Episodes Of Hepatic Encephalopathy Research Articles

Lights and Shadows in Hepatic Encephalopathy Diagnosis.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is caused by liver insufficiency and/or portal-systemic shunting. The exact nature of HE is debated; as such, conflicting uses of the term “HE” may cause inconsistencies in its detection and management. This review highlights the meaning of the term “HE” on the basis of its historical origins and current consensus. It also provides criteria for the diagnosis of the condition based on its phenotypes and risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical reporting of HE episodes is discussed.

Current Practice of Branched Chain Amino Acids Administration in Patients with Liver Cirrhosis: A Physician Survey

Introduction: Protein Energy Malnutrition (PEM) is prevalent in about 65-90% of patients with liver disorders. PEM is usually associated with poor quality of life, high risk of complications, morbidity and mortality, and longer duration of hospital stays. PEM is also associated with decreased skeletal muscle mass and reduced levels of serum albumin and Branched Chain Amino Acids (BCAAs). Therefore, BCAAs are recommended as nutritional therapy in various liver disorders. Aim: To understand the current practice of BCAA use in patients with liver cirrhosis in India. Materials and Methods: A cross-sectional, questionnaire-based survey was conducted pan India involving 100 gastroenterologists over a period of four months from September 2019 to December 2019. Each physician participated in the survey after verbal consent. Ample time was given for completion of the questionnaires. Results: Out of 83 participating physicians, nearly 3/4th considered liver cirrhosis as the most common Gastrointestinal (GI) disorder where nutrition is important in patient management. Malnutrition was commonly observed in patients with cirrhosis by nearly over 80% physicians and was most common in patients with decompensated cirrhosis. Weight loss and loss of appetite can be early signs of sarcopenia as these were common profiles observed in patients with malnutrition. Total 51.8% physicians considered BCAA administration in all Child-Pugh class patients. The practice of BCAA treatment with regards to its dose and duration highly varied for patients with cirrhosis, Hepatic Encephalopathy (HE), and Liver Transplantation (LT). Proteins from vegetarian source (50.6%) and BCAA supplementation (96.4%) were considered as major treatments for HE patients. Majority of the physicians reported that BCAA administration improved quality of life (52.4%), reduced HE episodes (49.4%), improved muscle mass (50%), and reduced hospitalisation rates (49.4%) in 20-40% of their patients. In all, 92.8% of physicians suggested that early administration of oral BCAA can prolong the waiting period for LT. Conclusion: Branched Chain Amino Acids (BCAA) is an integral part of nutritional management in patients with liver cirrhosis in India. Further studies are required to guide the decision on dose and duration of BCAA treatment in the management of cirrhosis.

Budget impact of optimizing rifaximin-α use for the prevention of recurrent hepatic encephalopathy in The Netherlands

Aims Rifaximin-α as an adjunct to lactulose is reimbursed in the Netherlands for prevention of the third and subsequent episodes of overt Hepatic Encephalopathy (HE) in cirrhotic patients. However, use of rifaximin-α remains limited. This study evaluates the clinical and economic impact of treating all patients eligible under Dutch reimbursement conditions with rifaximin-α as an adjunct to lactulose for the prevention of overt HE in the Netherlands from a hospital and healthcare payer’s perspective. Materials and methods A budget impact analysis was performed following national and international guidelines. Resource use was based on Dutch real-world data. HE-related cost inputs were based on the declaration codes, Dutch cost manual, and actual drug list prices. Several sensitivity and scenario analyses were conducted to assess model robustness. Results Treating eligible HE patients with rifaximin-α in addition to lactulose saves €4,487 and costs €249 per patient over a 5-year period compared with lactulose monotherapy from hospital and healthcare payer’s perspectives, respectively. In the Netherlands, an estimated 38% of the 2,567 eligible patients are currently being treated with rifaximin-α. Optimizing rifaximin-α use by treating all eligible patients with the rifaximin-α + lactulose could save more than 3,000 hospital admissions, almost 15,000 hospital bed days, and 300 deaths over a 5-year period. Despite increased drug costs, treatment is estimated to result in potential cost savings over a 5-year period of 7.2 million euros from a Dutch hospital perspective. The budget impact is 397,770 euros from a healthcare payer’s perspective. Conclusions Next to a clinical perspective, also from an economic perspective, wider prescription of rifaximin-α adhering to guidelines could be beneficial to reduce costs from a hospital perspective. From a healthcare payer’s perspective, costs increase with addition of rifaximin-α due to relative better survival causing relatively higher drug and liver transplantation-related costs.

Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis.

Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). This study aims to explore whether low-dose rifaximin can prevent overall complications and prolong survival in cirrhotic patients. In this multi-centre randomized open-labelled prospective study, 200 patients with decompensated cirrhosis were randomly assigned at a ratio of 1:1. Patients in rifaximin group were administered 400mg rifaximin twice daily for 6months, and all other therapeutic strategies were kept unchanged in both groups as long as possible. The primary efficacy endpoints were the incidence of overall complications and liver transplantation-free survival. The secondary endspoints were the incidence of each major cirrhosis-related complication, as well as the Child-Pugh score and class. The major baseline characteristics were similar in the two groups except for HE. The cumulative incidence and frequency of overall complications were significantly lower in rifaximin group than in the control group (p < 0.001). Though liver transplantation-free survival was not significantly different between the two groups, subgroup analysis showed rifaximin markedly prolonged liver transplantation-free survival in patients with Child-Pugh score ≥ 9 (p = 0.007). Moreover, rifaximin markedly reduced the episodes of ascites exacerbation (p < 0.001), HE (p < 0.001) and gastric variceal bleeding (EGVB, p = 0.031). The incidence of adverse events was similar in the two groups. Low-dose rifaximin significantly decreases the occurrence of overall complications, leading to prolonged survival in patients with advanced stages of cirrhosis in this trail. Further study should be carried out to compare the effect of this low-dose rifaximin with normal dose (1200mg/day) rifaximin in preventing cirrhosis-related complications. NCT02190357.

Role of Zinc in Patients Presenting with Recurrent Hepatic Encephalopathy in Medical Unit of Tertiarycare Hospital Lahore

Abstract Objective: To observe the effects of zinc replacement on hepatic encephaopahty. To reducce hospital admission and heath burden by reducing episodes of recurrent hepatic encephalopathy. Methods: This study was carried out on 160 patients presenting with hepatic encephalopathy in medical ward of services hospital Lahore. The aim of the study was to assess the role of zinc in the improvement of encephalopathy. Results: The mean age of patients in group A was 55.78 and that in group B was 56.88years.There was significant difference in mean value of hepatic encephalopathy grade in both groups A and B after 3 months of follow up (p.value 0.027) indicating zinc is beneficial in treatment of hepatic encephalopathy. Conclusion: Our study showed that zinc replacement improved outcome in patients with Hepatic encephalopathy. Key words: Hepatic encephalopathy, zinc supplementation, chronic liver disease.

The role of the hospitalist in the continuum of care for patients with hepatic encephalopathy: treatment of inpatient episodes and preventing outpatient recurrence and readmissions

: Hepatic encephalopathy (HE) is a common complication of advanced cirrhosis that is seen in the majority of patients at some point. Manifesting as a wide spectrum of neuropsychiatric abnormalities, HE has many consequences; increased morbidity and mortality, bothersome symptoms affecting quality of life and routine activities (e.g., working, driving), substantial caregiver burden, frequent hospital admissions and readmissions and associated economic strains. The manifestations of HE are potentially reversible with medical treatment, frequently in the inpatient setting, and preventable with outpatient maintenance of remission. However, breakdowns across the continuum of care for HE patients are responsible for frequent hospital readmissions; hospitalists, who play a pivotal role in improving the management of HE, can improve these outcomes. The authors are US hepatologists with expertise and experience in managing HE and members of the Chronic Liver Disease Foundation (CLDF), a nonprofit 501(c)(3) educational organization dedicated to raising awareness of liver disease. The goals of this article are to provide a thorough review of HE; to describe how HE is currently managed and identify ways to improve diagnosis and treatment; to review the role of the hospitalist in managing and preventing HE episodes; and to provide strategies to reduce hospital readmissions and improve outcomes.

