Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbabl...Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.展开更多
Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies w...Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.展开更多
Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be di...Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.展开更多
BACKGROUND Skeletal muscle abnormalities,such as muscle mass depletion(sarcopenia)and fatty infiltration of the muscle(myosteatosis),are frequent complications in cirrhotic patients scheduled for transjugular intrahep...BACKGROUND Skeletal muscle abnormalities,such as muscle mass depletion(sarcopenia)and fatty infiltration of the muscle(myosteatosis),are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt(TIPS).AIM To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy(HE)and mortality after TIPS.METHODS The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved.The transversal psoas muscle thickness(TPMT)and psoas muscle attenuation(PMA)measured from the unenhanced abdominal computed tomography(CT)at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis,respectively.The area under curve(AUC)was used to evaluate the discriminative power of TPMT,PMA,and relevant clinical parameters.Furthermore,log-rank test was performed to compare the incidence of overt HE and survival between the different groups,and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models.RESULTS A total of 108 patients were collected.Among these patients,45.4%of patients developed overt HE after TIPS treatment.Furthermore,32.4%and 28.7%of these patients were identified to have myosteatosis and sarcopenia,respectively.Myosteatosis(51.0%vs 16.9%,P<0.001)and sarcopenia(40.8 vs 18.6%,P=0.011)were found to be more frequent in patients with overt HE,when compared to patients without overt HE.The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE(AUC=0.713 and 0.778,respectively)was higher when compared to the neutrophil lymphocyte ratio(AUC=0.636).The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis,followed by patients with myosteatosis or sarcopenia,while this was the lowest in patients without sarcopenia and myosteatosis.In addition,sarcopenia and myosteatosis were independently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients.CONCLUSION CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.展开更多
Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated wi...Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated with a worse prognosis and increased risk of complication.Serum levels of branched-chain amino acids(BCAAs)are decreased in patients with liver cirrhosis.The imbalance of amino acids levels has been suggested to be associated with the development of complications,such as hepatic encephalopathy and sarcopenia,and to affect the clinical presentation and prognosis of these patients.Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis,but uncertainties remain about the real efficacy,the best route of administration,and dosage.展开更多
BACKGROUND Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts.Surgical shunt occlusion has been standard treatment,although recently the less invasive balloon-occluded retrograd...BACKGROUND Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts.Surgical shunt occlusion has been standard treatment,although recently the less invasive balloon-occluded retrograde transvenous obliteration(B-RTO)has gained increasing attention.Thus far,there have been no reports on the treatment of portosystemic shunts with B-RTO in patients aged over 90 years.In this study,we present a case of hepatic encephalopathy caused by shunting of the left common iliac and inferior mesenteric veins,successfully treated with B-RTO.CASE SUMMARY A 97-year-old woman with no history of liver disease was admitted to our hospital because of disturbance of consciousness.She had no jaundice,spider angioma,palmar erythema,hepatosplenomegaly,or asterixis.Her blood tests showed hyperammonemia,and abdominal contrast-enhanced computed tomography revealed a portosystemic shunt running between the left common iliac vein and the inferior mesenteric vein.She was diagnosed with hepatic encephalopathy secondary to a portosystemic shunt.The patient did not improve with conservative treatment:Lactulose,rifaximin,and a low-protein diet.B-RTO was performed,which resulted in shunt closure and improvement in hyperammonemia and disturbance of consciousness.Moreover,there was no abdominal pain or elevated levels of liver enzymes due to complications.The patient was discharged without further consciousness disturbance.CONCLUSION Portosystemic shunt-borne hepatic encephalopathy must be considered in the differential diagnosis for consciousness disturbance,including abnormal behavior and speech.展开更多
