Episodes Of Hepatic Encephalopathy Research Articles

Oral LPCN 1148 improves sarcopenia and hepatic encephalopathy in male patients with cirrhosis: A randomized, placebo-controlled phase 2 trial.

Sarcopenia is highly prevalent in patients with liver cirrhosis and is associated with adverse clinical outcomes including hepatic encephalopathy (HE). Androgen receptor agonists, ARAs, can address these conditions through multimodal mechanisms of action, however their safety and efficacy in patients with cirrhosis have not been well established. In this multicenter, double-blind, phase 2 trial, men with sarcopenia and cirrhosis awaiting liver transplant were randomized 1:1 to receive either oral ARA LPCN 1148 or placebo for 24 weeks (NCT04874350). The primary endpoint was the change from baseline to 24 weeks in skeletal muscle index measured by computed tomography scan of the L3 region (L3-SMI), analyzed with a prespecified modified intent-to-treat population. The secondary endpoint was the number of overt HE events. 29 participants (mean age=59y, MELD=17) received at least one dose of LPCN 1148 (n=15) or placebo (n=14). Baseline characteristics were similar between groups. Primary endpoint analysis demonstrated an increase in L3-SMI in the LPCN 1148 group (n=15) compared to placebo (n=10), with a mean group difference of 4.4cm2/m2 (95% CI, 1.3-7.4cm2/m2, p=0.007). Participants in LPCN 1148 experienced fewer episodes of overt HE (CTCAE grade ≥2; p=0.02) than placebo. The number and severity of treatment-emergent adverse events were similar between arms. LPCN 1148 treatment improved sarcopenia and reduced the number of overt HE episodes in men with cirrhosis and sarcopenia awaiting liver transplant. These findings support additional research on the efficacy of LPCN 1148 in treating sarcopenia and preventing HE recurrence.

Validation of EncephalApp Stroop Test for Diagnosing Minimal Hepatic Encephalopathy in the Romanian Population.

Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy. MHE has been associated with impairment of quality of life and job performance, and is a major cause of premature retiring in cirrhotic patients. However, MHE is usually overlooked by most physicians, due to its asymptomatic nature. We aim to present our experience with the EncephalApp Stroop Test for diagnosing MHE in cirrhotic patients. We also want to establish if Stroop test performance correlates with age, educational level, liver disease severity (as assessed by the MELD and Child-Pugh scores), duration of disease, previous episodes of overt hepatic encephalopathy, and other relevant clinical or laboratory parameters. A cross-sectional observational single-center study, in which 100 adult patients diagnosed with liver cirrhosis were evaluated for the presence of MHE by using the EncephalApp Stroop Test. In parallel, 45 healthy adult controls without liver cirrhosis were recruited and tested under the same conditions as the patients. There were no age-related differences between the two groups (p=0.6). Stroop test performance of the controls (143.1 ± 20.8 seconds) was significantly better than that of the patients (171.9 ± 33.3 seconds) (p<0.0001). Stroop test results correlated with the MELD (R=0.28, p=0.005) and Child-Pugh scores (R=0.2, p=0.04). There was a positive correlation between Stroop test results and age in patients (R=0.45, p<0.0001) and controls (R=0.75, p<0.0001). Stroop test performance was not influenced by the duration of liver disease (p=0.4) or prior episodes of overt hepatic encephalopathy (p=0.25). Gender and level of education did not have an impact on Stroop test results. Alcoholic liver disease, diabetes mellitus, hyperglycemia, anemia and hyponatremia were associated with poorer performances. EncephalApp Stroop Test proved to be a quick and simple method for diagnosing minimal hepatic encephalopathy in the hospital setting. Test performance was influenced primarily by age, but also by liver disease severity, anemia, hyponatremia and hyperglycemia.

