Overt Hepatic Encephalopathy Research Articles

Hepatic encephalopathy: issues relevant to clinical practice

Hepatic encephalopathy (HE) remains one of the most serious complications of liver cirrhosis. Its clinical spectrum sometimes creates difficulties in the optimal diagnosis at the patient’s bedside and treatment. To present new data on the field of clinical management of cirrhotic patients with hepatic encephalopathy. The role of ammonia in the diagnosis of HE is still under discussion. In clinical practice, in patients with suspected overt HE, normal ammonia concentration can be used to exclude this diagnosis. In contrast, a high concentration of ammonia in the absence of clinical signs of HE should not serve as a criterion for this diagnosis and as a guide for treatment. A separate issue for discussion is the covert HE. The simplest and most affordable test for screening for covert HE and evaluating the effectiveness of therapy is the animal naming test, which can be done on bedside by physician or caregivers. Patients with covert HE need treatment that is similar in approach to overt HE. The diagnosis of overt HE and the methods of its therapy are well known. According to Russian recommendations, depending on the disease course in a certain patient, lactulose, rifaximin, L-ornithine L-aspartate can be used as first-line drugs, which is applicable to the treatment of both overt and latent PE. The main issues on the management of HE in liver cirrhosis relate to the diagnostic role of ammonia, optimal diagnosis and treatment strategy for covert HE, therapy of choice for both overt and latent HE. There are expert opinions and consensus documents on all these issues. Treatment of overt and latent PE is carried out according to the same principles. Drugs of choice: lactulose, rifaximin and L-Ornithine L-Aspartate.

Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy.

Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE. Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE. Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02–1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12–2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18–1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54–1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54–0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients. Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.

Comparison of Transjugular Intrahepatic Portosystemic Shunt in the Treatment of Cirrhosis With or Without Portal Vein Thrombosis: A Retrospective Study.

Aim: The purpose of our study was to conduct a retrospective analysis to compare the effectiveness of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of patients with cirrhosis with or without portal vein thrombosis (PVT).Methods: We included a total of 203 cirrhosis patients successfully treated with TIPS between January 2015 and January 2018, including 72 cirrhosis patients with PVT (35.5%) and 131 without PVT (64.5%). Our subjects were followed for at least 1 year after treatment with TIPS. Data were collected to estimate the mortality, shunt dysfunction, and complication rates after TIPS creation.Results: During the mean follow-up time of 19.5 ± 12.8 months, 21 (10.3%) patients died, 15 (7.4%) developed shunt dysfunction, and 44 (21.6%) experienced overt hepatic encephalopathy (OHE). No significant differences in mortality (P = 0.134), shunt dysfunction (P = 0.214), or OHE (P = 0.632) were noted between the groups. Age, model for end-stage liver disease (MELD) score, and refractory ascites requiring TIPS were risk factors for mortality. A history of diabetes, percutaneous transhepatic variceal embolization (PTVE), 8-mm diameter stent, and platelet (PLT) increased the risk of shunt dysfunction. The prevalence of variceal bleeding and recurrent ascites was comparable between the two groups (16.7 vs. 16.7% P = 0.998 and 2.7 vs. 3.8% P = 0.678, respectively).Conclusions: Transjugular intrahepatic portosystemic shunts are feasible in the management of cirrhosis with PVT. No significant differences in survival or shunt dysfunction were noted between the PVT and no-PVT groups. The risk of recurrent variceal bleeding, recurrent ascites, and OHE in the PVT group was generally similar to that in the no-PVT group. TIPS represents a potentially feasible treatment option in cirrhosis patients with PVT.

Abnormal corpus callosum induced by overt hepatic encephalopathy impairs interhemispheric functional coordination in cirrhosis patients.

