Hepatic Encephalopathy Grade Research Articles

Response to Congly and Leise

To the Editor: We read with interest the concerns raised by Congly et al. (1) about the mortality and antibiotic coverage of infections in our study (2). The majority of patients enrolled in our study had advanced liver disease (>70% were Child's B and C) and severe hepatic encephalopathy (HE) (grade ≥3.80%) (2). We excluded patients with a history, as told by close relatives, of active alcohol intake in the 4 weeks preceding the present episode of HE. We did not perform liver biopsy in these patients, as they were critically ill. Some of our patients even showed symptoms similar to those in patients with acute on chronic liver failure, with sepsis, spontaneous bacterial peritonitis, and variceal bleed being the acute insult on underlying chronic liver disease.

Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts

Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced.

Study of the relation between diabetes mellitus and hepatic encephalopathy in patients with liver cirrhosis

Objective This study was designed to determine the role of diabetes mellitus (DM) in the pathogenesis of hepatic encephalopathy (HE) in patients with liver cirrhosis. Background DM and its complications may play a role in the mortality of hepatitis C virus (HCV)-related cirrhotic patients. DM is considered a comorbid disease in these patients and strict control of blood glucose level could improve survival in HCV-related cirrhosis. Patients and methods This study was carried out on 100 cirrhotic patients with DM [50 encephalopathic patients (group I) and 50 nonencephalopathic patients (group II)]. All patients in the study were subjected to a thorough assessment of history taking and thorough physical examination, laboratory investigations, including complete blood picture, liver function tests, liver, viral HBsAg and HCVAb, kidney function tests, serum sodium and potassium levels, abdominal ultrasonography, serum ammonia level, fasting and postprandial blood sugar levels, glycosylated hemoglobin (HbA1c) as well as tests to detect the presence of autonomic neuropathy (tilt-table test and diurnal variation of blood pressure measurements). Results The present study found a significant positive tilt-table test result and diurnal variation in blood pressure measurements in the encephalopathic group in comparison with the nonencephalopathic group, and a highly significant positive correlation between duration of DM and HbA1c levels when compared with grades of HE in the encephalopathic group. Conclusion Cirrhotic patients with longstanding and uncontrolled DM are more likely to have higher grades of HE. Autonomic neuropathy, which may complicate cirrhotic patients with longstanding uncontrolled diabetes, may play a role in the pathogenesis of HE in these patients.

Chapter 34 - Hepatic encephalopathy in alcoholic cirrhosis

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of cirrhosis in alcoholic patients that is characterized clinically by personality changes, sleep abnormalities, and impaired motor coordination, as well as cognitive dysfunction progressing to stupor and coma. Procedures used for diagnosis and grading of HE include neurologic assessment, electroencephalography, psychometric testing, and use of the critical flicker frequency test. Neuropathologically, HE in cirrhosis is principally a disorder of neuroglia characterized by Alzheimer type II astrocytosis and activation of microglia. However, thalamic and cerebellar neuronal pathologies have been noted as well as lesions to globus pallidus and substantia nigra, leading to a condition known as "parkinsonism in cirrhosis." Multiple mechanisms have been proposed to account for the pathogenesis of HE in cirrhosis, including the neurotoxic actions of ammonia and manganese (normally removed via the hepatobiliary route), impaired brain energy metabolism, central proinflammatory mechanisms, and alterations of both excitatory and inhibitory neurotransmission. Treatment of HE in cirrhosis continues to rely on ammonia-lowering strategies such as lactulose, antibiotics, probiotics and l-ornithine l-aspartate with nutritional management consisting of adequate (but not excessive) dietary protein and vitamin B1 supplements. l-DOPA may improve parkinsonian symptoms. Liver transplantation leads to recovery of central nervous system function in the majority of cases.

