Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

Magnetic resonance imaging scanning susceptibility weighted imaging sequences in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy

BACKGROUND Magnetic resonance imaging(MRI)scanning with susceptibility weighted imaging(SWI)sequences plays a significant role in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy(HIE).AIM To observe the role of MRI multi-parameter quantitative indexes in the diagnosis of neonatal HIE.METHODS The imaging data from 23 cases of neonatal HIE admitted to the Imaging Department of Ganyu District People's Hospital of Lianyungang City and 23 neonates without HIE admitted during the same period were analyzed retrospectively from August,2021 to December,2023.The results of clinical judgment were compared with the results of computed tomography(CT)and MRI examinations.RESULTS The degree of cerebral edema(more than moderate),the number of damaged brain regions(>2),the number of cerebral hemorrhages(>2),and the percentage of small venous dilatation detected were higher in MRI than in CT examination,and the differences were statistically significant(P<0.05).The total area of the largest region of cerebral damage and of cerebral hemorrhage observed by MRI examination were significantly larger than those of CT examination(P<0.01).Multiparametric quantitative MRI combined with diffusion weighted imaging and SWI had higher sensitivity and accuracy than CT diagnosis,and the difference was statistically significant(P<0.05).The difference in the specificity of the two modes of diagnosis was not significant(P>0.05).CONCLUSION The use of MRI multi-parameter quantitative indexes can accurately diagnose and evaluate neonatal HIE.

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.

Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.

Classical bovine spongiform encephalopathy and chronic wasting disease:two sides of the prion coin

Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.

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.

Portocaval shunts'role in gut microbiota and hepatic encephalopathy:The gut-to-brain pathway

I read the study by Zhao et al with great interest.Although the study design was quite complicated,it was successful in raising awareness of science and relevant researchers.Thirty patients with liver cirrhosis and portal hypertension secondary to chronic hepatitis B were included in the study.They were treated for variceal bleeding and underwent trans-jugular intrahepatic portosystemic shunt to prevent the recurrence of variceal bleeding and to reduce portal pressure.The authors evaluated the effects of changes in gut microbiota(GM)on hepatic encephalopathy secondary to portocaval bypass.The GM is greatly affected by local and general factors,including herbal and medical drugs,a person's dietary characteristics(carnivorous,vegan,vegetarian),supplementary foods,drinking water sources,and living in a city center or town.Therefore,I congratulate Zhao et al for their concise and comprehensive study on a multifactorial subject.

Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension

BACKGROUND Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy(HE).It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt(TIPS)is related to postoperative HE.AIM To investigate the relationship between spleen volume and the occurrence of HE.METHODS This study included 135 patients with liver cirrhosis who underwent TIPS,and liver and spleen volumes were elevated upon computed tomography imaging.The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes.Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE(OHE).Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk.RESULTS The results showed that 37(27.2%)of 135 patients experienced OHE during a 1-year follow-up period.Compared with preoperative spleen volume(901.30±471.90 cm3),there was a significant decrease in spleen volume after TIPS(697.60±281.0 cm^(3))in OHE patients.As the severity of OHE increased,the spleen volume significantly decreased(P<0.05).Compared with patients with a spleen volume≥782.4 cm^(3),those with a spleen volume<782.4 cm^(3) had a higher incidence of HE(P<0.05).Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE(hazard ratio=0.494,P<0.05).Restricted cubic spline model showed that with an increasing spleen volume,OHE risk showed an initial increase and then decrease(P<0.05).CONCLUSION Spleen volume is related to the occurrence of OHE after TIPS.Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

Rifaximin discontinuation during broad-spectrum antibiotic treatment in critically ill patients with hepatic encephalopathy

