Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

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.

Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment?

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.

Fecal microbiota transplantation in the treatment of hepatic encephalopathy:A perspective

Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use.New evidence suggests that gut micro-biota plays a significant role in cerebral homeostasis.Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies.Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics,prebiotics and the latest fecal microbiota transplantation(FMT).Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE.However,questions over the appropriate dose,duration and route of administration for best treatment outcome remains unsettled.

Progress in pathogenesis and treatment of type A hepatic encephalopathy in acute liver failure:a comprehensive review

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.

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis

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.

Contributory roles of sarcopenia and myosteatosis in development of overt hepatic encephalopathy and mortality after transjugular intrahepatic portosystemic shunt

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.

Prevention and treatment of hepatic encephalopathy during the perioperative period of transjugular intrahepatic portosystemic shunt

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.

Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis:Evidence and uncertainties

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.

Treatment of portosystemic shunt-borne hepatic encephalopathy in a 97-year-old woman using balloon-occluded retrograde transvenous obliteration:A case report

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.

Changing face of hepatic encephalopathy:Role of inflammation and oxidative stress

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.

Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis

Background: Minimal hepatic encephalopathy(MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE.Data sources: Seven electronic databases were searched for relevant randomized controlled trials(RCTs)published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated.Results: A total of 14 RCTs(combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test(NCT; week 4: MD =-30.25, 95% CI:-49.85 to-10.66), improve MHE(week 4: OR = 0.18,95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression(week4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels(week 4: MD =-0.33 μmol/L, 95% CI:-5.39 to 4.74; week 8: MD = 6.22 μmol/L, 95% CI:-24.04 to 36.48), decrease NCT(week 8: MD = 3.93, 95% CI:-0.72 to 8.58), improve MHE(week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE(week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12:OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics(week 4: MD = 6.7, 95% CI: 0.58 to 12.82).Conclusion: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.

Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity

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.

Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy

Lactulose is known to improve cognitive function in patients with early hepatic encephalopa- thy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cog- nitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.

Relationship between pre-TIPS hepatic hemodynamics and postoperative incidence of hepatic encephalopathy

BACKGROUND: Hepatic encephalopathy (HE) is one of the complications that have limited the effectiveness of transjugular intrahepatic portosystemic shunt (TIPS) most significantly. Up to the present, the predicting factors of HE post-TIPS have been debated controversially. This study was undertaken to verify the relationship between pre-TIPS intrahepatic hemodynamics and the incidence of post-TIPS HE. METHODS: The hepatic blood dynamics was evaluated in 41 patients with liver cirrhosis before TIPS and at one month after TIPS by ultrasonography. The patients were divided into two groups according to Doppler findings before TIPS: group 1, patients with prograde portal flow, and group 2, patients with hepatofugal or back-forth portal flow. The clinical characteristics (age, sex, etiology of liver disease, pre-TIPS Child-Pugh score, incidence of pre-TIPS HE, and portacaval pressure gradient), incidence of post TIPS HE, and pre-/post-TIPS hepatic arterial resistant index (RI) in the two groups were compared. The independent prognostic value of pre-TIPS variables for the onset of HE after TIPS, including age, Child-Pugh score, presence of HE before TIPS, and the pattern of portal flow, was tested with a multiple-factor regression analysis. RESULTS: No significant difference in age, etiology of liver disease, indications of TIPS placement, incidence of HE before TIPS, and portacaval gradient before and after TIPS was observed between the two groups; but liver failure was more severe in group 2 (P<0.05). The incidence of post-TIPS HE in group 2 was significantly lower than that in group 1 (P<0.01). Pre-TIPS, the RI of the hepatic artery in group 1 was significantly higher than that in group 2 (P<0.01). However, TIPS induced a significantly decreased RI in group 1 (P <0.01), but not in group 2. Multiple-factor regression analysis demonstrated that the pattern of portal flow before TIPS was closely associated with the onset of post TIPS HE. CONCLUSIONS: Pre-TIPS intrahepatic hetnodynamics is closely related to the incidence of post-TIPS HE. Hepatic hetnodynamics of patients with hepatofugal portal blood flow only changes a little after TIPS and still provides compensatory blood supply of the hepatic artery, and the hepatic function is less affected. Hence HE is unlikely. Hepatic hemodynamics of patients with prograde portal blood flow changes a lot after TIPS, and dual blood supply of the portal vein and hepatic artery changes into compensatory blood supply of the hepatic artery, and hepatic function suffers greatly in a short time. Thus HE is mostly likely.