Transjugular intrahepatic portosystemic shunt(TIPS)is an established procedure for treating the complications of portal hypertension in liver cirrhosis.While the pathogenesis of postoperative TIPS-related hepatic ence...Transjugular intrahepatic portosystemic shunt(TIPS)is an established procedure for treating the complications of portal hypertension in liver cirrhosis.While the pathogenesis of postoperative TIPS-related hepatic encephalopathy(HE)has yet to be fully understood,intraoperative portosystemic shunts may provide a pathological basis for the occurrence of postope-rative HE in patients with liver cirrhosis.Studies at home and abroad have expressed mixed opinions about TIPSrelated HE.This study presents a literature review on the risk factors for and prevention and treatment of perioperative TIPS-related HE in patients with liver cirrhosis,aiming to optimize the procedure and reduce the incidence of postoperative HE.展开更多
Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic p...Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.展开更多
The face of hepatic encephalopathy(HE) is changing.This review explores how this neurocognitive disorder,which is associated with both acute and chronic liver injury,has grown to become a dynamic syndrome that spans a...The face of hepatic encephalopathy(HE) is changing.This review explores how this neurocognitive disorder,which is associated with both acute and chronic liver injury,has grown to become a dynamic syndrome that spans a spectrum of neuropsychological impairment,from normal performance to coma.The central role of ammonia in the pathogenesis of HE remains incontrovertible.However,over the past 10 years,the HE community has begun to characterise the key roles of inflammation,infection,and oxidative/nitrosative stress in modulating the pathophysiological effects of ammonia on the astrocyte.This review explores the current thoughts and evidence base in this area and discusses the potential role of existing and novel therapies that might abrogate the oxidative and nitrosative stresses inflicted on the brain in patients with,or at risk of developing,HE.展开更多
AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; rang...AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.展开更多
Hepatic encephalopathy(HE) is one of the worst complications of liver disease and can be greatly influenced by nutritional status. Ammonia metabolism, inflammation and muscle wasting are relevant processes in HE patho...Hepatic encephalopathy(HE) is one of the worst complications of liver disease and can be greatly influenced by nutritional status. Ammonia metabolism, inflammation and muscle wasting are relevant processes in HE pathophysiology. Malnutrition worsens the prognosis in HE, requiring early assessment of nutritional status of these patients. Body composition changes induced by liver disease and limitations superimposed by HE hamper the proper accomplishment of exams in this population, but evidence is growing that assessment of muscle mass and muscle function is mandatory due to the role of skeletal muscles in ammonia metabolism. In this review, we present the pathophysiological aspects involved in HE to support further discussion about advantages and drawbacks of some methods for evaluating the nutritional status of cirrhotic patients with HE, focusing on body composition.展开更多
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 imperceptibl...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.展开更多
BACKGROUND Hepatic encephalopathy(HE)is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50%of cirrhotic patients.Studies examining the prognostic significance of HE are limited despit...BACKGROUND Hepatic encephalopathy(HE)is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50%of cirrhotic patients.Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.AIM To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.METHODS All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over46-mo(2012–2016)were identified via pharmacy dispensing records.Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded.Medical records were reviewed to determine baseline characteristics and survival.The Kaplan-Meier method was used to calculate survival probability.Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis.The primary outcome was 12-mo mortality following commencement of Rifaximin.RESULTS188 patients were included.Median age was 57 years(IQR 50-65),71%were male and median model for end stage liver disease and Child Pugh scores were 25(IQR 18-31)and 11(IQR 9-12)respectively.The most common causes of cirrhosis were alcohol(62%),hepatitis C(31%)and non-alcoholic fatty liver disease(20%).A precipitating cause for HE was found in 92%patients with infection(43%),GI bleeding(16%),medication non-compliance(15%)and electrolyte imbalance(14%)the most common.During a mean follow up period of 12±13 mo 107(57%)patients died and 32(17%)received orthotopic liver transplantation.Themost common causes of death were decompensated chronic liver disease(57%)and sepsis(19%).The probability of survival was 44%and 35%at 12-and 24-mo respectively.At multivariate analysis a model for end stage liver disease>15 and international normalised ratio reached statistical significance in predicting mortality.CONCLUSION Despite advances made in the management of HE patients continue to have poor survival.Thus,in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.展开更多