S1018 Fecal Microbiota Transplant Improves Cognitive Function in Patients With Hepatic Encephalopathy: A Systematic Review of Randomized Clinical Trial

INTRODUCTION: Hepatic encephalopathy (HE) is a leading cause of readmission, disability, and mortality despite the use of standard of care (Rifaximin + Lactulose) and is associated with microbial dysbiosis. Intestinal dysbiosis with increased gut permeability allows the translocation of pathogen-associated molecules into the systemic circulation. Fecal Microbial Transplant (FMT) may improve microbial dysbiosis and cognitive dysfunction in patients with HE. This review aims to summarize clinical trials using FMT in patients with HE. METHODS: A comprehensive literature search was performed using PubMed, Embase, Web of Science, and Clinicaltrials.gov for the identification of clinical trials. Studies were selected based on the PRISMA guideline. RESULTS: A total of four studies were included. Data were extracted into Table 1. FMT was used in combination with SOC in two studies. In a phase I study (Bajaj et al), FMT was administered via enema, there was no significant change in the MELD score after transplant. SAE was lower in the FMT arm. The number of hospitalization as well as HE episodes was significantly lower. In a phase III study (Woodhouse et al) there was no significant change in the MELD score after transplant but there was a decrease in the ammonia level. Cognitive outcomes: In a phase I study (Bajaj et al 2017), there was improvement in the amount of time taken to complete the Encephaloapp stroop test (FMT arm : tday 0: 247 , Δt (day 0–20): 29.1 ± 27.9 vs Control arm tday 0: 282 Δt (Day 0–20) -43.5 ± -95.7) as well as PHES score (FMT arm : pday 0: -7.4 , Δp (day 0–20) : -3.1 ±-2.1 vs control arm pday 0: -8.6 ,Δp day 0–20: 0.0 ± 3.1). Similar findings were shown in a recent phase I trial (Bajaj et al 2019). In this study, there was improvement in time to complete Encepahloapp stroop test (FMT arm: 245 , 200, 225 at day 0,20 , >1 year vs control arm : 260, 250 , 250 at day 0, 20, >1 year), as well as the PHES scoring system (FMT arm : -7,-4-6 at day 0,20 , >1 year vs control arm: -8,-8,-11). A phase II study (Bloom et al) demonstrated 56-sec improvement in day 0 right after FMT and 22 sec on day 30 using encephaloapp, they also demonstrated 2.6 points improvement in PHES score at day 0 and 3.9 points improvement at day 30. CONCLUSION: The FMT showed improvement in cognition in patients with HE. Large randomized clinical trials are needed to validate the results.Table 1.: Clinical Trial Results of FMT in Patients with Cirrhosis and Hepatic Encephalopathy

Incidence and Bedside Predictors of the First Episode of Overt Hepatic Encephalopathy in Patients With Cirrhosis.

Hepatic encephalopathy (HE) is associated with marked increases in morbidity and mortality for patients with cirrhosis. We aimed to determine the risk of and predictors for HE in contemporary patients. We prospectively enrolled 294 subjects with Child A-B (70% Child A) cirrhosis and portal hypertension without previous HE from July 2016 to August 2018. The primary outcome was the development of overt HE (grade >2). We assessed the predictive power of model for end-stage liver disease-sodium (MELD-Na) score, the Inhibitory Control Test, the Sickness Impact Profile score, and the Bilirubin-Albumin-Beta-Blocker-Statin score. We also derived a novel predictive model incorporating MELD-Na score, impact of cirrhosis on daily activity (Likert 1-9), frailty (chair-stands per 30 seconds), and health-related quality of life (Short-Form 8, 0-100). The cohort's median age was 60 years, 56% were men, and the median MELD-Na score was 9. During a follow-up of 548 ± 281 days, 62 (21%) had incident overt HE with 1-year probability of 14% ± 2%, 10% ± 2%, and 25% ± 5% for Child A and B. The best model for predicting the risk of overt HE included MELD-Na, Short-Form 8, impact on activity rating, and chair-stands within 30 seconds. This model-MELDNa-Actvity-Chairstands-Quality of Life Hepatic Encephalopathy Score-offered an area under the receiver operating curve (AUROC) for HE development at 12 months of 0.82 compared with 0.55, 0.61, 0.70, and 0.72 for the Inhibitory Control Test, Sickness Impact Profile, Bilirubin-Albumin-Beta-Blocker-Statin, and MELD-Na, respectively. The AUROC for HE-related hospitalization was 0.92. This study provides the incidence of HE in a well-characterized cohort of contemporary patients. Bedside measures such as activity, quality of life, and physical function accurately stratified the patient's risk for overt HE.

Early, late, or no shunt embolization in patients with cirrhosis- and portosystemic shunt-related hepatic encephalopathy.