Randomized, Placebo-Controlled Trial of Transdermal Rivastigmine for the Treatment of Encephalopathy in Liver Cirrhosis (TREC Trial)

Objectives: Cognitive dysfunction in patients with hepatic encephalopathy (HE) may be caused by alterations in cholinergic neurotransmission. The objective of the study was to evaluate the efficacy and safety of transdermal rivastigmine in improving cognitive function in patients with overt HE. Design: Randomized, controlled pilot study in which patients with grade 2 or 3 HE were treated with lactulose and randomized to receive either transdermal rivastigmine or placebo for 21 days. The modified encephalopathy scale (MES), object recognition test (ORT), trail test (TT), and serum ammonia were assessed at baseline weekly. Electroencephalography was performed at baseline and the final week of the study. Results: Patients were treated with lactulose (20 g/30 mL three times per day) and either transdermal rivastigmine (4.6 mg/d; n = 15) or placebo (n = 15). Transdermal rivastigmine significantly improved MES, ORT, and TT results compared with placebo (P ≤ 0.0001 at all 3 weeks for all 3 assessments). Serum ammonia improved in both treatment groups, although there was significantly greater improvement with placebo than rivastigmine after 2 weeks of treatment (P What is already known about this subject? ? Current approaches to the management of HE are primarily designed to reduce the levels of ammonia and other gut-derived toxins. ? Traditional strategies for HE treatment have included non-absorbable disaccharides (to decrease bowel transit time) or rifamixin (non-absorbable antibiotics to reduce ammoniogenic flora). ? No transdermal cholinomimetic agents have been used with oral lactulose to date, in HE. What are the new findings? ? Transdermal rivastigmine is safe for use in patients with grade 2 & 3 HE. ? Transdermal rivastigmine in combination with oral lactulose in this study is far superior to lactulose alone in improving cognitive function. How might it impact on clinical practice in the foreseeable future? ? Transdermal rivastigmine in combination with oral lactulose can be used safely in clinical practice. ? Transdermal rivastigmine in combination with oral lactulose is efficacious in improving cognitive function in moderate HE (grade 2/3). Further validation through large randomized clinical trials is required before this is adopted in universal clinical practice of treating HE.

Sonographic and clinical features of collateral vessels at the splenic hilum in cirrhosis

To examine the sonographic features of shunt vessels derived from the splenic vein at splenic hilum (SS), and explore the relationship between the SS pattern and clinical presentations. This prospective study in cirrhotic patients consisted of study I (n = 15), which compared the anatomical features of SS at ultrasonography versus angiography, and study II (n = 233), which examined the incidence/haemodynamics of SS and SS-related presentations. Study I showed that SS1 (running toward the upper pole of the spleen) corresponded to short gastric veins, and SS2 (running toward the lower pole of the spleen) corresponded to splenorenal/retroperitoneal shunts. In study II, SS were detected in 47.6% of patients (111/233), SS1 in 77.5% (86/111), SS2 in 17.1% (19/111), and SS3 (both SS1 and SS2) in 5.4% (6/111). The incidence of gastric cardia varices was significantly higher in patients with SS2 (6/19) than in those with SS1 (8/86, p = 0.0097), whereas the incidence of gastric fundal varices was significantly higher in patients with SS1 (44/86) than in those with SS2 (1/19, p = 0.00025) or SS3 (0/6, p = 0.015). There was no difference in the incidence of oesophageal varices among the three SS groups. The Child-Pugh score and grade of ascites was significantly worse in patients with SS3 than in those with SS1 (p < 0.0001, p = 0.0009). Hepatic encephalopathy grade was significantly worse in patients with SS2 (p = 0.0047) or SS3 (p < 0.0001) compared to SS1. The SS pattern facilitates estimation of the possible manifestations, indicating the direction of clinical management of cirrhosis patients. Potential poor liver function is noted in patients with SS3.