Rifaximin alone vs combination with norfloxacin for secondary prophylaxis of spontaneous bacterial peritonitis with hepatic encephalopathy: randomized controlled trial

BackgroundIn liver cirrhosis, events of spontaneous bacterial peritonitis (SBP) and hepatic encephalopathy (HE) portend a poor prognosis. Gut dysbiosis remains a common pathogenetic mechanism for both SBP and HE. Recent data suggests the role of rifaximin in gut modulation and improving intestinal dysbiosis. Due to emergence of multidrug-resistant organisms, gut-selective antibiotics with minimal systemic effects are warranted for secondary prophylaxis in patients of cirrhosis. We compared rifaximin alone vs combination with norfloxacin for secondary prophylaxis of patients of cirrhosis presenting with SBP and HE. This was a prospective, open-label, RCT which included all patients of cirrhosis with SBP and HE on admission. On discharge, in addition to standard medical treatment, patients were randomized to rifaximin 400 mg three times a day (group I) and rifaximin 400 mg three times a day with norfloxacin 400 mg once a day (group II) as a secondary prophylaxis of SBP. Primary outcomes were recurrent episodes of SBP and HE at 6 months and 28-day, 90-day, and 6-month mortalities. Secondary outcomes included number of rehospitalizations, episodes of upper gastrointestinal bleed, new acute kidney injury episodes, and change in Child–Turcotte–Pugh (CTP) and model for end-stage liver disease (MELD) scores over next 6 months.ResultsAfter screening 87 patients of cirrhosis with SBP and HE, 12 patients had in-hospital mortality and another 25 were excluded, one patient was lost to follow-up, and, finally, 49 patients were randomized into group I (n = 24) and group II (n = 25). The HE was grade 2 (18 vs 16) and grade 3 (6 vs 9) in groups I and II respectively. Primary outcomes as recurrent SBP (3 vs 2; P = 0.67); recurrent HE at 6 months (5 vs 2; P = 0.24); and 28-day (2 vs 2; P = 1.0) and 90-day mortality (4 vs 3; P = 0.72) and 6-month mortality (6 vs 8, P = 0.52) were comparable between two groups respectively. Secondary outcomes as number of rehospitalizations (3 vs 8, P = 0.07), new episodes of UGI bleed (2 vs 3, P = 0.1), new AKI episodes (4 vs 1, P = 0.06), ∆CTP (− 4 vs − 4), and ∆MELD (− 9 vs − 8) over the next 6 months were not significantly different between two groups respectively.ConclusionsRifaximin was effective in secondary prevention of both SBP and HE in patients of cirrhosis.Trial registrationThe randomized controlled trial was registered in CTRI/2021/09/036321 dated September 7, 2021.

Acquired chronic hepatocerebral degeneration (CAHD) - Simulation of parkinsonism, secondary to chronic liver disease.

Acquired chronic hepatocerebral degeneration (CAHD) is a rare and irreversible neurological disorder that can occur in patients with chronic liver disease. It is characterized by neurological symptoms similar to parkinsonism and the presence of brain damage secondary to manganese deposition. We present the case of a 60-year-old patient with episodes of recurrent hepatic encephalopathy and diagnosis of CAHD.

Medically Tailored Meals for Patients With Cirrhosis and Hepatic Encephalopathy: The BRAINFOOD Proof-of-concept Trial

Background and AimsGuidelines recommend that patients with Hepatic Encephalopathy (HE) receive a high-protein diet (roughly 1 g/kg actual body weight). Concommitant sodium restriction, low health literacy, and food insecurity limit patients’ ability to meet this goal. We aimed to determine the feasibility of home-delivered high protein medically tailored meals (MTM) for patients with a recent episode of overt HE. MethodWe enrolled patients with prior overt HE on active HE therapy in a 6 month trial of MTM. All received 12 weeks of 21 home-delivered meals/week with protein snacks (mid-day and bedtime). Patients completed follow-up at week 24. The primary outcome was feasibility. Additional outcomes included change in protein and micronutrient intake (measured using 24-hour dietary recalls performed by dieticians), cognitive function (animal naming test, ANT; encephalapp stroop), physical function (liver frailty index, LFI), and quality of life (SF-8). Healthcare utilization was also assessed. Results10 patients competed the study with >90% of MTM consumed. Protein intake rose from 74.6+25.1g at baseline to 93.8+24.3g on MTM (p=0.04). Branched-chain amino acids also increased – valine 3.73+1.26g to 5.17+1.28, isoleucine 3.32+1.18 to 4.69+1.55, leucine 5.83+2.00 to 7.49+2.07, all p<0.001. LFI improved from 4.42±0.32 to 3.96±0.82 by the end of the MTM phase (p=0.03). SF-8 quality of life scores improved from 55.5±15.5 at baseline to 64.7±18.3 after the MTM phase, to 64.4±19.1 at the end of the study (p=0.1). EncephalApp-Stroop time improved from 227±94 to 194±58s by the end of the MTM phase (p=0.08). ANT scores were similarly non-significantly improved. ConclusionHome delivered MTM are feasible, increase protein consumption, and may improve patient well-being. A randomized trial is needed.

