Clinical risk factors for portal hypertension-related complications in systemic therapy for hepatocellular carcinoma.

BACKGROUND: During systemic therapy, the management of portal hypertension (PH)-related complications is vital. This study aimed to clarify factors associated with the incidence and exacerbation of PH-related complications, including the usefulness of contrast-enhanced computed tomography (CECT) in the management of PH-related complications during systemic therapy. METHODS: A total of 669 patients who received systemic therapy as first-line treatment (443 patients for sorafenib, 131 for lenvatinib, and 90 for atezolizumab/bevacizumab [ATZ/BEV]) were enrolled in this retrospective study. Additionally, the lower esophageal intramural vessel diameters (EIV) on CECT and endoscopic findings in 358 patients were compared. RESULTS: The cutoff values of the EIV diameter on CECT were 3.1 mm for small, 5.1 mm for medium, and 7.6 mm for large varices, demonstrating high concordance with the endoscopic findings. esophageal varices (EV) bleeding predictors include EIV ≥ 3.1 mm and portal vein tumor thrombosis (PVTT). In patients without EV before systemic therapy, factors associated with EV exacerbation after 3 months were EIV ≥ 1.9 mm and ATZ/BEV use. Predictors of hepatic encephalopathy (HE) include the ammonia level or portosystemic shunt diameter ≥ 6.8 mm. The incidence of HE within 2 weeks was significantly higher (18%) in patients with an ammonia level ≥ 73 µmol/L and a portosystemic shunt ≥ 6.8 mm. The exacerbating factors for ascites after 3 months were PVTT and low albumin levels. CONCLUSIONS: Careful management is warranted for patients with risk factors for exacerbation of PH-related complications; moreover, the effective use of CECT is clinically important.

Association between proton pump inhibitors and risk of hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore, HE is a financial burden to a patient's family and significantly affects the patient's quality of life. In clinical practice, proton pump inhibitors (PPIs) are widely used for the treatment of HE. The use of PPIs is associated with an increased risk of post-TIPS HE; however, findings on the risk relationship between PPIs and post-TIPS HE are inconsistent. Therefore, a systematic evaluation of the relationship is needed to further provide valid evidence for the rational use of PPIs in patients who undergo TIPS. METHODS AND ANALYSIS: PubMed, Web of Science, Cochrane Library and Embase will be searched extensively for relevant information. Information from 1 July 2023 to 31 July 2023 in these databases will be included. Primary outcomes will be the use of PPIs and incidence of HE after TIPS; secondary outcomes will be survival, dose dependence and adverse events. This meta-analysis will be reported in accordance with the 50 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The risk of bias, heterogeneity and quality of evidence of the included studies will be evaluated prior to the data analysis. All data will be analysed using Review Manager (V.5.4.1) and Stata (V.17.0) statistical software. ETHICS AND DISSEMINATION: Ethical approval will not be necessary for this review and meta-analysis. The results of the study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022359208.

The Health Care Burden of Hepatic Encephalopathy.

Hepatic encephalopathy-a common and debilitating complication of cirrhosis-results in major health care burden on both patients and caregivers through direct and indirect costs. In addition to risk of falls, inability to work and drive, patients with hepatic encephalopathy often require hospital admission (and often readmission), and many require subacute care following hospitalization. The costs and psychological impact of liver transplantation often ensue. As the prevalence of chronic liver disease increases throughout the United States, the health care burden of hepatic encephalopathy will continue to grow.