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.

Nutritional assessment in cirrhotic patients with hepatic encephalopathy

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.

Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis

BACKGROUND:Minimal hepatic encephalopathy (MHE) impairs quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients.Diagnosis of MHE requires cumbersome tests.Lactulose is effective in the treatment of MHE.This study aimed to evaluate the use of critical flicker frequency (CFF) for the diagnosis of MHE in cirrhotic patients after treatment.METHODS:One hundred and ten patients were evaluated by psychometry (number connection tests A,B or figure connection tests A,B),P300 auditory event related potential (P300ERP),venous ammonia,and CFF for MHE.MHE was diagnosed by abnormal psychometry (>2SD age matched controls) and P300ERP.MHE patients were treated with lactulose for one month.Response was defined by normalization (<2SD of matched controls) of both psychometry and P300ERP.RESULTS:Of the 110 patients [Child Turcott Pugh score A:B:C 39:42:29,(age 41.6±11.6 years,M:F 82:28)],75 (68%) had abnormal results of psychometric tests,and 74 (67%) had prolonged P300ERP.Fifteen (20%) patients with abnormal results of psychometric tests had normal P300ERP.Thus sixty (54.5%) patients were diagnosed as having MHE.After treatment for one month,34 (57%) recovered while 26 (43%) continued to have abnormal resents of psychometric or P300ERP tests.CFF was <39 Hz in 72 (65.4%) patients before treatment and in 20 (33.3%) after treatment.CFF sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy for the assessment of recovery of MHE were 65%,91%,85%,77% and 80%,respectively.CONCLUSION:CFF is a simple,relatively reliable,and accurate test without any dependence on age or literacy in the diagnosis and assessment of recovery of patients with MHE.

Research progress in hepatic encephalopathy in recent 10 years A Web of Science-based literature analysis

OBJECTIVE： To analyze international research trends in hepatic encephalopathy and examine the role of neuroelectrophysiology and neuroimaging in diagnosis of hepatic encephalopathy. DATA RETRIEVAL： We performed a bibliometric analysis of studies on hepatic encephalopathy published during 2002-2011 retrieved from Web of Science. SELECTION CRITERIA： Inclusion criteria： （1） peer-reviewed published articles on hepatic encephalopathy; （2） original article, review, meeting abstract, proceedings paper, book chapter, editorial material, news items, and （3） published during 2002-2011. Exclusion criteria： （1） articles that required manual searching or telephone access; （2） documents that were not published in the public domain; and （3） corrected papers from the total number of articles. MAIN OUTCOME MEASURES： （1）Annual publication output; （2） type of publication; （3） publication by research field; （4） publication by journal; （5） publication by author; （6） publication by institution; （7） publication by country; （8） publication by institution in China; （9） most-cited papers. RESULTS： A total of 3 233 papers regarding hepatic encephalopathy were retrieved during 2002-2011. The number of papers gradually increased over the 10-year study period and was highest in 2010. Most papers appeared in journals with a focus on gastroenterology and hepatology. Among the included journals, Hepatology published the greatest number of papers regarding hepatic encephalopathy, and the published studies were highly cited. Thus, Hepatology appears to represent a key journal publishing papers on hepatic encephalopathy. Regarding distribution by country for publications on hepatic encephalopathy indexed in Web of Science during 2002-2011, the United States published highest number of papers, with China ranked ninth As per distribution by institute for publications, the University of Montreal in Canada published the highest number of papers （n = 111 ）. Among the Chinese institutes, Zhejiang University in China was the most prolific institute with 15 papers. CONCLUSION： The present bibliometric analysis on hepatic encephalopathy provides an overview of research progress, as well as identifying the most active institutes and experts in this research field during 2002-2011. Research into hepatic encephalopathy has revealed changes in neural injury and regeneration in hepatic encephalopathy. Neuroelectrophysiological and neuroimaging examinations are important for determining clinical classifications and disease severity of hepatic encephalopathy, providing a foundation for further research.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care

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.

Portal hypertension exacerbates intrahepatic portosystemic venous shunt and further induces refractory hepatic encephalopathy: A case report

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.