Pathophysiology of Hepatic Encephalopathy

Jaffe, Ariel; Lim, Joseph K.; Jakab, Simona

doi:10.1016/j.cld.2020.01.002

Cited by 32 publications

(35 citation statements)

References 55 publications

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“…Understanding the underlying pathophysiology and molecular mechanisms of HE is essential for targeted management. Several new pathogenetic mechanisms have recently been identified while neurotoxicity from hyperammonemia remains the central underlying cause of HE [10,11,28,29]. Figure 1 illustrates the gut-liver-brain axis pathway considering porto-systemic hemodynamics.…”

Section: Pathogenesis and Molecular Mechanismsmentioning

confidence: 99%

“…Besides the direct correlation between blood ammonia levels and the degree of HE, further mechanisms in HE have recently been discussed [41,42]. An increased inhibitory neurotransmission by γ-aminobutyric acid (GABA) is another possible factor [11]. GABA can be formed in the colon by bacterial decarboxylation of glutamate, and, in the event of liver failure due to reduced hepatic clearance via the blood-CSF barrier, can reach the CNS [43].…”

Section: Additional Mechanisms Underlying Hementioning

confidence: 99%

“…The GABA receptor on the postsynaptic membrane contains binding sites for benzodiazepines [44]. By binding them, the affinity of the receptor for GABA itself is significantly increased [11,44]. This explains why benzodiazepines can trigger or worsen HE in cirrhosis of the liver [45].…”

Section: Additional Mechanisms Underlying Hementioning

confidence: 99%

“…However, hepatic encephalopathy (HE) occurs frequently after TIPS procedures with an incidence of 20% to 50% [6,7]. The mechanism of HE is complex, including reduced hepatic filter function in liver dysfunction and splanchnic blood shunting into the systemic circulation, as well as an overproduction of enteric neurotoxins and increased cerebral inflammation and neurotoxins [8][9][10][11][12]. Yet, hyperammonemia remains the central underlying cause [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism of HE is complex, including reduced hepatic filter function in liver dysfunction and splanchnic blood shunting into the systemic circulation, as well as an overproduction of enteric neurotoxins and increased cerebral inflammation and neurotoxins [8][9][10][11][12]. Yet, hyperammonemia remains the central underlying cause [8][9][10][11][12]. The clinical effects range from mild cognitive alteration to coma, and are commonly graded using the West Haven Criteria [13,14].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Shunt-Induced Hepatic Encephalopathy in TIPS: Current Approaches and Clinical Challenges

Schindler

Heinzow

Trebicka

et al. 2020

JCM

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Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE.

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Section: Pathogenesis and Molecular Mechanismsmentioning

confidence: 99%

Section: Additional Mechanisms Underlying Hementioning

confidence: 99%

Section: Additional Mechanisms Underlying Hementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Shunt-Induced Hepatic Encephalopathy in TIPS: Current Approaches and Clinical Challenges

Schindler

Heinzow

Trebicka

et al. 2020

JCM

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Rifaximin protects SH‐SY5Y neuronal cells from iron overload‐induced cytotoxicity via inhibiting STAT3/NF‐κB signaling

Zhang

et al. 2022

Cell Biology International

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Acute or chronic liver disease‐caused liver failure is the cause of hepatic encephalopathy (HE), characterized by neuropsychiatric manifestations. Liver diseases potentially lead to peripheral iron metabolism dysfunction and surges of iron concentration in the brain, contributing to the pathophysiological process of degenerative disorders of the central nervous system. In this study, the mechanism of rifaximin treating HE was investigated. Ferric ammonium citrate (FAC)‐induced iron overload significantly reduced the proliferation and boosted the apoptosis in SH‐SY5Y cells through increasing reactive oxygen species (ROS) levels and inducing iron metabolism disorder. Rifaximin treatment could rectify the FAC‐induced iron overload and lipopolysaccharide (LPS)‐induced iron deposition, therefore, effectively protecting SH‐SY5Y cells from ROS‐induced cell injury and apoptosis. Signal transducer and activator of transcription 3 (STAT3)/nuclear factor‐kappa B (NF‐κB) signaling is involved in the protective function of rifaximin against LPS‐induced iron deposition. The therapeutic effect of rifaximin on HE associated with acute hepatic failure in mouse model was ascertained. In conclusion, Rifaximin could effectively protect SH‐SY5Y cells against injury caused by iron overload through the rectification of the iron metabolism disorder via the STAT3/NF‐κB signaling pathway.

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Nitazoxanide versus rifaximin in preventing the recurrence of hepatic encephalopathy: A randomized double‐blind controlled trial

Glal

Mostafa

2021

J Hepato Biliary Pancreat

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Background/Purpose: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver cirrhosis. HE is associated with poor survival and detrimental effects on quality of life (QOL). The drawbacks of the long-term use of rifaximin in HE necessitates searching for alternative therapies. In this context, our study aimed at evaluating the safety and efficacy of nitazoxanide (NTZ) as compared to rifaximin (RFX) in preventing the recurrence of HE and assessing its impact on QOL. Patients and Methods: This prospective, randomized, double-blind controlled study included 60 patients who were randomly assigned to receive either rifaximin 550 mg twice daily (group 1; n = 30) or nitazoxanide 500 mg twice daily (group 2; n = 30) for 24 weeks. During the study period, the patients' neurological symptoms, mental status, and performance were monitored. The serum levels of HE triggers (ammonia, TNF-α, and octopamine) were assessed. The patients' health-related quality of life was also evaluated. Results: Six months after treatment, patients on NTZ therapy showed a statistically significant improvement in CHESS score and mental status. NTZ provided 136 days of remission vs 67 days of remission for patients on RFX (P 1 = .0001) and significant reduction in Child score (P 1 = .018). Additionally, NTZ showed a statistically significant decrease in serum ammonia, TNF-α, and octopamine levels as compared to rifaximin. Regarding QOL, NTZ group showed an improvement in total Chronic Liver Disease Questionnaire (CLDQ) score. Both groups experienced minor controllable side effects. Conclusion: Nitazoxanide may represent a suitable and safe alternative therapy to rifaximin in preventing the recurrence of hepatic encephalopathy.

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Pathophysiology of Hepatic Encephalopathy

Cited by 32 publications

References 55 publications

Shunt-Induced Hepatic Encephalopathy in TIPS: Current Approaches and Clinical Challenges

Shunt-Induced Hepatic Encephalopathy in TIPS: Current Approaches and Clinical Challenges

Rifaximin protects SH‐SY5Y neuronal cells from iron overload‐induced cytotoxicity via inhibiting STAT3/NF‐κB signaling

Nitazoxanide versus rifaximin in preventing the recurrence of hepatic encephalopathy: A randomized double‐blind controlled trial

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