Factors Of Hepatic Encephalopathy Research Articles

Precipitating Factors and Outcomes of Hepatic Encephalopathy in Patients with Chronic Liver Disease

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric condition that significantly impacts patients with chronic liver disease (CLD), leading to hospital admissions and contributing to the economic burden on healthcare systems. The condition's pathogenesis involves various precipitating factors, yet its management remains challenging due to the multifaceted nature of its presentation. Objective: This study aims to identify the precipitating factors of HE in patients with CLD, assess the severity and outcomes of HE, and evaluate the correlation between precipitating factors and the severity and outcomes of HE in patients admitted to PNS Shifa Hospital, Karachi, Pakistan. Methods: A descriptive cross-sectional study was conducted over six months, from February 2022 to July 2022, at the Department of Medicine, PNS Shifa, Karachi. A total of 78 patients meeting the inclusion criteria were enrolled through convenience sampling. Informed consent was obtained from each participant. The severity of liver disease was assessed using the Child-Pugh Classification, and the presence and grade of HE were determined using the West Haven criteria. Precipitating factors of HE were evaluated, and patients were followed until discharge to assess the length of hospital stay and in-hospital mortality. Data were analyzed using SPSS version 25, focusing on descriptive and inferential statistics. Results: The mean age of the participants was 48.77 ± 13.37 years, with the duration of CLD averaging 3.19 ± 1.45 years. Hospital stays ranged from 1 to 7 days, with a median of 5.0 days. Child-Pugh classification revealed 35.9% of patients in Class A, 33.3% in Class B, and 30.8% in Class C. HE grades were distributed as follows: Grade I in 48.7%, Grade II in 24.4%, Grade III in 15.4%, and Grade IV in 11.5% of patients. In-hospital mortality was observed in 15.4% of cases. The most common precipitating factors identified were constipation (59.0%), followed by hypoglycemia (52.6%), and recent excessive paracentesis (48.7%). Conclusion: The study underscores the importance of identifying and managing precipitating factors of HE in patients with CLD to mitigate the severity of HE and improve patient outcomes. Constipation, hypoglycemia, and recent excessive paracentesis were the most prevalent precipitating factors, suggesting targeted interventions in these areas could reduce the incidence and severity of HE.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Hyponatremia and its Clinical Outcome Among Patients with Hepatic Encephalopathy Due to Liver Cirrhosis Presenting to ATH Abbottabad

Introduction: Hepatic encephalopathy (HE) is a potentially reversible complication of liver cirrhosis causing significant mortality. Hyponatremia in cirrhosis is caused by hampered renal function to eliminate free water that results in water retention disproportionate to sodium retention leading to reduced plasma osmolality and is associated with significant morbidity and mortality. The purpose of study was to determine the frequency of hyponatremia among patients of liver cirrhosis with hepatic encephalopathy. Methods: The design of this study was an observational study design which was hospital-based survey and was conducted on 130 patients of liver cirrhosis. A specialized questionnaire was designed to collect all the study information. All data was analyzed using SPSS Statistics version 24. Chi-square test and Spearman's rank test were employed to correlate hyponatremia with HE and its severity. A p-value of &lt;0.05 was considered statistically significant. Results: Among the patients, 92 (71%) males and 38 (29%) females; the mean age of the patients was 56±11.3 years. Hyponatremia was present in 48 (36.9%) patients. Among these, 25 (52%) were male and 23 (48%) were female; 12 (25%) patients had mild Hyponatremia, 28(58.3%) had moderate, and 8 (16.6%) had severe Hyponatremia. HE was significantly associated with hyponatremia with p value of lea than 0.001. Practical Implication: The benefit of our study was undertaken to determine the frequency of hyponatremia among patients of liver cirrhosis with hepatic encephalopathy to provide evidence for hyponatremia as a prognostic factor in HE so that early detection and management of hyponatremia in such patients will help reduce disease burden and mortality in liver cirrhosis. Conclusion: Patients with lower levels of sodium had higher grades/severity of HE. Significant association of hyponatremia was seen with liver cirrhosis and encephalopathy. Keywords: Abbottabad, Cirrhosis, Hepatic encephalopathy, Hyponatremia, Liver.

Old and New Precipitants in Hepatic Encephalopathy: A New Look at a Field in Continuous Evolution.