Prophylaxis of hepatic encephalopathy: current and future drug targets.

Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.

The Management of Hepatic Encephalopathy from Ward to Domiciliary Care: Current Evidence and Gray Areas.

Hepatic encephalopathy (HE) is a common complication of advanced liver disease and acute liver failure. It is a condition that features several neuropsychiatric symptoms that affect mortality, morbidity and the quality of patients' and caregivers' lives. An HE diagnosis is generally an exclusion diagnosis. Once the patient is admitted to the hospital, clinical examination, blood tests and eventually neuroimaging should be performed with the aim of ruling out other causes of acute brain dysfunction. Moreover, HE is recognized using various precipitants that can potentially promote its onset, alone or in combination, and must be identified. Once the diagnostic process is complete, a correct treatment should be started. The anti-HE treatment is based on a combination of the correction of precipitants; non-absorbable antibiotics, such as rifaximin; and non-absorbable disaccharides. Once the patient is discharged from the hospital, specific anti-HE therapy should be maintained in order to prevent other HE episodes.

Current Management of Hepatic Encephalopathy: A Review Article

Hepatic encephalopathy, a neuropsychiatric syndrome stemming from liver failure, manifests in acute and chronic cases. The prevailing cause behind its development involves the neurotoxicity resulting from elevated ammonia levels in the brain, which can occur due to increased ammonia production or impaired ammonia excretion. The main objective in treating hepatic encephalopathy is to decrease ammonia levels. The detoxification of ammonia in this condition is regulated by two enzymes: glutaminase and glutamine synthetase. Numerous drugs, such as lactulose, rifaximin, BCAA, LOLA, glycerol phenylbutyrate, and zinc, have been utilized to treat hepatic encephalopathy. In terms of future research, experimental treatment options like fecal microbiota transplant, probiotics, bromocriptine, minocycline, indomethacin, ibuprofen, and flumazenil warrant investigation. Furthermore, albumin infusions have been shown to enhance cognitive function and improve the psychosocial quality of life, possibly by alleviating endothelial dysfunction in patients with minimal hepatic encephalopathy or previous episodes of hepatic encephalopathy. This review article offers a comprehensive overview of the current management strategies for hepatic encephalopathy.

Multiple ammonia-induced episodes of hepatic encephalopathy provoke neuronal cell loss in bile-duct ligated rats

Hepatic encephalopathy (HE) is defined as a reversible syndrome and therefore should resolve following liver transplantation (LT). However, neurological complications have been reported in up to 47% of LT recipients, which have been documented to be associated with a history of overt HE pre-LT. We hypothesise that multiple episodes of HE lead to permanent cell injury and exacerbate neurological dysfunction. Our goal was to evaluate the impact of cumulative HE episodes on neurological status and brain integrity in rats with chronic liver disease. Episodes of overt HE (loss of righting reflex) were induced following injection of ammonium acetate in bile duct ligation (BDL) rats (BDL-Ammonia) every 4 days starting at week 3 post-BDL. Neurobehaviour was evaluated after the last episode. Upon sacrifice, plasma ammonia, systemic oxidative stress, and inflammation markers were assessed. Neuronal markers including neuron-specific nuclear antigen and SMI311 (anti-neurofilament marker) and apoptotic markers (cleaved caspase-3, Bax, and Bcl2) were measured. Total antioxidant capacity, oxidative stress marker (4-hydroxynonenal), and proinflammatory cytokines (tumour necrosis factor-alpha and interleukin-1β) were measured in brain (hippocampus, frontal cortex, and cerebellum). Proteomic analysis was conducted in the hippocampus. In hippocampus of BDL-Ammonia rats, cleaved caspase-3 and Bax/Bcl2 ratio were significantly increased, whereas NeuN and SMI311 were significantly decreased compared with BDL-Vehicle rats. Higher levels of oxidative stress-induced post-translational modified proteins were found in hippocampus of BDL-Ammonia group which were associated with a lower total antioxidant capacity. Ammonia-induced episodes of overt HE caused neuronal cell injury/death in BDL rats. These results suggest that multiple bouts of HE can be detrimental on the integrity of the brain, translating to irreversibility and hence neurological complications post-LT. Hepatic encephalopathy (HE) is defined as a reversible neuropsychiatric syndrome resolving following liver transplantation (LT); however, ∼47% of patients demonstrate neurological impairments after LT, which are associated with a previous history of overt HE pre-LT. Our study indicates that multiple episodes of overt HE can cause permanent neuronal damage which may lead to neurological complications after LT. Nevertheless, preventing the occurrence of overt HE episodes is critical for reducing the risk of irreversible neuronal injury in patients with cirrhosis.

