Hepatic Encephalopathy Grade Research Articles

Predictors of Inpatients Mortality in Patients with Liver Cirrhosis with Hepatic Encephalopathy

Background Hepatic encephalopathy has high risk of recurrence and is associated with advanced cirrhosis of liver. It features a spectrum of reversible neuropsychiatric abnormalities. The purpose of the research was to study the inpatients mortality and its predictors among cirrhotic patients with hepatic encephalopathy. MethodsA cross-sectional, hospital-based study comprising of 182 cirrhotic patients with hepatic encephalopathy were evaluated. West Haven Classification (Grade I to IV) was used for grading of hepatic encephalopathy. The data analysis was done using SPSS version 20 and p-value of ≤0.05 was considered significant. ResultsMajority of patients (39.6%) presented with Grade II encephalopathy followed by Grade III (26.4%). Inpatient mortality was 22.5%. Mortality was seen in 95% patients with HE of grade IV. Univariate analysis showed male sex [p-value=0.01, OR-0.37, CI (0.17-0.820)], shock at presentation [p-value=0.0001, OR-42, CI (16.05 -109.9)], CTP [p-value=0.03, OR-3.8, CI (1.1-13.3)], presence of more than two precipitating factors [P=0.0001, OR-48, CI (10.3-216.3)], presence of SBP [p-value=0.0001, OR-23.4, CI (9.1-60.4)] as statistically significant predictive factors. Multivariate analysis showed shock [P=0.0001, OR-85.3, CI (12.7-571.7)], presence of more than two precipitating factors [p-value=0.0001, OR-101.8, CI (3.32-3119.32)] and SBP [p-value=0.0001, OR-44.7, CI (6.49-309.5)] as statistically significant predictive factors for mortality in patients with liver cirrhosis with hepatic encephalopathy. Conclusions Inpatient mortality was high with increasing grades of encephalopathy among cirrhotic patients. Initial presentation with shock, presence of more than two precipitating factors and SBP were independent predictors of inpatient mortality in patients with liver cirrhosis with hepatic encephalopathy.

Serum zinc level in liver cirrhosis with hepatic encephalopathy and its correlation with different stages of hepatic encephalopathy.

Hepatic encephalopathy (HE) severe complication of liver cirrhosis with high mortality. Few studies have found zinc deficiency in liver cirrhosis and HE patients and found it as a precipitating factor for the development of HE. This study was done to measure the serum zinc level in patients with liver cirrhosis with HE and a correlation was obtained between serum zinc level with grades of HE. A cross-sectional observational study was done on 150 patients with liver cirrhosis with HE at a tertiary care center in Jharkhand. All cases were evaluated by history taking, clinical examination, and a questionnaire and classified into different WHC grades of HE and CPC classes of cirrhosis. Routine blood investigations, imaging studies, and morning serum zinc levels were done for all patients. Majority of patients with liver cirrhosis with HE had zinc deficiency. There was a statistically highly significant (P < .00001) association between low serum zinc levels and WHC grades of HE. The serum zinc levels in different classes of cirrhosis showed highly significant differences (P < .00001). The mean serum zinc level was significantly low in patients who died (35.56 ± 11.65 vs 48.36 ± 10.91, P < .0001). The study revealed a strong positive correlation (r = .88, P = .048) between serum zinc and serum albumin levels. Serum zinc is deficient in patients with liver cirrhosis and HE. Zinc deficiency is significantly associated with higher severity of cirrhosis and higher grades of HE. All patients with liver cirrhosis with HE and hypoalbuminemia should be evaluated for zinc deficiency.