BackgroundAlthough overt hepatic encephalopathy (OHE) patients were shown to have bilaterally symmetrical structural and functional abnormalities in the whole brain, few studies have focused on the bilateral cerebral hemisphere commissural fibers and measured functional coordination between bilateral hemispheres. This study aimed to investigate the structural changes of the corpus callosum (CC) and interhemispheric functional coordination in patients with OHE and to test the hypothesis that abnormal CC induced by OHE impairs interhemispheric functional coordination in cirrhosis patients.MethodsThe microstructural integrity and the volumes of each subregion of the CC were analyzed by diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging. Voxel-mirrored homotopic connectivity (VMHC) was derived from resting-state functional magnetic resonance imaging (MRI).ResultsCompared with the healthy controls (HCs) and patients without hepatic encephalopathy (noHE), the OHE group showed decreased volumes in all subregions of the CC. In OHE patients, the decreased fractional anisotropy (FA) of CC-5 correlated with decreased VMHC in the middle occipital gyrus (MOG) and precuneus. The value of FA in CC-5 and the volumes of CC-3, CC-4, and CC-5 showed correlations with neuropsychological performance in patients with OHE.ConclusionsThese findings suggest that impairment of interhemispheric white matter pathways may disturb the functional connectivity associated with coordination and neurocognitive performance.

The improvement in body composition including subcutaneous and visceral fat reduces ammonia and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

BackgroundSarcopenia and myosteatosis have been associated to a poor prognosis of cirrhosis and to a higher incidence of hepatic encephalopathy (HE). The prognostic implications of visceral and subcutaneous adiposity are less known.AimTo evaluate the modifications of visceral and subcutaneous adipose tissue after TIPS and to investigate their relationships with the modification of muscle mass and with the incidence of post‐TIPS HE.Patients and Methods35 cirrhotic patients submitted to TIPS were retrospectively studied. The modification of skeletal muscle index (SMI), muscle attenuation (myosteatosis), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), assessed by CT‐scan and plasma ammonia were evaluated before and after a mean follow‐up of 19 ± 15 months after TIPS. The number of episodes of overt HE was also recorded.ResultsDuring the follow‐up, the mean SMI and muscle attenuation increased significantly; SATI significantly increased while VATI significantly decreased, although not uniformly in all patients. By comparing the patients with or without improvement in their nutritional status after TIPS, MELD remained stable while the number of episodes of overt HE was significantly lower in the patients with improved SMI and in the patients with improved SATI. Finally, inverse correlation was observed between the variation of ammonia and SATI (r = −.40; P < .05).ConclusionIn addition to muscle mass, adipose tissue is modified after TIPS. The improvement of subcutaneous adipose tissue as well as of sarcopenia and myosteatosis is associated to the amelioration of cognitive impairment independently of liver function. The correlation between adipose tissue and ammonia modification may suggest an active role of the adipose tissue in the inter‐organ ammonia trafficking.

Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial

Rifaximin-α is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism of action remains unclear. We postulated that rifaximin-α reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver of HE. In a placebo-controlled, double-blind, mechanistic study, 38 patients with cirrhosis and HE were randomised 1:1 to receive either rifaximin-α (550mg BID) or placebo for 90 days. 50% reduction in neutrophil oxidative burst (OB) at 30 days. changes in psychometric hepatic encephalopathy score (PHES) and neurocognitive functioning, shotgun metagenomic sequencing of saliva and faeces, plasma and faecal metabolic profiling, whole blood bacterial DNA quantification, neutrophil toll-like receptor (TLR)-2/4/9 expression and plasma/faecal cytokine analysis. Patients were well-matched: median MELD (11 rifaximin-α vs. 10 placebo). Rifaximin-α did not lead to a 50% reduction in spontaneous neutrophil OB at 30 days compared to baseline (p= 0.48). However, HE grade normalised (p= 0.014) and PHES improved (p= 0.009) after 30 days on rifaximin-α. Rifaximin-α reduced circulating neutrophil TLR-4 expression on day 30 (p= 0.021) and plasma tumour necrosis factor-α (TNF-α) (p <0.001). Rifaximin-α suppressed oralisation of the gut, reducing levels of mucin-degrading sialidase-rich species, Streptococcus spp, Veillonella atypica and parvula, Akkermansia and Hungatella. Rifaximin-α promoted a TNF-α- and interleukin-17E-enriched intestinal microenvironment, augmenting antibacterial responses to invading pathobionts and promoting gut barrier repair. Those on rifaximin-α were less likely to develop infection (odds ratio 0.21; 95% CI 0.05-0.96). Rifaximin-α led to resolution of overt and covert HE, reduced the likelihood of infection, reduced oralisation of the gut and attenuated systemic inflammation. Rifaximin-α plays a role in gut barrier repair, which could be the mechanism by which it ameliorates bacterial translocation and systemic endotoxemia in cirrhosis. ClinicalTrials.gov NCT02019784. In this clinical trial, we examined the underlying mechanism of action of an antibiotic called rifaximin-α which has been shown to be an effective treatment for a complication of chronic liver disease which effects the brain (termed encephalopathy). We show that rifaximin-α suppresses gut bacteria that translocate from the mouth to the intestine and cause the intestinal wall to become leaky by breaking down the protective mucus barrier. This suppression resolves encephalopathy and reduces inflammation in the blood, preventing the development of infection.