Role of Probiotics in Secondary Prophylaxis of Hepatic Encephalopathy

Aim: To determine the role of probiotics in combination with standard therapy in secondary prophylaxis of hepatic encephalopathy. Methods: This Randomized Controlled Trial was carried out in the Medical Wards of King Edward Medical University/Mayo Hospital, Lahore from 15th October, 2018 to 14th January, 2020. 166 patients selected via simple random sampling technique were divided into two groups. Group A received Lactulose whereas Group B received Lactulose plus Probiotic. A three months follow up for each patient was done. Absence of hepatic encephalopathy at the end of treatment was considered Effective treatment response. Primary end point was completion of three months or development of hepatic encephalopathy. Patients' responses were noted on a pre-designed proforma. Data analysis was done using SPSS version 23.0. Results: Out of a total of 166 patients comprising 83 males and 83 females, mean age of the patients was 54.11±7.76 years. A statistically significant difference was found between the study groups inserum ammonia levels(p-value=&lt;0.001). At 3rd month follow up 79(47.59%) patients had no episode of hepatic encephalopathy as assessed on West Haven grading (grade 0) followed by hepatic encephalopathy noted in 56(33.73%) patients; 25(15.06%)ingrade 3, 22(13.25%)ingrade 4 and 9(5.42%)in grade 2 respectively. p-value between the study groups and end result of the patients demonstrated statistically significant difference(p-value=0.028) Practical Implication: Overt hepaticencephalopathy is a common and frequent complication in patients with decompensated chronic liver disease. Various treatment modalities have proven beneficial. In this study we have shown the adjuvant role of probiotics with the standard lactulose therapy in remission and secondary prophylaxis of overt hepatic encephalopathy. Conclusion: Probiotics in conjunction with conventional lactulose therapy is more effective than standard lactulose therapy alone in remission and maintenance of secondary prophylaxis of overt hepatic encephalopathy. Keywords: Hepatic Encephalopathy, Secondary prophylaxis, Standard therapy, Probiotic

#3739 SHUNT PORTOSYSTEMIC COMPLICATED BY HYPERAMMONEMIA AND HEPATIC ENCEPHALOPATHY SUPPORTED BY DAILY DIALYSIS IN A CHRONIC HEMODIALYSIS PATIENT