STUDY OF SERUM AMMONIA IN HEPATIC ENCEPHALOPATHY AND ITS CORRELATION WITH SEVERITY

Background and objectives: Hepatic encephalopathy (HE) encompasses a spectrum of manifestations ranging confusion and coma. Data on correlation of serum ammonia levels with grades of HE is inconsistent. This study was undertaken to find the correlation between serum ammonia levels and grades of HE. Methodology: This hospital based descriptive cross-sectional study was undertaken in the Department of General Medicine, from a tertiary care hospital situated in South Karnataka from November 2018 to May 2020. A total of 86 patients with HE were included in the study. Results: Majority of the patients (83.72%) were males and the male to female ratio was 5.14:1. The mean age was 54.01±11.55 years and most of the patients (36.05%) were aged from 51 to 60 years. Most of the patients had lack of awareness (47.67%) followed by disorientation (24.42%). According to West heaven criteria, most of the patients (47.67%) had grade 1 HE followed by grade 2 (24.42%), grade 3 (23.26%) and grade 4 (4.65%). The mean serum ammonia levels were 105.43±49.66 and 88.65 µg/dl. Majority of the patients (96.51%) had serum ammonia levels of &gt;60 µg/dl. There was strong positive correlation between HE grades and serum ammonia levels (ρ=0.752; R 2 =0.455; p&lt;0.001). Also, mean serum ammonia levels in grade 4 HE (203.50±107.87 µg/dl) were significantly high compared to grade 3 (139.20±41.48µg/dl), 2 (112.57±36.91µg/dl) and 1 (75.75±20.20µg/dl) (p&lt;0.001). Conclusion and Interpretation: The serum ammonia level were elevated in patients with HE. There is strong positive correlation between HE grades and serum ammonia levels which corresponds to the severity of HE.

Pathomorphology of severe Grade 3-4 hepatic encephalopathy in decompensated cirrhosis patients with acute-on-chronic liver failure

The study was aimed to determine of the most significant pathomorphological signs of severe hepatic encephalopathy (HE) in deceased cirrhotic patients with acute-on-chronic liver failure (ACLF) syndrome based on changes of the glioneuronal complex and the level of tissue ammonia. Using pathohistological, histochemical, and immunohistochemical methods, the cerebral cortex, thalamus, striatum, and cerebellum of 21 deceased patients with acutely decompensated liver cirrhosis with ACLF syndrome and HE Grade 3-4 were examined in comparison with control group, which included 30 deceased patients from acute cardiovascular failure. The study revealed that during HE Grade 3-4 as a component of ACLF, in all studied brain regions, there was a reliably (p&lt;0.05) higher histochemical level of tissue ammonia (up to 500%), increased numbers (up to 215.69%) of apoptotic neurons (according to caspase-3), reduced (up to 119.60%) level of synaptophysin, increased expression of glutamine synthetase (up to 253.02%) and aquaporin-4 (up to 481.81%) associated by reduced (up to 296.81%) expression of glial fibrillary acidic protein in astrocytes, increased (up to 11-fold) numbers of Alzheimer type 2-astrocytes, expansion of perivascular and pericellular «edematous» spaces (up to 890.81%), increased numbers of amyloid bodies (up to 5-fold), increased area of immunopositive material of CD68+ microgliocytes (up to 114.78%) with an increase (up to 71.91%) in the proportion of CD68+ amoeboid microglia. The above-mentioned changes confirm that the loss of consciousness and other psychoneurological manifestations of severe HE Grade 3-4 are due to compound am­monia-associated changes in the components of the glioneuronal complex, namely: adaptive remodeling and dystro­phic changes in astrocytes, reduced synaptic transmission and apoptotic neuronal death, reactive changes in microglia with a small proportion of microgliocytes involved in phagocytosis, cytotoxic brain edema and dysfunction of the glymphatic system

Safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy associated with spontaneous portosystemic shunts

This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P < 0.05). In the IPTW cohort, baseline characteristics were comparable between the two groups (all P > 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P < 0.05). Subsequent subgroup analyses indicated that patients with serum ammonia level > 60 μmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P < 0.05). No early procedural complications were observed in the embolization group. The incidence of long-term postoperative complications was comparable to that in the control group (all P > 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.

Restoration of hippocampal adult neurogenesis by CDRI-08 (Bacopa monnieri extract) relates with the recovery of BDNF-TrkB levels in male rats with moderate grade hepatic encephalopathy.

