Analysis of Changes over Time in Blood Amino Acids During Online Haemodiafiltration Dialysis in Acute Liver Failure Patients with Hepatic Encephalopathy.

Acute liver failure (ALF) is a disease associated with severe symptoms, including rapid deterioration of liver function and impaired consciousness. Recently, online hemodiafiltration (OLHDF), an artificial liver replacement therapy, has attracted attention as a treatment option for comatose ALF. In this study, changes over time in blood aromatic amino acids (AAAs) and ammonia (NH3), the causative agents of hepatic coma, during OLHDF in patients with ALF were analysed. Nine patients aged 20 years or older with high-grade hepatic encephalopathy admitted to the Kagoshima University Hospital Emergency Centre between October 2020 and September 2021 were included. OLHDF settings were blood flow 100 mL/min, dialysate flow 300 mL/min, and replacement fluid flow 100 mL/min. The analysis items were blood NH3 concentration before and after OLHDF, blood amino acid concentration from before to 24 hours after the start of OLHDF, and the presence or absence of conscious awakening after OLHDF. Of the 11 amino acids measured in this study, the AAAs (tyrosine and phenylalanine) had concentrations higher than the reference range before the start of OLHDF, but were within the reference range 24 hours after OLHDF. NH3 was significantly reduced and the conscious awakening rate was 88.9%. When NH3 and AAAs, which were considered causative agents of hepatic coma and whose concentrations were higher than the reference range, were removed by OLHDF, the level of consciousness improved significantly. Regarding branched chain amino acids (BCAAs: valine, isoleucine, and leucine), which is considered a protective factor in hepatic coma, the concentration range before starting OLHDF was within the reference range, but the concentration 24 hours after starting OLHDF was below the reference range. The Fisher ratio, the ratio of BCAAs to AAAs, increased from before to after 24 hours starting OLHDF, but was lower than the reference range. Therefore, supplementation should be considered if OLHDF is continued for a longer period of time. Changes over time of 11 amino acids and NH3 in patients with ALF coma were analysed. NH3 and AAAs, which were abnormally high, decreased to within the reference range 24 hours after the start of OLHDF and the level of consciousness improved. On the other hand, BCAAs, which is considered a protective factor in hepatic coma, the concentration 24 hours after starting OLHDF was below the reference range. Further studies are needed to elucidate the changes in biologically useful substances during OLHDF.

Construction of a prediction model for hepatic encephalopathy in acute-on-chronic liver failure patients.

OBJECTIVE: Hepatic encephalopathy (HE) is a serious complication of acute-on-chronic liver failure (ACLF) that requires early detection and intervention to positively impact patient prognosis. This study aimed to develop a reliable model to predict HE in ACLF patients during hospitalization. METHODS: Retrospectively recruiting 255 hepatitis B-related ACLF patients, including 67 who developed HE during hospitalization, the study analysed clinical data and biochemical indices collected during the first week of admission. The least absolute shrinkage and selection operator (LASSO) was used to identify characteristic predictors for hospitalization HE events, and a logistic regression model was subsequently developed. Receiver operating characteristic (ROC) curves, calibration curves, and bootstrap resampling were used to evaluate the model's discrimination, consistency, and accuracy, and a nomogram was created to visualize the model. An external validation cohort of 236 liver failure patients collected from the same medical centre between 2007 and 2010 was used to validate the model. RESULTS: The study found that blood urea nitrogen (BUN), alpha-fetoprotein (AFP), international normalized ratio (INR), serum ammonia, and infection complications during hospitalization were risk factors for HE in ACLF patients. The new model predicted the development of HE in ACLF patients with an area under the receiver operating characteristic curve (AUROC) of 85.2%, which was superior to other models. The best threshold for the new model was 0.28, resulting in a specificity of 81.4% and a sensitivity of 80.6%. In the validation group, the new model showed similar results, with an AUROC of 79% and a specificity of 83.6% and a sensitivity of 56.6%. CONCLUSION: This study developed and validated a new prediction model for HE in ACLF patients offering a useful tool for early identification of patients with a high risk of HE in clinical settings. However, to ascertain the model's general effectiveness, future prospective multicentre studies are warranted.