Disparity Among African Americans in Transjugular Intrahepatic Portosystemic Shunt Procedure: A National Inpatient Sample Analysis from 2015 to 2020.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to alleviate patients with chronic liver cirrhosis and portal hypertension. Racial disparities were present in TIPS where numerous studies suggested African American patients experience higher in-hospital mortality rates. However, the incidence of post-TIPS surgical complications, such as HE, has yet to be examined among African Americans. Therefore, this study aimed to provide a comprehensive examination of the disparities in TIPS procedures among African American patients. METHODS: The study compared African American and Caucasian patients who underwent TIPS procedures in the National Inpatient Sample (NIS) database from the last quarter of 2015-2020 after ICD-10 change. Preoperative variables, including demographics, comorbidities, primary payer status, and hospital characteristics, were examined and multivariable analysis was used to assess outcomes correcting preoperative variables with p < 0.1. RESULTS: Compared to Caucasians, African Americans had higher in-hospital mortality (16.18 vs 8.22%, aOR 1.781, p < 0.01), hepatic encephalopathy (33.09 vs 27.44%, aOR 1.300, p = 0.05), and acute kidney injury (45.59 vs 29.60%, aOR 2.019, p < 0.01). Using the generalized linear model, African Americans have longer length of stay (11.04 ± 0.77 days vs 8.54 ± 0.16 days, p < 0.01). CONCLUSION: Despite a higher prevalence of cirrhosis, African Americans continue to have marked underrepresentation in TIPS procedures in recent years. Their underrepresentation, in conjunction with higher mortality, morbidity, and increased comorbidity conditions, could imply disparity in accessing care. This finding underscores the necessity for improved access to diagnostic and therapeutic services for African Americans with liver cirrhosis.

Regression-based Chinese norms of number connection test A and digit symbol test for diagnosing minimal hepatic encephalopathy.

Number connection test A (NCT-A) and digit symbol test (DST), the preferential neuropsychological tests to detect minimal hepatic encephalopathy (MHE) in China, haven't been standardized in Chinese population. We aimed to establish the norms based on a multi-center cross-sectional study and to detect MHE in cirrhotic patients. NCT-A and DST were administered to 648 healthy controls and 1665 cirrhotic patients. The regression-based procedure was applied to develop demographically adjusted norms for NCT-A and DST based on healthy controls. Age, gender, education, and age by education interaction were all predictors of DST, while age, gender, and education by gender interaction were predictors of log10 NCT-A. The predictive equations for expected scores of NCT-A and DST were established, and Z-scores were calculated. The norm for NCT-A was set as Z ≤ 1.64, while the norm for DST was set as Z ≥ - 1.64. Cirrhotic patients with concurrent abnormal NCT-A and DST results were diagnosed with MHE. The prevalence of MHE was 8.89% in cirrhotic patients, and only worse Child-Pugh classification (P = 0.002, OR = 2.389) was demonstrated to be the risk factor for MHE. The regression-based normative data of NCT-A and DST have been developed to detect MHE in China. A significant proportion of Chinese cirrhotic patients suffered from MHE, especially those with worse Child-Pugh classification.

Preventing variceal rebleeding in cirrhotic patients with portal vein thrombosis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Preventing rebleeding is crucial, but the best prevention technique for patients with cirrhosis and portal vein thrombosis (PVT) remains debatable. Therefore, this systematic review and meta-analysis compared a transjugular intrahepatic portosystemic shunt (TIPS) with endoscopic therapy (ET) plus nonselective beta-blockers (NSBBs) for preventing variceal rebleeding in this patient population. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception until May 18, 2023. The studies were screened using predetermined criteria, relevant data were extracted, and pooled analyses were performed using the Reviewer Manager 5.4.1 software. RESULTS: We retrieved 1032 studies, of which 5 studies comprising a total of 272 patients were included. The postoperative variceal rebleeding rate was significantly lower in the TIPS group than in the ET + NSBBs group (odds ratio [OR] = 0.19, 95% confidence interval [CI] = 0.11-0.35, P < 0.05, I2 = 0%), but the portal vein recanalization rate was higher (OR = 7.92, 95% CI = 3.04-20.67, P < 0.05, I2 = 0%). The rates of hepatic encephalopathy (HE) and mortality did not differ between the groups. CONCLUSIONS: Our results suggest that TIPS prevents variceal rebleeding without increasing the hepatic encephalopathy risk more effectively than ET plus NSBBs, but this benefit did not translate into improved survival. Thus, it may be preferable to ET plus NSBBs for preventing variceal rebleeding in patients with cirrhosis and PVT. However, more large-scale and multicenter randomized controlled trials involving other patient populations are required to verify the clinical efficacy of both these treatments and ensure generalizability.