Hepatic encephalopathy (HE) is a common complication in patients with advanced liver disease. It is a brain dysfunction characterized by neurological and psychiatric symptoms that significantly affects quality of life, morbidity and mortality of patients. HE has various precipitants that can potentially promote its onset, alone or in combination. Among the historically well-known precipitants, such as infections, gastrointestinal bleeding, dehydration, electrolyte disorders and constipation, recent studies have highlighted the role of malnutrition and portosystemic shunts as new precipitating factors of HE. The identification, management and correction of these factors are fundamental for effective HE treatment, in addition to pharmacological therapy with non-absorbable disaccharides and/or antibiotics.

Low lymphocyte-to-monocyte ratio, calcitriol level, and CD206 level predict the development of acute-on-chronic liver failure in patients cirrhosis with acute decompensation.

Cirrhosis-related acute-on-chronic liver failure (ACLF) is associated with high morbidity and mortality rates. Prognostic models of ACLF have been developed; however, few studies have focused on the occurrence of ACLF. This study aimed to identify the factors that predict the development of ACLF, hepatic encephalopathy (HE), and infection in patients with cirrhosis. Patients with cirrhosis were enrolled, and the serum levels of calcitriol, Cluster of Differentiation 26 (CD206), and macrophage-inducible lectin receptor (Mincle) were measured, and lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio were calculated; all the patients were tracked for 6 months. A generalized estimating equation (GEE) was used to assess the factors associated with ACLF development, HE, and infection. The aforementioned model was derived based on immunological markers, and receiver operating characteristic analysis with area under the curve (AUC) was adopted to evaluate accuracy. After screening 325 patients with cirrhosis, 65 patients were eligible. In the GEE model, low levels of calcitriol (odds ratio [OR] = 3.259; 95% confidence interval [CI] = 1.118-8.929) and CD206 (OR = 2.666; 95% CI = 1.082-6.567) were associated with the development of ACLF, and the LMR was a protective factor (OR = 0.356; 95% CI = 0.147-0.861). Low calcitriol levels were a risk factor for HE (OR = 3.827) and infection (OR = 2.489). LMR was found to be a protective factor against HE (OR = 0.388). An immunological model for the discrimination of ACLF development within 6 months was proposed, with an AUC of 0.734 (95% CI = 0.598-0.869). Single and combined immunological markers, including low LMR and low levels of calcitriol and CD206, were promising for early prediction of the development of ACLF, HE, and infection in patients with cirrhosis.

Transjugular Intrahepatic Portosystemic Shunt Outcomes in the Elderly Population: A Systematic Review and Meta-Analysis.

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure typically utilized to treat refractory ascites and variceal bleeding. However, TIPS can lead to significant complications, most commonly hepatic encephalopathy (HE). Advanced age has been described as a risk factor for HE, as the elderly population tends to have decreased cognitive reserve and increased sarcopenia. We conducted a systematic review and meta-analysis of the available literature to summarize the association between advanced age and risk of adverse events after undergoing TIPS. A comprehensive search strategy to identify reports of specific outcomes (HE, 30-day and 90-day mortality, and 30-day readmission due to HE) in elderly patients after undergoing TIPS was developed in Embase (Embase.com, Elsevier). We compared outcomes and performed separate data analyses for patients aged < 70 vs. > 70 years and patients aged < 65 vs. > 65 years. Six studies with a total of 1,591 patients met our inclusion criteria and were included in the final meta-analysis. Three studies divided patients by age < 65 vs. > 65 years, with a total of 816 patients who were 54% male. The remaining three studies divided patients by age < 70 vs. > 70 years, with a total of 775 patients who were 63% male. Results demonstrated a significantly lower risk of post-TIPS HE (risk ratio (RR): 0.42, confidence interval (CI): 0.185 - 0.953, P = 0.03, I2 = 49%), 30-day mortality (RR: 0.37, CI: 0.188 - 0.74, P = 0.005, I2 = 0%), and 90-day mortality (RR: 0.35, CI: 0.24 - 0.49, P = 0.001, I2 = 0%) in patients aged > 70 vs. < 70 years, as well as a trend towards lower risk of 30-day readmission due to HE. There was no significant difference in post-TIPS HE, 30-day or 90-day mortality, or 30-day readmission due to HE between patients aged < 65 vs. > 65 years. Age > 70 years is associated with significantly higher rates of HE and 30-day and 90-day mortality rates in patients after undergoing TIPS, as well as a trend towards higher 30-day readmission due to HE.

