Hepatic Encephalopathy-Associated Cerebral Vasculopathy in Acute-on-Chronic Liver Failure: Alterations on Endothelial Factor Release and Influence on Cerebrovascular Function

The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F1α releases were increased, whereas thromboxane (TX) B2 was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI2 synthase, and TXA2S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE.

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Bacopa monnieriExtract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/535013 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Papia Mondal ◽

Surendra Kumar Trigun

Keyword(s):

Nitric Oxide ◽

Hepatic Encephalopathy ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Apoptosis Pathway ◽

Nitric Oxide Level ◽

Nmdar Activation ◽

Oxide Synthase ◽

The Brain

Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells.Bacopa monnieri(BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE.

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Cirrhosis and acute on chronic liver failure: is ammonia a predictor of hepatic encephalopathy and mortality?

Journal of Hepatology ◽

10.1016/s0168-8278(17)31533-7 ◽

2017 ◽

Vol 66 (1) ◽

pp. S559

Author(s):

M. Sheikh ◽

N. Arias ◽

K. Thomsen ◽

R. Gallego-Durán ◽

B. Agarwal ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure

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Liver failure

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0321 ◽

2020 ◽

pp. 3089-3100

Author(s):

Jane Macnaughtan ◽

Rajiv Jalan

Keyword(s):

Liver Transplantation ◽

Liver Disease ◽

Hepatic Encephalopathy ◽

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Organ Failure ◽

Clinical Manifestations ◽

Chronic Liver ◽

Chronic Liver Failure

Liver failure occurs when loss of hepatic parenchymal function exceeds the capacity of hepatocytes to regenerate or repair liver injury. Acute liver failure is characterized by jaundice and prolongation of the prothrombin time in the context of recent acute liver injury, with hepatic encephalopathy occurring within 8 weeks of the first onset of liver disease. Acute-on-chronic liver failure is characterized by hepatic and/or extrahepatic organ failure in patients with cirrhosis associated with an identified or unidentified precipitating event. The commonest causes of acute liver failure are acute viral hepatitis and drugs. Acute-on-chronic liver failure is most commonly precipitated by infection, alcohol abuse, and superimposed viral infection. The main clinical manifestations are hepatic encephalopathy, coagulopathy, jaundice, renal dysfunction, and haemodynamic instability. Infection and systemic inflammation contribute to pathogenesis and critically contribute to prognosis. Specific therapy for the underlying liver disease is administered when available, but this is not possible for most causes of liver failure. Treatment is predominantly supportive, with particular emphasis on (1) correction or removal of precipitating factors; (2) if encephalopathy is present, using phosphate enemata, nonhydrolysed disaccharide laxatives, and/or rifaximin; (3) early detection and prompt treatment of complications such as hypoglycaemia, hypokalaemia, cerebral oedema, infection, and bleeding. The onset of organ failure should prompt discussion with a liver transplantation centre. The mortality of acute liver failure (without liver transplantation) is about 40%. Patients with acute liver failure who do not develop encephalopathy can be expected to recover completely. Those who recover from an episode of acute-on-chronic liver failure should be considered for liver transplantation because otherwise their subsequent mortality remains high.

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Hepatic encephalopathy in chronic liver failure

Comparative Biochemistry and Physiology Part A Physiology ◽

10.1016/0300-9629(86)90115-5 ◽

1986 ◽

Vol 83 (1) ◽

pp. 204

Keyword(s):

Hepatic Encephalopathy ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure

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Hepatic Encephalopathy in Chronic Liver Failure

International Journal of Biochemistry ◽

10.1016/0020-711x(86)90026-1 ◽

1986 ◽

Vol 18 (1) ◽

pp. 100

Keyword(s):

Hepatic Encephalopathy ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure

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Hepatic disorders

10.1093/med/9780199229581.003.0021 ◽

2011 ◽

Author(s):

Carl Waldmann ◽

Neil Soni ◽

Andrew Rhodes

Keyword(s):

Hepatic Encephalopathy ◽

Liver Function ◽

Liver Failure ◽

Acute Liver Failure ◽

Serum Bilirubin ◽

Liver Function Tests ◽

Abnormal Liver Function ◽

Chronic Liver ◽

Bile Pigments ◽

Chronic Liver Failure

Jaundice 348Acute liver failure 350Hepatic encephalopathy 352Chronic liver failure 354Abnormal liver function tests 356Jaundice (icterus) is the accumulation of bile pigments in serum and tissues including sclerae and skin. Jaundice is usually clinically detectable once serum bilirubin exceeds 50...

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Chronic Hepatic Failure

DeckerMed Surgery ◽

10.2310/surg.2413 ◽

2019 ◽

Author(s):

Derek J Erstad ◽

Motaz Qadan

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Portal Hypertension ◽

Hepatic Encephalopathy ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure ◽

End Stage Liver Disease ◽

End Stage

Continued hepatic injury by genetic or environmental factors results in a state of chronic inflammation, fibrosis, and progressive hepatocyte dysfunction that can progress to cirrhosis and end stage liver disease (ESLD). Cirrhosis is the eighth leading cause of mortality in the United States, while the burden of disease is even greater in regions with endemic viral hepatitis. Common risk factors include a history of hepatitis; alcohol or IV drug abuse; use of certain medications; and other risk factors associated with transmission of viral hepatitis, including tattoos, sexual promiscuity, and incarceration. Although many patients with cirrhosis are asymptomatic and remain undiagnosed, many will eventually develop secondary complications from chronic liver failure, which can be difficult to manage and are associated with significant morbidity, including: portal hypertension, variceal bleeding, coagulopathy, hepatic encephalopathy, and renal failure. In addition, hepatocellular carcinoma (HCC) is estimated to be 30 times more common among patients with cirrhosis, which can be an aggressive malignancy with 5-year overall survival of less than 15%. In this chapter, we provide a comprehensive overview of chronic liver failure, including the epidemiology of cirrhosis, pathophysiology of liver injury, and assessment and management of cirrhosis and associated downstream complications. Finally, we discuss the role of liver transplantation for both ESLD and HCC. This review contains 6 figures, 9 tables, and 53 references. Key Words: chronic liver failure, cirrhosis, coagulopathy, end stage liver disease, hepatic encephalopathy, hepatocellular carcinoma, hepatorenal syndrome, liver transplantation, portal hypertension, varices

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