Undiagnosed Cirrhosis and Hepatic Encephalopathy in a National Cohort of Veterans With Dementia.

Importance: Dementia and hepatic encephalopathy (HE) are challenging to distinguish clinically. Undiagnosed cirrhosis in a patient with dementia can lead to missed opportunities to treat HE. Objective: To examine the prevalence and risk factors of undiagnosed cirrhosis and therefore possible HE in veterans with dementia. Design, Setting, and Participants: A retrospective cohort study was conducted between 2009 and 2019 using data from the Veterans Health Administration (VHA) and 2 separate validation cohorts from the Richmond Veterans Affairs Medical Center. Data analysis was conducted from May 20 to October 15, 2023. Participants included 177 422 US veterans with a diagnosis of dementia at 2 or more clinic visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) score. Exposures: Demographic and clinical characteristics. Main Outcomes and Measures: An FIB-4 score (>2.67 suggestive of advanced fibrosis and >3.25 suggestive of cirrhosis), capped at age 65 years even for those above this cutoff who were included in the analysis. Results: Among 177 422 veterans (97.1% men; 80.7% White; mean (SD) age, 78.35 [10.97] years) 5.3% (n = 9373) had an FIB-4 score greater than 3.25 and 10.3% (n = 18 390) had an FIB-4 score greater than 2.67. In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with older age (odds ratio [OR], 1.07; 95% CI, 1.06-1.09), male gender (OR, 1.43; 95% CI, 1.26-1.61), congestive heart failure (OR, 1.48; 95% CI, 1.43-1.54), viral hepatitis (OR, 1.79; 95% CI, 1.66-1.91), Alcohol Use Disorders Identification Test score (OR, 1.56; 95% CI, 1.44-1.68), and chronic kidney disease (OR, 1.11; 95% CI, 1.04-1.17), and inversely associated with White race (OR, 0.79; 95% CI, 0.73-0.85), diabetes (OR, 0.78; 95% CI, 0.73-0.84), hyperlipidemia (OR, 0.84; 95% CI, 0.79-0.89), stroke (OR, 0.85; 95% CI, 0.79-0.91), tobacco use disorder (OR, 0.78; 95% CI, 0.70-0.87), and rural residence (OR, 0.92; 95% CI, 0.87-0.97). Similar findings were associated with the FIB-4 greater than 2.67 threshold. These codes were associated with cirrhosis on local validation. A local validation cohort of patients with dementia showed a similar percentage of high FIB-4 scores (4.4%-11.2%). Conclusions and Relevance: The findings of this cohort study suggest that clinicians encountering patients with dementia should be encouraged to screen for cirrhosis using the FIB-4 score to uncover reversible factors associated with cognitive impairment, such as HE, to enhance outcomes.

Advanced chronic renal disease is an independent risk factor for inpatient mortality following transjugular intrahepatic portosystemic shunt procedure.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to alleviate portal hypertension in patients with decompensated liver cirrhosis. However, the risks and outcomes associated with TIPS in patients with advanced chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the perioperative outcomes of TIPS procedures in patients with advanced CKD using the National Inpatient Sample (NIS) database, a comprehensive all-payer inpatient database in the US. METHODS: The study identified patients who underwent TIPS procedures in the NIS database from Q4 2015 to 2020. Patients with advanced CKD were identified using specific ICD-10-CM codes, and they were compared to patients without CKD. Preoperative variables, including demographics, indications for TIPS, comorbidities, APR-DRG subclass, primary payer status, and hospital characteristics, were noted. Perioperative outcomes were examined by multivariable logistic regression. RESULTS: A total of 248 patients with advanced CKD and 5511 patients without CKD undergoing TIPS procedures were identified in the NIS database. Compared to non-CKD, patients with advanced CKD had higher mortality (13.70% vs. 8.60%, aOR = 1.56, P  = 0.03), acute kidney injury (51.21% vs. 29.34, aOR = 1.46, P  < 0.01), transfer out (25.00% vs. 12.84%, aOR = 1.88, P  < 0.01), and length of stay over 7 days (64.11% vs. 38.97%, aOR = 2.34, P  < 0.01). However, there was no difference in hepatic encephalopathy (31.85% vs. 27.19%, aOR = 1.12, P  = 0.42). CONCLUSION: Advanced CKD patients undergoing TIPS are at higher risk of mortality and AKI compared to patients without CKD; HE was mildly elevated but NS. Long-term prognosis of patients with advanced CKD who had TIPS is needed in future studies.