Rifaximin microbial resistance and its efficacy and safety as a secondary prophylaxis of hepatic encephalopathy in patients with hepatitis C virus-related cirrhosis.

Rifaximin is an oral antibiotic with promising efficacy in the reduction of hepatic encephalopathy (HE) recurrence. Development of microbial resistance to rifaximin is not studied yet in HE. The study aim was to assess the microbial resistance, safety and efficacy of rifaximin as secondary prophylaxis of HE. In this open-label parallel, prospective interventional study, 100 patients were randomly allocated either to receive 400mg rifaximin 3 times/d plus 30-45mL lactulose 3 times/d (intervention group) or to receive the standard of care only which is lactulose alone (control group) for 6months. The primary outcome of the study was the difference between minimum inhibitory concentration (MIC) of rifaximin among the two studied groups at the end of treatment. The secondary outcomes included the time to first episode of HE, time to first hospitalisation, and patient's survival. The MIC did not differ significantly after treatment exposure compared with baseline either between groups or within the same group. The time to new episode of HE was 18.84±6.49weeks (mean±SD) in the intervention group and was significantly longer (P=.002) than that in the control group 14±7.52weeks. Moreover, only 23 (46%) patients developed overt HE in the intervention group compared with 35 patients (70%) in the control group (P=.005). Also, there was an observed 32% reduction in the risk of hospitalisation in intervention group compared with control group. Rifaximin succeeded to maintain remission from new episodes of HE in hepatitis C virus cirrhotic patients with limited potential for development of microbial resistance over the study period. ClinicalTrials.gov Identifier: NCT04736836.

Handgrip strength stratifies the risk of covert and overt hepatic encephalopathy in patients with cirrhosis.

Handgrip strength (HGS) is a simple and convenient method to assess nutrition status in patients with cirrhosis. This retrospective study aimed to investigate the utility of HGS for predicting patients with covert hepatic encephalopathy (CHE) and patients at high risk of overt hepatic encephalopathy (OHE). We reviewed 963 patients with cirrhosis and consequently enrolled eligible 270 patients. HGS was measured using a digital grip dynamometer. CHE was diagnosed using a computer-aided neuropsychiatric test. Factors associated with CHE were estimated using the logistic regression model. Predictors associated with OHE occurrence were analyzed using the Fine-Gray competing risk regression model. Of the 270 eligible patients, reduced HGS was observed in 102 (38%), reduced muscle mass in 107 (40%), and CHE in 53 (20%). Multivariate analysis showed that serum ammonia levels (odds ratio [OR], 2.23; 95% CI, 1.14-4.36; P = 0.014) and reduced HGS (OR, 3.68; 95% CI, 1.93-7.03; P < 0.001) were independently associated with CHE. During the median follow-up period of 24.5 months, 43 (16%) patients experienced OHE. After adjusting for possible confounding factors, multivariate analysis showed that reduced HGS (subdistribution hazard ratio, 2.36; 95% CI, 1.27-4.38; P = 0.007) was a significant predictor in the development of OHE. Patients with reduced HGS had a higher prevalence of CHE and a higher risk for OHE occurrence than those with normal HGS. The measurement of HGS could be a simple bedside modality to stratify the patients' risk for CHE and OHE.