Serum and ascitic fluid serotonin levels and 5-hydroxyindoleacetic acid urine excretion in the liver of cirrhotic patients with encephalopathy

The excess and deficit of serotonin can be the cause of somatic and mental disorders. The aim of this study was to evaluate serotonin levels in blood and ascitic fluid as well as excretion of 5-hydroxyindoleacetic acid (5-HIAA) in urine in patients with hepatic encephalopathy (HE). The study included 75 alcoholic cirrhotic patients divided into 3 groups (HE1, HE2, HE3), 25 patients each, with grade 1, 2 and 3 of hepatic encephalopathy according to West-Haven classification. The control group (C) included 25 clinically healthy volunteers. Venous blood and ascitic fluid were collected in fasting. On the same day a 24-hour urine collection was performed. Immunoenzymatic method was used to determine the serotonin level in serum and ascitic fluid, and 5-HIAA in urine (IBL-RE-59121, RE-59131). In the control group, mean serum serotonin level (ng/ml) was 155.5 ± 38.1 and in the 3 study groups: HE1 - 175.2 ± 32.4 (NS), HE2 - 137.2 ± 28.6 (NS), HE3 - 108.3 ± 46.3 (p<0.001). Serotonin concentration in ascitic fluid was on the average about 25% of its level in serum. The excretion of 5-HIAA in urine (mg/24h) in all groups, was: C - 5.9 ± 2.1, HE1 - 5.8 ± 1.8 (NS), HE2 - 4.8 ± 1.2(NS), HE3 - 4.3 ± 1.3 (p<0.05). The results of our study indicate that serum and ascitic fluid level of serotonin and urine excretion of 5-HIAA depends on the grade of hepatic encephalopathy. In patients with severe hepatic encephalopathy serotonin concentration in blood is decreased which can affect some clinical manifestation of this disease.

Causes and Outcomes of Acute Liver Failure in China

ObjectivesNo extensive investigation has been performed and thus no representative data are available regarding acute liver failure (ALF) in China. This study aims to investigate the causes and outcomes of ALF in China and establish a prognostic model. MethodsPatients diagnosed as ALF in seven hospitals in different areas of China from January 2007 to December 2012 were retrospectively selected. ResultsOf the 177 patients included in this study, 112 (63.28%) eventually died. The common causes of ALF were drug toxicity (43.50%), indeterminate etiology (29.38%) and acute viral hepatitis (11.30%). Additionally, traditional Chinese herbs predominated in the causes of drug-induced ALF (30/77). No patients in this study received liver transplantation. In the established model for predicting death in ALF, four variables were finally selected out, including age (P=0.01), the entry hepatic encephalopathy grade (P=0.04), international normalized ratio (P<0.01) and arterial blood ammonia (P=0.02). Using a threshold value of 0.5683, this model had a sensitivity of 95.24% and a specificity of 91.30%. ConclusionsTraditional Chinese medicine was a major cause of ALF in China. The spontaneous mortality of ALF was high, whereas the rate of liver transplantation was significantly low. The established prognostic model of ALF had superior sensitivity and specificity.

Abstract C26: Development and validation of a scoring system using insulin-like growth factor to assess hepatic reserve in hepatocellular carcinoma.