Portosystemic shunts (PSS) are associated with recurrent or persistent hepatic encephalopathy (HE), severe portal hypertensive (PHT) complications, and poor survival in cirrhosis patients. Shunt embolization improves HE in patients with recurrent or persistent HE. The role of early shunt embolization (ESE) in comparison with no and late SE (LSE) in cirrhosis patients with PSS and associated clinical outcomes are not studied. ESE was defined as occlusion of PSS in patients with the first episode of spontaneous HE, while LSE was that when performed in patients with recurrent/persistent PSS-related HE. We retrospectively analyzed (November 2016 to March 2019) clinical outcomes, liver disease severity, and survival between patients undergoing ESE (n = 22) vs. LSE (n = 23) and compared ESE with matched historical controls (n = 22) not undergoing shunt embolization, followed-up for 18months. Males predominated, and the lienorenal type of shunt was the most frequent. Significantly larger and multiple shunts were noted in the LSE group. Arterial ammonia, total bilirubin, and Child-Pugh scores were significantly higher at baseline in the LSE group. Post-procedure length of stay in the intensive unit (mean 0.6 vs. 2.1days; p = 0.04), infections (31.8% vs. 66.7% beyond 100days; p = 0.02), recurrence of HE in first 9months (4.5% vs. 28.6%; p = 0.03), and liver- and PHT-related clinical events beyond 10months were significantly higher in LSE compared with those in the ESE group respectively. HE beyond 10months was comparable between both the groups. 18.2% died in ESE while 60.87% died in the LSE group (p = 0.002). Compared with patients on only standard medical care, the occurrence of ascites, variceal bleeding, recurrence of HE, and portal vein thrombosis were significantly lower in those undergoing ESE, even though differences in survival were not significant. Our study demonstrates the benefits of ESE of large PSS in patients with cirrhosis, probably by improving survival through a reduction in liver and PHT events that warrant validation through prospective randomized controlled multicenter trials.

Risk of recurrent hepatic encephalopathy in patients with liver cirrhosis: a German registry study

Patients with hepatic encephalopathy (HE) show low quality of life, recurrent hospitalizations and an increased mortality. We aimed to assess the natural course of patients after a recent episode of overt HE and to identify risk factors for HE recurrence in Germany. Fifteen sites took part in a prospective, observational study including patients with liver cirrhosis who had been hospitalized for HE within 3 months before recruitment. Clinical data, psychometric hepatic encephalopathy score (PHES) and critical flicker frequency were assessed quarterly for 1 year. Primary endpoint was HE recurrence requiring hospitalization, all-cause-mortality was treated as a competing risk factor. From January 2014 to March 2016, a total of 115 patients were recruited. Overall 14 premature deaths were documented. For 78 subjects follow-up data were available in accordance with the protocol. After a median of 118 days, more than half of the per-protocol cohort was readmitted to hospital due to HE (N = 34) or died (N = 11). The risk for hospitalization was significantly increased in patients who had been recruited by liver transplant centers (P = 0.003), had had frequent HE relapses prior to recruitment (P = <0.0001) or an abnormal PHES result of <-4 (P = 0.044). Abnormal PHES results barely missed level of significance as an independent risk factor for re-hospitalization in a multivariable competing risk model (P = 0.093). Patients with a history of HE are at high risk for the development of recurrent overt HE demanding hospitalization. The PHES test may aid in detection, monitoring and risk stratification of recurrent HE.

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

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. To assess the incremental cost-effectiveness of rifaximin ± lactulose versus lactulose monotherapy in patients with overt HE. 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. 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. 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. 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.

Where does TIPS fit in the management of patients with cirrhosis?

SummaryIn this review, we summarise the current knowledge on the indications and contraindications of transjugular intrahepatic portosystemic shunt (TIPS) placement for the treatment of the complications of portal hypertension in cirrhosis, specifically variceal haemorrhage and ascites. Moreover, we discuss the role of TIPS for the treatment of portal vein thrombosis (PVT) and the prevention of complications after extrahepatic surgery (‘preoperative TIPS’) in patients with cirrhosis. The position of TIPS in the treatment hierarchy depends on the clinical setting and on patient characteristics. In acute variceal haemorrhage, preemptive TIPS is indicated in patients at a high risk of failing standard therapy, that is those with a Child-Pugh score of 10–13 points or Child-Pugh B with active bleeding at endoscopy, although the survival benefit in the latter group still remains to be established. Non-preemptive TIPS is a second-line therapy for the prevention of recurrent variceal haemorrhage and for the treatment of ascites. Of note, TIPS may also improve sarcopenia. Contraindications to TIPS placement, independent of clinical setting, include very advanced disease (Child-Pugh >13 points), episodes of recurrent overt hepatic encephalopathy without an identifiable precipitating factor, heart failure, and pulmonary hypertension. In patients with PVT, TIPS placement not only controls complications of portal hypertension, but also promotes portal vein recanalisation. Although the severity of portal hypertension correlates with poor outcomes after extrahepatic surgery, there is no evidence to recommend preoperative TIPS placement.

