Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension.

BACKGROUND: Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt (TIPS) is a critical intervention for managing PHT, it carries risks like hepatic encephalopathy, thus affecting patient survival prognosis. To our knowledge, existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes. Consequently, the development of an innovative modeling approach is essential to address this limitation. AIM: To develop and validate a Bayesian network (BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS. METHODS: The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed. Variables were selected using Cox and least absolute shrinkage and selection operator regression methods, and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT. RESULTS: Variable selection revealed the following as key factors impacting survival: age, ascites, hypertension, indications for TIPS, postoperative portal vein pressure (post-PVP), aspartate aminotransferase, alkaline phosphatase, total bilirubin, prealbumin, the Child-Pugh grade, and the model for end-stage liver disease (MELD) score. Based on the above-mentioned variables, a BN-based 2-year survival prognostic prediction model was constructed, which identified the following factors to be directly linked to the survival time: age, ascites, indications for TIPS, concurrent hypertension, post-PVP, the Child-Pugh grade, and the MELD score. The Bayesian information criterion was 3589.04, and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16. The model's accuracy, precision, recall, and F1 score were 0.90, 0.92, 0.97, and 0.95 respectively, with the area under the receiver operating characteristic curve being 0.72. CONCLUSION: This study successfully developed a BN-based survival prediction model with good predictive capabilities. It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

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.

Prediction of Mortality and Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Placement: Baseline and Longitudinal Body Composition Measurement.

PURPOSE: To investigate effects of baseline and early longitudinal body composition changes on mortality and hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: This is a case-control study with analysis of a TIPS registry (1995-2020) including data from patients with cirrhosis with computed tomography (CT) scans obtained within 1 month before and 3 months after TIPS. Core muscle area (CMA), macroscopic subcutaneous adipose tissue (mSAT), macroscopic visceral adipose tissue (mVAT) area, and muscle adiposity index (MAI) on CT were obtained. Multipredictor Cox proportional hazards models were used to assess the effect of body composition variables on mortality or HE. RESULTS: In total, 280 patients (158 men; median age, 57.0 years; median Model for End-stage Liver Disease-sodium [MELD-Na] score, 14.0) were included. Thirty-four patients had post-TIPS imaging. Median baseline CMA was 68.3 cm2 (interquartile range, 57.7-83.5 cm2). Patients with higher baseline CMA had decreased risks of mortality (hazard ratio [HR]: 0.82; P = .04) and HE (HR: 0.82; P = .009). It improved prediction of mortality over MELD-Na and post-TIPS right atrial pressure alone (confidence interval = 0.729). An increase in CMA (HR: 0.60; P = .043) and mSAT (HR: 0.86; P = .022) or decrease in MAI (HR: 1.50; P = .049) from before to after TIPS was associated with a decreased risk of mortality. An increase in mSAT was associated with an increased risk of HE (HR: 1.11; P = .04). CONCLUSIONS: CMA on CT scan 1 month before TIPS placement predicts mortality and HE in patients with cirrhosis. Changes in body composition on CT measured 3 months after TIPS placement independently predict mortality and HE.

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.

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.

The incidence and outcome of postoperative hepatic encephalopathy in patients with cirrhosis.

BACKGROUND: Cirrhosis is associated with increased perioperative risks related to hepatic decompensation. However, data are lacking regarding the incidence and outcomes of postoperative hepatic encephalopathy (HE). OBJECTIVE: To determine the incidence of HE postoperatively, factors associated with its development, and its association with in-hospital mortality. METHODS: Retrospective cohort study of 583 patients with cirrhosis undergoing non-hepatic surgery over a 10-year period. Outcomes included postoperative HE and in-hospital mortality and were, respectively, evaluated using multi-state modeling and Fine-Gray competing risk regression (with postoperative HE as a time-varying covariate). RESULTS: Overall, the median Model for End-Stage Liver Disease Sodium was 10, 61.7% had a history of ascites, 49.9% esophageal varices, and 34.6% HE. The most common surgeries including abdominal/non-bowel (33.3%), orthopedic (18.0%), and bowel (12.2%). A total of 42 (7.2%) patients developed HE postoperatively during admission. The cumulative risk of HE was 7.2%, which was most associated with a history of HE, ASA class, postoperative AKI, and postoperative infection. In-hospital mortality occurred in 34 (5.8%) individuals. Only ASA class was independently associated (HR 2.46, 95%CI 1.21-5.02), but there was a trend for postoperative HE (HR 1.71, 95%CI 0.73-3.98). DISCUSSION: HE is an uncommon but not rare postoperative complication that increases the risk of patient harm. This study implies its development is predictable. Consequently, at-risk patients should have consultation with a hepatologist before undergoing elective surgery.

