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 recomm...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.展开更多
Hepatic encephalopathy(HE)is a common and serious neuropsychiatric complication of cirrhosis,acute liver failure,and porto-systemic shunting.HE largely contributes to the morbidity of patients with liver disease,sever...Hepatic encephalopathy(HE)is a common and serious neuropsychiatric complication of cirrhosis,acute liver failure,and porto-systemic shunting.HE largely contributes to the morbidity of patients with liver disease,severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis.Its presentation is largely variable,manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma.The pathogenesis of HE is complex and has historically been linked with hyperammonemia.However,in the last years,it has become evident that the interplay of multiple actors,such as intestinal dysbiosis,gut hyperpermeability,and neuroinflammation,is of crucial importance in its genesis.Therefore,HE can be considered a result of a dysregulated gut-liverbrain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by“gut-centric”therapies,such as non-absorbable disaccharides,non-absorbable antibiotics,probiotics,prebiotics,and fecal microbiota transplantation.In this context dietary modifications,by modulating the intestinal milieu,can also provide significant benefit to cirrhotic patients with HE.This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis.Furthermore,it will explore the currently available therapies and the most promising future treatments for the management of patients with HE,with a special focus on the dietary approach.展开更多
Hepatic encephalopathy(HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life.Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammo...Hepatic encephalopathy(HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life.Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy.Non-absorbable antibiotics,such as neomycin and paramomycin,are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects.To overcome these limitations,rifaximin use has been proposed.Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention,with a similar incidence of side-effects.Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern.Following long-term rifaximin therapy,Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients.In addition,selection of resistant mutants of both Gram-negative and-positive bacteria in the gastrointestinal tract cannot be definitely ruled out.Electrolyte alterations(sodium and potassium) have been reported during rifaximin therapy,a warning for its long-term use in cirrhotics.Moreover,a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients.The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides.While waiting for further safety data,caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to nonabsorbable disaccharides.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
AIM:Steroids can increase hepatitis C virus(HCV) replication.After liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages.Steroids ca...AIM:Steroids can increase hepatitis C virus(HCV) replication.After liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages.Steroids can worsen the outcome of recurrent HCV infection.Therefore, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS:Thirty patients undergoing LTx received initial steroid-free immunosuppression.Indication for LTx included 7 patients with HCV related cirrhosis.Initial immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMF)2×15mg/kg.d po.The tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L thereafter.Manifestations of acute rejection were verified histologically. RESULTS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years.Acute rejection occurred in 8/30 patients, including 1 HCV infected recipient.All HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after LTx.The virus load was not remarkably increased during the first year after LTx.Histologically,grafts had no severe recurrent hepatitis. CONCLUSION:From our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients.Furthermore,none of the HCV infected patients developed serious chronic liver diseases.It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.展开更多
The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time ...The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.展开更多
AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive e...AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive effect of IFN plusribavirin treatment are lacking.METHODS:A total of 101 patients(62 males and 39 females,mean age 55.1±1.4 years)with histologically proven HCVrelated liver cirrhosis plus compatible biochemistry andultrasonography were enrolled in the study.Biochemistryand ultrasonography were performed every 6 mo.Ultrasoundguided liver biopsy was performed on all detected focallesions.Follow-up lasted for 5 years.Cellular proliferation,evaluated by measuring Ag-NOR proteins in hepatocytesnuclei,was expressed as AgNOR-Proliferative index(AgNOR-PI)(cut-off=2.5).Forty-one patients(27 males,14 females)were only followed up after the end of anyearly treatment with IFN-alpha2b(old treatment controlgroup=OTCG).Sixty naive patients were stratified accordingto sex and AgNOR-PI and then randomized in two groups:30 were treated with IFN-alpha2b+ribavirin(treatmentgroup=TG),the remaining were not treated(control group=CG).Nonresponders(NR)or relapsers in the TG receivedfurther IFN/ribavirin treatments after a 6 mo of withdrawal.RESULTS:AgNOR-PI was significantly lowered by IFN(P<0.001).HCC incidence was higher in patients withAgNOR-PI>2.5(26% vs3%,P<0.01).Two NR in the OTCG,none in the TG and 9 patients in the CG developed HCCduring follow-up.The Kaplan-Mayer survival curves showedstatistically significant differences both between OTCG andCG(P<0.004)and between TG and CG(P<0.003).CONCLUSION:IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best resultsin terms of HCC prevention.AgNOR-PI is a useful markerof possible HCC development.展开更多
文摘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.