Impact of nutritional status on the outcome of transjugular intrahepatic portosystemic shunt in patients with cirrhosis: a systematic review.

OBJECTIVES: Malnutrition and sarcopenia have been reported to adversely affect the outcome of patients with cirrhosis of the liver. There is an emerging body of evidence suggesting malnutrition and sarcopenia increase the risk of hepatic encephalopathy (HE) and mortality after transjugular intrahepatic portosystemic shunt (TIPS). The current systematic review aims to determine whether the body of evidence supports an association between nutritional status and post-TIPS outcomes in patients with cirrhosis. METHODS: Electronic databases of PubMed, Embase, and Scopus were searched from inception to June 3, 2023, for studies analysing the effect of nutritional status on post-TIPS outcomes in patients with cirrhosis. RESULTS: A total of 22 studies were included in the systemic review. Assessment of sarcopenia was done by skeletal muscle index (SMI) at the L3 level, transversal psoas muscle thickness, psoas muscle density, malnutrition as per ICD, relative sarcopenia with excess adiposity, lipid profile, controlling nutritional status score, body composition analysis, hospital frailty risk score, and visceral and subcutaneous fat area index. Ten out of 12 studies in this systematic review showed a significant association with the incidence of post-TIPS HE. Thirteen out of 14 studies reported that the presence of malnutrition was associated with increased odds of mortality following TIPS. One study reported sarcopenia as an independent predictor of liver failure, and another study reported that Pre-TIPS SMI was an independent predictor of substantial improvement in post-TIPS SMI. CONCLUSIONS: The current systematic review shows that the presence of pre-TIPS malnutrition or sarcopenia is an independent predictor of adverse outcomes after TIPS. Incorporating these parameters into present prediction models can provide additional prognostic information. ADVANCES IN KNOWLEDGE: Nutritional assessment should be part of the evaluation of patients planned for TIPS for prediction of adverse events after the procedure.

Thirty-Day Readmissions Are Largely Not Preventable in Patients With Cirrhosis.

INTRODUCTION: Hospital readmissions are common in patients with cirrhosis, but there are few studies describing readmission preventability. We aimed to describe the incidence, causes, and risk factors for preventable readmission in this population. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized at a single center between June 2014 and March 2020 and followed up for 30 days postdischarge. Demographic, clinical, and socioeconomic data, functional status, and quality of life were collected. Readmission preventability was independently and systematically adjudicated by 3 reviewers. Multinomial logistic regression was used to compare those with (i) preventable readmission, (ii) nonpreventable readmission/death, and (iii) no readmission. RESULTS: Of 654 patients, 246 (38%) were readmitted, and 29 (12%) were preventable readmissions. Reviewers agreed on preventability for 70% of readmissions. Twenty-two (including 2 with preventable readmission) died. The most common reasons for readmission were hepatic encephalopathy (22%), gastrointestinal bleeding (13%), acute kidney injury (13%), and ascites (6%), and these reasons were similar between preventable and nonpreventable readmissions. Preventable readmission was often related to paracentesis timeliness, diuretic adjustment monitoring, and hepatic encephalopathy treatment. Compared with nonreadmitted patients, preventable readmission was independently associated with racial and ethnic minoritized individuals (odds ratio [OR] 5.80; 95% CI, 1.96-17.13), nonmarried marital status (OR 2.88; 95% CI, 1.18-7.05), and admission in the prior 30 days (OR 3.45; 95% CI, 1.48-8.04). DISCUSSION: For patients with cirrhosis, readmission is common, but most are not preventable. Preventable readmissions are often related to ascites and hepatic encephalopathy and are associated with racial and ethnic minorities, nonmarried status, and prior admissions.