Indication of Liver Transplantation in the Treatment of Newly Categorized Acute-on-Chronic Liver Failure In Japan.

AIM: This study aims to validate Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) and confirm the feasibility of performing transplantation. METHODS: We included 60 patients with acute liver injury. Demographic and clinical features were retrospectively collected, and the primary outcome was compared among 4 types: acute liver failure (ALF) with hepatic coma (n = 23), ALF without hepatic coma (n = 12), acute liver injury (n = 20), and ACLF (n = 5). Moreover, 80 transplanted patients were enrolled to compare the difficulty of transplantation between ALF (n = 8) vs non-ALF (n = 72) patients. RESULTS: Seven patients in the ALF with hepatic coma group and 1 patient in the ACLF with hepatic coma group were transplanted. Ten patients who could not be registered for transplantation died. In univariate analysis, liver failure type (P < .0001), total bilirubin level (P = .05), and prothrombin time internationalized ratio (P < .0001) were associated with patient survival. In multivariate analysis, liver failure type was associated with patient survival (P < .0001). The respective 1-, 3-, and 5-year patient survival rates were 45.9%, 45.9%, and 45.9% for ALF patients with hepatic coma; 100.0%, 100.0%, and 100.0% for ALF patients without hepatic coma and acute liver injury; and 80.0%, 80.0%, and 80.0% for ACLF patients (P < .0001). Chronic liver disease did not affect operation time (P = .46) and bleeding volume (P = .49). CONCLUSION: Patients diagnosed with ACLF via Japanese criteria presented significantly higher survival rates than ALF patients with hepatic coma.

Role of anthraquinones in Cassia occidentalis induced hepato-myo-encephalopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: The different plant parts of Cassia occidentalis Linn, (CO) such as root, leaves, seeds and pods have traditionally been used in multifarious medicines for the treatment of dysentery, diarrhea, constipation, fever, eczema, cancer and venereal diseases. MATERIALS AND METHODS: A systematic search of literature has been done in books and scientific databases like Science Direct, Pubmed, Google Scholar and Scopus etc. These sources were used to compile, analyze and review the information regarding the phytochemistry, toxicology and mechanism of toxicity of CO. The various references on this subject are cited in our review ranging from 1956 to 2019. RESULTS: Unintentional exposure of CO causes serious pathological condition in children, known as hepato-myo-encephalopathy (HME). The toxicity after CO consumption is associated with the presence of anthraquinones (AQs), a class of secondary plant metabolites. These AQs at high concentrations are known to cause detrimental effects on essential vital organs such as liver, kidney, spleen, brain, muscle and reproductive organs. The animal studies in rodent models as well as clinical investigations have clearly revealed that CO toxicity is associated with enhanced hepatotoxicity serum markers (ALT, AST, and LDH) and presence of necrotic lesions in liver. Furthermore, CO also causes vacuolization in muscle tissue and increases the level of CPK which is a prominent muscle damage marker. Apart from these target organs, CO consumption also causes neuronal damage via disturbing the levels of different proteins such as (GFAP and b-tubulin III). The mechanistic studies show that AQs present in CO have the potential to disturb the cellular homeostasis via binding to DNA, increasing the production ROS and showing inhibitory effects on essential enzymes etc. Therefore, AQs have been observed to be the primary culprit agents contributing to the toxicity of CO in children and animals. CONCLUSION: Despite its therapeutic potential, CO consumption can be detrimental if consumed in high amounts. A thorough analysis of literature reveals that AQs are the primary factors contributing to toxicity of CO seeds. Exposure to CO seeds causes HME, which is a serious life threatening condition for the malnourished children from lower strata. Multiple mechanisms are involved in the CO induced HME in patients. Lack of appropriate diagnostic measures and a poor understanding of the CO toxicity mechanism in humans and animals complicate the clinical management of CO poisoning subjects. Therefore, development of point of care diagnostic kits shall help in early diagnosis & suitable management of CO poisoning.

