Establishment and validation of a nomogram model for riskprediction of hepatic encephalopathy: a retrospective analysis.

To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63-0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541-0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer-Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ2 = 1.237587, P = 0.998, and for the validation set, χ2 = 31.90904, P = 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.

Investigation of therapeutic effects of rhubarb decoction retention enema on minimal hepatic encephalopathy in rats based on 16S rDNA gene sequencing and bile acid metabolomics.

Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE), with high incidence and a high rate of clinically missed diagnosis. Early diagnosis of MHE and effective clinical intervention are of great importance. Rhubarb decoction (RD)-induced retention enema can effectively improve the cognitive function of patients with MHE, whereas disturbances in the enterohepatic circulation of bile acid (BAs) can induce MHE. However, the molecular mechanisms underlying the therapeutic effects of RD have not been examined from the perspective of intestinal microbiota and bile metabolomics. In this study, we investigated the effects of RD-induced retention enema on intestinal microbiota and bile metabolites in rats with CCl4- and TAA-induced MHE. RD-induced retention enema significantly improved liver function, reduced blood ammonia levels, alleviated cerebral oedema and restored cognitive function in rats with MHE. In addition, it increased the abundance of intestinal microbes; partially reversed the disorder in the composition of intestinal microbiota, including the Bifidobacterium and Bacteroides genera; and regulated BA metabolism, such as taurine combined with increased BA synthesis. In conclusion, this study highlights the potential importance of BA enterohepatic circulation for RD to improve cognitive function in MHE rats, providing a new perspective on the mechanism of this herb. The findings of this study will facilitate experimental research on RD and help to develop RD-based strategies for clinical application.

Metabolite profiling analysis of hepatitis B virus-induced liver cirrhosis patients with minimal hepatic encephalopathy using gas chromatography-time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry.

This study used gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) and ultra-performance liquid chromatography-quadrupole TOFMS (UPLC-QTOFMS) metabonomic analytical techniques in combination with bioinformatics and pattern recognition analysis methods to analyze the serum metabolite profiling of hepatitis B virus (HBV)-induced liver cirrhosis patients with minimal hepatic encephalopathy (MHE), to find the specific biomarkers of MHE, to reveal the pathogenesis of MHE, and to determine a promising approach for early diagnosis of MHE. Serum samples of 100 normal controls (NC group), 29 HBV-induced liver cirrhosis patients with MHE (MHE group), and 24 HBV-induced liver cirrhosis patients without MHE [comprising 12 cases of compensated cirrhosis (CS group) and 12 cases of decompensated cirrhosis (DS group)] were collected and employed into GC-TOFMS and UPLC-QTOFMS platforms for serum metabolite detection; the outcome data were then analyzed using principal component analysis and orthogonal partial least squares-discriminant analysis (OPLS-DA). There were no significant differential metabolites between the NC group and the CS group. A series of key differential metabolites were detected. According to the variable influence in projection values and P-values, 60 small-molecule metabolites were considered to be dysregulated in the MHE group (compared to the NC group); 27 of these 60 dysregulated differential metabolites were considered to be the potential biomarkers (see Table 4, marked in bold); 66 small-molecule metabolites were considered to be dysregulated in the DS group (compared to the NC group); 34 of these 66 dysregulated differential metabolites were considered to be the potential biomarkers (see Table 5, marked in bold). According to the fold-change values, 9 of these 27 metabolites, namely valine, oxalic acid, erythro-sphingosine, 4,7,10,13,16,19-docosahexaenoic acid, isoleucine, allo-isoleucine, thyroxine, rac-octanoyl carnitine, and tocopherol (vitamin E), were downregulated in the MHE group (compared to the NC group); the other 18, namely adenine, glycochenodeoxycholic acid, fucose, allothreonine, glycohyocholic acid, glycoursodeoxycholic acid, tyrosine, taurocheno-deoxycholate, phenylalanine, 2-hydroxy-3-methyl-butanoic acid, hydroxyacetic acid, taurocholate, sorbitol, rhamnose, tauroursodeoxycholate, tolbutamide, pyroglutamic acid, and malic acid, were upregulated; 6 of these 34 metabolites were downregulated in the DS group (compared to the NC group), and the other 28 were upregulated, as shown in Table 5. (a) GC-TOFMS and UPLC-QTOFMS metabonomic analytical platforms can detect a range of metabolites in the serum; this might be of great help to study the pathogenesis of MHE and may provide a new approach for the early diagnosis of MHE. (b) Metabonomics analysis in combination with pattern recognition analysis might have great potential to distinguish the HBV-induced liver cirrhosis patients who have MHE from the normal healthy population and HBV-induced liver cirrhosis patients without MHE.

Chinese herbal medicine formula Jieduhuayu granules improves cognitive and neurophysiological functions in patients with cirrhosis who have minimal hepatic encephalopathy: a randomized controlled trial.

BACKGROUND: Minimal hepatic encephalopathy (MHE) impairs patients' cognitive and neurophysiological functions. In this study, we investigated the effect of treatment-related improvement in cognitive and neurophysiological functions. METHODS: We measured psychometric performance by number connection tests part A (NCT-A), digit symbol test (DST), mini-mental state examination (MMSE) and event related potential P300 wave of 80 patients with cirrhosis who have minimal hepatic encephalopathy on inclusion into the study and 15 days later. They were randomly assigned in a 1:1:1:1 ratio to four groups, to receive treatment of Chinese herbal medicine formula (HMG) or lactulose (LG) or Chinese herbal medicine formula combined with lactulose (HMCLG) for 15 days (n=20) or no treatment (CG) (n=20). This study was not blind. RESULTS: The mean number of NCT-A and MMSE scores improved significantly in patients in the HMG (0 day, 102.00±24.49 for NCT-A, 18.55±2.89 for MMSE; 15 days, 78.30±22.55 for NCT-A, 24.20±2.78 for MMSE) compared with patients in the CG after 15 days of follow-up (0 day, 103.00±24.98 for NCT-A, 17.90±2.99 for MMSE; 15 days, 95.65±24.34 for NCT-A, 18.85±3.12 for MMSE), P<0.05; the mean number of P300 latency (ms) and wave amplitude (µV) improved significantly among patients in the HMG after 15 days of treatment (0 day, 341.90±14.04 for latency, 8.40±1.73 for wave amplitude; 15 days, 305.45±23.95 for latency, 13.00±3.80 for wave amplitude) compared with patients in the CG after 15 days of follow-up (0 day, 343.85±14.88 for latency, 8.29±1.77 for wave amplitude; 15 days, 340.40±13.06 for latency, 8.50±1.82 for wave amplitude), P<0.05. Similar improvement were also found among patients in the LG and HMCLG; improvements among patients in the HMG were significantly greater than they were in the LG (P<0.05). Synergistic action were shown among patients in the HMCLG (P<0.05). CONCLUSION: Treatment with Chinese herbal medicine formula Jieduhuayu granules and lactulose may improve cognitive and neurophysiological functions in patients with cirrhosis who have MHE. Compared with lactulose alone, Chinese herbal medicine formula Jieduhuayu granules has higher efficacy of improving cognitive and neurophysiological functions in patients with cirrhosis who have MHE, and the two of them together show synergistic action. TRIAL REGISTRATION NUMBER: ACTRN12614000193673.