Abstract Background and Aims Hepatic encephalopathy is a neuropsychiatric syndrome that may develop as a consequence of liver insufficiency. In acute liver failure, hepatic encephalopathy suggests the severity of the disease. In end-stage chronic liver diseases, episodes of hepatic encephalopathy are frequently fully and spontaneously reversible. Clinical manifestations vary from mild neuropsychiatric disorders to coma. The pathogenesis of hepatic encephalopathy is complex and not clearly understood. Ammonia plays a key role. In the healthy individual, ammonia is, during its first hepatic passage, directly degraded into urea, itself excreted by the kidney and the stools, and to a lesser degree in glutamine. Ammonia is also metabolized by the muscle striped. In case of liver failure and/or shunts portosystemic, there is a defect in hepatic clearance ammonia which is then found in excess in systemic circulation. Decreased muscle mass, linked to malnutrition, frequent in the patient cirrhotic and chronic hemodialysis, also helps to decrease metabolism ammonia. Due to the increase in permeability of the blood-brain barrier, the brain is exposed to excessive concentrations ammonia causing functional brain abnormalities and structural, which can partly explain the signs neurology of hepatic encephalopathy. In end stage chronic renal failure, clearance of ammonia via extracorporeal treatment has not been systematically evaluated. Several studies with small samples have demonstrated the effectiveness of hemodialysis, compared to peritoneal dialysis, in terms of ammonium purification in chronic renal failure, on dialysis or not on dialysis. The aim of this study was to evaluate the effectiveness of daily dialysis for the purification of ammoniumin a chronic hemodialysis patient with hepatic encephalopathy. Case Report A 40-year-old man undergoing chronic hemodialysis was referred to gastroenterology department of Mohammed VI University center of Marrakesh for inoperable shunt portosystemic complicated by hyperammonemia causing hepatic encephalopathy consisting of headaches and seizures. His medical history was significant for liver cirrhosis caused by infection with hepatitis B, end stage kidney disease due to membranoproliferative glomerulonephritis, for which the patient is on hemodialysis at the rate of 3 sessions per week. The patient went on to develop portal hypertension and ascites requiring frequent hospital admissions and treatment with diuretics. He was on a low-protein and low-sodium diet. While on oral furosemide 250 mg daily and spironolactone 100 mg daily, his diuresis was adequate. Before referral, this patient had already suffered 4 episodes of tonic clonic seizures. His 1st hemodialysis session in our training was on January 10, 2023, he was given daily hemodialysis sessions with daily blood tests, including immediate pre and post dialysis ammonia. Pre-dialytic ammonia levels varied between 103 and 161 µmol/l, as well as post-dialytic ammonia levels varied between 24 and 37 µmol/l, knowing that the normal value of laboratory ammonia varied between 10 and 51 µmol/l. The evolution was marked by a clear clinical improvement, with a disappearance of the seizures without a significant drop in ammonia after 14 daily hemodialysis sessions. Serum creatinine and urea declined, and sodium increased. Accumulation of ascites slowed and the patient could eat and sleep normally and was again independent with self care. The patient returned home on January 24. Conclusion This study shows the interest of daily hemodialysis sessions as a potential treatment for hyperammonemia in a patient on chronic intermittent hemodialysis, with a portosystemic shunt. The interest lies in the fact that the improvement is mainly clinical than biological (persistent hyperammonemia).

Efficacy and Safety of Rifaximin in the Prevention of Recurrent Episodes of Hepatic Encephalopathy: A Systematic Review and Meta-analysis.

Rifaximin is an oral antimicrobial drug with a broad-spectrum effect. It locally regulates the function and structure of intestinal bacteria and decreases intestinal endotoxemia. We aimed to investigate the preventive role of rifaximin in recurrent episodes of hepatic encephalopathy in cases with a history of hepatic diseases. We searched PubMed, Scopus, and Web of Science for the relevant studies using the following search strategy: "(Rifaximin) OR (Xifaxan) AND (cirrhosis) OR (encephalopathy)." We assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: recurrence of hepatic encephalopathy, adverse events, mortality rate, and time to the first episode of hepatic encephalopathy from the time of randomization (days). We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was performed under the random-effects model. We analyzed data obtained from 999 patients from 7 included trials. The overall risk ratio proved that the rifaximin group was associated with a lower recurrence rate than the control group (risk ratio [RR] = 0.61[0.50, 0.73], P = .001). We found no significant variation in both groups regarding adverse events (RR = 1.08 [0.89, 1.32], P = .41), and mortality rates (RR = 0.98 [0.61, 1.57], P = .93). The overall risk of bias results was low. The meta-analysis showed that in patients allocated to the rifaximin group, the incidence rate of hepatic encephalopathy was significantly lower when compared with those in the control group with no difference in both groups regarding adverse events and mortality rates.

Post-transjugular Intrahepatic Portosystemic Shunt Hepatic Encephalopathy: Sarcopenia Adds Insult to Injury.