Serum copeptin level is a biomarker associated with ascites retention and the formation of a portosystemic shunt in chronic liver disease.

BACKGROUND AND AIM: Copeptin is a stable cleavage product of the arginine vasopressin precursor and is equimolarly secreted with arginine vasopressin. We aimed to assess whether copeptin is the surrogate marker for complications related chronic liver disease (CLD) such as ascites, hepatic encephalopathy (HE), portosystemic shunts (PSSs), and all causes of mortality in CLD. METHODS: Serum copeptin was measured in 170 CLD patients upon hospital admission. The association of copeptin levels with liver enzymes, liver functional reserve, and clinical parameters was investigated. Cox proportional hazard regression, logistic regression, and Kaplan-Meier analyses were performed to evaluate the associations of copeptin and ascites, HE and PSS formation, and prognostic factors with short-term (1 year) and long-term (4 years) mortality. RESULTS: Serum copeptin levels were significantly correlated with liver and renal function, elevated in parallel with liver disease progression, and also associated with HE. Serum copeptin, albumin-bilirubin score and hepatocellular carcinoma were independent predictors of PSS formation and decreased rate of survival. Serum copeptin and albumin-bilirubin scores were independent predictors of ascites retention. The short-term and long-term cumulative mortality rate was significantly decreased in patients with serum copeptin >5.5 or >4.8 pmol/mL compared with patients in whom serum copeptin levels were <5.5 or <4.8 pmol/mL (P < 0.0001; P < 0.0001). CONCLUSIONS: Serum copeptin level is a predictor for ascites retention and HE and PSS formation associated with portal hypertension. Moreover, serum copeptin level may be useful in predicting the rate of survival in patients with CLD.

Long-term clinical outcome and survival predictors in patients with cirrhosis after 10-mm-covered transjugular intrahepatic portosystemic shunt.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival. METHODS: This was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan-Meier method was used to measure survival and predictors of survival were identified with the Cox regression model. RESULTS: A total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/-9.9) and the median MELD was 13.3 (IQR 9.5-16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%. CONCLUSIONS: TIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.

Disparities in Mortality and Health Care Utilization for 460,851 Hospitalized Patients with Cirrhosis and Hepatic Encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a common cause of hospitalizations and readmissions for patients with decompensated cirrhosis. In this study, we proposed to investigate recent trends in in-hospital mortality and utilization for patients with cirrhosis and HE and to explore the effect of various sociodemographic, hospital, and clinical factors on mortality. METHODS: We performed an observational study using serial cross-sectional data from the 2009-2013 National Inpatient Sample to examine hospitalizations of patients with cirrhosis and HE. We collected data on in-hospital mortality, length of stay, and total hospital costs. We used negative binomial regression and logistic regression to investigate trends in utilization and multilevel modeling to examine the association between sociodemographic, hospital, and clinical factors and in-hospital mortality. RESULTS: The annual total number of hospitalizations from HE has steadily risen from 75,475 in 2009 to 106,915 in 2013 (P < 0.001). Annual in-hospital mortality (11.9-10.2%, P < 0.001) and length of stay (7.5-7.1 days, P = 0.015) have significantly decreased over this timeframe. The presence of septicemia, GI bleeding, and being uninsured were associated with 29.6%, 16.7%, and 15.7% of in-hospital death, respectively. Patients hospitalized in the South, Medicare beneficiaries, and patients hospitalized in the Midwest had a 9.8%, 9.2%, and 8.9% chance of dying in the hospital. CONCLUSION: The number of hospitalizations from HE has increased while in-hospital mortality has concomitantly decreased from 2009 to 2013. Both traditional risk factors (sepsis and GI bleeding) strongly influence the probability of in-hospital death. However, disparities in mortality by sociodemographic factors (insurance status and geography) also exist.