Single-Centre Retrospective Training Cohort Using Artificial Intelligence for Prognostic Prediction of Encephalopathy, Mortality, and Liver Dysfunction after Early TIPS Creation.

Based on an artificial intelligence approach, this study attempted to establish prognostic models to predict 3-month overt hepatic encephalopathy (OHE) occurrence, 1-year mortality, and liver dysfunction for cirrhotic patients with acute variceal bleeding (AVB) treated with early transjugular intrahepatic portosystemic shunt (TIPS) creation. This retrospective study included patients treated with early TIPS between January 2016 and November 2019. Independent risk factors associated with occurrence of OHE within 3months, 1-year mortality, and liver dysfunction after early TIPS were identified using univariate and multivariate logistic analyses. Artificial neural network (ANN) models and prognostic nomograms based on the independent risk factors were established and validated internally. A total of 207 patients were included, with 33 (15.9%) experienced OHE within 3months after TIPS creation. The albumin-bilirubin grade (P = 0.015), age (≤ 65, > 65years) (P < 0.001), gender (P = 0.002), and alcoholic cirrhosis (P = 0.013) was identified as independent risk factors associated with 3-month OHE. Presence of portal vein thrombosis (P = 0.034) and model for end-stage liver disease score (P = 0.063) were identified as independent risk factors associated with 1-year mortality. The platelet-albumin-bilirubin grade (P = 0.041) and a history of hepatic encephalopathy (P = 0.018) were identified as independent risk factors associated with liver dysfunction after TIPS creation. Three ANN models and three nomograms were then established and validated with high accuracy. The ANN and nomogram models have potential to accurately predict early occurrence of OHE, mortality, and liver dysfunction after early TIPS creation for cirrhotic patients with AVB.

Hepatic Encephalopathy is Associated With Slow Speech on Objective Assessment.

There are no available low-burden, point-of-care tests to diagnose, grade, and predict hepatic encephalopathy (HE). We evaluated speech as a biomarker of HE in 76 English-speaking adults with cirrhosis. Three speech features significantly correlated with the following neuropsychiatric scores: speech rate, word duration, and use of particles. Patients with low neuropsychiatric scores had slower speech (22 words/min, P = 0.01), longer word duration (0.09 seconds/word, P = 0.01), and used fewer particles (0.85% fewer, P = 0.01). Patients with a history of overt HE had slower speech (23 words/min, P = 0.005) and longer word duration (0.09 seconds/word, P = 0.005). HE is associated with slower speech.

Neuromarkers from Whole-Brain Functional Connectivity Reveal the Cognitive Recovery Scheme for Overt Hepatic Encephalopathy after Liver Transplantation.

Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with overt hepatic encephalopathy (OHE). Liver transplantation (LT) can restore liver function, but how it reverses the impaired brain function is still unclear. MRI of resting-state functional connectivity can help reveal the underlying mechanisms that lead to these cognitive deficits and cognitive recovery. In this study, 64 patients with cirrhosis (28 with OHE; 36 without OHE) and 32 healthy control subjects were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated presurgical and postsurgical neurocognitive performance in cirrhosis patients using psychomotor tests. Network-based statistics found significant disrupted connectivity in both groups of cirrhotic patients, with OHE and without OHE, compared with control subjects. However, the presurgical connectivity disruption in patients with OHE affected a greater number of connections than those without OHE. The decrease in functional connectivity for both OHE and non-OHE patient groups was reversed after LT to the level of control subjects. An additional hyperconnected network (i.e., higher connected than control subjects) was observed in OHE patients after LT. Regarding the neural–behavior relationship, the functional network that predicted cognitive performance in healthy individuals showed no correlation in presurgical cirrhotic patients. The impaired neural–behavior relationship was re-established after LT for non-OHE patients, but not for OHE patients. OHE patients displayed abnormal hyperconnectivity and a persistently impaired neural–behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery compared with those without, which needs further clarification in future studies.