Association between sarcopenia and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: a systematic review and meta-analysis.

PURPOSE: The association between the presence of sarcopenia in patients with cirrhosis and the onset of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) is yet to be established. We conducted a systematic review and meta-analysis to provide a thorough summary of the available evidence on this association. METHODS: A thorough search of the literature was performed in the PubMed, EMBASE, and Web of Science databases. The protocol was duly registered on PROSPERO (CRD42023398856). The hazard ratio (HR) and corresponding 95% confidence intervals (CIs) for the occurrence of HE after TIPS were extracted from studies comparing cirrhotic patients with and without sarcopenia. These data were then combined using a random-effect model. RESULTS: A total of 1135 patients from seven cohort studies that met our eligibility criteria were included in the meta-analysis. Our findings indicate a significantly higher risk of post-TIPS HE among cirrhotic patients with sarcopenia compared to those without sarcopenia (HR, 2.35; 95% CIs 1.32-4.19; p = 0.004; I2 = 75%). The findings remained consistent across subgroups stratified by liver disease etiology, study location, and severity of hepatic dysfunction. CONCLUSION: The study demonstrated that sarcopenia was strongly linked to an increased likelihood post-TIPS HE among cirrhotic patients.

Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis.

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients. METHODS: A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use. RESULTS: The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103-1.581, P = 0.002), decompensation (HR 1.646, 95% CI 1.477-1.835, P < 0.001), HE (HR 1.968, 95% CI 1.372-2.822, P < 0.001), SBP (HR 1.751, 95% CI 1.649-1.859, P < 0.001), and infection (HR 1.370, 95% CI 1.148-1.634, P < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results. CONCLUSION: PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.

Comparative efficacy of early TIPS, Non-early TIPS, and Standard treatment in patients with cirrhosis and acute variceal bleeding: a network meta-analysis.

BACKGROUND: Cirrhosis is a chronic disease characterized by chronic liver inflammation and diffuse fibrosis. A combination of vasoactive drugs, preventive antibiotics, and endoscopy is the recommended standard treatment for patients with acute variceal bleeding; however, this has been challenged. We compared the effects of early transjugular intrahepatic portosystemic shunt (TIPS), non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. MATERIALS AND METHODS: The present network meta-analysis was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Assessing the methodological quality of systematic reviews guidelines. The review has been registered with the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and World Health Organization-approved trial registry databases were searched for randomized controlled trials (RCTs) evaluating early TIPS, non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. RESULTS: Twenty-four RCTs (1894 patients) were included in the review. Compared with standard treatment, early TIPS [odds ratio (OR), 0.53; 95% credible interval (Cr), 0.30-0.94; surface under the cumulative ranking curve (SUCRA), 98.3] had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI, 0.11-0.28; SUCRA, 98.2) and non-early TIPS (OR, 0.30; 95% CrI, 0.23-0.42; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR, 2.78; 95% CrI, 1.89-4.23, SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions. CONCLUSION: Based on the moderate-to-high quality evidence presented in this study, early TIPS placement was associated with reduced all-cause mortality [with a median follow-up of 1.9 years (25th-75th percentile range 1.9-2.3 years)] and rebleeding compared to standard treatment and non-early TIPS. Although early TIPS and standard treatment had a comparable incidence of hepatic encephalopathy, early TIPS showed superiority over non-early TIPS in this aspect. Recent studies have also shown promising results in controlling TIPS-related hepatic encephalopathy. However, it is important to consider individual patient characteristics and weigh the potential benefits against the risks associated with early TIPS. Therefore, we recommend that clinicians carefully evaluate the patient's condition, considering factors such as severity of variceal bleeding, underlying liver disease, and overall clinical status, before making a treatment decision. Further well-designed RCTs comparing early TIPS with non-early TIPS are needed to validate these findings and provide more definitive guidance.