Cognitive Tests and Stool Frequency at Hospital Discharge Do Not Predict Outcomes in Hepatic Encephalopathy.

OBJECTIVES: Hepatic encephalopathy (HE) is associated with hospital readmissions and mortality. We sought to determine whether cognitive testing and stool frequency at discharge predicted 30-day readmission or death in cirrhotic patients admitted with overt HE. METHODS: We approached consecutive inpatients with cirrhosis and overt HE when they were within 48 hours of discharge. Patients underwent cognitive tests, including Psychometric Hepatic Encephalopathy Score (PHES), and stool frequency was documented. Chart review identified Model for End-Stage Liver Disease-sodium (MELD-Na) and the presence of non-HE extrahepatic organ failures. Cox proportional hazards models were used to evaluate predictors of time to the primary composite outcome of hospital readmission for HE or death within 30 days, censoring for liver transplantation. RESULTS: Of 51 patients consented and enrolled, 14 patients met the primary composite outcome. In unadjusted Cox models, 4 variables predicted HE readmission or death: MELD-Na (hazard ratio [HR] 1.10 [1.01-1.20], P = 0.03), respiratory failure (HR 4.26 [1.47-12.35], P = 0.008), total number of HE extrahepatic organ failures (HR 1.79 [1.12-2.88], P = 0.02), and score on a PHES subtest, Number Connection Test A (per 30 seconds; HR 1.25 [1.06-1.47], P = 0.01). PHES and 24-hour stool frequency did not predict the primary outcome. When controlling for MELD-Na, respiratory failure predicted the primary outcome (HR 3.67 [1.24-10.86], P = 0.02). CONCLUSION: Cognitive testing and stool frequency at discharge did not predict poor outcomes in patients admitted with HE, while respiratory failure appeared to be a strong predictor.

Early identification using the referral system prolonged the time to onset for hepatic encephalopathy after diagnosing severe acute liver injury.

In 2004, we implemented a referral system for patients with acute liver injury (ALI) based on an established formula that estimates the risk of progression to acute live failure (ALF); however, the benefits of the system for patients with severe acute liver injury (SLI) remain unclear. We have evaluated the clinical significance of the referral system for SLI patients. Patients with ALI/SLI who were consecutively and prospectively listed on the system between 2004 and 2018 were analyzed. Of the 371 ALI/SLI/ALF patients on the system, 124 satisfied the criteria for SLI; 34 of these 124 progressed to SLI after registration. Multivariate analysis using age, sex, AST, ALT, creatinine, total bilirubin, prothrombin, presence of hepatic encephalopathy (HE), and SLI at registration revealed that HE was associated with high mortality. Among the 23 patients who developed HE, five who progressed to SLI after registration showed an increased time to HE development compared with patients who had SLI at the time of registration. However, there was no significant difference in survival time after HE development. We concluded that early identification of SLI patients using the referral system increased the time from SLI diagnosis to HE development.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. AIM: To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care. METHODS: All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012-2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin. RESULTS: 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality. CONCLUSION: Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

A nomogram to predict the risk of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in Cirrhotic Patients.