Hepatic encephalopathy, which is a serious complication, and sarcopenia are undesirable consequences in cirrhosis. Transjugular intrahepatic portosystemic shunt increases the risk of hepatic encephalopathy. We investigated the effect of sarcopenia on the incidence of post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy. Clinical data of patients who underwent transjugular intrahepatic portosystemic shunt were extracted retrospectively. Computed tomography images at L3 level of scans performed prior to transjugular intrahepatic portosystemic shunt were analyzed to assess skeletal muscle index-expressed as skeletal muscle area (cm2)/ height (m2). Of 210 patients who underwent transjugular intrahepatic portosystemic shunt, complete information was available in 79 [male: 68 (86%); age: 50.5 ± 11.2 years; Child-Turcotte-Pugh score: 8.81 ± 1.23; etiology-alcohol: 44 (56%), non-alcoholic steatohepatitis: 16 (20%), others: 19 (24%); transjugular intrahepatic portosystemic shunt indication-ascites: 56 (71%); bleed: 23 (29%); sarcopenics: 42 (53%)]. Post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy developed in 29 (37%) patients. In patients who developed hepatic encephalopathy, both serum ammonia [177.6 ± 82.5 vs. 115.5 ± 40.5 µg/dL, P =.008] and prevalence of sarcopenia [69% vs. 44%; P =.02; odds ratio (95% CI): 2.8 (1.08-7.4), P =.02] were higher, with sarcopenics having 3 times higher risk of hepatic encephalopathy and 8 times higher risk of multiple episode of hepatic encephalopathy [31% vs. 5.4%; odds ratio (95% CI): 8.2 (1.68- 40.5), P =.009]. In multivariate analysis, age [odds ratio (95% CI): 1.05 (1.001-1.11), P =.047], serum albumin [odds ratio (95% CI): 0.162 (0.05-0.56), P =.004], and skeletal muscle index [odds ratio (95% CI): 0.925 (0.89-0.99), P =.017] were independently associated with post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy. Sarcopenia is present in nearly half of the cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt, which increases the risk of a single episode of hepatic encephalopathy by 3-fold and that of multiple episodes of hepatic encephalopathy by 8-fold after transjugular intrahepatic portosystemic shunt procedure. Increased skeletal muscle index is associated with decreased risk of hepatic encephalopathy.

Prediction and prevention of the first episode of overt hepatic encephalopathy in patients with cirrhosis.

Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients' quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.

Transjugular intrahepatic portosystemic shunt reduction for refractory hepatic encephalopathy: a case series

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a therapeutic intervention for refractory ascites and variceal bleeding. However, the development of hepatic encephalopathy (HE) is a known complication. TIPS diameter can be reduced to decrease further HE episodes when refractory to pharmacotherapy. However, TIPS reduction for refractory hepatic encephalopathy (rHE) is poorly described. This case series identifies various characteristics and outcomes among this unique patient cohort. Case Presentation: In this cohort of 8 patients, 63% were male, 75% were Caucasian, and 38% had alcohol-associated cirrhosis. Following TIPS reduction, the number of HE-related admissions (mean, median) decreased from 2.1 and 2 to 1.6 and 0.5 while the number of non-HE admissions following TIPS reduction increased from 0.6 and 0 to 1 and 0.5. Conclusion: TIPS reduction reduced the number of hospitalizations for rHE but the total number of hospitalizations for all causes increased, demonstrating the high resource utilization for those with rHE following TIPS. Therefore, careful selection for initial TIPS placement remains a priority.

Frequency of Recurrence of Hepatic Encephalopathy in Patients of Chronic Liver Disease Treated With Rifaximin

Aim: To determine the frequency of recurrence of hepatic encephalopathy in patients treated with Rifaximin. Study design: Observational cross-sectional study. Setting &amp; duration: Department of Medicine, Services institute of Medical Sciences Lahore for duration of 12 months. Methodology: Hepatic encephalopathy was diagnosed using West-Haven classification in patients of chronic liver disease. Recurrence was considered if a new episode of hepatic encephalopathy occurred within 3 months after initiation of treatment. A total 120 patients of chronic liver disease having had an episode of recent hepatic encephalopathy within the last 3 months, of both genders, above 20 years of age with hepatic encephalopathy were included in the study. The patients were followed for 3 months after initiation of therapy and any episode of recurrence of hepatic encephalopathy was recorded. Results: Mean age was 51.5±12.2 years and 52.3±12.8 years respectively in Rifaximin and Placebo groups. Fourteen (23.3%) patients in Rifaximin group and 17(28.3%) in placebo group were younger than 40 years of age. Thirty-three (55%) patients in Rifaximin group were male versus 29(48.3%) patients in Placebo group. Fifteen (25%) patients in Rifaximin Group developed hepatic encephalopathy by 3 months of follow up as compared to 31(51.7%) patients in Placebo Group Conclusion: Frequency of recurrence of hepatic encephalopathy is significantly lower in Rifaximin treated patients. Keywords: Hepatic Encephalopathy, Recurrence, Rifaximin.

Inadequate practices for hepatic encephalopathy management in the inpatient setting.