The new model for predicting hepatic encephalopathy (HE) in patients with hepatitis B related acute-on-chronic liver failure (ACLF) demonstrated high accuracy with an area under the receiver operating characteristic curve (AUROC) of 85.2%, outperforming existing models such as MELD, CLIF-C AD and rJHEP.Key risk factors for HE development in ACLF patients were identified as blood urea nitrogen, alpha-fetoprotein, international normalized ratio, serum ammonia, and infection complications within the first week of hospitalization.

Correlation of ammonia and blood laboratory parameters with hepatic encephalopathy: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition. METHODS: A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE. RESULTS: This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients. CONCLUSIONS: These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE.

The Value of Ammonia as a Biomarker in Patients with Cirrhosis.

Ammonia is a product of amino acid metabolism that accumulates in the blood of patients with cirrhosis and plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE). Despite being one of the main drivers of brain dysfunction, for many years international societies stated that increased blood ammonia does not add any diagnostic, staging, or prognostic value for HE in patients with cirrhosis. Nonetheless, in the last decades, evidence is emerging that supports the utility of ammonia for risk stratification, but its role in guiding HE diagnosis, staging, and treatment is unclear and there is equipoise in its use in clinical practice. This review provides the latest evidence on the value of ammonia as a biomarker in patients with cirrhosis. Although correct measurement of ammonia requires disciplined sample collection, it provides extremely useful clinical guidance for the diagnosis of HE, offers prognostic information, and it defines a therapeutic target.

Serum Prolactin as a Marker of the Severity of Liver Cirrhosis in a Tertiary Hospital in India: A Cross-Sectional Study.

BACKGROUND: In India, cirrhosis is becoming a growing concern, leading to an unmet need for new non-invasive markers to assess the severity of liver disease. Serum prolactin is one such marker. AIM: To determine the association between serum prolactin, the severity of liver cirrhosis, and its complications such as ascites, hepatic encephalopathy, and esophageal varices. METHODS: This cross-sectional study involved 117 patients with liver cirrhosis. They were evaluated for some complications such as ascites, esophageal varices, and hepatic encephalopathy, as well as for severity by using the Child-Turcotte-Pugh (CTP) score. Serum prolactin levels were measured, and their relationship with both the severity and complications of liver cirrhosis was determined. A P value of < 0.05 was considered significant. RESULTS: The mean age of the patients was 48.3 ± 12.08 years, and the majority (80.3%) were males. Seventy-one percent of the patients had elevated serum prolactin levels (>19.40 ng/mL). Elevated serum prolactin was found in approximately 95.0% and 86.8% of patients with hepatic encephalopathy and ascites, respectively. The median serum prolactin levels were significantly associated with esophageal varices grades (P = 0.043) and hepatic encephalopathy (P < 0.001). The sensitivity and specificity of serum prolactin for predicting severe CTP scores were 81.6% and 91.2%, respectively, with a diagnostic accuracy of 87.2%. On multivariate regression analysis, ascites (AOR = 3.8, 95%CI = 1.29-10.98, P = 0.015), hepatic encephalopathy (AOR = 6.1, 95%CI = 0.68-53.78, P = 0.012), CTP class B (AOR = 5.9, 95%CI = 1.39-24.68, P = 0.016), and CTP class C (AOR = 13.4, 95%CI = 2.25-82.21, P = 0.004) were significantly associated with elevated serum prolactin levels. CONCLUSION: There was a significant association between serum prolactin levels and CTP classes, esophageal varices, ascites, and hepatic encephalopathy in patients with liver cirrhosis.

Vitamin D deficiency stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis: A retrospective cohort study.