Analysis of the Dose-Response Relationship Between the International Normalized Ratio and Hepatic Encephalopathy in Patients With Liver Cirrhosis Using Restricted Cubic Spline Functions.

BackgroundThe International Normalized Ratio (INR) is significantly associated with Hepatic Encephalopathy (HE) in patients with liver cirrhosis. However, the dose-response relationship between continuous INR changes and HE risk has not been clearly defined. Thus, our goal was to explore the continuous relationship between HE and INR among patients hospitalized with liver cirrhosis and to evaluate the role of the INR as a risk factor for HE in these patients.MethodsA total of 6,266 people were extracted from the Big Data Platform of the Medical Data Research Institute of Chongqing Medical University. In this study, unconditional logistic regression and restricted cubic spline (RCS) model were used to analyze the dose-response association of INR with HE. Alcoholic liver disease, smoking status, and drinking status were classified for subgroup analysis.ResultsThe prevalence of HE in the study population was 8.36%. The median INR was 1.4. After adjusting for alcoholic liver disease, age, smoking status, drinking status, total bilirubin, neutrophil percentage, total hemoglobin, aspartate aminotransferase, serum sodium, albumin, lymphocyte percentage, serum creatinine, red blood cell, and white blood cell, multivariate logistic regression analysis revealed that INR ≥ 1.5 (OR = 2.606, 95% CI: 2.072–3.278) was significantly related to HE risk. The RCS model showed a non-linear relationship between the INR and HE (non-linear test, χ2 = 30.940, P < 0.001), and an increased INR was an independent and adjusted dose-dependent risk factor for HE among patients with liver cirrhosis.ConclusionThis finding could guide clinicians to develop individualized counseling programs and treatments for patients with HE based on the INR risk stratification.

Effect of underdilated stent on the occurrence of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt creation

Objective: To evaluate whether underdilated stent could reduce the occurrence of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. Methods: A total of 197 patients with decompensated liver cirrhosis, who had underwent TIPS creation at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively, including 110 males and 87 females with age 25-79 (54±11) years old. Uncovered and covered stents with 8 mm diameter were implanted in all subjects, and then dilated by balloon catheters with 6 mm or 8 mm diameter. The patients were divided into two groups, including underdilated group (6 mm, n=105) and control group (8 mm, n=92).Kaplan-Meier curves were used to illustrate cumulative rate of HE, and the differences were assessed with the log-rank test. Multivariate analyses with a Cox regression model were conducted to explore the risk factors for HE. Results: During a median follow-up period of 29 (12-54) months, 16 (15.2%) patients developed HE in the underdilated group and 27 (29.3%) patients in the control group. There was a significant difference in the cumulative rate of HE (P=0.014), but no statistical differences were found in terms of variceal rebleeding, shunt dysfunction and survival between the two groups (P=0.608, P=0.659, P=0.968). In multivariated analysis, group assignment (underdilated vs. control, HR=0.291, 95%CI 0.125-0.674, P=0.004) was identified as an independent risk factor for HE after TIPS creation. Conclusion: Underdilated TIPS could reduced the risk of HE compared with completely dilated TIPS, with comparable risk of variceal rebleeding, shunt dysfunction and mortality. And it is worthy of applying this technique to a large sample of patients in clinical practice.