Successful Surgical Intervention for Recurring Severe Hepatic Encephalopathy Caused by Portosystemic Collaterals After Living-Donor Liver Transplantation: A Case Report

IntroductionPortosystemic collaterals (PsC) are a common finding in patients with cirrhosis who need liver transplantation (LT), and PsCs may cause several problems before and after LT. We report a case of successful surgical treatment of severe hepatic encephalopathy (HE) caused by PsC after living-donor LT (LDLT). CaseA 71-year-old woman with hepatocellular carcinoma underwent LDLT for chronic hepatitis C virus infection at 64 years of age. The splenocaval collateral vein was ligated during LDLT to prevent portal flow steal. A recurrent episode of coma due to HE was triggered 7 years after LDLT and gradually became refractory to any drug treatments. Contrast-enhanced computed tomography revealed the development of the right gastroepiploic vein (RGEV), which flowed to the inferior vena cava via the inferior mesenteric vein (IMV). Owing to the chronic kidney disease (estimated glomerular filtration rate, 11-31 mL/min), interventional radiology (IVR) was not indicated, so surgical treatment was selected to treat the symptom. PsC was resected at the point of the RGEV and IMV, just before flowing into the IVC with vascular staplers. Antegrade portal blood flow was obtained by ultrasonography 2 days after surgery, and the patient was discharged from the hospital 26 days after the operation. After discharge, she has had no recurrent episode of HE. ConclusionSurgical resection of the PsC was effective for treatment of HE caused by shunt flow after LDLT.

Psychological Burden of Hepatic Encephalopathy on Patients and Caregivers.

OBJECTIVES:Hepatic encephalopathy (HE) is common in advanced cirrhosis and is characterized by marked neuropsychiatric abnormalities. However, despite its severity and effects on brain function, the impact of HE on psychological status of patients has not been adequately assessed. The aim of this study was to evaluate the effect of HE on psychological status of patients and their informal caregivers.METHODS:Fifteen patients with cirrhosis and episodic or persistent HE and their corresponding informal caregivers were included. Semistructured interviews were performed in patients and caregivers. Quality of life (QoL) was assessed by the short-form 36 in both patients and caregivers, and the Zarit burden score was measured in caregivers. The analysis of interviews was performed using qualitative methodology.RESULTS:HE causes a major psychological impact on patients with HE. The first episode of HE caused a very significant impact that was reported with deep feelings, mainly of fear, anger, misery, anxiety, and sorrow, which persisted with time. Symptoms causing more psychological impact on patients were impaired ability to walk and speak. All effects were associated with a marked impairment in QoL. The psychological impact was also marked in caregivers who had a major burden, as assessed by the Zarit score. Moreover, QoL, particularly the mental component score, was markedly impaired in caregivers in intensity similar to that of patients.DISCUSSION:HE has a profound psychological impact on patients and their informal caregivers, associated with a marked negative influence on QoL. The psychological effects of HE on patients and caregivers should be evaluated and treated.

A retrospective study of drug utilization and hospital readmissions among Medicare patients with hepatic encephalopathy.