Prediction of mortality and overt hepatic encephalopathy undergoing transjugular intrahepatic portosystemic shunt: a retrospective cohort study.

PURPOSE: Data on medium- and long-term efficacy and safety of Transjugular intrahepatic portosystemic shunt (TIPS) using Viatorr stents in Chinese patients are limited. This study aimed to evaluate the 5-year mortality and the incidence of overt hepatic encephalopathy (OHE) after Viatorr stent insertion, and construct a model to predict post-TIPS OHE preoperatively. METHODS: One hundred thirty-two patients undergoing Viatorr stent insertion in our institution between August 2016 and December 2019 were included, and randomly divided into training and validation cohort at a 70/30 ratio. Patients were followed up until death or the end date of follow-up (December 31st, 2021). The primary end point was all-cause mortality, and the secondary end points were OHE, variceal rebleeding, recurrent ascites and shunt dysfunction. RESULTS: The 1-, 2-, 3-, 4- and 5-year cumulative survival rates were 92.4%, 87.9%, 85.3%, 80.2% and 80.2%, respectively. Post-TIPS OHE and Child-Pugh grade were independent prognostic factors. The rates of variceal rebleeding, recurrent ascites, shunt dysfunction and post-TIPS OHE were 9.1%, 14.3%, 5.3% and 28.0%, respectively. The variables of nomogram predicting post-TIPS OHE included age, diabetes and ascites grade. The area under time-dependent receiver operation characteristic (ROC) curve (AUC) in training and validation cohort were 0.806 and 0.751, respectively. The decision curve analysis (DCA) showed good net benefit both in training and validation cohort. CONCLUSION: Post-TIPS OHE and Child-Pugh grade are independent prognostic factors for early mortality in cirrhosis patients, thus we construct a simple and convenient prediction model for post-TIPS OHE to identify high-risk patients preoperatively.

Episodic overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt does not increase mortality in patients with cirrhosis.

BACKGROUND & AIMS: Overt hepatic encephalopathy (OHE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS) placement, given its high incidence and possibility of refractoriness to medical treatment. Nevertheless, the impact of post-TIPS OHE on mortality has not been investigated in a large population. METHODS: We designed a multicenter, non-inferiority, observational study to evaluate the mortality rate at 30 months in patients with and without OHE after TIPS. We analyzed a database of 614 patients who underwent TIPS in three Italian centers and estimated the cumulative incidence of OHE and mortality with competitive risk analyses, setting the non-inferiority limit at 0.12. RESULTS: During a median follow-up of 30 months (IQR 12-30), 293 patients developed at least one episode of OHE. Twenty-seven (9.2%) of them experienced recurrent/persistent OHE. Patients with OHE were older (64 [57-71] vs. 59 [50-67] years, p <0.001), had lower albumin (3.1 [2.8-3.5] vs. 3.25 [2.9-3.6] g/dl, p = 0.023), and had a higher prevalence of pre-TIPS OHE (15.4% vs. 9.0%, p = 0.023). Child-Pugh and MELD scores were similar. The 30-month difference in mortality between patients with and without post-TIPS OHE was 0.03 (95% CI -0.042 to 0.102). Multivariable analysis showed that age (subdistribution hazard ratio 1.04, 95% CI 1.02-1.05, p <0.001) and MELD score (subdistribution hazard ratio 1.09, 95% CI 1.05-1.13, p <0.001), but not post-TIPS OHE, were associated with a higher mortality rate. Similar results were obtained when patients undergoing TIPS for variceal re-bleeding prophylaxis (n = 356) or refractory ascites (n = 258) were analyzed separately. The proportion of patients with persistent OHE after TIPS was significantly higher in the group of patients who died. The robustness of these results was increased following propensity score matching. CONCLUSION: Episodic OHE after TIPS is not associated with mortality in patients undergoing TIPS, regardless of the indication. IMPACT AND IMPLICATIONS: Overt hepatic encephalopathy (OHE) is a common complication in patients with advanced liver disease and it is particularly frequent following transjugular intrahepatic portosystemic shunt (TIPS) placement. In patients with cirrhosis outside the setting of TIPS, the development of OHE negatively impacts survival, regardless of the severity of cirrhosis or the presence of acute-on-chronic liver failure. In this multicenter, non-inferiority, observational study we demonstrated that post-TIPS OHE does not increase the risk of mortality in patients undergoing TIPS, irrespective of the indication. This finding alleviates concerns regarding the weight of this complication after TIPS. Intensive research to improve patient selection and risk stratification remains crucial to enhance the quality of life of patients and caregivers and to avoid undermining the positive effects of TIPS on survival.