BACKGROUND Hepatic encephalopathy(HE)remains an enormous challenge in patients who undergo transjugular intrahepatic portosystemic shunt(TIPS)implantation.The preoperative indocyanine green retention rate at 15 min(IC...BACKGROUND Hepatic encephalopathy(HE)remains an enormous challenge in patients who undergo transjugular intrahepatic portosystemic shunt(TIPS)implantation.The preoperative indocyanine green retention rate at 15 min(ICG-R15),as one of the liver function assessment tools,has been developed as a prognostic indicator in patients undergoing surgery,but there are limited data on its role in TIPS.AIM To determine whether the ICG-R15 can be used for prediction of post-TIPS HE in decompensated cirrhosis patients with portal hypertension(PHT)and compare the clinical value of ICG-R15,Child-Pugh score(CPS),and model for end-stage liver disease(MELD)score in predicting post-TIPS HE with PHT.METHODS This retrospective study included 195 patients with PHT who underwent elective TIPS at Beijing Shijitan Hospital from January 2018 to June 2019.All patients underwent the ICG-R15 test,CPS evaluation,and MELD scoring 1 wk before TIPS.According to whether they developed HE or not,the patients were divided into two groups:HE group and non-HE group.The prediction of one-year post-TIPS HE by ICG-R15,CPS and MELD score was evaluated by the areas under the receiver operating characteristic curves(AUCs).RESULTS A total of 195 patients with portal hypertension were included and 23%(45/195)of the patients developed post-TIPS HE.The ICG-R15 was identified as an independent predictor of post-TIPS HE.The AUCs for the ICG-R15,CPS,and MELD score for predicting post-TIPS HE were 0.664(95%confidence interval[CI]:0.557-0.743,P=0.0046),0.596(95%CI:0.508-0.679,P=0.087),and 0.641(95%CI:0.554-0.721,P=0.021),respectively.The non-parametric approach(Delong-Delong&Clarke-Pearson)showed that there was statistical significance in pairwise comparison between AUCs of ICG-R15 and MELD score(P=0.0229).CONCLUSION The ICG-R15 has appreciated clinical value for predicting the occurrence of post-TIPS HE and is a choice for evaluating the prognosis of patients undergoing TIPS.展开更多
BACKGROUND Intrahepatic portosystemic venous shunt(IPSVS)is a rare hepatic disease with different clinical manifestations.Most IPSVS patients with mild shunts are asymptomatic,while the patients with severe shunts pre...BACKGROUND Intrahepatic portosystemic venous shunt(IPSVS)is a rare hepatic disease with different clinical manifestations.Most IPSVS patients with mild shunts are asymptomatic,while the patients with severe shunts present complications such as hepatic encephalopathy.For patients with portal hypertension accompanied by intrahepatic shunt,portal hypertension may lead to hemodynamic changes that may result in exacerbated portal shunt and increased shunt flow.CASE SUMMARY A 57-year-old man,with the medical history of chronic hepatitis B and liver cirrhosis,was admitted to our hospital with abnormal behavior for 10 mo.He had received the esophageal varices ligation and entecavir therapy 1 year ago.Comparing with former examination results,the degree of esophageal varices was significantly reduced,while the right branch of the portal vein was significantly expanded and tortuous.Meanwhile,abdominal ultrasound presented the right posterior branch of portal vein connected with the retrohepatic inferior vena cava.The imaging findings indicated the diagnosis of IPSVS and hepatic encephalopathy.Instead of radiologic interventions or surgical therapies,this patient had only accepted symptomatic treatment.No recurrence of hepatic encephalopathy was observed during 1-year follow-up.CONCLUSION Hemodynamic changes may exacerbate intrahepatic portosystemic shunt.The intervention or surgery should be carefully applied to patients with severe portal hypertension due to the risk of hemorrhage.展开更多
BACKGROUND Hepatic 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 ris...BACKGROUND Hepatic 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.AIM To assess the effectiveness of rifaximin in the management of recurrent episodes of HE and recurrent acute exacerbations on persistent HE,in“real life conditions”.METHODS In 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.RESULTS Rifaximin 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).CONCLUSION In 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.展开更多
AIM:To propose an alternative model of hepatic encephalopathy(HE) in mice,resembling the human features of the disease.METHODS:Mice received two consecutive intraperitoneal injections of thioacetamide(TAA) at low dosa...AIM:To propose an alternative model of hepatic encephalopathy(HE) in mice,resembling the human features of the disease.METHODS:Mice received two consecutive intraperitoneal injections of thioacetamide(TAA) at low dosage(300 mg/kg).Liver injury was assessed by serum transaminase levels(ALT) and liver histology(hematoxylin and eosin).Neutrophil infiltration was estimated by confocal liver intravital microscopy.Coagulopathy was evaluated using prolonged prothrombin and partial thromboplastin time.Hemodynamic parameters were measured through tail cuff.Ammonia levels were quantified in serum and brain samples.Electroencephalography(EEG) and psychomotor activity score were performed to show brain function.Brain