Hepatic encephalopathy (HE) is a complication occurring in patients with cirrhosis and is associated with neuropsychiatric and motor abnormalities. Symptomatic HE episodes almost always require hospitalization and the frequent recurrence of episodes is associated with poor prognosis and increased medical costs. The utilization of existing therapies for management of HE and adherence to them has yet to be evaluated using real-world claims data.The aim of this study was to evaluate HE drug regimens and adherence and their association with hospital readmissions in Medicare Advantage plan patients.This was a retrospective cohort study of patients discharged from a HE-related hospitalization or emergency room visit. Based on subsequent enrollment in the plan they were categorized into cohorts of 1 month, 3, and 6 months follow-up, and medication regimen was evaluated within the first month. The drugs evaluated included lactulose, rifaximin, and neomycin. Multivariable logistic regression was conducted to evaluate the association of drug regimen and medication adherence measured as proportion of days covered with HE readmissions.There were 347 patients hospitalized for HE with 184 patients having 30-day enrollment and either a drug refill or an outpatient visit in this duration. Medications were not refilled by 67 (36.4%) patients. Various drug regimens had different adherence with mean (standard deviation) proportion of days covered ranging from 0.56 (0.29) to 0.82 (0.16) at 3 months and 0.48 (0.3) to 0.77 (0.15) at 6 months. The results of logistic regression at 3 and 6 months did not show a significant association of medication use or medication adherence with hospital readmissions.Despite availability of therapy, medication utilization was alarmingly low after discharge of patients from HE-related hospitalization. Medication adherence was also low, which may affect the rate of recurrence and costs associated with readmissions. Efforts are needed in both care coordination of these patients to ensure they are prescribed appropriate medications and to enhance adherence to them.

Cognitive Function in Liver Transplantation.

Purpose of ReviewLiver transplantation (LT) remains the only way to cure patients with severe liver diseases. Important questions about neurological sequelae and quality of life after LT have emerged. In this review, we discuss the neurocognitive changes associated with LT and we conclude with recommendations in this regard for patients, caregivers, and physicians.Recent FindingsCompared with other solid organ recipients, LT patients tend to have a higher incidence (up to 30%) of neurological complications post-LT. Even in absence of previous episodes of hepatic encephalopathy (HE), some patients display new onset of neurological symptoms post-LT, raising the concern about the role of other factors that may have a direct impact on cognitive function.SummaryDifferent mechanisms have been postulated to explain these postoperative neurological symptoms. They include sequelae of HE, persistent impairment of cognitive function due to cirrhosis, or postoperative decompensation of an unknown or undiagnosed neurodegenerative disorder.

Abstract No. 646 Natural history of transjugular intrahepatic portosystemic shunts: long-term analysis of survival and protective factors

To evaluate long-term survival in patients with portal hypertension treated with transjugular intrahepatic portosystemic shunts (TIPS) and to identify patient characteristics associated with improved survival. This is a multicenter retrospective cohort study. Patients who received TIPS between January 1, 2008 and December 31, 2014 were included in this study. Patient data was collected between the time of procedure and September 1, 2019. Statistical analysis was performed using SPSS (IBM, New York). 129 patients are included in this study, 84 males and 45 females, with a median age of 61. 32% of patients had chronic hepatitis C, 33% had a history of alcohol use disorder, and 19% of patients had nonalcoholic steatohepatitis (NASH). The remainder of patients had miscellaneous etiologies of cirrhosis including autoimmune biliary cirrhosis, hepatitis B, and cystic fibrosis. 77% of patients had variceal bleeding and 34% of patients had refractory ascites prior to their procedures. 14% of patients had a history of hepatic encephalopathy. The technical success rate was 91% and overall complication rate was 30%. 1-, 3-, 5-, 7-, and 10-year survival rates are as follows: 93%, 74%, 58%, 38%, and 15%. 19% of patients had at least one episode of ascites requiring therapeutic paracentesis and 16% of patients experienced variceal hemorrhage during the follow-up period. 28% of patients required revision to expand their TIPS and 4% of patients required revision to constrain their TIPS. 56% of patients had episodes of hepatic encephalopathy during the follow-up period requiring hospitalization. 25% of patients experienced a decline in renal function of at least one stage. 21% of patients underwent subsequent liver transplantation. Female sex, preprocedural variceal bleeding rather than ascites, and NASH etiology of cirrhosis were associated with higher rates of overall survival. TIPS are crucial for many patients with symptomatic portal hypertension. Female sex, preprocedural variceal bleeding rather than ascites, and NASH as etiology of cirrhosis are associated with increased rates of long-term survival.