Abstract Background: The Child-Turcotte-Pugh (CTP) score inaccurately predicts survival in patients with chronic liver disease, including hepatocellular carcinoma (HCC), yet remains the standard tool for assessing hepatic reserve and guiding therapeutic decisions. CTP scoring relies on objective laboratory values for albumin, bilirubin, and prothrombin time and subjective clinical grading of hepatic encephalopathy and ascites. Since liver production of insulin-like growth factor 1 (IGF-1) is significantly reduced in patients with cirrhosis, we hypothesized that IGF-1 could be a valid surrogate for hepatic reserve to replace the subjective parameters in CTP score. Methods: We prospectively enrolled patients and collected data and retrospectively tested plasma IGF-1 levels in four independent cohorts: two HCC cohorts from the United States, n=310 (training set) and n=99 (validation set 1); one HCC cohort from Korea, n=188 (validation set 2); and one cirrhosis cohort from Egypt, n=71 (validation set 3). Recursive partitioning identified within the training set three optimal IGF-1 ranges that correlated with survival: &amp;gt;50 ng/mL = 1 point; 26-50 ng/mL = 2 points; and &amp;lt;26 ng/mL = 3 points. We modified the CTP score by replacing ascites and encephalopathy grading with IGF-1 value, subjected both the resulting IGF score and the CTP score to log-rank analysis, and quantified the prognostic values with C-statistics to compare the scores’ performance in all cohorts. Results: The IGF score was significantly more accurate in predicting survival and improved the stratification of all CTP classes in the training and validation cohorts. Conclusion: The new IGF score is simple and blood-based, and validated well on multiple independent HCC cohorts. It could identify a subpopulation of patients who may benefit from active therapy because of their preserved hepatic reserve, as distinct from patients for whom therapy can be deferred or avoided. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C26. Citation Format: Ahmed O. Kaseb, Lianchun Xiao, Rania Naguib, Wafaa El-Shikh, Manal Hassan, Hesham Hassabo, Jeong-Hoon Lee, Jung-Hwan Yoon, Hyo-Suk Lee, Young Kwang Chae, James L. Abbruzzese, Jeffrey Morris. Development and validation of a scoring system using insulin-like growth factor to assess hepatic reserve in hepatocellular carcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C26.

Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF)

In spite of the high incidence of hepatic encephalopathy (HE) in cirrhosis, there are few observational studies. We performed an analysis to define the characteristics of HE and associated features using the database of the Canonic Study. Clinical, laboratory and survival data of 1348 consecutive cirrhotic patients admitted with an acute decompensation were compared according to the presence (n=406) or absence of HE and of acute-on-chronic liver failure (ACLF) (n=301). HE development was independently associated with previous HE episodes; survival probabilities worsen in relation to the presence and grade of HE. There were marked differences between HE associated (n=174) and not associated (n=286) to ACLF. HE not associated with ACLF occurred in older cirrhotics, inactive drinkers, without severe liver failure or systemic inflammatory reaction and in relation to diuretic use. In contrast, HE associated with ACLF occurred in younger cirrhotics, more frequently alcoholics, with severe liver failure and systemic inflammatory reaction, and in relation to bacterial infections, active alcoholism and/or dilutional hyponatremia. Prognosis was relatively preserved in the first and extremely poor in the second group. Independent risk factors of mortality in patients with HE were age, bilirubin, INR, creatinine, sodium, and HE grade. In cirrhosis, previous HE identifies a subgroup of patients that is especially vulnerable for developing new episodes of HE. The course of HE appears to be different according to the presence of ACLF.

Risk Factors of Mortality in Children with Hepatic Encephalopathy

Background: Hepatic encephalopathy is a serious but potentially reversible complication in children with liver disease. The aim of this study is to evaluate the risk factors of mortality in children with hepatic encephalopathy. Method: Totally 42 patients including 22 boys and 20 girls with clinical diagnosis of hepatic encephalopathy who admitted to Pediatric Intensive Care Unit at Nemazee Hospital affiliated to Shiraz University of Medical Sciences, during 5 years period were enrolled in this study. Demographic features, cause of hepatic failure, grade of hepatic encephalopathy, predisposing factors, concurrent clinical manifestations and laboratory data, as possible prognostic factors were evaluated. The survival states of the patients (survivors or non-survivors) as final outcome were also documented. Results: The most common underlying liver diseases were cryptogenic (57.2%), hepatitis A (23.8%), Wilson disease (7.1%), and autoimmune hepatitis (7.1%). The total mortality rate was 54%. There was no statistically significant difference in age, weight and hospital stay between survivors or non-survivors groups. Only gastrointestinal bleeding had significant association with mortality (37% vs 92%; p=0.001). The most common predisposing factor was infection (52.5%). Patients with higher international normalized ratio and partial thromboplastin time and lower serum sodium and bicarbonate on admission and those with higher bilirubin, international normalized ratio, partial thromboplastin time, aspartate aminotransferase and lower platelets and serum bicarbonate level on last day were more likely to die. Conclusion: Poor prognostic factors for hepatic encephalopathy were included gastrointestinal bleeding, higher international normalized ratio, partial thromboplastin time, bilirubin, and aspartate aminotransferase, and lower serum sodium and bicarbonate levels and platelet counts.