edema was evaluated using magnetic resonance imaging.RESULTS:Mice submitted to the TAA regime developed massive liver injury,as shown by elevation of serum ALT levels and a high degree of liver necrosis.An intense hepatic neutrophil accumulation occurred in response to TAA-induced liver injury.This led to mice mortality and weight loss,which was associated with severe coagulopathy.Furthermore,TAA-treated mice presented with increased serum and cerebral levels of ammonia,in parallel with alterations in EEG spectrum and discrete brain edema,as shown by magnetic resonance imaging.In agreement with this,neuropsychomotor abnormalities ensued 36 h after TAA,fulfilling several HE features observed in humans.In this context of liver injury and neurological dysfunction,we observed lung inflammation and alterations in blood pressure and heart rate that were indicative of multiple organ dysfunction syndrome.CONCLUSION:In summary,we describe a new murine model of hepatic encephalopathy comprising multiple features of the disease in humans,which may provide new insights for treatment.展开更多
BACKGROUND Hepatic encephalopathy(HE)can be considered a result of dysregulated gutliver-brain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by"gut-centri...BACKGROUND Hepatic encephalopathy(HE)can be considered a result of dysregulated gutliver-brain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by"gut-centric"therapies,such as the administration of nonabsorbable disaccharides,nonabsorbable antibiotics,probiotics and prebiotics.AIM To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle(EcN)1917 strain compared to lactulose and rifaximin in patients with minimal/mild HE.METHODS From January 2017 to March 2020,a total of 45 patients with HE were enrolled in this prospective,single-centre,open-label,randomized study.Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups:The EcN group(n=15),lactulose group(n=15)or rifaximin group(n=15)for a 1 mo intervention period.The main primary outcomes of the study were changes in serum ammonia and Stroop test score.The secondary outcomes were markers of a chronic systemic inflammatory response(ІL-6,ІL-8,and IFN-γ)and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period.RESULTS Patients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group.However,the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of E.coli with altered properties and pathogenic enterobacteria in patient faeces.In the primary outcome analysis,improvements in the Stroop test parameters in all intervention groups were observed.Moreover,EcN-treated patients performed 15%faster on the Stroop test than the lactulose group patients(P=0.017).Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ,IL-6 and IL-8.EcN was more efficient than lactulose in reducing proinflammatory cytokine levels.CONCLUSION The use of the probiotic EcN strain was safe and quite efficient for HE treatment.The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines,normalized the gut microbiota composition and improved the cognitive function of patients with HE.The application of the EcN strain was more effective than lactulose treatment.展开更多
The present letter to editor is related to Bohra A et al Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.World J Gastroenterol 2020;26(18):2221-2231....The present letter to editor is related to Bohra A et al Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.World J Gastroenterol 2020;26(18):2221-2231.Hepatic encephalopathy(HE)is a significant and frequent major decompensating event in cirrhosis.However clinical studies examining the clinical outcome of HE are lacking despite its high prevalence.展开更多
BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult wit...BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult without a clear history of cirrhosis.Liver transplantation (LT) is effective to alleviate symptoms, however, there arefew reports about LT in the treatment of status epilepticus with HE. To ourknowledge, this is the first report of status epilepticus present as initialmanifestation of HE.CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalizedfor generalized tonic-clonic seizures. She reported no history of episodes of HE,stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding.Neurological examination revealed a comatose patient, without papilledema.Laboratory examination suggested liver cirrhosis. Plasma ammonia levels uponadmission were five times normal. Brain computed tomography (CT) was normal,while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis andsplenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm,consistent with HE, and sharp waves during ictal EEG corresponding to clinicalsemiology of focal tonic seizures. The symptoms were reversed by continuousantiepileptic treatment and lactulose. She was given oral levetiracetam, and focalaware seizures occasionally affected her 10 mo after LT.CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE,and LT is effective to prevent the relapse.展开更多
基金Supported by the Chang Gung Medical Research Project,No.CMRPG3M1931-1932the National Science and Technology Council,No.MOST 110-2314-B-182A-093-and No.NMRPG3L0331.