Modulation of in vivo adult neurogenesis (AN) is an evolving concept in managing neurodegenerative diseases. CDRI-08, a bacoside-enriched fraction of Bacopa monnieri, has been demonstrated for its neuroprotective actions, but its effect on AN remains unexplored. This article describes the status of AN by monitoring neuronal stem cells (NSCs) proliferation, differentiation/maturation markers and BDNF-TrkB levels (NSCs signalling players) vs. the level of neurodegeneration and their modulations by CDRI-08 in the hippocampal dentate gyrus (DG) of male rats with moderate grade hepatic encephalopathy (MoHE). For NSC proliferation, 10mg/kg b.w. 5-bromo-2'-deoxyuridine (BrdU) was administered i.p. during the last 3days, and for the NSC differentiation study, it was given during the first 3days to the control, the MoHE (developed by 100 mg/kg b.w. of thioacetamide i.p. up to 10days) and to the MoHE male rats co-treated with 350 mg/kg b.w. CDRI-08. Compared with the control rats, the hippocampus DG region of MoHE rats showed significant decreases in the number of Nestin+/BrdU+ and SOX2+/BrdU+ (proliferating) and DCX+/BrdU+ and NeuN+/BrdU+ (differentiating) NSCs. This was consistent with a similar decline in BDNF+/TrkB+ NSCs. However, all these NSC marker positive cells were observed to be recovered to their control levels, with a concordant restoration of total cell numbers in the DG of the CDRI-08-treated MoHE rats. The findings suggest that the restoration of hippocampal AN by CDRI-08 is consistent with the recovery of BDNF-TrkB-expressing NSCs in the MoHE rat model of neurodegeneration.

Intravenous versus oral ‘l-ornithine-l-aspartate’ in overt hepatic encephalopathy: a randomized comparative study

Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. In this RCT, we compared the efficacy of intravenous (IV) l-ornithine-l-aspartate(LOLA) versus Oral LOLA in patients with chronic liver disease(CLD) enduring overt Hepatic Encephalopathy(OHE). 40 CLD patients with OHE were randomly assigned IV or oral LOLA in a 1:1 ratio. Patients were graded for HE and monitored for serum ammonia levels from day 1 to day 5. The aim was to compare IV versus oral LOLA efficacy in HE grades improvement and its correlation with ammonia levels. The study was registered with clinical trials registry-India, CTRI/2020/12/029943. Baseline characteristics of patients in both groups were similar. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511). Significant reductions in ammonia levels were observed from day 1 to day 5 within each group (p < 0.001). HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE.

Bacterial DNA Translocation Is Associated With Overt Hepatic Encephalopathy and Mortality in Patients With Cirrhosis.

Data on the relationship between bacterial translocation, hepatic encephalopathy (HE), and mortality are scarce. This study aimed to assess the association between bacterial DNA (bactDNA) translocation, inflammatory response, ammonia levels, and severity of HE in patients with cirrhosis, as well as the role of bactDNA translocation in predicting mortality. Cirrhotic patients without bacterial infection were prospectively enrolled between June 2022 and January 2023. Grading of HE was classified by the West Haven Criteria and Psychometric Hepatic Encephalopathy Score ≤ -5. Overall, 294 cirrhotic patients were enrolled, with 92 (31.3%) and 58 (19.7%) having covert and overt HE, respectively. BactDNA translocation was detected in 36.1% of patients (n = 106). Patients with overt HE had more bactDNA translocation and higher serum lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, interleukin-6 (IL-6), and ammonia levels than those without HE. Patients with detectable bactDNA had higher white cell counts and serum LBP and IL-6 levels than those without. By contrast, bactDNA, serum LBP, and soluble CD14 levels were comparable between patients with covert HE and those without HE. The multivariate Cox regression analysis revealed that bactDNA translocation (hazard ratio [HR] = 2.49, 95% confidence interval [CI]: 1.22-5.11), Model for End-Stage Liver Disease score (HR = 1.12, 95% CI: 1.09-1.16), age (HR = 1.05, 95% CI: 1.000-1.002), and baseline IL-6 (HR = 1.001, 95% CI: 1.000-1.002) were independent factors associated with 6-month mortality. Apart from hyperammonemia, bactDNA translocation is a possible factor associated with overt HE in cirrhotic patients. BactDNA translocation and IL-6 are independent factors associated with 6-month mortality.

Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model.

Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. Not applicable as this is a retrospective study.

The restoration of hippocampal nerve de-myelination by methylcobalamin relates with the enzymatic regulation of homocysteine level in a rat model of moderate grade hepatic encephalopathy.