Clinical impact of arterial ammonia levels in ICU patients with different liver diseases

Increased arterial ammonia levels are associated with high mortality in patients with acute liver failure (ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis. The patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group. Overall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30, 49 and 27%, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (p<0.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (p<0.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (p<0.01), ALF (p<0.05) and cirrhosis (p<0.05), respectively. Elevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.

The clinical features and outcomes of acute liver failure associated with dengue infection in adults: a case series

ObjectiveTo describe the clinical manifestations and outcome of acute liver failure (ALF) associated with dengue viral infection, a rare but severe complication. MethodsOne hundred and fifty five consecutive patients with ALF admitted to the national liver centre from 2001 to 2009 were reviewed retrospectively. Eight cases due to dengue infection were identified and their clinical characteristics are described. ResultsAll patients had severe dengue with one dengue shock syndrome. The median (minimum, maximum) age was 33.5 (17, 47) years with 50% female. The median (minimum, maximum) duration from the onset of fever to development of ALF was 7.5 (5, 13) days and the maximum hepatic encephalopathy (HE) grade were III in five patients and II in three patients. Three patients had systemic inflammatory responses (SIRS) on admission and were in grade III HE. The presence of SIRS on admission was associated with higher grade of HE and its development during the course of hospitalization was associated with worsening HE grade. The hepatitis was characterized by marked elevations in: alanine transaminase [median admission 1140.5u/L (639, 4161); median peak 2487u/L (998, 5181)], serum bilirubin [median admission 29μmol/L (23, 291); median peak 127μmol/L (72, 592)], and prothrombin time [median admission 16.8s (15.3, 26.2); median peak 22s (15.3, 40.7)]. The survival rate with standard medical therapy alone was 100%. ConclusionsDengue associated ALF manifest about one week after the onset of fever with severe hepatitis and encephalopathy. In our experience, the outcome with standard medical therapy alone is excellent.

Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placebo-controlled clinical trial

N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those <2 years old. These results do not support broad use of NAC in non-APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults.