Hepatic encephalopathy(HE)is one of the main complications of cirrhosis,characterized by a wide spectrum of neuropsychiatric alterations that lead to an increase in mortality,morbidity and recurrent hospitalizations.Due to the central role in HE pathogenesis of ammonia and other neurotoxins primarily produced by the gut microbiota,the main therapeutic approaches for the treatment of HE are based on the modulation of the gut microbiota.Rifaximin is a non-absorbable broad-spectrum antibiotic,that is effective against ammonia-producing grampositive,gram-negative,and anaerobic species,approved for the treatment of HE in secondary prophylaxis.The chronic administration of rifaximin in this setting is associated with a lower risk of HE recurrence and mortality,while the role of rifaximin for the treatment of an overt-HE episode in inpatients is still unclear.Limited data exist about the coadministration of rifaximin and broad-spectrum antibiotics commonly used to treat concomitant infections,as patients receiving or recently treated with antibiotics were frequently excluded from clinical trials.In this editorial we comment on the article by Ward et al published in the recent issue of the World Journal of Hepatology.It is a single center,retrospective,quasiexperimental,pharmacist-driven protocol,with the aim to evaluate the feasibility and safety of rifaximin discontinuation in critically ill patients with HE and chronic liver disease receiving broad-spectrum antibiotic therapies in intensive care units.The study revealed no differences between the protocol and control group in terms of primary outcome(days alive and free of delirium and coma to day 14)and secondary outcomes which include:Intensive care mortality,intensive care length of stay,intravenous vasopressor requirement changes and adverse effects rate.Therefore,rifaximin discontinuation during broad-spectrum antibiotic therapy does not appear to negatively impact the clinical status of critically ill liver patients,with a similar safety profile and significant cost savings,as compared to the coadministration of rifaximin and broad-spectrum antibiotics.In agreement with Ward et al,a recently published double-blind,randomized controlled trial provided additional evidence to support the feasibility of withholding rifaximin during broad-spectrum antibiotic therapy in critically ill cirrhotic patients.However,given the limitations of these studies,further multicentric and prospective clinical trials,enrolling a larger sample of non-critically ill patients,are needed to better establish the role of rifaximin in this setting.

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.

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

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.

Observation on the Effect of Parental Participation in Nursing Under the IMCHB Model in Neonatal Hypoxic-Ischemic Encephalopathy

Objective:To investigate the clinical effects of parental participation in nursing under the Interaction Model of Client Health Behavior(IMCHB)model in neonatal hypoxic-ischemic encephalopathy(HIE).Methods:The First Affiliated Hospital of Gannan Medical University included 46 newborns with HIE admitted from October 2021 to October 2023 into the study population.They were divided into a control group and an observation group according to the random number table method,with the control group adopting routine nursing,and the observation group implementing parental participation in nursing under the IMCHB model.The indicators of physical,intellectual,and psychomotor development of the two groups were compared before and after nursing.Results:The physical,intellectual,and psychomotor development of the observation group was higher than that of the control group after 3 months of nursing,and the difference was statistically significant(P<0.05).Conclusion:The implementation of the IMCHB model of parental participation in the clinical care of HIE neonates can further promote their physical,intellectual,and psychomotor development.

Discrimination for minimal hepatic encephalopathy based on Bayesian modeling of default mode network

In order to classify the minimal hepatic encephalopathy （MHE） patients from healthy controls, the independent component analysis （ICA） is used to generate the default mode network （DMN） from resting-state functional magnetic resonance imaging （fMRI）. Then a Bayesian voxel- wised method, graphical-model-based multivariate analysis （GAMMA）, is used to explore the associations between abnormal functional integration within DMN and clinical variable. Without any prior knowledge, five machine learning methods, namely, support vector machines （SVMs）, classification and regression trees （ CART ）, logistic regression, the Bayesian network, and C4.5, are applied to the classification. The functional integration patterns were alternative within DMN, which have the power to predict MHE with an accuracy of 98%. The GAMMA method generating functional integration patterns within DMN can become a simple, objective, and common imaging biomarker for detecting MIIE and can serve as a supplement to the existing diagnostic methods.

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy

Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor,intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances.This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension.It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy This review explores the complex mechanisms that lead to hepatic encephalopathy.However,noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology.Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses.