In patients having transjugular intrahepatic portosystemic shunt, rifaximin prevented overt hepatic encephalopathy.

Bureau C, Thabut D, Jezequel C, et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled trial. Ann Intern Med. 2021;174:633-40. 33524293.

Additional L-Carnitine Reduced the Risk of Hospitalization in Patients with Overt Hepatic Encephalopathy on Rifaximin

Background: Data regarding the additional effect on the recurrence of hepatic encephalopathy (HE) after oral L-carnitine administration are scarce. Objective: This study aimed to assess the additional effects of L-carnitine in patients who were receiving rifaximin for HE. Methods: This randomized study comprised a screening visit and a 12-week treatment period. Patients who fulfilled the eligibility criteria were randomized to either group A (additional rifaximin) or group B (additional L-carnitine and rifaximin). Group A received 1,200 mg/day of rifaximin. Group B received 1,500 mg/day of L-carnitine and rifaximin at 1,200 mg/day. The endpoints were the changes in the portal systemic encephalopathy (PSE) index and the admission rate from the baseline for the duration of the study in both groups. Results: Eighty-three patients were randomized to either group A (n = 42) or group B (n = 41). In group A, the PSE index decreased from 0.35 ± 0.09 at baseline to 0.27 ± 0.11 on the final evaluation day (p = 0.001). In group B, the PSE index decreased from 0.37 ± 0.09 at baseline to 0.24 ± 0.11 on the final evaluation day (p = 0.001). Although there was not a significant reduction in the PSE index in group A compared to that in group B (p = 0.202), the admission rates were 30.9% and 9.8% in groups A and B, respectively. Additional L-carnitine significantly reduced the admission rate (p = 0.028). Conclusion: L-Carnitine addition reduced the risk of hospitalization for patients who received rifaximin for HE.

Liver-Unrelated Comorbid Conditions Do Not Affect Cognitive Performance or Hepatic Encephalopathy Progression in Cirrhosis.

We aimed to determine the effect of comorbidities on covert hepatic encephalopathy (CHE) diagnosis and overt hepatic encephalopathy (OHE) development. Cirrhotic outpatients underwent CHE testing and 2-year follow-up. Cox regression was performed for time to OHE. In total, 700 patients (60 years, 84% men, model for end-stage liver disease 11) and 33% prior OHE underwent testing and follow-up. Major comorbidities were hypertension (54%), diabetes (35%), and depression (29%). Common medications were proton pump inhibitor (49%), beta-blockers (32%), and opioids (21%). Approximately 90 (40%) prior-OHE patients developed recurrence 93 (30,206) days post-testing predicted only by liverrelated variables. Demographics, cirrhosis characteristics, and opioid use, but not other comorbid conditions, were associated with CHE diagnosis and OHE progression.

Retrograde transvenous obliteration for the prevention of variceal rebleeding in patients with hepatocellular carcinoma: a multicentre retrospective study

To evaluate the effectiveness and safety of retrograde transvenous obliteration (RTO) for the prevention of variceal rebleeding variceal rebleeding in patients with hepatocellular carcinoma (HCC). This multicentre retrospective study enrolled 79 patients with HCC who underwent RTO for the prevention of variceal rebleeding. Successful occlusion of the gastrorenal shunt and obliteration of the gastric varices were achieved in 74 patients, with a technical success rate of 93.7%. Of the remaining 74 patients (mean age, 64.9±10.3 years; 56 men), 66 (90.4%) had gastroesophageal varices and seven (9.6%) had isolated gastric varices. Thirty-two patients (43.8%) underwent balloon-occluded RTO, 40 patients (54.8%) underwent plug-assisted RTO, and one patient (1.4%) underwent coil-assisted RTO. No patients had major procedural complications. Rebleeding occurred in seven patients (9.6%) during the follow-up period. The 6-week and 1-year actuarial probabilities of patients remaining free of rebleeding were 90.8±3.6% and 88.6±4.1%, respectively. The median survival was 12.6 (95% confidence interval [CI] 8-17.3) months. The 6-week, 1-year, and 3-year actuarial probabilities of survival were 83.2±4.4%, 51.1±6.6%, and 32.7±7%, respectively. New or worsening ascites and oesophageal varices occurred in 12 (16.4%) and 13 patients (17.8%), respectively, during the follow-up period. Overt hepatic encephalopathy occurred in one patient (1.4%) during the follow-up period. The Child-Pugh score remained comparable to that at baseline at 1 and 3 months. RTO was effective and safe in preventing variceal rebleeding in patients with HCC.