文摘Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.
文摘Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.
基金supported by the National Nature Science Foundation of China(Grants 81974533,81530098).
文摘Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.
基金Natural Science Foundation of Anhui Province,No.2108085MH301The Key Project of University Research Found of Anhui Province Education Department,No.2022AH040189.
文摘BACKGROUND Skeletal muscle abnormalities,such as muscle mass depletion(sarcopenia)and fatty infiltration of the muscle(myosteatosis),are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt(TIPS).AIM To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy(HE)and mortality after TIPS.METHODS The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved.The transversal psoas muscle thickness(TPMT)and psoas muscle attenuation(PMA)measured from the unenhanced abdominal computed tomography(CT)at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis,respectively.The area under curve(AUC)was used to evaluate the discriminative power of TPMT,PMA,and relevant clinical parameters.Furthermore,log-rank test was performed to compare the incidence of overt HE and survival between the different groups,and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models.RESULTS A total of 108 patients were collected.Among these patients,45.4%of patients developed overt HE after TIPS treatment.Furthermore,32.4%and 28.7%of these patients were identified to have myosteatosis and sarcopenia,respectively.Myosteatosis(51.0%vs 16.9%,P<0.001)and sarcopenia(40.8 vs 18.6%,P=0.011)were found to be more frequent in patients with overt HE,when compared to patients without overt HE.The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE(AUC=0.713 and 0.778,respectively)was higher when compared to the neutrophil lymphocyte ratio(AUC=0.636).The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis,followed by patients with myosteatosis or sarcopenia,while this was the lowest in patients without sarcopenia and myosteatosis.In addition,sarcopenia and myosteatosis were independently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients.CONCLUSION CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.
文摘Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated with a worse prognosis and increased risk of complication.Serum levels of branched-chain amino acids(BCAAs)are decreased in patients with liver cirrhosis.The imbalance of amino acids levels has been suggested to be associated with the development of complications,such as hepatic encephalopathy and sarcopenia,and to affect the clinical presentation and prognosis of these patients.Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis,but uncertainties remain about the real efficacy,the best route of administration,and dosage.
文摘BACKGROUND Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts.Surgical shunt occlusion has been standard treatment,although recently the less invasive balloon-occluded retrograde transvenous obliteration(B-RTO)has gained increasing attention.Thus far,there have been no reports on the treatment of portosystemic shunts with B-RTO in patients aged over 90 years.In this study,we present a case of hepatic encephalopathy caused by shunting of the left common iliac and inferior mesenteric veins,successfully treated with B-RTO.CASE SUMMARY A 97-year-old woman with no history of liver disease was admitted to our hospital because of disturbance of consciousness.She had no jaundice,spider angioma,palmar erythema,hepatosplenomegaly,or asterixis.Her blood tests showed hyperammonemia,and abdominal contrast-enhanced computed tomography revealed a portosystemic shunt running between the left common iliac vein and the inferior mesenteric vein.She was diagnosed with hepatic encephalopathy secondary to a portosystemic shunt.The patient did not improve with conservative treatment:Lactulose,rifaximin,and a low-protein diet.B-RTO was performed,which resulted in shunt closure and improvement in hyperammonemia and disturbance of consciousness.Moreover,there was no abdominal pain or elevated levels of liver enzymes due to complications.The patient was discharged without further consciousness disturbance.CONCLUSION Portosystemic shunt-borne hepatic encephalopathy must be considered in the differential diagnosis for consciousness disturbance,including abnormal behavior and speech.