Quality of life in patients with minimal hepatic encephalopathy

Minimal hepatic encephalopathy(MHE) represents the mildest type of hepatic encephalopathy(HE). This condition alters the performance of psychometric tests by impairing attention, working memory, psychomotor speed, and visuospatial ability, as well as electrophysiological and other functional brain measures. MHE is a frequent complication of liver disease, affecting up to 80% of tested patients, depending of the diagnostic tools used for the diagnosis. MHE is related to falls, to an impairment in fitness to drive and the development of overt HE, MHE severely affects the lives of patients and caregivers by altering their quality of life(QoL) and their socioeconomic status. MHE is detected in clinically asymptomatic patients through appropriate psychometric tests and neurophysiological methods which highlight neuropsychological alterations such as video-spatial orientation deficits, attention disorders, memory, reaction times, electroencephalogram slowing, prolongation of latency evoked cognitive potentials and reduction in the critical flicker frequency. Several treatments have been proposed for MHE treatment such as non-absorbable disaccharides, poorly absorbable antibiotics such rifaximin, probiotics and branched chain amino acids. However, because of the multiple diagnosis methods, the various endpoints of treatment trials and the variety of agents used in trials, to date the treatment of MHE is not routinely recommended apart from on a case-by-case basis. Aim of this review is analyze the burden of MHE on QoL of patients and provide a brief summary of therapeutic approaches.

Prevalence of minimal hepatic encephalopathy and quality of life evaluations in hospitalized cirrhotic patients in China

AIM:To investigate the prevalence of minimal hepatic encephalopathy(MHE)and to assess corresponding health-related quality of life(HRQoL)in hospitalized cirrhotic patients in China.METHODS:This multi-center cross-sectional study included 16 teaching hospitals,which were members of "Hepatobiliary Cooperation Group,Society of Gastroenterology,Chinese Medical Association",from different areas of China carried out between June and October in 2011.All the eligible hospitalized cirrhotic patients(n = 538)were required to complete triplicate number connection tests combined with one digit symbol test for diagnosing MHE.Patients' clinical examination data were complemented by a modified questionnaire assessing HRQoL.Written informed consent was obtained from each patient.RESULTS:Male was predominant(68.6%)in 519 patients who met the criteria of the study,with a mean age of 49.17 ± 11.02 years.The most common cause of liver cirrhosis was chronic hepatitis B(55.9%).The prevalence of MHE was 39.9% and varied by ChildPugh-Classification score(CPC-A:24.8%,CPC-B:39.4% and CPC-C:56.1%,P < 0.01).MHE(P < 0.01)and higher CPC scores(P < 0.01)were associated with a high HRQoL scores(reflecting poorer quality of life).The prevalence of MHE was proportionate to CPC(P = 0.01)and high quality of life scores(P = 0.01).CONCLUSION:Hospitalized cirrhotic patients have a high prevalence of MHE that is proportionate to the degree of liver function and HRQoL impairment.

Natural history of covert hepatic encephalopathy: An observational study of 366 cirrhotic patients

AIM To explore the natural history of covert hepatic encephalopathy(CHE) in absence of medication intervention.METHODS Consecutive outpatient cirrhotic patients in a Chinese tertiary care hospital were enrolled and evaluated for CHE diagnosis. They were followed up for a mean of 11.2 ± 1.3 mo. Time to the first cirrhosis-related complications requiring hospitalization, including overt HE(OHE), resolution of CHE and death/transplantation, were compared between CHE and no-CHE patients. Predictors for complication(s) and death/transplantation were also analyzed.RESULTS A total of 366 patients(age: 47.2 ± 8.6 years, male: 73.0%) were enrolled. CHE was identified in 131 patients(35.8%). CHE patients had higher rates of death and incidence of complications requiring hospitalization, including OHE, compared to unimpaired patients. Moreover, 17.6% of CHE patients developed OHE, 42.0% suffered persistent CHE, and 19.8% of CHE spontaneously resolved. In CHE patients, serum albumin < 30 g/L(HR = 5.22, P = 0.03) was the sole predictor for developing OHE, and blood creatinine > 133 μmol/L(HR = 4.75, P = 0.036) predicted mortality. Child-Pugh B/C(HR = 0.084, P < 0.001) and OHE history(HR = 0.15, P = 0.014) were predictors of spontaneous resolution of CHE.CONCLUSION CHE exacerbates, persists or resolves without medication intervention in clinically stable cirrhosis. Triage of patients based on these predictors will allow for more cost-effect management of CHE.

Chinese guidelines on management of hepatic encephalopathy in cirrhosis

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists’ consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.