BACKGROUND AND AIM: Hepatic encephalopathy (HE) is a serious complication of decompensated liver cirrhosis, affecting the prognosis of patients underwent transjugular intrahepatic portosystemic shunts (TIPS). We aim to create a nomogram to predict hepatic encephalopathy- free survivals (HEFS) after TIPS in cirrhotic patients and select appropriate candidates for TIPS. METHODS: Cirrhotic patients underwent TIPS from 2015 to 2018 in our department were included. Multivariable Cox regression was conducted to estimate the predictors of overt HE (OHE) after TIPS within one year. A nomogram based on the Cox proportional hazard model using data from a retrospective training cohort (70% of the patients) was developed. Then the prediction model was validated in the remaining 30% patients by Harrell's C-indexes, ROC curves and calibration plots. RESULTS: Of 373 patients, 117 developed postoperative OHE (31.4%). The training and validation groups comprised 83 (31.4%) and 34 (31.2%) patients, respectively. The cumulative survival rates of patients with HE at 1, 2 and 3 years were 90%, 83% and 76%, respectively. The nomogram included the following variables: age, Child-Turcotte-Pugh class (CTP class), diabetes mellitus (DM), serum creatinine and serum sodium (C-index = 0.772). The C-index for HEFS prediction was 0.773 for the validation cohort. The ROC for predicting HEFS was 0.809 and 0.783, respectively. CONCLUSIONS: We created a nomogram of predicting postoperative HEFS in cirrhotic patients received TIPS. This nomogram could be an important tool of HE risk prediction before TIPS to guide the therapeutic strategy in cirrhotic patients.

Outcome Prediction of Covert Hepatic Encephalopathy in Liver Cirrhosis: Comparison of Four Testing Strategies.

INTRODUCTION: Despite the negative impact of covert hepatic encephalopathy on the outcome of patients with liver cirrhosis, data regarding the ability of different testing strategies to predict overt hepatic encephalopathy (OHE) development and mortality are limited. This study aimed to compare the ability of Psychometric Hepatic Encephalopathy Score (PHES), critical flicker frequency (CFF), simplified animal naming test (S-ANT1), and clinical covert hepatic encephalopathy (CCHE) score to predict OHE development and mortality. METHODS: A total of 224 patients with liver cirrhosis were tested with different testing strategies and prospectively followed up regarding clinically relevant outcomes (OHE or death/liver transplantation). RESULTS: Prevalence of pathological results varied among the testing strategies: PHES 33.9%, CFF 17.9%, S-ANT1 41.5%, and CCHE score 33.9%. All testing strategies were independent predictors of OHE development after adjusting for model of end-stage liver disease (MELD) score and history of OHE. The predictive performances of PHES (area under the receiver operating characteristic curve, 0.742) and CCHE (area under the receiver operating characteristic curve, 0.785) regarding OHE development during the next 180 days were significantly better than those of CFF and S-ANT1. In multivariable analysis, pathological results in PHES, S-ANT1, and CCHE score were independently associated with higher mortality. CFF did not correlate with mortality in the whole cohort. In the subgroup of patients with a MELD score <15, pathological results in PHES, CFF, or CCHE score were independent predictors of higher mortality. DISCUSSION: PHES and CCHE score predict OHE development and mortality in patients with liver cirrhosis. In particular, in patients with low MELD score, both testing strategies could help to identify patients who might benefit from liver transplantation.

Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis.

BACKGROUND: Hepatic encephalopathy is a devastating complication of cirrhosis. AIM: To describe the outcomes after developing hepatic encephalopathy among contemporary, aging patients. METHODS: We examined data for a 20% random sample of United States Medicare enrolees with cirrhosis and Part D prescription coverage from 2008 to 2014. Among 49 164 persons with hepatic encephalopathy, we evaluated the associations with transplant-free survival using Cox proportional hazard models with time-varying covariates (hazard ratios, HR) and incidence rate ratios (IRR) for healthcare utilisation measured in hospital-days and 30-day readmissions per person-year. We validated our findings in an external cohort of 2184 privately insured patients with complete laboratory values. RESULTS: Hepatic encephalopathy was associated with median survivals of 0.95 and 2.5 years for those ≥65 or <65 years old and 1.1 versus 3.9 years for those with and without ascites. Non-alcoholic fatty-liver disease posed the highest adjusted risk of death among aetiologies, HR 1.07 95% CI (1.02, 1.12). Both gastroenterology consultation and rifaximin utilisation were associated with lower mortality, respective adjusted-HR 0.73 95% CI (0.67, 0.80) and 0.40 95% CI (0.39, 0.42). Thirty-day readmissions were fewer for patients seen by gastroenterologists (0.71 95% CI [0.57-0.88]) and taking rifaximin (0.18 95% CI [0.08-0.40]). Lactulose alone was associated with fewer hospital-days, IRR 0.31 95% CI (0.30-0.32), than rifaximin alone, 0.49 95% CI (0.45-0.53), but the optimal therapy combination was lactulose/rifaximin, IRR 0.28 95% CI (0.27-0.30). These findings were validated in the privately insured cohort adjusting for model for endstage liver disease-sodium score and serum albumin. CONCLUSIONS: Hepatic encephalopathy remains morbid and associated with poor outcomes among contemporary patients. Gastroenterology consultation and combination lactulose-rifaximin are both associated with improved outcomes. These data inform the development of care coordination efforts for subjects with cirrhosis.