Population characteristics, healthcare pathways and outcomes of patients with cirrhosis hospitalized with overt hepatic encephalopathy in France: A study of the French Hospital-Discharge Database.

Hepatic encephalopathy (HE) is a severe complication of cirrhosis, independently associated with a poor survival. The objectives of this study were to describe the prevalence of overt hepatic encephalopathy (OHE) requiring hospitalization, and the healthcare pathways and outcomes of patients hospitalized for OHE in France. Data from the French Hospital-Discharge Database (Programme de Medicalisation des Systemes d'information, PMSI) within the 5-year period from 2014 to 2018 were analysed. Since the disease lacks a PMSI code in the ICD-10, an identification algorithm was developed. The analysis identified 57,191 patients with OHE including 48,566 patients (85 %) who had been hospitalized twice or more during the study period. Each year, an average of over 20,000 patients were hospitalized in France for OHE as the primary or secondary reason for hospitalization. Among these patients, between 11,500 and 13,500 had been hospitalized at least twice in that year with an average of 3.4 hospitalisations per year. 25 % of admissions occurred following consultation at the emergency unit. Among hospitalisations, 15 % involved admission to the critical care resuscitation unit or intensive care. For all patients identified as suffering from OHE and hospitalized, the 5-year mortality was 46.5 % (26,621 patients). This pioneering study revealed that, in France, despite a probable underestimation of OHE episodes due to the lack of specific PMSI coding, the prevalence of OHE was very high, with frequent recurrences and readmissions, and high mortality.

Effectiveness and prognosis of covered stents with different diameters in transjugular intrahepatic portosystemic shunt: a meta-analysis.

PURPOSE: This meta-analysis was designed to evaluate the clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) conducted utilizing stents of different diameters, thus providing recommendations for more logical selections of covered stents for patients with portal hypertension, in particular for the Asian population. MATERIALS AND METHODS: Web of Science, PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang were searched for randomized controlled trials and cohort studies from inception until February 2023. The meta-analysis was carried out using Revman 5.4 Software. Heterogeneity between researches was assessed by the χ2 test and I2 index. The outcomes evaluated were the incidence of post-TIPS hepatic encephalopathy (HE), variceal rebleeding, shunt dysfunction, 1-year overall survival and decrease in portal pressure gradient (PPG). RESULTS: Eight appropriate clinical trials with 1246 patients were selected (638 and 608 patients in the experimental and control groups, respectively). In regards to preoperative PPG reduction, there was no discernible difference between the two groups [mean difference = 1.15, 95% confidence interval (CI) = -0.29-2.58, P = 0.12]. The rate of post-TIPS HE was significantly higher in patients in the 8 mm stent group than in the 6-7 mm stent group [odds ratio (OR) = 0.54, 95% CI = 0.42-0.70, P < 0.00001, I2 = 46%]. There were no significant differences in the rates of variceal rebleeding (OR = 1.05, 95% CI = 0.67-1.65, P = 0.84, I2 = 0%), shunt dysfunction (OR = 0.88, 95% CI = 0.53-1.47, P = 0.64, I2 = 0%) and 1-year overall survival (OR = 0.86, 95% CI = 0.50-1.50, P = 0.61, I2 = 0%). CONCLUSION: Asian populations with portal hypertension may benefit more from TIPS with 6-7 mm covered stents because they can reduce the risk of postoperative HE while offering similar efficacy when compared to 8 mm covered stents.