This article describes how methylcobalamin (MeCbl) restores nerve myelination in a moderate- grade hepatic encephalopathy (MoHE) model of ammonia neurotoxicity. The comparative profiles of myelin basic protein (MBP), homocysteine (Hcy) and methionine synthase (MS: a MeCbl- dependent enzyme) activity versus nerve myelination status were studied in the hippocampus of the control, the MoHE (developed by administering 100 mg/kg bw thioacetamide i.p. for 10 days) and the MoHE rats treated with MeCbl (500 µg/kg BW i.p.) for 7 days. Compared to those of control rats, the hippocampal CA1 and CA3 regions of the MoHE rats showed significantly lower myelinated areas and MBP immunostaining. This coincided with the deranged myelin layering in TEM images, decreased MBP protein and its transcript levels in hippocampus of MoHE rats. However, all these parameters recovered to normal levels after MeCbl treatment. MeCbl is a cofactor of MS that catalyzes the conversion of Hcy to methionine as a feeder step of methylation reactions. We observed significantly increased serum and hippocampal Hcy levels in MoHE rats, however, these levels were restored to control values with a concordant activation of MS due to MeCbl treatment. A significant recovery in neurobehavioral impairments in the MoHE rats due to MeCbl treatment was also observed. These findings suggest that MoHE pathogenesis is associated with deranged nerve myelination in the hippocampus and that MeCbl treatment is able to restore it mainly by activating MS, a MeCbl-dependent Hcy-metabolizing enzyme.

Association of low serum 25-Hydroxy vitamin D [25(OH) d] with hepatic encephalopathy in patients with decompensated liver cirrhosis

Background and study aimsThe mechanism of hepatic encephalopathy is complex and has not been conclusively established. Recent studies support lower serum 25-Hydroxy Vitamin D [25(OH) D] levels in patients with hepatic encephalopathy. This study aimed to evaluate the association between serum 25(OH) D and hepatic encephalopathy in patients with decompensated cirrhosis of liver. Patients and methodsA total of 70 cirrhosis patients (35 cases of hepatic encephalopathy and 35 patients without encephalopathy as control, mean age 53.07 ± 12.99 years, 67 % male) were recruited for this study. Assessment of the severity of cirrhosis was done by using a model for end-stage liver disease(MELD) and Child Turcotte Pugh (CTP) scores, and assessment of the severity of hepatic encephalopathy was done according to West Haven criteria. Serum 25 (OH) D level was measured by Chemiluminescent Microparticle Immuno Assay(CMIA). ResultsThe mean serum 25(OH) D level among hepatic encephalopathy patients was significantly lower in comparison to the control group without encephalopathy (18.76 ± 8.84 nmol/L vs 31.19 ± 13.9 nmol/L, P<0.0001). 91.4 % of hepatic encephalopathy patients had moderate to severe 25(OH)D deficiency as compared to 51.4 % in the control group. There was a significant correlation observed between the severity of the 25 (OH) D deficiency and the severity of liver disease (r = − 0.35, P = 0.002). No statistically significant difference in serum 25(OH) D levels was found among patients with different hepatic encephalopathy grades (P = 0.416). ConclusionA significant association was found between a low serum 25(OH) D leveland hepatic encephalopathy. It requires further large-scale multicenter studies to establish it as a risk factor and predictor of hepatic encephalopathy.

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.

Effect of plasma exchange with albumin replacement on albumin functionality and organ dysfunction in acute-on-chronic liver failure

Effective treatments for acute-on-chronic liver failure (ACLF) are a major unmet need. This proof-of-concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with albumin 5% (PE-A5%) on albumin functional capacity and organ dysfunction in patients with ACLF. Ten adult patients were enrolled in a single-center phase II, prospective, open-label, non-controlled study. Six PE-A5% sessions were performed in 10 days followed by a 1-month follow-up visit. Albumin functional capacity and circulatory function were assessed, as were renal, cerebral, and liver function, and systemic inflammation. The main safety variable was the percentage of PE sessions associated with at least one procedure-related adverse event (AE). Patients with ACLF showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure compared to healthy donors (n= 19). From baseline to day 11, PE-A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3±1.6mg/ml to 18.9±1.7mg/ml; p= 0.003), fatty acid-binding capacity (8.2±1.4μM to 3.1±1.5μM; p= 0.013) and antioxidant capacity (human mercaptalbumin 9.5±1.5mg/ml to 14.6±1.6mg/ml; p= 0.001). Native albumin levels were increased throughout day 1-11PE-A5% sessions (6.5±1.0mg/ml to 10.2±1.4mg/ml; p= 0.035). PE-A5% improved systemic hemodynamics (mean arterial pressure, heart rate, cardiac index), renal function (creatinine level, blood urea nitrogen), cerebral function (hepatic encephalopathy grade), liver parameters (transaminases, bilirubin) and inflammatory parameters (C-reactive protein, leukocyte count). All patients had at least one of the 78 AEs reported, mostly mild (product/procedure-related: 36%). Sixteen serious AEs were reported in eight patients (procedure/product-related: none). PE-A5% was a safe procedure associated with positive effects on albumin functionality, and circulatory, renal, cerebral, and liver function in patients with ACLF. Acute-on-chronic liver failure (ACLF) is a clinical condition characterized by severe systemic inflammation, organ failure, and high mortality. Plasma exchange removes patient's plasma containing pathogenic substances, replacing it with 5% albumin and fresh frozen plasma (PE-A5%). In this study, cirrhotic patients with ACLF were treated with PE-A5%, which was a safe procedure that increased binding and antioxidant capacity of patients' albumin, while improving circulatory, kidney, brain, and liver functions. These beneficial effects could impact survival in ACLF. NCT01201720. 2010-021360-15.

