in hospitalized cirrhotic patients, in comparison with patients without liver disease, with and without infection. One hundred and fifty cirrhotic patients were prospectively enrolled. Eighty-one patients without liver disease constituted the control group. Bacterial infections and sepsis were actively searched in all patients independently of their clinical evidence at entry. Neurological and psychometric assessment was performed at admission and in case of nosocomial infection. The patients were re-evaluated after the resolution of the infection and 3months later. Cognitive impairment (overt or subclinical) was recorded in 42% of cirrhotics without infection, in 79% with infection without SIRS and in 90% with sepsis. The impairment was only subclinical in controls and occurred only in patients with sepsis (42%). Multivariate analysis selected infection as the only independent predictor of cognitive impairment (OR 9.5; 95% CI 3.5-26.2; p=0.00001) in cirrhosis. The subclinical alterations detected by psychometric tests were also strongly related to the infectious episode and reversible after its resolution. Infections are associated with a worse cognitive impairment in cirrhotics compared to patients without liver disease. The search and treatment of infections are crucial to ameliorate both clinical and subclinical cognitive impairment of cirrhotic patients.

Effect of Renal Impairment on Mortality of Patients With Cirrhosis and Spontaneous Bacterial Peritonitis

The effects of end-stage renal disease (ESRD) on the mortality of patients with cirrhosis and spontaneous bacterial peritonitis (SBP) have not been determined. We collected data from Taiwan's National Health Insurance Database on 2592 patients with cirrhosis who were hospitalized with SBP from January 1 to December 31, 2004. Patients were matched with individuals from a national mortality database; 30-day and 1-year mortalities were calculated for each group and compared to calculate hazard ratios (HRs). Of the patients with cirrhosis and SBP, 300 (11.5%) had renal function impairment. Of these, 145 had acute renal failure, 70 had ESRD, and 75 had chronic kidney disease. Overall, 30-day and 1-year mortality were 21.3% and 51.7%, respectively. After adjusting for age, sex, and underlying comorbidities, HRs for 30-day mortality from renal function impairment, acute renal failure, ESRD, and chronic kidney disease were 3.00, 4.68, 1.93, and 1.37, respectively. The HRs for 1-year mortality from renal function impairment, acute renal failure, ESRD, and chronic kidney disease were 2.03, 2.78, 1.70, and 1.37, respectively. The adjusted HRs for 30-day and 1-year mortality of patients with acute renal failure were 2.6 and 1.6, respectively, compared with patients with ESRD. Acute renal failure is a better determinant of 30-day and 1-year mortality than renal function impairment in cirrhotic patients with SBP.

Serum levels of astroglial S100-beta and neuron-specific enolase in hepatic encephalopathy patients

To find a reliable, noninvasive method for the diagnosis of cognitive impairment in patients with hepatic cirrhosis we measured serum levels of astroglial S100beta and neuron-specific enolase in cirrhotic patients with and without hepatic encephalopathy (HE). S100beta levels showed a significant increase in groups with HE stage 1 and 2 compared to both control and cirrhosis patients. However serum neuron-specific enolase levels were not significantly different between the studied groups. S100beta levels had a specificity of 91.3% and sensitivity of 51.7% for detection of HE from cirrhosis. Serum S100beta may be a useful surrogate marker for the diagnosis of mild cognitive impairment in cirrhotic patients before they progress to more advanced stages of HE.

Neural mechanism of cognitive control impairment in patients with hepatic cirrhosis: a functional magnetic resonance imaging study

Many studies have claimed the existence of attention alterations in cirrhotic patients without overt hepatic encephalopathy (HE). No functional magnetic resonance imaging (fMRI) study in this respect has been published. To investigate the neural basis of cognitive control deficiency in cirrhotic patients using fMRI. 14 patients with hepatic cirrhosis and 14 healthy volunteers were included in the study. A modified Stroop task with Chinese characters was used as the target stimulus, and block-design fMRI was used to acquire resource data, including four stimulus blocks and five control blocks, each presented alternatively. Image analysis was performed using statistical parametric mapping 99. After fMRI examinations were complete, behavior tests of Stroop interference were performed for all subjects. Overall reaction time and error numbers were recorded. Both healthy volunteers and patients with hepatic cirrhosis had Stroop interference effects. Patients with hepatic cirrhosis had more errors and longer reaction time in performing an incongruous color-naming task than healthy volunteers (P<0.001); there was no significant difference in performing an incongruous word-reading task (P = 0.066). Compared with controls, patients with hepatic cirrhosis had greater activation of the bilateral prefrontal cortex and parietal cortex when performing the incongruous word-reading task. With increased conflict, activation of the anterior cingulate cortex (ACC), bilateral prefrontal cortex (PFC), parietal lobe, and temporal fusiform gyrus (TFG) was decreased when patients with hepatic cirrhosis performed the incongruous color-naming task. This study demonstrates that patients with hepatic cirrhostic have cognitive control deficiency. The abnormal brain network of the ACC-PFC-parietal lobe-TFG is the neural basis of cognitive control impairment in cirrhotic patients.