Hepatic encephalopathy: Diagnosis and management

Portal hypertension is the main consequence of liver cirrhosis, leading to severe complications such as variceal hemorrhage, ascites or hepatic encephalopathy. As an attempt to decompress the portal venous system, portal flow is derived into the systemic venous system through spontaneous portosystemic shunts (SPSSs), bypassing the liver. In this review, we aim to provide an overview of the published reports in relation to the prevalence and physiopathology behind the appearance of SPSS in liver cirrhosis, as well as the complications derived from its formation and its management. The role of SPSS embolization is specifically discussed, as SPSSs have been assessed as a therapeutic target, mainly for patients with recurrent/persistent hepatic encephalopathy and preserved liver function. Furthermore, different aspects of the role of SPSS in liver transplantation, as well as in candidates for transjugular intrahepatic portosystemic shunt are reviewed. In these settings, SPSS occlusion has been proposed to minimize possible deleterious effects, but results are so far inconclusive.

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“… 69 HE is driven by the accumulation of those neurotoxins due to liver disease and aggravated by SPSSs. 67 , 70 …”

Section: Hepatic Encephalopathymentioning

confidence: 99%

Spontaneous portosystemic shunts in liver cirrhosis: new approaches to an old problem

Vidal‐González

Quiroga

Simón-Talero

et al. 2020

Therap Adv Gastroenterol

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“…Hepatic encephalopathy (HE) is a significant complication of severe acute or chronic hepatic insufficiency, which is characterized by a wide range of changes in mental state from minimal signs of altered brain function to deep coma [1,2]. HE is caused by a combination of distinct pathophysiological mechanisms, including inflammation, oxidative stress, increased blood-brain barrier permeability, and energy metabolism, as well as putative neurotoxins, including ammonia, short-chain fatty acids, mercaptans, false neurotransmitters (e.g., tyramine, octopamine, and beta-phenylethanolamines), manganese, and γ-aminobutyric acid (GABA) -though ammonia [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Lower levels of serum albumin are associated with impairment of cognitive function in cirrhotic patients with early-stage hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials of rifaximin in Japan

Kaji¹,

Okita²,

Suzuki³

et al. 2020

Preprint

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Background Because covert hepatic encephalopathy (CHE) has been shown to affect the prognosis of cirrhotic patients, early diagnosis of HE is a prerequisite for preservation of patients’ quality of life and for prophylaxis of overt HE. Currently, neuropsychological tests are used for the diagnosis of early-stage HE including CHE. However, it would be inefficient to apply them to all cirrhotic patients. Thus, some biomarkers correlated with the above diagnostic modalities are available for screening examination. The aim of this study was to identify a clinical parameter to predict impairment of cognitive function in cirrhotic patients with early-stage HE.Methods This exploratory data analysis was based on the data from 172 patients with cirrhotic or idiopathic portosystemic shunt (PSS) in phase II/III trials of rifaximin in Japan. Their data at baseline before treatment with rifaximin were utilized to analyze the relationship between cognitive dysfunction and different clinical parameters We Classification and regression trees (CART) were constructed to identify clinical profiles related to cognitive dysfunction, as indicated by the prolongation of time required for the number connection test (NCT-B).Results CART analysis detected age 65 years as the variable for the initial split, and serum albumin level was selected as the variable for the second split among patients aged ≤ 65 years. In 27 cirrhotic patients aged ≤ 65 years without PSS, receiver-operating characteristic curve analysis revealed that the optimal albumin level cutoff point was 3.05 g/dL, and the area under the curve was 0.80 for the prolongation of NCT-B time, which was higher than that of other HE-related parameters including the branched-chain amino acids-to-tyrosine ratio (0.46), the prothrombin time–international normalized ratio (PT-INR) (0.68), serum ammonia (0.61), and total bilirubin (0.69).Conclusions Lower serum albumin level as a clinical biomarker associated with impaired cognitive function is available as a screening examination for early-stage HE in cirrhotic patients aged ≤ 65 years without PSS before undergoing neuropsychological tests.

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“…Indeed, endotoxemia are observed in 75-93.3% of acute liver failure and severe hepatitis [23]. The common treatment such as reducing blood ammonia, arti cial liver support system and transjugular intrahepatic portosystemic shunt (TIPS) can only relieve the symptoms, but cannot delay the progression of the delicate disease [24]. Up to now, with inspiring march in stem cell technology, an enthusiasm with cell-based therapy has been accumulated with the hope that the tragic outcome of liver failure can be saved.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

Jiang¹,

Xia²,

Yang³

et al. 2020

Preprint

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Background Endotoxemia based on liver failure has been reported to be related to the worse clinical outcomes, but its management remains unsatisfactory. The addition of bone marrow mesenchymal stem cells (BMSCs) could promote the recovery of liver function and increase the survival with the liver failure. However, little is known about the potential of cell therapy with endotoxemia based on liver failure. Methods BMSCs were isolated from rats, and their morphology, differentiation potential, surface markers, and cell cycle were assayed. Thioacetamide-induced acute liver failure rats were randomized to groups with or without BMSCs. During the experiment, survival was recorded. Diamine oxidase (DAO), endotoxin, interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-α) and tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), histology, and western blot. Bromodeoxynucleoside uracil (BrdU) incorporation assay was performed to observe the migration of BMSCs. The intestinal epithelial differentiation of BMSCs was induced by co culture with small intestinal crypt in rats (IEC-6). Immunofluorescence was used to analyze the expression of intestinal endothelial markers. Western blot analysis was further performed to examine the differentiation effect when inhibiting the phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Results BrdU-traced BMSCs targeted migrate to intestinal injury sites. Mortality was significantly decreased and intestinal damage was repaired following BMSCs transplantation. Proteomics revealed higher expression of DAO, endotoxin, IL-6 and TNF-α in the model animals, but these changes were reversed after BMSCs transplantation. In the in vitro study, the intestinal epithelial differentiation of BMSCs was exhibited following co-culture. Moreover, the blocking of PI3K/AKT/mTOR signal pathway inhibited this differentiation. Conclusions These evidences indicate that BMSCs eliminate endotoxemia and reduce mortality in the animal model of acute liver failure by reducing intestine damage.

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Hepatic encephalopathy: Diagnosis and management

Cited by 52 publications

References 79 publications

Spontaneous portosystemic shunts in liver cirrhosis: new approaches to an old problem

Spontaneous portosystemic shunts in liver cirrhosis: new approaches to an old problem

Lower levels of serum albumin are associated with impairment of cognitive function in cirrhotic patients with early-stage hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials of rifaximin in Japan

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

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