Validation of the chronic liver disease questionnaire in Serbian patients

To translate into Serbian and to investigate the validity of the cross-culturally adapted the chronic liver disease questionnaire (CLDQ). The questionnaire was validated in 103 consecutive CLD patients treated between October 2009 and October 2010 at the Clinic for Gastroenterology, Clinical Centre of Serbia, Belgrade (Serbia). Exclusion criteria were: age < 18 years, psychiatric disorders, acute complications of CLD (acute liver failure, variceal bleeding, and spontaneous bacterial peritonitis), hepatic encephalopathy (grade > 2) and liver transplantation. Evaluation of the CLDQ was done based on the following parameters: (1) acceptance is shown by the proportion of missing items; (2) internal reliabilities were assessed for multiple item scales by using Cronbach alpha coefficient; and (3) in order to assess whether the allocation of items in the domain corresponds to their distribution in the original questionnaire (construction validity), an exploratory factor analysis was conducted. Discriminatory validity was determined by comparing the corresponding CLDQ score/sub-score in patients with different severity of the diseases. The Serbian version of CLDQ questionnaire completed 98% patients. Proportion of missing items was 0.06%. The total time needed to fill the questionnaire was ranged from 8 to 15 min. Assistance in completing the questionnaire required 4.8% patients, while 2.9% needed help in reading, and 1.9% involved writing assistance. The mean age of the selected patients was 53.8 ± 12.9 years and 54.4% were men. Average CLDQ score was 4.62 ± 1.11. Cronbach's alpha for the whole scale was 0.93. Reliability for all domains was above 0.70, except for the domain "Activity" (0.49). The exploratory factor analysis model revealed 6 factors with eigenvalue of greater than 1, explaining 69.7% of cumulative variance. The majority of the items (66%) in the Serbian version of the CLDQ presented the highest loading weight in the domain assigned by the CLDQ developers: "Fatigue" (5/5), "Emotional function" (6/8), "Worry" (5/5), "Abdominal symptoms" (0/3), "Activity" (0/3), "Systemic symptoms" (3/5). The scales "Fatigue" and "Worry" fully corresponded to the original. The factor analysis also revealed that the factors "Activity" and "Abdominal symptoms" could not be replicated, and two new domains "Sleep" and "Nutrition" were established. Analysis of the CLDQ score/sub-score distribution according to disease severity demonstrated that patients without cirrhosis had lower total CLDQ score (4.86 ± 1.05) than those with cirrhosis Child's C (4.31 ± 0.97). Statistically significant difference was detected for the domains "Abdominal symptoms" [F (3) = 5.818, P = 0.001] and "Fatigue" [F (3) = 3.39, P = 0.021]. Post hoc analysis revealed that patients with liver cirrhosis Child's C had significantly lower sub-score "Abdominal symptoms" than patients without cirrhosis or liver cirrhosis Child's A or B. For domain "Fatigue", patients with cirrhosis Child's C had significantly lower score, than non-cirrhotic patients. The Serbian version of CLDQ is well accepted and represents a valid and reliable instrument in Serbian sample of CLD patients.

The different etiology of fulminant hepatic failure (FHF) in Korea and prognostic factors in patients undergoing liver transplantation for FHF

The prognosis of fulminant hepatic failure (FHF) depends on the etiology and reversibility. In this study, we identified the etiological difference of FHF in Korea and analyzed the prognostic factors after liver transplantation (LT) for FHF. We retrospectively reviewed 42 patients with FHF who underwent LT from April 1999 to April 2011 at Samsung Medical Center, Seoul, Korea. The patients were categorized into two groups according to the short-term result of LT, and perioperative profiles were compared to identify the short-term poor prognostic factors. Unlike Western countries, there was no paracetamol-related FHF but herbal/folk medicines were the most frequent causes of FHF (26.2%). HAV-related FHF increased significantly and comprised the main portion of FHF with Herbal/folk medicines after 2005. Encephalopathy grade, onset time, pre-transplantation need of renal replacement, and ventilator treatment were significantly different between groups in univariate analysis. In multivariate analysis, pre-transplantation renal replacement treatment and hepatic encephalopathy grade IV were the independent prognostic factors after LT. The etiologies of FHF in Korea were different compared with Western reports. The requirement of renal replacement treatment and hepatic encephalopathy grade IV were identified as independent poor prognostic factors after LT for FHF in this study.