Role of lactulose for prophylaxis against hepatic encephalopathy in cirrhotic patients with upper gastrointestinal bleeding: A randomized trial.

We aimed toassess the efficacy of lactulose as prophylaxis against hepatic encephalopathy (HE) in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB). We conducted a randomized, double-blinded, placebo-controlled, multicenter study from October 2012 to February 2014. Cirrhotic patients presenting with AUGIB (aged 18-80years, without HE at the time of admission) were enrolled and randomized to receive blinded medications (both physically indistinguishable), labeled "Lactulose A" and "Lactulose B" for 5days along with standard treatment depending on the type of bleeding (variceal and nonvariceal). The primary endpoint was the development of overt HE according to the West-Haven criteria. Modified intention-to-treat analysis was performed. Forty-six patients completed the protocol: Lactulose A (placebo, n= 22) and Lactulose B (lactulose, n= 24). There was no significant difference in baseline characteristics and clinical outcomes between the two groups. Nine (19.6%) patients developed HE: five (22.7%) in the placebo group and four (16.7%) in the lactulose group (p= 0.718). One patient (2.2%) died inlactulose group. All patients tolerated the medication and no significant difference in adverse effects was detected (59.1% inplacebo vs. 50.0% inlactulosegroup, p= 0.536). On multivariate analysis, increased baselineChild-Turcotte-Pugh (CTP) score (odds ratio [OR] 2.176; 95% confidence interval [CI] 1.012-4.681, p= 0.047) and presence of diarrhea (OR 16.261; 95% CI 1.395-189.608, p= 0.026) were independent risk factors for the development of HE. Five-day lactulose is ineffective as prophylaxis against HE in cirrhotic patients with AUGIB. Unnecessarytreatment with laxatives should be avoided in these patients. Clinical trial registry number TCTR20200526003 (retrospectively registered).

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis.

Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.

Potential Benefits of Underdilation of 8-mm Covered Stent in Transjugular Intrahepatic Portosystemic Shunt Creation.

INTRODUCTION:Hepatic encephalopathy (HE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS) creation. This study was aimed to determine whether underdilated TIPS with 8-mm polytetrafluoroethylene-covered stents could reduce the risk of HE and liver damage yet maintain clinical and hemodynamic efficacy.METHODS:This retrospective case-controlled study included 134 patients treated with TIPS from March 2017 to November 2019. All the TIPS procedures were created using 8-mm covered stents, and according to the diameter of expansion balloon catheters, the patients were divided into 2 groups, an underdilated group (6-mm balloon catheter, n = 73) and a control group (8-mm balloon catheter, n = 61).RESULTS:The Kaplan-Meier analysis indicated that the cumulative incidence of overt HE in the underdilated group was significantly lower than that in the control group (11.0% vs 29.5%, log rank P = 0.007), but no statistical differences were found toward variceal rebleeding, shunt dysfunction, and survival between groups. In multivariate analysis, the independent risk factors for overt HE were identified as age (hazard ratio [HR] = 1.036, 95% confidence interval [CI] = 1.003–1.069, P = 0.032), Child-Pugh score (HR = 1.519, 95% CI = 1.212–1.905, P < 0.001), and group assignment (HR = 0.291, 95% CI = 0.125–0.674, P = 0.004).DISCUSSION:Underdilated TIPS with 8-mm polytetrafluoroethylene-covered stents could reduce the risk of HE and liver function impairment compared with completely dilated TIPS, but not increase the risk of variceal rebleeding, shunt dysfunction, and death.