文摘Transjugular intrahepatic portosystemic shunt(TIPS)is an established procedure for treating the complications of portal hypertension in liver cirrhosis.While the pathogenesis of postoperative TIPS-related hepatic encephalopathy(HE)has yet to be fully understood,intraoperative portosystemic shunts may provide a pathological basis for the occurrence of postope-rative HE in patients with liver cirrhosis.Studies at home and abroad have expressed mixed opinions about TIPSrelated HE.This study presents a literature review on the risk factors for and prevention and treatment of perioperative TIPS-related HE in patients with liver cirrhosis,aiming to optimize the procedure and reduce the incidence of postoperative HE.
基金Ningxia Natural Science Foundation,No.2020AAC03329the Key Research and Development Projects of Ningxia,No.2022BEG03128.
文摘Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.
基金Supported by A5 year UK Department of Health HEFCE Clinical Senior Lectureship (to Dr.Shawcross DL)
文摘The face of hepatic encephalopathy(HE) is changing.This review explores how this neurocognitive disorder,which is associated with both acute and chronic liver injury,has grown to become a dynamic syndrome that spans a spectrum of neuropsychological impairment,from normal performance to coma.The central role of ammonia in the pathogenesis of HE remains incontrovertible.However,over the past 10 years,the HE community has begun to characterise the key roles of inflammation,infection,and oxidative/nitrosative stress in modulating the pathophysiological effects of ammonia on the astrocyte.This review explores the current thoughts and evidence base in this area and discusses the potential role of existing and novel therapies that might abrogate the oxidative and nitrosative stresses inflicted on the brain in patients with,or at risk of developing,HE.
文摘AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.
基金Supported by Sao Paulo Research Foundation(FAPESP),CAPES and PROPe/UNESP,Nos.2013/15121-8 and 2013/11761-2
文摘Hepatic encephalopathy(HE) is one of the worst complications of liver disease and can be greatly influenced by nutritional status. Ammonia metabolism, inflammation and muscle wasting are relevant processes in HE pathophysiology. Malnutrition worsens the prognosis in HE, requiring early assessment of nutritional status of these patients. Body composition changes induced by liver disease and limitations superimposed by HE hamper the proper accomplishment of exams in this population, but evidence is growing that assessment of muscle mass and muscle function is mandatory due to the role of skeletal muscles in ammonia metabolism. In this review, we present the pathophysiological aspects involved in HE to support further discussion about advantages and drawbacks of some methods for evaluating the nutritional status of cirrhotic patients with HE, focusing on body composition.
基金Supported by the Mexican Institute of Social Security,No.FFIS/IMSS/PROT/G16/1589National Council for Science and Technology(CONACYT),No.SALUD-2014-C01-233823.
文摘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.
文摘BACKGROUND Hepatic encephalopathy(HE)is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50%of cirrhotic patients.Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.AIM To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.METHODS All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over46-mo(2012–2016)were identified via pharmacy dispensing records.Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded.Medical records were reviewed to determine baseline characteristics and survival.The Kaplan-Meier method was used to calculate survival probability.Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis.The primary outcome was 12-mo mortality following commencement of Rifaximin.RESULTS188 patients were included.Median age was 57 years(IQR 50-65),71%were male and median model for end stage liver disease and Child Pugh scores were 25(IQR 18-31)and 11(IQR 9-12)respectively.The most common causes of cirrhosis were alcohol(62%),hepatitis C(31%)and non-alcoholic fatty liver disease(20%).A precipitating cause for HE was found in 92%patients with infection(43%),GI bleeding(16%),medication non-compliance(15%)and electrolyte imbalance(14%)the most common.During a mean follow up period of 12±13 mo 107(57%)patients died and 32(17%)received orthotopic liver transplantation.Themost common causes of death were decompensated chronic liver disease(57%)and sepsis(19%).The probability of survival was 44%and 35%at 12-and 24-mo respectively.At multivariate analysis a model for end stage liver disease>15 and international normalised ratio reached statistical significance in predicting mortality.CONCLUSION Despite advances made in the management of HE patients continue to have poor survival.Thus,in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.