Cost-Effectiveness of Rifaximin Treatment in Patients with Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis of the liver causing neuropsychiatric abnormalities. Clinical manifestations of overt HE result in increased health care resource utilization and effects on patient quality of life. While lactulose has historically been the mainstay of treatment for acute HE and maintenance of remission, there is an unmet need for additional therapeutic options with a favorable adverse event profile. Compared with lactulose alone, rifaximin has demonstrated proven efficacy in complete reversal of HE and reduction in the incidence of HE recurrence, mortality, and hospitalizations. Evidence suggests the benefit of long-term prophylactic therapy with rifaximin; however, there is a need to assess the economic impact of rifaximin treatment in patients with HE. OBJECTIVE: To assess the incremental cost-effectiveness of rifaximin ± lactulose versus lactulose monotherapy in patients with overt HE. METHODS: A Markov model was developed in Excel with 4 health states (remission, overt HE, liver transplantation, and death) to predict costs and outcomes of patients with HE after initiation of maintenance therapy with rifaximin ± lactulose to avoid recurrent HE episodes. Cost-effectiveness of rifaximin was evaluated through estimation of incremental cost per quality-adjusted life-year (QALY) or life-year (LY) gained. Analyses were conducted over a lifetime horizon. One-way deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in results. RESULTS: The rifaximin ± lactulose regimen provided added health benefits despite an additional cost versus lactulose monotherapy. Model results showed an incremental benefit of $29,161 per QALY gained and $27,762 per LY gained with rifaximin ± lactulose versus lactulose monotherapy. Probabilistic sensitivity analyses demonstrated that the rifaximin ± lactulose regimen was cost-effective ~99% of the time at a threshold of $50,000 per QALY/LY gained, which falls within the commonly accepted threshold for incremental cost-effectiveness. CONCLUSIONS: The clinical benefit of rifaximin, combined with an acceptable economic profile, demonstrates the advantages of rifaximin maintenance therapy as an important option to consider for patients at risk of recurrent HE. DISCLOSURES: This analysis was funded by Salix Pharmaceuticals, a division of Bausch Health US. Salix and Xcenda collaborated on the methods, and Salix, Xcenda, Jesudian, and Ahmad collaborated on the writing of the manuscript and interpretation of results. Bozkaya and Migliaccio-Walle are employees of Xcenda. Ahmad reports speaker fees from Salix Pharmaceuticals, unrelated to this study. Jesudian reports consulting and speaker fees from Salix Pharmaceuticals, unrelated to this study. The results from this model were presented at AASLD: The Liver Meeting 2014; November 7-11; Boston, MA.

Long-term outcomes in patients with decompensated alcohol-related liver disease, steatohepatitis and Maddrey's discriminant function <32.