Effect of splenectomy on the outcomes in patients with cirrhosis receiving transjugular intrahepatic portosystemic shunt.

Background and AimPatients indicated to transjugular intrahepatic portosystemic shunt (TIPS) placement may have splenectomy history due to thrombocytopenia. This study aimed to evaluate the effect of prior splenectomy on TIPS procedure and post‐TIPS outcomes.MethodsWe conducted a longitudinal analysis based on a cohort of 284 patients with cirrhosis submitted to TIPS; 74 patients had splenectomy history (splenectomy group) and 210 did not (non‐splenectomy group). Cox proportional hazards models were used to evaluate the association between splenectomy and outcomes after TIPS. The primary outcome was shunt dysfunction. Secondary outcomes included all‐cause mortality, clinical recurrence of bleeding or ascites, and overt hepatic encephalopathy (OHE).ResultsDuring a median follow‐up of 16.2 months, the splenectomy group had significantly lower rates of postoperative shunt patency (85.5% vs 95.6% at 1 year and 75.2% vs 86.5% at 2 years; adjusted hazard ratio [HR] 2.53; 95% confidence interval [CI] 1.21–5.12; P = 0.01) and higher risk of OHE (adjusted HR 1.82; 95% CI 1.03–3.54; P = 0.04). But the risk of mortality (adjusted HR 0.87; 95% CI 0.41–1.87; P = 0.73) and recurrent bleeding or ascites (adjusted HR 1.17; 95% CI 0.53–2.35; P = 0.77) showed no statistical difference. Multivariate analysis confirmed splenectomy history and endoscopic therapy as independent predictors of shunt dysfunction. Besides, pre‐TIPS splenectomy increased the difficulty of TIPS procedure by complicating portal vein puncture.ConclusionsFor patients with cirrhosis submitted to TIPS, prior splenectomy complicated TIPS procedure and increased the risk of shunt dysfunction and OHE after TIPS, but was not significantly associated with the occurrence of mortality and recurrent bleeding or ascites.

Usefulness of the Stroop Test in Diagnosing Minimal Hepatic Encephalopathy and Predicting Overt Hepatic Encephalopathy.

Minimal hepatic encephalopathy (MHE) adversely affects the clinical outcomes of patients with liver cirrhosis. This prospective study aimed to evaluate the utility of the Stroop test in the diagnosis of MHE and prediction of overt hepatic encephalopathy (OHE) in Japanese patients with cirrhosis. We enrolled 152 patients who underwent the Stroop test between November 2018 and February 2020. MHE was diagnosed using a combination of neuropsychological tests as the gold standard. The enrolled patients were followed up prospectively until the occurrence of OHE or August 2020. The optimal cutoff value of the Stroop test measurements was determined by receiver operating characteristic (ROC) curve analysis, and its predictive ability was assessed using the area under the ROC curve (AUC). Among the 139 eligible patients, 50 (36%) were diagnosed with MHE. The OffTime+OnTime cutoff value of 218.3 seconds had the best discriminative ability for MHE diagnosis, with an AUC of 0.77, a sensitivity of 74%, and a specificity of 75%. During a median follow‐up of 10.8 months, 6 (4%) patients developed OHE. The OffTime+OnTime cutoff value of 305.6 seconds had the highest predictive ability for OHE, with an AUC of 0.79, a sensitivity of 67%, and a specificity of 92%. This value predicted OHE occurrence independent of liver functional reserve and prior OHE (hazard ratio, 19.8; P = 0.003). These two cutoff values remained statistically significant even when patients with prior OHE were excluded from the analysis. Conclusion: The Stroop test was useful for diagnosing patients with MHE and predicting OHE in Japanese patients with cirrhosis.