Meld-sarcopenia score and skeletal muscle density predicts short-term readmission of patients with hepatic encephalopathy.

PURPOSE: To investigate whether the quality of skeletal muscle mass could predict short-term readmission in patients with hepatic encephalopathy (HE). METHOD: Patients with HE were enrolled from 2018 to 2022. Sarcopenia and myosteatosis were defined using the L3 skeletal muscle index (SMI) and skeletal muscle density (SMD) obtained from CT imaging. MELD-Sarcopenia score was calculated. Multivariable analysis and multiple linear regression were applied to identify predictors of 30-day readmission and length of hospitalization. RESULTS: 123 patients with HE were included. 55 (44.7%) and 87 (70.7%) patients were identified with sarcopenia and myosteatosis, respectively. Patients with sarcopenia exhibited a higher prevalence of myosteatosis, lower SMI and SMD (p < 0.05). Patients with myosteatosis were older, had a lower body mass index, a higher neutrophil-to-lymphocyte ratio and MELD-sarcopenia scores (p < 0.05). 10 (8.1%) patients were readmitted within 30 days. The readmitted group had a higher MELD-sarcopenia score (25.0 ± 6.6 vs. 19.5 ± 7.8, p = 0.034) and lower L3 SMD (28.3 ± 5.9 vs. 33.8 ± 6.9, p = 0.015). In the multivariable analysis, MELD-sarcopenia score (95% CI 1.388 [1.074-1.793], p = 0.012) and SMD (95% CI 0.778 [0.610-0.991], p = 0.042) were found to be significantly associated with the 30-day readmission of patients with HE. Age (p = 0.028), alcohol liver disease (p = 0.025), and hypertension (p = 0.003) were associated with the length of hospitalization for patients with HE. CONCLUSIONS: The MELD-sarcopenia score and SMD were identified as predictive factors for short-term readmission in patients diagnosed as HE.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

Evaluating clinical outcomes and prognosis in patients with cirrhosis and portal hypertension: a retrospective observational cohort study.

OBJECTIVE: Cirrhosis describes the end-stage of chronic liver disease. Irreversible changes in the liver cause portal hypertension, which can progress to serious complications and death. Only a few studies with small sample sizes have investigated the prognosis of cirrhosis with portal hypertension. We used electronic healthcare records to examine liver-related outcomes in patients with diagnosed/suspected portal hypertension. DESIGN: This retrospective observational cohort study used secondary health data between 1 January 2017 and 3 December 2020 from the TriNetX Network, a federated electronic healthcare records platform. Three patient groups with cirrhosis and diagnosed/suspected portal hypertension were identified ('most severe', 'moderate severity' and 'least severe'). Outcomes studied individually and as a composite were variceal haemorrhage, hepatic encephalopathy, complications of ascites and recorded mortality up to 24 months. RESULTS: There were 13 444, 23 299, and 23 836 patients in the most severe, moderate severity and least severe groups, respectively. Mean age was similar across groups; most participants were white. The most common individual outcomes at 24 months were variceal haemorrhage in the most severe group, recorded mortality and hepatic encephalopathy in the moderate severity group, and recorded mortality in the least severe group. Recorded mortality rate was similar across groups. For the composite outcome, cumulative incidence was 59% in the most severe group at 6 months. Alcohol-associated liver disease and metabolic-associated steatohepatitis were significantly associated with the composite outcome across groups. CONCLUSION: Our analysis of a large dataset from electronic healthcare records illustrates the poor prognosis of patients with diagnosed/suspected portal hypertension.