Study of Brain Changes in Chronic Hepatic Encephalopathy by Using MR Imaging

Background and study aim: Hepatic encephalopathy (HE) reflects a spectrum of neuro-psychiatric abnormalities. The aim of this study was to evaluate MR imaging of the brain in different grades of chronic HE and its correlation with clinical neurological abnormalities. Patients and Methods: Sixty patients were included, 40 patients with chronic HE were divided into group I (GI) chronic persistent HE (n=20), group II (GII) chronic relapsing HE (n=20), another 20 patients with early compensated cirrhosis were chosen as control group (GIII), all patients were subjected to full clinical and laboratory investigations, estimation of serum ammonia and Manganese level in the blood, psychometric tests ,conventional MRI and MRS. Results: A statistically significant increase in serum level of ammonia and manganese in GI (162.155.8 mol/L, 3.350.34 ug/dl, respectively) when compared to other groups. By conventional MRI there was statistically significant increased signal intensity of T1 and T2 in group I compared with other groups. By MRS, there was statistical significant increase of glutamine in GI (3.90.17 pp,) when compared to GII (3.70.13 ppm) & GIII (2.480.3 ppm) and significant reduction of both choline and myinstol among GI 1.980.17 ppm, 2.190.20 ppm, when compared to GII 2.290.17 ppm, 2.740.17 ppm and GIII 2.590.019 ppm, 3.150.11 ppm. Moreover there was significant elevation in signal intensity of T1 corresponding to elevation of serum manganese (2.910.6 ug/dl) and significant elevation of signal intensity in T2 corresponding to elevation of serum ammonia (116.949 mol/L), as well as highly significant positive correlation between serum ammonia and glutamine (r = 0.86) and highly significant negative correlation between serum ammonia and choline (r = -0.42) and myinstol (r = -0.47). Conclusion: Changes in brain metabolites as detected by MRS may be sensitive markers for clinical monitoring of brain dysfunction and cognitive impairment in patient with chronic HE.

Brain Magnetic Resonance Spectroscopy in Episodic Hepatic Encephalopathy

Brain magnetic resonance (MR) study has shown metabolic abnormalities and changes in water distribution of the brain tissue that may relate to the pathogenesis of hepatic encephalopathy (HE). We designed a study to investigate the disturbances in brain water and metabolites during episodic HE using a 3-T MR scanner. Cirrhotic patients with different grades of HE underwent MR during hospitalization (n=18). The MR was repeated at 6 weeks' follow-up (n=14). The results were compared with those of a group of healthy volunteers (n=8). During episodic HE, brain diffusion-weighted imaging showed a high apparent diffusion coefficient (ADC) (12% to 14%) that decreased during follow-up (-1% to -4%). These disturbances were accompanied by high glutamine (581%), low choline (-31%), and low myo-inositol (-86%) peaks on MR spectroscopy. In overt HE, patients showed high glutamine that decreased during follow-up (-22%). In addition, these patients exhibited a rise in plasma S100 beta and enlargement of brain white-matter lesions. In conclusion, several disturbances detected by MR support the presence of impaired brain water homeostasis during episodic HE. Although astrocytes have a major role in this condition, brain edema during episodic HE may be extracellular and does not appear to be directly responsible for the development of neurologic manifestations.

Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic encephalopathy

BackgroundRecent observations suggest that inflammatory response may be important in the pathogenesis of hepatic encephalopathy. The aim of the study was to measure arterial ammonia, tumour necrosis factor-alpha, Interleukin-6, Interleukin-18, and serum endotoxin levels and their correlation with different grades of hepatic encephalopathy. Methods120 patients with cirrhosis were enrolled: 20 patients each of cirrhosis with grades I, II, III and IV hepatic encephalopathy, cirrhosis with and without minimal hepatic encephalopathy and healthy controls were tested for arterial ammonia, tumour necrosis factor-alpha, Interleukin-6, Interleukin-18 and serum endotoxin levels. ResultsMedian arterial ammonia, tumour necrosis factor-alpha, Interleukin-6, Interleukin-18 and serum endotoxin levels were significantly higher in patient with hepatic encephalopathy and minimal hepatic encephalopathy as compared to patients without minimal hepatic encephalopathy and healthy controls. Arterial ammonia (r=0.72, p=0.03), tumour necrosis factor alpha (r=0.87, p=0.02), Interleukin-6 (r=0.50, p=0.05), Interleukin-18 (r=0.76, p=0.02) and serum endotoxin (r=0.91, p=0.01) correlated with higher grades of hepatic encephalopathy. ConclusionIn hepatic encephalopathy arterial ammonia, inflammatory mediators, and serum endotoxin are elevated and correlate with encephalopathy grade.

Lactulose in the treatment of hepatic encephalopathy: New evidence for an old modality

See article in J. Gastroenterol. Hepatol. 2012; 27: 1329–1335.