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

World Journal of Hepatology 2024年第1期16卷 17-32页

作者： Yash R Shah Hassam Ali Angad Tiwari David Guevara-Lazo Natalia Nombera-Aznaran Bhanu Siva Mohan Pinnam Manesh Kumar Gangwani Harishankar Gopakumar Amir H Sohail SriLakshmiDevi Kanumilli Ernesto Calderon-Martinez Geetha Krishnamoorthy Nimish Thakral Dushyant Singh Dahiya Department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States Division of Gastroenterology and Hepatology East Carolina University/Brody School of MedicineGreenvilleNC 27858United States Department of Internal Medicine Maharani Laxmi Bai Medical CollegeJhansi 284001India Faculty of Medicine Universidad Peruana Cayetano HerediaLima 15102Peru Department of Internal Medicine John H.Stroger Hospital of Cook CountyChicagoIL 60612United States Department of Internal Medicine The University of ToledoToledoOH 43606United States Department of Gastroenterology and Hepatology University of Illinois College of Medicine at PeoriaPeoriaIL 61605United States Department of Surgery University of New MexicoAlbuquerqueNM 87106United States Department of Internal Medicine GSL Medical CollegeRajamahendravaram 533296India Department of Internal Medicine Universidad Nacional Autonoma de MexicoCiudad De Mexico 04510Mexico Department of Digestive Diseases and Nutrition University of KentuckyLexingtonKY 40536United States Division of Gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityKS 66160United States

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.

关键词： hepatic encephalopathy Fecal microbiota transplant Cognitive impairment Liver cirrhosis Chronic liver disease

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

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World Journal of Hepatology 2024年第5期16卷 678-683页

作者： Arghya Samanta Moinak Sen Sarma Department of Pediatric Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014India

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.

关键词： Fecal microbiota Dysbiosis hepatic encephalopathy Cirrhosis

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

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World Journal of Hepatology 2024年第2期16卷 115-119页

作者： Chien-Hao Huang Piero Amodio Division of Hepatology Department of Gastroenterology and HepatologyChang-Gung Memorial HospitalLinkou Medical CenterTaoyuan 333Taiwan Department of Clinical and Experimental Medicine University of PaduaPadova 35122Italy

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

关键词： Rifaximin discontinuation hepatic encephalopathy Broad-spectrum antibiotics Crit-ically ill Medical intensive care unit Pharmacist-driven protocol

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

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World Journal of Clinical Cases 2023年第4期11卷 945-951页

作者： Akihiro Nishi Tsuneaki Kenzaka Misa Sogi Shuichiro Nakaminato Takahiro Suzuki General Medicine Awa Regional Medical CenterTateyama 2940014ChibaJapan Division of Community Medicine and Career Development Kobe University Graduate School of MedicineKobe 6500017HyogoJapan Department of Radiology Kameda Medical CenterKamogawa 2968602ChibaJapan

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.

关键词： hepatic encephalopathy Hyperammonemia Portosystemic shunt Balloon-occluded retrograde transvenous obliteration Elderly Case report

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

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World Journal of Gastroenterology 2023年第18期29卷 2875-2887页

作者： Liang Yin Sen-Lin Chu Wei-Fu Lv Chun-Ze Zhou Kai-Cai Liu Yi-Jiang Zhu Wen-Yue Zhang Cui-Xia Wang Yong-Hui Zhang Dong Lu De-Lei Cheng Department of Interventional Radiology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230022Anhui ProvinceChina Infection Hospital The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230000Anhui ProvinceChina

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

关键词： Sarcopenia Myosteatosis hepatic encephalopathy Transjugular intrahepatic portosystemic shunt Transjugular intrahepatic portosystemic shunt

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

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World Journal of Gastroenterology 2023年第19期29卷 2905-2915页

作者： Giuseppe Marrone Amato Serra Luca Miele Marco Biolato Antonio Liguori Antonio Grieco Antonio Gasbarrini Medical and Surgical Sciences Fondazione Policlinico Universitario A.Gemelli-IRCCSUniversita Cattolica del Sacro CuoreRome 00168Italy

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.