BACKGROUNDS & AIMS: This study aimed to investigate the association between vitamin D deficiency and covert hepatic encephalopathy (CHE), overt hepatic encephalopathy (OHE) occurrence, and mortality in patients with cirrhosis. METHODS: This retrospective study reviewed 679 patients with cirrhosis. Vitamin D deficiency was defined as serum 25-hydorxyvitamin D (25-OHD) levels < 20 ng/mL. The associations between 25-OHD and CHE, OHE occurrence, and mortality were assessed using logistic regression, Fine-Gray competing risk regression, and Cox proportional hazards regression models, respectively. RESULTS: Of 428 eligible patients, 75% had vitamin D deficiency and 23% had CHE. The prevalence of CHE was higher in patients with vitamin D deficiency than in those without vitamin D deficiency (28% vs. 13%, p = 0.002). During the median follow-up period of 2.3 years, 14% of the patients developed OHE and 27% died. Patients with vitamin D deficiency had a higher incidence of OHE (p = 0.002) and mortality (p = 0.006) than those without vitamin D deficiency. After adjustment for potential covariates, multivariate analyses showed that 25-OHE was associated with CHE (odds ratio, 0.95; 95% confidence interval [CI], 0.91-0.99; p = 0.023), OHE occurrence (sub-distribution hazard ratio, 0.92; 95% CI, 0.86-0.98; p = 0.013) and mortality (hazard ratio, 0.96; 95% CI, 0.93-0.99; p = 0.020) in patients with cirrhosis. CONCLUSIONS: Vitamin D deficiency is highly prevalent and is associated with CHE, OHE, and mortality in patients with cirrhosis. Evaluation of vitamin D is essential to predict the outcomes of patients with cirrhosis.

Elevated serum neurofilament light chain levels are associated with hepatic encephalopathy in patients with cirrhosis.

Increasing evidences implicate vital role of neuronal damage in the development of hepatic encephalopathy (HE). Neurofilament light chain (NfL) is the main frame component of neurons and is closely related to axonal radial growth and neuronal structural stability. We hypothesized that NfL as a biomarker of axonal injury may contribute to early diagnosis of HE. This study recruited 101 patients with liver cirrhosis, 10 healthy individuals, and 7 patients with Parkinson's disease. Minimal hepatic encephalopathy (MHE) was diagnosed using psychometric hepatic encephalopathy score. Serum NfL levels were measured by the electrochemiluminescence immunoassay. Serum NfL levels in cirrhotic patients with MHE were significantly higher than cirrhotic patients without MHE, and increased accordingly with the aggravation of HE. Serum NfL levels were associated with psychometric hepatic encephalopathy score, Child-Pugh score, model for end-stage liver disease score, and days of hospitalization. Additionally, serum NfL was an independent predictor of MHE (odds ratio of 1.020 (95% CI 1.005-1.034); P = 0.007). The discriminative abilities of serum NfL were high for identifying MHE (AUC of 0.8134 (95% CI 0.7130-0.9219); P ˂ 0.001) and OHE (AUC of 0.8852 (95% CI 0.8117-0.9587); P ˂ 0.001). Elevated serum NfL levels correlated with the presence of MHE and associated with the severity of HE, are expected to be a biomarker in patients with cirrhosis. Our study suggested that neuronal damage may play a critical role in the development of HE.

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.

Substitution of One Meat-Based Meal With Vegetarian and Vegan Alternatives Generates Lower Ammonia and Alters Metabolites in Cirrhosis: A Randomized Clinical Trial.

INTRODUCTION: Diet can affect ammoniagenesis in cirrhosis and hepatic encephalopathy (HE), but the impact of dietary preferences on metabolomics in cirrhosis is unclear. As most Western populations follow meat-based diets, we aimed to determine the impact of substituting a single meat-based meal with an equal protein-containing vegan/vegetarian alternative on ammonia and metabolomics in outpatients with cirrhosis on a meat-based diet. METHODS: Outpatients with cirrhosis with and without prior HE on a stable Western meat-based diet were randomized 1:1:1 into 3 groups. Patients were given a burger with 20 g protein of meat, vegan, or vegetarian. Blood for metabolomics via liquid chromatography-mass spectrometry and ammonia was drawn at baseline and hourly for 3 hours after meal while patients under observation. Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between/within groups. RESULTS: Stool microbiome composition was similar at baseline. Serum ammonia increased from baseline in the meat group but not the vegetarian or vegan group. Metabolites of branched chain and acylcarnitines decreased in the meat group compared with the non-meat groups. Alterations in lipid profile (higher sphingomyelins and lower lysophospholipids) were noted in the meat group when compared with the vegan and vegetarian groups. DISCUSSION: Substitution of a single meat-based meal with a non-meat alternatives results in lower ammoniagenesis and altered serum metabolomics centered on branched-chain amino acids, acylcarnitines, lysophospholipids, and sphingomyelins in patients with cirrhosis regardless of HE or stool microbiome. Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis.