基金Beijing Municipal Science and Technology Commision,No.Z181100001718097.
文摘BACKGROUND Hepatic encephalopathy(HE)remains an enormous challenge in patients who undergo transjugular intrahepatic portosystemic shunt(TIPS)implantation.The preoperative indocyanine green retention rate at 15 min(ICG-R15),as one of the liver function assessment tools,has been developed as a prognostic indicator in patients undergoing surgery,but there are limited data on its role in TIPS.AIM To determine whether the ICG-R15 can be used for prediction of post-TIPS HE in decompensated cirrhosis patients with portal hypertension(PHT)and compare the clinical value of ICG-R15,Child-Pugh score(CPS),and model for end-stage liver disease(MELD)score in predicting post-TIPS HE with PHT.METHODS This retrospective study included 195 patients with PHT who underwent elective TIPS at Beijing Shijitan Hospital from January 2018 to June 2019.All patients underwent the ICG-R15 test,CPS evaluation,and MELD scoring 1 wk before TIPS.According to whether they developed HE or not,the patients were divided into two groups:HE group and non-HE group.The prediction of one-year post-TIPS HE by ICG-R15,CPS and MELD score was evaluated by the areas under the receiver operating characteristic curves(AUCs).RESULTS A total of 195 patients with portal hypertension were included and 23%(45/195)of the patients developed post-TIPS HE.The ICG-R15 was identified as an independent predictor of post-TIPS HE.The AUCs for the ICG-R15,CPS,and MELD score for predicting post-TIPS HE were 0.664(95%confidence interval[CI]:0.557-0.743,P=0.0046),0.596(95%CI:0.508-0.679,P=0.087),and 0.641(95%CI:0.554-0.721,P=0.021),respectively.The non-parametric approach(Delong-Delong&Clarke-Pearson)showed that there was statistical significance in pairwise comparison between AUCs of ICG-R15 and MELD score(P=0.0229).CONCLUSION The ICG-R15 has appreciated clinical value for predicting the occurrence of post-TIPS HE and is a choice for evaluating the prognosis of patients undergoing TIPS.
文摘BACKGROUND Intrahepatic portosystemic venous shunt(IPSVS)is a rare hepatic disease with different clinical manifestations.Most IPSVS patients with mild shunts are asymptomatic,while the patients with severe shunts present complications such as hepatic encephalopathy.For patients with portal hypertension accompanied by intrahepatic shunt,portal hypertension may lead to hemodynamic changes that may result in exacerbated portal shunt and increased shunt flow.CASE SUMMARY A 57-year-old man,with the medical history of chronic hepatitis B and liver cirrhosis,was admitted to our hospital with abnormal behavior for 10 mo.He had received the esophageal varices ligation and entecavir therapy 1 year ago.Comparing with former examination results,the degree of esophageal varices was significantly reduced,while the right branch of the portal vein was significantly expanded and tortuous.Meanwhile,abdominal ultrasound presented the right posterior branch of portal vein connected with the retrohepatic inferior vena cava.The imaging findings indicated the diagnosis of IPSVS and hepatic encephalopathy.Instead of radiologic interventions or surgical therapies,this patient had only accepted symptomatic treatment.No recurrence of hepatic encephalopathy was observed during 1-year follow-up.CONCLUSION Hemodynamic changes may exacerbate intrahepatic portosystemic shunt.The intervention or surgery should be carefully applied to patients with severe portal hypertension due to the risk of hemorrhage.
文摘BACKGROUND Hepatic 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.AIM To assess the effectiveness of rifaximin in the management of recurrent episodes of HE and recurrent acute exacerbations on persistent HE,in“real life conditions”.METHODS In 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.RESULTS Rifaximin 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).CONCLUSION In 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.
基金CNPq,Fapemig,PRONEX and CAPES for financial support.