文摘Hepatic encephalopathy(HE)is a common and serious neuropsychiatric complication of cirrhosis,acute liver failure,and porto-systemic shunting.HE largely contributes to the morbidity of patients with liver disease,severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis.Its presentation is largely variable,manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma.The pathogenesis of HE is complex and has historically been linked with hyperammonemia.However,in the last years,it has become evident that the interplay of multiple actors,such as intestinal dysbiosis,gut hyperpermeability,and neuroinflammation,is of crucial importance in its genesis.Therefore,HE can be considered a result of a dysregulated gut-liverbrain axis function,where cognitive impairment can be reversed or prevented by the beneficial effects induced by“gut-centric”therapies,such as non-absorbable disaccharides,non-absorbable antibiotics,probiotics,prebiotics,and fecal microbiota transplantation.In this context dietary modifications,by modulating the intestinal milieu,can also provide significant benefit to cirrhotic patients with HE.This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis.Furthermore,it will explore the currently available therapies and the most promising future treatments for the management of patients with HE,with a special focus on the dietary approach.
文摘Hepatic encephalopathy(HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life.Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy.Non-absorbable antibiotics,such as neomycin and paramomycin,are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects.To overcome these limitations,rifaximin use has been proposed.Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention,with a similar incidence of side-effects.Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern.Following long-term rifaximin therapy,Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients.In addition,selection of resistant mutants of both Gram-negative and-positive bacteria in the gastrointestinal tract cannot be definitely ruled out.Electrolyte alterations(sodium and potassium) have been reported during rifaximin therapy,a warning for its long-term use in cirrhotics.Moreover,a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients.The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides.While waiting for further safety data,caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to nonabsorbable disaccharides.
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.
文摘AIM:Steroids can increase hepatitis C virus(HCV) replication.After liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages.Steroids can worsen the outcome of recurrent HCV infection.Therefore, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS:Thirty patients undergoing LTx received initial steroid-free immunosuppression.Indication for LTx included 7 patients with HCV related cirrhosis.Initial immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMF)2×15mg/kg.d po.The tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L thereafter.Manifestations of acute rejection were verified histologically. RESULTS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years.Acute rejection occurred in 8/30 patients, including 1 HCV infected recipient.All HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after LTx.The virus load was not remarkably increased during the first year after LTx.Histologically,grafts had no severe recurrent hepatitis. CONCLUSION:From our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients.Furthermore,none of the HCV infected patients developed serious chronic liver diseases.It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.
基金supported by a grant from the Ministry of Science and Technological Development of Serbia,Scientific Project Number 175090
文摘The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.
文摘AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive effect of IFN plusribavirin treatment are lacking.METHODS:A total of 101 patients(62 males and 39 females,mean age 55.1±1.4 years)with histologically proven HCVrelated liver cirrhosis plus compatible biochemistry andultrasonography were enrolled in the study.Biochemistryand ultrasonography were performed every 6 mo.Ultrasoundguided liver biopsy was performed on all detected focallesions.Follow-up lasted for 5 years.Cellular proliferation,evaluated by measuring Ag-NOR proteins in hepatocytesnuclei,was expressed as AgNOR-Proliferative index(AgNOR-PI)(cut-off=2.5).Forty-one patients(27 males,14 females)were only followed up after the end of anyearly treatment with IFN-alpha2b(old treatment controlgroup=OTCG).Sixty naive patients were stratified accordingto sex and AgNOR-PI and then randomized in two groups:30 were treated with IFN-alpha2b+ribavirin(treatmentgroup=TG),the remaining were not treated(control group=CG).Nonresponders(NR)or relapsers in the TG receivedfurther IFN/ribavirin treatments after a 6 mo of withdrawal.RESULTS:AgNOR-PI was significantly lowered by IFN(P<0.001).HCC incidence was higher in patients withAgNOR-PI>2.5(26% vs3%,P<0.01).Two NR in the OTCG,none in the TG and 9 patients in the CG developed HCCduring follow-up.The Kaplan-Mayer survival curves showedstatistically significant differences both between OTCG andCG(P<0.004)and between TG and CG(P<0.003).CONCLUSION:IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best resultsin terms of HCC prevention.AgNOR-PI is a useful markerof possible HCC development.