Management of Large, Spontaneous Portosystemic Shunts in Liver Transplantation: Case Report and Review of Literature

BackgroundThe presence of collateral circulation in liver cirrhosis patients with portal hypertension is quite frequent due to re-permeabilization of closed embryonic channels. In some cases, these shunts could measure over 1 cm wide, therefore, containing a significative blood flow.Its management during liver transplantation could be challenging due to possible complications resulting from either ligation of the shunts or from ignoring them.We present the case of a patient with recurrent hepatic encephalopathy (HE) and a large spontaneous portosystemic shunt (SPSS) who submitted to liver transplant and review the literature identifying options, complications, and outcomes with the aim of facilitating decision making. Material and MethodsA 68-year-old, Spanish man diagnosed with liver cirrhosis with portal hypertension and recurrent episodes of HE is proposed for LT. The patient’s Child-Pugh score was A6-B7, and the Model for End-stage Liver Disease score was 12. Preoperatively, a computed tomography scan showed a large SPSS running to the inferior cava vein. During the surgery, a small-sized portal vein and a large shunt measuring almost 3 cm wide were identified.After reperfusion, portal vein flow was 1000 to 1100 mL/min. Owing to the previous HE and the risk of low portal flow, the shunt was closed increasing the portal flow to 1800 mL/min. The patient was discharged without any complications. ConclusionsThe presence of large SPSSs are frequent during LT. Decision making intraoperatively can be challenging due to possible complications derived from ligation of the SPSS or from ignoring it. Either preoperative assessment of a further HE risk or portal vein flow measurement after reperfusion are essential to achieve a correct resolution.

Lessons from "real life experience" of rifaximin use in the management of recurrent hepatic encephalopathy.

BACKGROUNDHepatic encephalopathy (HE) is a major complication of cirrhosis with independent prognostic significance. The current management of HE is mainly based on lactulose. Rifaximin has been shown to decrease the risk of HE recurrence in patients with episodic forms. HE can also be persistent. However, there is no drug support recommendation for rifaximin use in this setting.AIMTo assess the effectiveness of rifaximin in the management of recurrent episodes of HE and recurrent acute exacerbations on persistent HE, in “real life conditions”.METHODSIn this retrospective study, using a within-subjects design, we collected data of patients treated with rifaximin for HE in two liver diseases centers, during the six-month period before and during the six-month period after the initiation of rifaximin. The primary effectiveness endpoint was the total number of HE events involving hospitalization.RESULTSRifaximin was introduced for prevention of recurrent HE episodes in 29 out of 62 patients with normal mental status between episodes and for prevention of recurrent acute exacerbations on persistent HE in 33 out of 62 patients. In the “prevention of recurrent HE episodes” group, fewer HE events (0.79 vs 1.78; P = 0.013) were reported during the period of time when rifaximin was used. In the “prevention of recurrent acute exacerbations on persistent HE” group, there was no significant difference in the number of HE-events (1.48 vs 1.77; P = 0.582).CONCLUSIONIn this real-life experience, the effectiveness of rifaximin was confirmed in the prevention of HE episodes recurrence but was not proved in the prevention of acute exacerbations recurrence on persistent HE.

Animal Naming Test - a simple and accurate test for diagnosis of minimal hepatic encephalopathy and prediction of overt hepatic encephalopathy.

Aim of the studyMinimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encepha-lopathy (HE). We compared the usefulness of the Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) for the diagnosis of MHE and the prediction of the development of overt episodes of HE.Material and methods103 consecutive patients with liver cirrhosis without overt HE were subjected to PHES and ANT evaluation. The receiver-operating characteristic curve was used to determine the optimum cut-off of the ANT value for the diagnosis of MHE.ResultsThirty-seven (35.9%) patients had MHE as assessed by altered PHES. ANT (< 14) was positive in 36 (34.95%) patients with MHE with a sensitivity of 89.19% and specificity of 95.7%, positive predictive value (PPV) of 91.67%, negative predictive value (NPV) of 94.03% and diagnostic accuracy of 93.20%. The area under the curve for diagnosis of MHE was 0.978 (95% CI: 0.954-1.0). MHE patients had significantly lower ANT as compared to non-MHE patients and controls (10.81 ±0.324 vs. 15.27 ±0.147 vs. 15.78 ±0.192, respectively, p = 0.01). ANT correlated with PHES (r = 0.752, p = 0.001) and also with Child-Pugh (r = –0.408, p = 0.001) and MELD (r = –0.318, p = 0.001) scores. During follow-up, 14 patients in the MHE group and 4 in the non-MHE group developed overt episodes of HE (p = 0.001).ConclusionsANT is simple and accurate for the diagnosis of MHE and prediction of overt episodes of HE in patients with cirrhosis and correlates well with the Child-Pugh and MELD scores.