文摘AIM:To propose an alternative model of hepatic encephalopathy(HE) in mice,resembling the human features of the disease.METHODS:Mice received two consecutive intraperitoneal injections of thioacetamide(TAA) at low dosage(300 mg/kg).Liver injury was assessed by serum transaminase levels(ALT) and liver histology(hematoxylin and eosin).Neutrophil infiltration was estimated by confocal liver intravital microscopy.Coagulopathy was evaluated using prolonged prothrombin and partial thromboplastin time.Hemodynamic parameters were measured through tail cuff.Ammonia levels were quantified in serum and brain samples.Electroencephalography(EEG) and psychomotor activity score were performed to show brain function.Brain edema was evaluated using magnetic resonance imaging.RESULTS:Mice submitted to the TAA regime developed massive liver injury,as shown by elevation of serum ALT levels and a high degree of liver necrosis.An intense hepatic neutrophil accumulation occurred in response to TAA-induced liver injury.This led to mice mortality and weight loss,which was associated with severe coagulopathy.Furthermore,TAA-treated mice presented with increased serum and cerebral levels of ammonia,in parallel with alterations in EEG spectrum and discrete brain edema,as shown by magnetic resonance imaging.In agreement with this,neuropsychomotor abnormalities ensued 36 h after TAA,fulfilling several HE features observed in humans.In this context of liver injury and neurological dysfunction,we observed lung inflammation and alterations in blood pressure and heart rate that were indicative of multiple organ dysfunction syndrome.CONCLUSION:In summary,we describe a new murine model of hepatic encephalopathy comprising multiple features of the disease in humans,which may provide new insights for treatment.
文摘BACKGROUND Hepatic encephalopathy(HE)can be considered a result of dysregulated gutliver-brain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by"gut-centric"therapies,such as the administration of nonabsorbable disaccharides,nonabsorbable antibiotics,probiotics and prebiotics.AIM To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle(EcN)1917 strain compared to lactulose and rifaximin in patients with minimal/mild HE.METHODS From January 2017 to March 2020,a total of 45 patients with HE were enrolled in this prospective,single-centre,open-label,randomized study.Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups:The EcN group(n=15),lactulose group(n=15)or rifaximin group(n=15)for a 1 mo intervention period.The main primary outcomes of the study were changes in serum ammonia and Stroop test score.The secondary outcomes were markers of a chronic systemic inflammatory response(ІL-6,ІL-8,and IFN-γ)and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period.RESULTS Patients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group.However,the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of E.coli with altered properties and pathogenic enterobacteria in patient faeces.In the primary outcome analysis,improvements in the Stroop test parameters in all intervention groups were observed.Moreover,EcN-treated patients performed 15%faster on the Stroop test than the lactulose group patients(P=0.017).Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ,IL-6 and IL-8.EcN was more efficient than lactulose in reducing proinflammatory cytokine levels.CONCLUSION The use of the probiotic EcN strain was safe and quite efficient for HE treatment.The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines,normalized the gut microbiota composition and improved the cognitive function of patients with HE.The application of the EcN strain was more effective than lactulose treatment.
文摘The present letter to editor is related to Bohra A et al Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.World J Gastroenterol 2020;26(18):2221-2231.Hepatic encephalopathy(HE)is a significant and frequent major decompensating event in cirrhosis.However clinical studies examining the clinical outcome of HE are lacking despite its high prevalence.
基金Supported by Beijing MunicipalScience & TechnologyCommission, No.Z181100001718220.
文摘BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult without a clear history of cirrhosis.Liver transplantation (LT) is effective to alleviate symptoms, however, there arefew reports about LT in the treatment of status epilepticus with HE. To ourknowledge, this is the first report of status epilepticus present as initialmanifestation of HE.CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalizedfor generalized tonic-clonic seizures. She reported no history of episodes of HE,stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding.Neurological examination revealed a comatose patient, without papilledema.Laboratory examination suggested liver cirrhosis. Plasma ammonia levels uponadmission were five times normal. Brain computed tomography (CT) was normal,while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis andsplenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm,consistent with HE, and sharp waves during ictal EEG corresponding to clinicalsemiology of focal tonic seizures. The symptoms were reversed by continuousantiepileptic treatment and lactulose. She was given oral levetiracetam, and focalaware seizures occasionally affected her 10 mo after LT.CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE,and LT is effective to prevent the relapse.