Predictors of hepatic encephalopathy in patients with severe acute liver injury

severe acute liver injury (SALI) formerly known as severe acute hepatitis is an acute inflammation of the liver with markers of liver injury (elevated transaminases) and signs of hepatocellular failure (jaundice and INR greater than 1.5) according to the latest definition of the European Association for the Study of the Liver (EASL). An important prognostic factor in SALI is the development of hepatic encephalopathy (HE) and thus its progression to acute liver failure (ALF), formerly known as acute severe hepatitis. The purpose of this study is to investigate factors predicting the development of hepatic encephalopathy during SALI. we conducted a retrospective study of patients treated for SALI between January 2000 and December 2019. We divided patients into two groups depending on whether hepatic encephalopathy occurred. We performed an analytical study comparing the two groups according to their epidemiological, biological and evolutionary data. data from the medical records of fifty-nine patients were collected. A virus was the most frequent cause (63%). Hepatic encephalopathy occurred in 15 patients (25.4%). Factors predicting the development of HE in univariate analysis were a delay in consultation of more than 9 days, an INR level of more than 2.45, a bilirubin level of more than 230 μmol/l, creatinine greater than 60.5 μmol/l, urea greater than 5.5 mmol/l and MELD score greater than 26.5 (p=0.023, p=0.017, p=0.0001, p=0.049, p=0.0001, p=0.0001 respectively). Autoimmune hepatitis and an undetermined cause were associated with the development of HE (p=0,003 and p=0,044, respectively). In multivariate analysis, autoimmune aetiology and a urea level above 5.5 mmol/l were significantly associated with the occurrence of HE. No statistically significant differences were found between the two groups with regard to age, sex and diabetes. SALI is a rare disease, mainly due to a virus in our country. Predictive factors of HE are important for early identification of patients at risk of adverse outcomes.

Protective effect of probiotics and ascorbic acid on bile duct ligation-induced chronic hepatic encephalopathy in rats.

Background and purpose:Hepatic encephalopathy (HE) is a brain dysfunction caused by acute and chronic hepatic failure. The pathogenesis of HE is unknown, although small intestinal bacterial overgrowth associated with chronic liver damage, hyperammonemia, and oxidative stress are considered major factors for HE. Effective lowering of circulating ammonia and neuroinflammation is the main strategy for preventing and treating HE in cirrhosis. In the present study, the protective effect of probiotics (Lactobacillus plantarum and Bacillus clausii) and ascorbic acid in combination was assessed in bile duct ligation (BDL)-induced chronic HE in rats.Experimental approach:Sprague Dawley rats were divided into five groups (n = 6). All groups were subjected to double ligation of the bile duct and fed a hyperammonemia diet, except group I (normal control). Groups III and IV were treated with a low and high dose of combination therapy, respectively, while group V was given lactulose. Four weeks post ligation, behavioral, biochemical, and neurochemical parameters were measured. The liver and brain were dissected for histopathology and protein analyses.Findings / Results:Combination therapy reduced plasma AST, ALT, ALP, and ammonia levels and attenuated hepatic inflammation/fibrosis in cirrhotic rats. Furthermore, combination therapy significantly improved behavioral parameters and restored the antioxidant enzyme activity. Histological changes were observed in the brain and liver of BDL animals.Conclusion and implications:The additive impact of probiotics and ascorbic acid on BDL-induced chronic HE in rats was mediated by a reduction in ammonia and oxidative stress, implying the therapeutic potential of combination therapy in HE.

Proton Pump Inhibitor Therapy Does Not Affect Prognosis of Cirrhosis Patients With Acute Decompensation and Acute-on-Chronic Liver Failure: A Single-Center Prospective Study.

Background: The aim of this study was to investigate the impact of proton pump inhibitor (PPI) therapy on complications and prognosis in cirrhosis patients with and without acute-on-chronic liver failure (ACLF).Materials and Methods: Cirrhosis patients with acute decompensation (AD) (n = 489) admitted in our center were enrolled in this prospective observational cohort study. According to treatment received, patients were identified as users or nonusers of PPI. Clinical and laboratory data, complications during hospitalization, and overall survival were recorded in all the patients.Results: Of the 489 patients, 299 (61.1%) patients received PPI therapy. The logistic regression analysis showed that age, albumin, history of previous hepatic encephalopathy (HE), and the chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score were independent risk factors for HE in patients with decompensated cirrhosis [odds ratio (OR) = 1.07, 95% CI: 1.03–1.12, p = 0.001; OR = 1.13, 95% CI: 1.04–1.24, p = 0.006; OR = 242.52, 95% CI: 40.17–1464.11, p < 0.001; and OR = 2.89, 95% CI: 2.11–3.96, p < 0.001, respectively]. Previous severe liver injury and previous bacterial infections were independent risk factors for spontaneous bacterial peritonitis (SBP) in patients with decompensated cirrhosis (OR = 3.43, 95% CI: 1.16–10.17, p = 0.026 and OR = 6.47, 95% CI: 2.29–18.29, p < 0.001, respectively). The multivariate Cox proportional hazards regression model showed that the type and dose of the PPI used were not related to 28-day and 90-day mortality in cirrhosis patients with AD or ACLF.Conclusion: PPI use does not appear to increase mortality or the risk of HE and SBP in the hospitalized cirrhosis patients with and without ACLF.