Hepatic encephalopathy (HE) is an important complication of decompensated liver disease. Hospital admission for episodes of HE are very common, with these patients being managed by the hospitalists. These admissions are costly and burdensome to the health‐care system. Diagnosis of HE at times is not straightforward, particularly in patients who are altered and unable to provide any history. Precipitants leading to episodes of HE, should be actively sought and effectively tackled along with the overall management. This mandates timely diagnostics, appropriate initiation of pharmacological treatment, and supportive care. Infections are the most important precipitants leading to HE and should be aggressively managed. Lactulose is the front‐line medication for primary treatment of HE episodes and for prevention of subsequent recurrence. However, careful titration in the hospital setting along with the appropriate route of administration should be established and supervised by the hospitalist. Rifaximin has established its role as an add‐on medication, in those cases where lactulose alone is not working. Overall effective management of HE calls for attention to guideline‐directed nutritional requirements, functional assessment, medication reconciliation, patient education/counseling, and proper discharge planning. This will potentially help to reduce readmissions, which are all too common for HE patients. Early specialty consultation may be warranted in certain conditions. Numerous challenges exist to optimal care of hospitalized OHE patients. However, hospitalists if equipped with knowledge about a systematic approach to taking care of these frail patients are in an ideal position to ensure good inpatient and transition of care outcomes.

Risk factors for hepatic encephalopathy and mortality in cirrhosis: The role of cognitive impairment, muscle alterations and shunts.

Muscle alterations, portosystemic shunts (SPSS) and minimal hepatic encephalopathy (MHE) are related to hepatic encephalopathy (HE), however no studies have investigated the relative role of all these risk factors detected in the same patients. The aim of the study was to assess the prognostic impact of muscle alterations, MHE and SPSS on hepatic encephalopathy and transplant free survival. 114 cirrhotics were submitted to Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT) to detect MHE. CT scan was used to analyze the skeletal muscle index (SMI), muscle attenuation and SPSS. The incidence of the first episode of HE and survival were estimated. Previous HE was present in 47 patients (41%). The variables independently associated to previous HE were: sarcopenia, MHE and SPSS. 44 patients (39%) developed overt HE during 14±11 months; MHE and SPSS were the only variables significantly asociated to overt HE. During the same follow-up, 42 patients died (37%); MELD and sarcopenia were the only variables significantly asociated to transplant free survival. MHE, sarcopenia and SPSS are clinically relevant and should be sought for in cirrhotics. In particular, MHE and SPSS are the only risk factors significantly associated to the development of HE while MELD and sarcopenia are independently associated to overall mortality.

FRI492 - A network meta-analysis of numbers needed to treat to prevent an episode of overt hepatic encephalopathy in patients with cirrhosis treated for at least 6 months with lactulose alone, or lactulose plus rifaximin-alpha

FRI492 - A network meta-analysis of numbers needed to treat to prevent an episode of overt hepatic encephalopathy in patients with cirrhosis treated for at least 6 months with lactulose alone, or lactulose plus rifaximin-alpha

Improvement in metabolic indices including thyroid hormones via enhanced absorption of nutrients by Teduglutide in short bowel syndrome.

Introduction and importanceShort bowel syndrome is characterized by maldigestion and malabsorption resulting in deficiencies of multiple nutrients including vitamins and minerals. Most subjects required parental elimination for survival. GLP-2 RA Teduglutide was recently approved for treatment of short bowel syndrome especially for those requiring parenteral support. Our intent in reporting this subject is to demonstrate the utility of Teduglutide in improving multiple metabolic indices in presence of short bowel syndrome.Case presentation and clinical discussion66-year-old Caucasian female presented with a history of short bowel syndrome and associated vitamin deficiencies, hypothyroidism requiring large dose (300 μg) of levothyroxine, diarrhea and liver cirrhosis. Upon starting teduglutide the subject saw improvement in her symptoms. Moreover, daily dose of Levothyroxine required a gradual decrease to maintain desirable serum concentrations of Free T4, Free T3 and TSH. Serum levels of several vitamins attained greater than therapeutic concentrations requiring dosage reductions. Also notable was the improvement in her liver function tests, remission from ascites and episodes of hepatic encephalopathy and regeneration of liver nodules.ConclusionFollowing administration of GLP2 therapy, an adult subject with short bowel syndrome with concurrent hypothyroidism and multiple vitamin deficiencies, demonstrated a marked improvement in her metabolic parameters resulting in reduction in daily medication doses along with improvement in manifestations of liver cirrhosis.