Acute Liver Failure: a Review

Khan, Shahid A.; Shah, Naina; Williams, Roger; Jalan, Rajiv

doi:10.1016/j.cld.2006.05.010

Cited by 30 publications

(22 citation statements)

References 94 publications

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“…Acute and chronic liver diseases represent the most important causes of morbidity and mortality in the world [1,2]. Drug-related hepatotoxicity is the leading cause of acute liver failure in the United States [3], while chronic liver disease is mostly supported by Hepatitis C Virus (HCV) infection [4], alcoholism [5], and more recently, by nonalcoholic fatty liver disease (NAFLD) due to the increasing prevalence of obesity and metabolic syndrome [6].…”

Section: Introductionmentioning

confidence: 99%

Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases

Serviddio

Bellanti

Sastre

et al. 2010

CMC

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Mitochondrial dysfunction acts as a common pathogenetic mechanism in several acute and chronic liver diseases, such as Alcoholic and Non-Alcoholic Fatty Liver Disease (NAFLD), drug-induced steatohepatitis, viral hepatitis, biliary cirrhosis, hepatocellular carcinoma, ischemia/reperfusion injury and transplant rejection. In particular mitochondrial uncoupling,has been recently identified to play a determinant role in the pathogenesis of liver diseases by causing decrease of mitochondrial proton motive force and ATP depletion. Damaged mitochondria present defects in lipid homeostasis, bioenergetics impairment and overproduction of Reactive Oxygen Species (ROS), leading to lipid accumulation and oxidative stress. Dysfunctional and/or uncoupled mitochondria enhance the susceptibility of hepatocytes to cell death by necrosis, via ATP depletion, or by apoptosis, via membrane permeabilization. Thus, prevention of mitochondrial alterations promises to be an effective strategy for treatment of liver diseases. However, no therapy has proven to be absolutely effective, whereas those that are beneficial present several side effects. The present review summarizes the recent approaches in mitochondrial drug deliver systems and focuses on mitochondria-targeted molecules application in liver disease. New selective molecules and nanocarriers technology are also considered as potentially effective in the targeting of mitochondrial dysfunction in liver pathology.

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Section: Introductionmentioning

confidence: 99%

Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases

Serviddio

Bellanti

Sastre

et al. 2010

CMC

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“…It is widely stated that 90-95% of cases in UK are single large deliberate overdoses. The UK has very high rate of intentional overdose with approximately 60,000 hospitalisations due to intentional poisoning per year, mostly involving paracetamol (Khan et al 2006). The overwhelming majority of cases are reportedly due to products containing paracetamol alone.…”

Section: Introductionmentioning

confidence: 98%

FDA proposals to limit the hepatotoxicity of paracetamol (acetaminophen): are they reasonable?

et al. 2010

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Hepatotoxicity from paracetamol is of great concern because of the considerable number of patients who develop severe toxicity from this drug. A group of senior medical practitioners, academics and scientists were brought together on June 29 and 30, 2009 by the Food and Drug Administration of USA (FDA) with the aim of providing advice on how to limit the number of cases of hepatotoxicity due to paracetamol in USA. The most contentious recommendations were the reduction in the dose of paracetamol to 650 mg and the elimination of prescription combination products of paracetamol and opiates. The first recommendation indicates that many members of the committee consider, despite much evidence to the contrary, that therapeutic doses of paracetamol (up to 4 g daily) are associated with a significant incidence of hepatotoxicity. The second recommendation, if accepted by FDA, will require major changes in the therapeutic use of paracetamol and opiates. Adoption of these two recommendations may lead to the increased use of NSAIDs with the potential of increasing incidence of NSAIDs-related adverse reactions.

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“…It can occur within 10 days of liver dysfunction (hyper-acute), within 10–31 days (acute) or after more than 31 days (subacute). The pathophysiology of this condition consists of the loss of hepatocellular function causing severe metabolic derangements, impairment of plasma detoxification, hyperammonemia (elevated blood ammonia levels), neurological complications, and systemic organ failure [13, 14]. Acute-on-chronic liver disease occurs in patients with well compensated chronic liver disease in whom acute deterioration of liver function occurs due to events such as sepsis, gastrointestinal bleeding, ischemia or additional superimposed liver injury due to alcohol, hepatotoxic drugs, or viral infections.…”

Section: Liver Diseasesmentioning

confidence: 99%

Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

Sharma

Greenhough

Medine

et al. 2010

Journal of Biomedicine and Biotechnology

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The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

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Acute Liver Failure: a Review

Cited by 30 publications

References 94 publications

Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases

Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases

FDA proposals to limit the hepatotoxicity of paracetamol (acetaminophen): are they reasonable?

Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

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