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

BACKGROUND AND STUDY AIMS: The 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 METHODS: A 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). RESULTS: The 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). CONCLUSION: A 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.

Neurofilament light chain but not glial fibrillary acidic protein is a potential biomarker of overt hepatic encephalopathy in patients with cirrhosis.

INTRODUCTION AND OBJECTIVES: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE). MATERIALS AND METHODS: We included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays. RESULTS: ICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each). CONCLUSIONS: Plasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Serum Ammonia Levels Do Not Correlate With Overt Hepatic Encephalopathy Severity in Hospitalized Patients With Cirrhosis.

Although ammonia is involved in the pathophysiology of hepatic encephalopathy (HE), the use of ammonia levels in clinical practice is problematic.1-3 For example, in a study of 551 patients with overt HE (OHE) receiving lactulose who had ammonia levels tested, only 60% had an increased ammonia level (defined as >72 µmol/L).2 Overall, there was no correlation observed between lactulose dose and whether ammonia levels were obtained (ie, presence/absence of increased ammonia level did not guide therapy), or between time to OHE resolution and ammonia levels.2 Additionally, there is substantial interlaboratory variability in sample handling and processing, which may affect ammonia measurements.4.

Amino Acid Profile in Malnourished Patients with Liver Cirrhosis and Its Modification with Oral Nutritional Supplements: Implications on Minimal Hepatic Encephalopathy.

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer's ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE.

Association Between Serum Levels of Neurofilament Light Chains and Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis.

INTRODUCTION: Serum biomarkers for the diagnosis of minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis would be desirable. In this proof-of-concept study, we investigated the association between MHE and serum levels of neurofilament light chains (sNfL) in patients with liver cirrhosis. METHODS: sNfL were studied in patients with liver cirrhosis (with or without MHE) and controls (patients with ischemic stroke, transitory ischemic attack, and healthy individuals). MHE was diagnosed using the Psychometric Hepatic Encephalopathy Score. RESULTS: Patients with MHE showed higher sNfL than patients without MHE and controls. In multivariable analyses, higher sNfL were independently associated with the presence of MHE. sNfL had a reliable discriminative power for the detection of MHE with an area under the curve of 0.872. DISCUSSION: MHE is associated with higher sNfL.

Prediction of minimal hepatic encephalopathy by using an radiomics nomogram in chronic hepatic schistosomiasis patients.

OBJECTIVE: To construct an MR-radiomics nomogram to predict minimal hepatic encephalopathy (MHE) in patients with chronic hepatic schistosomiasis (CHS). METHODS: From July 2017 to July 2020, 236 CHS patients with non-HE (n = 140) and MHE (n = 96) were retrospective collected and randomly divided into training group and testing group. Radiomics features were extracted from substantia nigra-striatum system of a brain diffusion weighted images (DWI) and combined with clinical predictors to build a radiomics nomogram for predicting MHE in CHS patients. The ROC curve was used to evaluate the predicting performance in training group and testing group. The clinical decisive curve (CDC) was used to assess the clinical net benefit of using radiomics nomogram in predicting MHE. RESULTS: Low seralbumin (P < 0.05), low platelet count (P < 0.05) and high plasma ammonia (P < 0.05) was the significant clinical predictors for MHE in CHS patients. The AUC, specificity and sensitivity of the radiomics nomogram were 0.89, 0.90 and 0.86 in the training group, and were 0.83, 0.85 and 0.75 in the training group. The CDC analysis showed clinical net benefits for the radiomics nomogram in predicting MHE. CONCLUSIONS: The radiomics nomogram combining DWI radiomics features and clinical predictors could be useful tool to predict MHE in CHS patients.

Predictive Value of the Serum Matrix Metalloproteinase-9 Level on Hepatic Encephalopathy in Patients with Chronic Liver Disease.