BACKGROUND & AIMS: Patients with alcoholic hepatitis and a modified Maddrey's discriminant function (mDF) <32 have a low risk of short-term mortality. However, few data exist concerning long-term outcomes. The aims of this study were to evaluate 5-year survival rates and to identify predictive factors for long-term prognosis in this patient population. METHODS: We studied patients from 2 centers who were admitted for hepatic decompensation (ascites, hepatic encephalopathy, or jaundice) and who had histological findings of steatohepatitis and an mDF <32. Clinical and biological parameters were recorded at the time of liver biopsy and alcohol consumption was recorded during follow-up. We performed Cox proportional hazard survival analysis to identify factors associated with 5-year survival. RESULTS: One hundred and twenty-one patients were included (male: 64%, mean age: 51.5 ± 10.3 years, presence of cirrhosis: 84%). The median model for end-stage liver disease and mDF scores were 14 (IQR 11.7-16.1) and 19 (IQR 11.1-24), respectively. During follow-up, 30% of the patients remained abstinent. Survival rates at 1, 6, 12, 24, and 60 months were 96.7 ± 1.6%, 90.1 ± 2.7%, 80.8 ± 3.6%, 69.9 ± 4.3%, and 50.7 ± 4.9%, respectively. The majority of deaths (80%) were liver related. In multivariable analysis, encephalopathy at baseline and alcohol abstinence were predictive of 5-year survival. The 5-year survival rates of patients without and with encephalopathy at baseline were 60.5 ± 5.8% and 29.7 ± 8.0%, respectively, and the 5-year survival rates of abstinent and non-abstinent patients were 74.0 ± 8.0% and 40.9 ± 5.8%, respectively. CONCLUSIONS: The mortality rate of patients with alcoholic hepatitis and an mDF <32 is around 50% at 5 years. Hepatic encephalopathy at baseline and lack of alcohol abstinence impair long-term prognosis. New treatment strategies, including measures to ensure abstinence, are required. LAY SUMMARY: Patients with alcoholic hepatitis that is of intermediate severity have a low risk of short-term mortality but not much is known regarding long-term outcomes for these patients. This study clearly indicates that patients with intermediate disease characteristics have poor long-term outcomes. The presence of hepatic encephalopathy at the time of diagnosis and the absence of alcohol abstinence during follow-up are factors that predict poor long-term mortality.

[Prognostic significance and economic burden of hepatic encephalopathy in liver cirrhosis in German hospitals based on G-DRG data]. / Mortalität und ökonomische Auswirkungen der hepatischen Enzephalopathie bei Leberzirrhose in deutschen Krankenhäusern auf der Basis von G-DRG-Kostendaten.

INTRODUCTION: Hepatic encephalopathy (HE) represents a frequent complication of liver cirrhosis with negative effects on patients' lives. The prevalence of clinical HE is estimated to be between 30-45 %. Regardless of its clinical and prognostic relevance HE is considered to be underdiagnosed. METHODS: Beyond a systematic analysis of mortality of HE, we investigated the economic impact and reimbursement situation for HE in patients with liver cirrhosis in Germany. For the retrospective analysis, anonymized data (2011-2015) concerning expenses and diagnoses (§â€Š21-4 KHEntgG) were obtained from 74 participating hospitals of the Diagnosis Related Groups (DRG) Project of the German Gastroenterological Association (DGVS). Furthermore, results were compared with case data from all German hospitals provided by the German Federal Authority on Statistics (Statistische Bundesamt (Destatis), Wiesbaden). RESULTS: In participating hospitals 59 093 cases with liver cirrhosis were identified of which 14.6 % were coded as having HE. Hospital mortality was threefold increased compared to cirrhosis-patients without HE (20.9 versus 7.5 %). Cases with cirrhosis as well as the proportion with HE increased over time. Compared to all patients with cirrhosis, reimbursement for HE patients produced a deficit (of up to 634 € for HE grade 4). DISCUSSION: Mortality is threefold increased in patients with cirrhosis when an additional HE is diagnosed. Hospitals participating in the DGVS-DRG-project coded 2 % more HE cases among their cirrhosis cases than the rest of hospitals either because of a selection bias for greater disease severity or because of better coding quality. At present, reimbursement for HE patients on the basis of F-DRG-system produced a deficit.