Pattern Clustering of Symmetric Regional Cerebral Edema on Brain MRI in Patients with Hepatic Encephalopathy.

Metabolic abnormalities in hepatic encephalopathy (HE) cause brain edema or demyelinating disease, resulting in symmetric regional cerebral edema (SRCE) on MRI. This study aimed to investigate the usefulness of the clustering analysis of SRCE in predicting the development of brain failure. MR findings and clinical data of 98 consecutive patients with HE were retrospectively analyzed. The correlation between the 12 regions of SRCE was calculated using the phi (Φ) coefficient, and the pattern was classified using hierarchical clustering using the φ2 distance measure and Ward's method. The classified patterns of SRCE were correlated with clinical parameters such as the model for end-stage liver disease (MELD) score and HE grade. Significant associations were found between 22 pairs of regions of interest, including the red nucleus and corpus callosum (Φ = 0.81, p < 0.001), crus cerebri and red nucleus (Φ = 0.72, p < 0.001), and red nucleus and dentate nucleus (Φ = 0.66, p < 0.001). After hierarchical clustering, 24 cases were classified into Group I, 35 into Group II, and 39 into Group III. Group III had a higher MELD score (p = 0.04) and HE grade (p = 0.002) than Group I. Our study demonstrates that the SRCE patterns can be useful in predicting hepatic preservation and the occurrence of cerebral failure in HE.

Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Association Of Electroencephalogram Patterns With Ammonia Levels In Hepatic Encephalopathy Patients

Objective: To find out the association between electroencephalogram (EEG) and hepatic encephalopathy.&#x0D; Methodology: This cross-sectional study included 100 patients (with the age of52.5±6.09years for males and 51.7 ± 6.10 years for females) of reported hepatic encephalopathy, visiting the medical department (indoor and OPD) at Federal Government Polyclinic Hospital, Islamabad. The study was conducted from January 2020 to May 2021. Patients who had known epileptic and structural brain lesions or strokes were excluded from the study. Statistical analysis was done using GraphPad Prism software. The significance of data (p-value or R2 value) was calculated through a two-tailed test or correlation coefficient.&#x0D; Results: All the patients in hepatic encephalopathy grade IV reported abnormal EEG representing triphasic waves and flattening of EEG pattern. There was no correlation observed between age, gender and hepatic encephalopathy grades. However, a significant correlation (R2= 0.9032) was observed between serum ammonia levels and hepatic encephalopathy grades. Elevated serum ammonia levels depicted the severity of hepatic encephalopathy. Overall, the percentage of patients with abnormal EEG increased with increasing grade of hepatic encephalopathy. It was quite intriguing to note that EEG, being the common method to diagnose hepatic encephalopathy grades, is not dependent on patients’ socio-economic status.&#x0D; Conclusion: Data concluded that serum ammonia levels are well associated with the progression of hepatic encephalopathy. Moreover, the EEG patter provides the appropriate information about the neurological abnormalities associated with the severity of hepatic encephalopathy. Hence, serum ammonia levels and EEG both should accurately be used as indicators for diagnosis and monitoring the response to the treatment of various grades of hepatic encephalopathy. Data warrant further investigations to get a better insight into hepatic encephalopathy's relationship with EEG patterns through the inclusion of molecular parameters.