BACKGROUND: Early diagnosis of hepatic encephalopathy (HE) in chronic liver disease (CLD) is difficult clinically. OBJECTIVE: The aim of this study was to evaluate whether serum matrix metalloproteinase-9 (MMP-9) levels could identify early HE in patients with CLD. METHODS: Serum MMP-9 levels in 1,187 patients with CLD were measured at baseline. A total of 1,187 patients with CLD were followed for a mean of 48 months (range: 4-50). The association between MMP-9 and the risk of HE was evaluated by logistic regression analysis and Cox regression analysis. RESULTS: Patients with higher serum MMP-9 levels had higher rates of HE history and HE events during follow-up (all P<0.001). The multivariate logistic regression analysis revealed that MMP-9 (OR=2.84, 95% CI 1.63-7.11, P=0.004) was independently associated with HE history, with an increased grade of aggravation on liver fibrosis at baseline. Multivariate Cox proportional hazard analysis revealed that MMP-9 (HR=2.21, 95% CI 1.09-5.02, P<0.001) was an independent predictor for HE events by sensitivity analysis. The Kaplan-Meier analysis demonstrated that patients with MMP-9 above the median value (176.2 mg/d) had a higher rate of new HE events than patients who had MMP-9 levels below the median value (P<0.001). CONCLUSIONS: Elevated serum RBP4 levels were associated with a higher risk of HE events during follow-up. These results may suggest that serum MMP-9 has good predictive value for detecting HE in patients with CLD, which provides some clinical reference value to clinicians for the early diagnosis of HE.

Probiotics combined with rifaximin influence the neurometabolic changes in a rat model of type C HE.

Type C hepatic encephalopathy (HE) is a neuropsychiatric disease caused by chronic liver disease. Management of type C HE remains an important challenge because treatment options are limited. Both the antibiotic rifaximin and probiotics have been reported to reduce the symptoms of HE, but longitudinal studies assessing their effects on brain metabolism are lacking and the molecular mechanisms underpinning their effects are not fully understood. Therefore, we evaluated in detail the effects of these different treatments on the neurometabolic changes associated with type C HE using a multimodal approach including ultra-high field in vivo 1H MRS. We analyzed longitudinally the effect of rifaximin alone or in combination with the probiotic Vivomixx on the brain metabolic profile in the hippocampus and cerebellum of bile duct ligated (BDL) rats, an established model of type C HE. Overall, while rifaximin alone appeared to induce no significant effect on the neurometabolic profile of BDL rats, its association with the probiotic resulted in more attenuated neurometabolic alterations in BDL rats followed longitudinally (i.e. a smaller increase in Gln and milder decrease in Glu and Cr levels). Given that both rifaximin and some probiotics are used in the treatment of HE, the implications of these findings may be clinically relevant.

Sociodemographic characteristics, complications requiring hospital admission and causes of in-hospital death in patients with liver cirrhosis admitted at a district hospital in Ghana.

BACKGROUND: Chronic liver diseases including liver cirrhosis are a major cause of morbidity and mortality globally. Despite the high burden of liver cirrhosis in Ghana, data on this disease is lacking. OBJECTIVE: To determine the sociodemographic characteristics, reasons for admission, and in-hospital mortality of patients with cirrhosis of the liver seen at a district hospital in Ghana. METHODS: A prospective study was conducted involving one hundred and eighty-six (186) patients admitted on the medical wards in St. Dominic hospital with liver cirrhosis from 1st January 2018 to 24th June 2020. The patient's demographic and clinical features were documented using a standardized questionnaire. Diagnostic biochemical and haematological tests as well as abdominal ultrasound scans were performed for all patients. They were followed up until death or discharge from hospital. RESULTS: One hundred and eighty-six patients (186) with a median age of 46 years were included in the study. HBV was the main etiology of liver cirrhosis (38.7%) followed closely by alcohol consumption (38.3%). In-hospital mortality was 41.3% and the most frequent cause of death was hepatic encephalopathy (68.4%). The following were associated with death; Jaundice, weight loss, elevated bilirubin, international normalized ratio (INR), creatinine, blood urea nitrogen(BUN), Child-Pugh score, model for end-stage liver disease sodium score (MELDNa), and low sodium. However, hepatic encephalopathy, MELDNa, INR and BUN were independent predictors of in-hospital mortality on logistic regression analysis. CONCLUSIONS: In-hospital mortality in cirrhotic patients was high with the leading cause of death being hepatic encephalopathy. Timely diagnosis and adequate management of hepatic encephalopathy are necessary to prevent death from liver cirrhosis.