关键词： Branched-chain amino acids hepatic encephalopathy Sarcopenia Liver cirrhosis

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Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment

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World Journal of Hepatology 2022年第3期14卷 634-646页

作者： Elina Manzhalii Valentyna Moyseyenko Vitalii Kondratiuk Nataliia Molochek Tetyana Falalyeyeva Nazarii Kobyliak Department of Propedeutics of Internal Medicine Bogomolets National Medical UniversityKyiv 01601Ukraine Educational and Scientific Centre“Institute of Biology and Medicine” Taras Shevchenko National University of KyivKyiv 01601Ukraine Department of Pediatrics Bogomolets National Medical UniversityKyiv 01601Ukraine Department of Scientific Medical Laboratory CSDKyiv 01004Ukraine Department of Endocrinology Bogomolets National Medical UniversityKyiv 01601Ukraine

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 *** was more efficient than lactulose in reducing proinflammatory cytokine levels.CONCLUSION The use of the probiotic EcN strain was safe and qu

关键词： hepatic encephalopathy Chronic liver disease cirrhosis Gut microbiota E.coli Nissle 1917 Cognitive functions Stroop test Rifaximin Lactulose

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Evidence-based approach to management of hepatic encephalopathy in adults

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World Journal of Hepatology 2022年第4期14卷 670-681页

作者： Gilles Jadd Hoilat Fathima Keshia Suhail Talal Adhami Savio John Department of Medicine SUNY Upstate Medical UniversitySyracuseNY 13210United States Department of Gastroenterology Cleveland Clinic FoundationClevelandOH 44195United States Department of Gastroenterology SUNY Upstate Medical UniversitySyracuseNY 13210United States

hepatic encephalopathy(HE)is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease.Although ammonia is clearly implicated in the pathogenesis of HE,the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells.The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support.Thereafter,focus should be on identifying and treating the precipitating factors.There are many therapeutic agents available for the management of HE,most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level.This review aims to provide an update on the conventional and emerging treatment options for HE.

关键词： hepatic encephalopathy Lactulose Rifaximin Fecal microbiota transplant Zinc L-ornithine L-aspartate

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

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世界胃肠外科杂志:英文版(电子版) 2023年第8期15卷 1564-1573页

作者： Lan-Jing Wang Xin Yao Qi Qi Jian-Ping Qin Department of Gastroenterology The General Hospital of Western Theater CommandChengdu 610083Sichuan ProvinceChina

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.

关键词： Portosystemic shunt Transjugular intrahepatic hepatic encephalopathy Liver cirrhosis Hypertension Portal Therapeutics

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Molecular targeted therapy causes hepatic encephalopathy in patients after Transjugular intrahepatic portosystemic shunt(TIPS):A case report and literature review

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Journal of Interventional Medicine 2022年第1期5卷 37-39页

作者： Chen Zhou Yang Chen Jiacheng Liu Qin Shi Bin Xiong Department of Radiology Union HospitalTongji Medical CollegeWuhan430022HubeiChina Huazhong University of Science and Technology Hubei Province Key Laboratory of Molecular ImagingWuhan430022HubeiChina

We report two cases of hepatic encephalopathy caused by molecular targeted drugs after the Transjugular intrahepatic portosystemic shunt(TIPS)procedure in our center.The liver toxicities and anti-angiogenic effects induced by targeted drugs may generate an imbalance in ammonia metabolism,elevating blood ammonia levels.TIPS diverts partial blood supply from the liver,aggravates liver impairment,and shunts ammonia-rich blood from the intestine into the systemic circulation.These may be the mechanisms leading to hepatic encephalopathy caused by molecular targeted drugs following TIPS.When clinicians choose molecular targeted therapy as the second or third targeted therapy for patients who have undergone TIPS,the consequence of drug-induced hepatic encephalopathy should also be considered.

关键词： Transjugular intrahepatic portosystemic shunt(TIPS) hepatic encephalopathy Molecular targeted therapy Case report

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