Portosystemic shunt placement reveals blood signatures for the development of hepatic encephalopathy through mass spectrometry

Elective transjugular intrahepatic portosystemic shunt (TIPS) placement can worsen cognitive dysfunction in hepatic encephalopathy (HE) patients due to toxins, including possible microbial metabolites, entering the systemic circulation. We conducted untargeted metabolomics on a prospective cohort of 22 patients with cirrhosis undergoing elective TIPS placement and followed them up to one year post TIPS for HE development. Here we suggest that pre-existing intrahepatic shunting predicts HE severity post-TIPS. Bile acid levels decrease in the peripheral vein post-TIPS, and the abundances of three specific conjugated di- and tri-hydroxylated bile acids are inversely correlated with HE grade. Bilirubins and glycerophosphocholines undergo chemical modifications pre- to post-TIPS and based on HE grade. Our results suggest that TIPS-induced metabolome changes can impact HE development, and that pre-existing intrahepatic shunting could be used to predict HE severity post-TIPS.

Assessment of Serum Zinc Levels in Patients With Decompensated Cirrhosis of the Liver and Its Association With Disease Severity and Hepatic Encephalopathy: A Prospective Observational Study From North India.

Background Zinc, an essential trace element, plays a vital role in cellular metabolism, and the liver is the main organ responsible for its metabolism. Because serum zinc levels are found to be lowered in chronic liver diseases, it has been hypothesized to be a precipitating factor for the development of hepatic encephalopathy. Methodology This prospective, observational study included patients with decompensated cirrhosis of the liver who were admitted to the medical intensive care unit of a tertiary care institute in northern India between September 2021 and April 2023. The diagnosis was based on history and detailed clinical examination. The serum zinc levels of patients were estimated using atomic absorption spectrometry at admission and compared to that of healthy controls. Serum zinc levels were correlated with the severity of liver disease and hepatic encephalopathy among the cases. Results A total of 100 cases of decompensated cirrhosis of the liver and 50 healthy controls were included. The mean serum zinc level of the cases was 40.5 ± 10.0 µg/dL which was significantly lower than the mean serum zinc level (104.0±9.1 µg/dL) of controls (p < 0.0001). Serum zinc level was significantly lower in patients with higher grades of hepatic encephalopathy (p = 0.000). Similarly, serum zinc level was significantly reduced among patients with higher Child-Pugh and Model for End-stage Liver Disease scores. Conclusions Serum zinc level is significantly reduced in patients with decompensated cirrhosis of the liver, and lower serum zinc level is associated with the increased severity of the disease and higher grades of hepatic encephalopathy. In patients with decompensated cirrhosis of the liver, maintenance of adequate serum zinc levels may prevent hepatic encephalopathy.

The Correlation between Nutritional Status and Clinical Outcome of Liver Sirosis Patients at RSUD Dr. Saiful Anwar Malang

Introduction: Nutritional status is often associated with mortality and disease morbidity, including liver cirrhosis. Assessment of Tricep Skin Fold (TSF) and mid-arm muscle circumference (MAMC) is an easy parameter of nutritional status.&#x0D; Objective: This study aims to determine the relationship between nutritional status and clinical outcomes in patients with liver cirrhosis.&#x0D; Methods: The study used a retrospective cohort observational design with a sample of 57 patients with liver cirrhosis with various etiologies. The data comes from the results of anthropometric measurements of patients in the poly or inpatient ward and interviews regarding the history of the disease and complications experienced during the last month. Data analysis used the Chi-square test with a 95% Confidence Interval (CI), p &lt; 0.05, to analyze the relationship between nutritional status (TSF and MAMC) with clinical outcomes of liver cirrhosis (hematemesis melena, degree of esophageal varices grade Hepatic encephalopathy (HE) and degree of ascites).&#x0D; Results: Based on the TSF and MAMC values, data on cirrhotic patients who experienced nutritional status with the “low” criteria were 33.3% and 57.89%, respectively. The 'low” TSF value significantly correlates with the HE incidence (p = 0.049) with the RR value of 0.461. The relationship between MAMC and the incidence of ascites was statistically significant (0.004), with an RR value of 0.462.&#x0D; Conclusion: Nutritional status affects the incidence of HE and ascites in liver cirrhosis patients