Recurrence of Hepatic Encephalopathy after TIPS: Effective Prophylaxis with Combination of Lactulose and Rifaximin.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. Methods: N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Results: Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Conclusions: Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.

Abstract No. 27 Proton pump inhibitor use is associated with increased risk of post–transjugular intrahepatic portosystemic shunt hepatic encephalopathy: replication in an independent patient cohort

Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunt (TIPS) procedures. Proton pump inhibitor (PPI) use has recently been implicated as a risk factor for HE, potentially due to alterations in the gastrointestinal tract microbiome or effects on ammonium ion excretion. Although generally supporting an association between PPI use and HE, multiple meta-analyses have reported heterogeneity and publication bias, and only two previous studies have examined the role of PPI use in post-TIPS HE.

Recurrent hepatic encephalopathy precipitated by urinary tract infection in patient with liver cirrhosis: a case report

Liver cirrhosis is a chronic liver injury marked by necro-inflammation and fibrogenesis. It is associated with several life-threatening complications. Hepatic encephalopathy remains to be one of the most debilitating complication of liver cirrhosis. The occurrence of hepatic encephalopathy may be directly related to endogenous worsening of liver function or occurs in the presence of specific precipitating factor. Infection such as urinary tract infection is a common precipitant of hepatic encephalopathy. We present a case of 66 year old female with recurrent hepatic encephalopathy in hepatitis B-related liver cirrhosis precipitated by urinary tract infection. Rapid and precise recognition of precipitating factor in hepatic encephalopathy is very substantial for implementation of preventive measures and optimal treatment plan in order to achieve better outcomes in liver cirrhosis patient.

Case–control study: Proton pump inhibitor use is a major risk factor for hepatic encephalopathy after TIPS

Case–control study: Proton pump inhibitor use is a major risk factor for hepatic encephalopathy after TIPS

The Prevalence, Predictors, and In-Hospital Mortality of Hepatic Encephalopathy in Patients with Liver Cirrhosis Admitted at St. Dominic Hospital in Akwatia, Ghana.

Background Hepatic encephalopathy (HE) is one of the most debilitating complications of cirrhosis leading to death. Decrease in HE mortality and recurrence has been linked with timely identification and early treatment. There is a need to document the burden, predictors, and treatment outcomes of HE in an adult population with liver cirrhosis in our setting as only reports from resource-endowed countries abound in the literature. This study aimed therefore to determine the prevalence, predictors, and treatment outcomes of patients with liver cirrhosis admitted at St. Dominic Hospital (SDH) in Akwatia, Ghana. Materials and Methods A prospective study was conducted involving one hundred and sixty-seven (167) patients admitted at the medical wards in SDH with liver cirrhosis from January 1st, 2018, to March 24th, 2020. The demographic and clinical features of the patients were collected using a standardized questionnaire. Biochemical, haematological, and abdominal ultrasound scans were done for all patients. Patients were then followed up until discharge or death. Results There were 109 (65.3%) males out of the 167 patients with a mean age of 45.8 and 47.5 years for those with and without HE, respectively. The prevalence of HE was 31.7% (53/167). Out of 53 participants with HE, 75.5% (40/53) died. There was a strong association between HE and death (p < 0.001). The major precipitating factor of HE was infection (64.2%). Severe ascites (OR = 0.009) were clinical feature independently associated with HE, whereas high creatinine (OR = 0.987), blood urea nitrogen (BUN) (OR = 1.199), Child–Pugh score (CPS) (OR = 5.899), and low platelets (OR = 0.992) were the laboratory parameters and scores independently predictive of HE. Conclusion HE was common among patients with liver cirrhosis admitted at SDH with high in-patient mortality. The commonest precipitating factor for HE was infection(s). Severe ascites, low platelet count, high creatinine, BUN, and CPS were independent predictors of HE.

Shunt-Induced Hepatic Encephalopathy in TIPS: Current Approaches and Clinical Challenges.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE.

Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner.

ABSTRACTAstrocyte dysfunction is a primary factor in hepatic encephalopathy (HE) impairing neuronal activity under hyperammonemia. In particular, the early events causing ammonia-induced toxicity to astrocytes are not well understood. Using established cellular HE models, we show that mitochondria rapidly undergo fragmentation in a reversible manner upon hyperammonemia. Further, in our analyses, within a timescale of minutes, mitochondrial respiration and glycolysis were hampered, which occurred in a pH-independent manner. Using metabolomics, an accumulation of glucose and numerous amino acids, including branched chain amino acids, was observed. Metabolomic tracking of 15N-labeled ammonia showed rapid incorporation of 15N into glutamate and glutamate-derived amino acids. Downregulating human GLUD2 [encoding mitochondrial glutamate dehydrogenase 2 (GDH2)], inhibiting GDH2 activity by SIRT4 overexpression, and supplementing cells with glutamate or glutamine alleviated ammonia-induced inhibition of mitochondrial respiration. Metabolomic tracking of 13C-glutamine showed that hyperammonemia can inhibit anaplerosis of tricarboxylic acid (TCA) cycle intermediates. Contrary to its classical anaplerotic role, we show that, under hyperammonemia, GDH2 catalyzes the removal of ammonia by reductive amination of α-ketoglutarate, which efficiently and rapidly inhibits the TCA cycle. Overall, we propose a critical GDH2-dependent mechanism in HE models that helps to remove ammonia, but also impairs energy metabolism in mitochondria rapidly.

Assessment of Precipitating Factors and Outcomes of Hepatic Encephalopathy in Cirrhotic Patients

Background: Hepatic encephalopathy (HE) is one of the major complications of liver cirrhosis (LC). It’s defined as a reversible neuropsychiatric event of liver cirrhosis. Up to fifty percent of cirrhotic patients will suffer from at least one attack of HE. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. The current study aimed to assess outcome of hepatic encephalopathy. Patients and methods: Over one year duration, 100 patients with HE were enrolled. All patients were subjected to full history taking and full examination. Patient with central nervous system lesion, metabolic disorders or post-ictal state was excluded. Abdominal ultrasound and ascitic fluid examination were performed in all patients. Patients were followed and their outcome was recorded. Results: Mean age of patients was 53.19 ±3.6 years and the majority of patients were males. Hepatitis C infection was the most frequent cause of LC. The main precipitating factor for HE was infection (29%) followed by hematemesis (24%) and constipation (19%). In 19 (19%) patients, there was evidence of ascitic fluid infection. Out of studied patients; 81 (81%) patients were alive. It was noticed that hematemesis and infection were significantly higher in dead patients. Conclusion: hepatic encephalopathy is a serious event in patients with LC. Major precipitating factors were infection, hematemesis and constipation. Infection and hematemesis are usually associated with poor outcome.

Diabetes mellitus increases the risk of hepatic encephalopathy after a transjugular intrahepatic portosystemic shunt in cirrhotic patients.

The aim of this study was to examine the effect of diabetes mellitus (DM) on the rate of hepatic encephalopathy (HE) in patients with decompensated liver cirrhosis after the creation of a transjugular intrahepatic portosystemic shunt (TIPS). This study retrospectively reviewed 436 consecutive patients with cirrhosis receiving TIPS in our department from 2008 to 2016. By comparing two groups of patients, with or without DM, the incidence of developing overt HE after TIPS, as well as the correlation between diabetes and HE, was analyzed. Data were analyzed using the χ-tests, unpaired t-tests, logistic regression, and Kaplan-Meier curves. After the initial data processing, we used a regression model to analyze whether or not DM is associated with the development of HE after TIPS. Of the 436 patients who underwent TIPS, 85 (19.5%) had diabetes at admission and 126 (28.9%) had HE after TIPS. Patients with DM more frequently had HE compared with those without DM (44.7 vs. 25.1%; P = 0.000). The logistic regression analysis showed that DM (P = 0.015) and age (P = 0.002) were independent risk factors for HE after TIPS. Finally, using the Kaplan-Meier curves, we found that diabetes significantly increases the incidence of overt HE (log-rank P = 0.026). Similar to old age, DM may increase the risk of HE in cirrhotic patients after the creation of TIPS.