Early increase in ammonia is a feature of non-alcoholic fatty liver disease and the ammonia lowering drug, ornithine phenylacetate (OCR-002) prevents progression of fibrosis in a rodent model

Chiara, Francesco De; Habtension, A.; Davies, N; Andreola, Fausto; Rombouts, Krista; Arias, Natalia; Thomsen, Karen Louise; Jalan, R

doi:10.1016/s0168-8278(17)30620-7

Cited by 5 publications

(4 citation statements)

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“…OP has been proven to reduce ammonia levels in animals with acute-on-chronic and acute liver failure [35,36], and our findings indicate that this may also reduce activation of HSCs [32]. Preliminary data from our own laboratories have shown similar results in a NASH animal model [37]. Also in humans, OP is considered safe and beneficial as an ammonia scavenger to treat hyperammonemia in healthy subjects and patients with cirrhosis [38].…”

Section: Discussionsupporting

confidence: 62%

Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis

et al. 2018

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from steatosis, through non-alcoholic steatohepatitis (NASH) to cirrhosis. The development of fibrosis is the most important factor contributing to NASH-associated morbidity and mortality. Hepatic stellate cells (HSCs) are responsible for extracellular matrix deposition in conditions of frank hepatocellular injury and are key cells involved in the development of fibrosis. In experimental models and patients with NASH, urea cycle enzyme gene and protein expression is reduced resulting in functional reduction in the in vivo capacity for ureagenesis and subsequent hyperammonemia at a pre-cirrhotic stage. Ammonia has been shown to activate HSCs in vivo and in vitro. Hyperammonemia in the context of NASH may therefore favour the progression of fibrosis and the disease. We therefore hypothesise that ammonia is a potential target for prevention of fibrosis progression of patients with NASH.

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Section: Discussionsupporting

confidence: 62%

Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis

et al. 2018

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“…We suggest that ammonia removal in NASH patients would lead to a more quiescent HSC phenotype and slow the progression of NAFLD. In preliminary studies, the administration of OCR-002, a drug known to reduce ammonia concentration, prevented progression of fibrosis (36). Furthermore, patients with NAFLD have been shown to have hyperammonemia and neuropsychological disturbances (17), although the mechanism underlying this has so far not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Urea cycle dysregulation in non-alcoholic fatty liver disease

Chiara

Heebøll

Marrone

et al. 2018

Journal of Hepatology

139

115

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In patients with fatty liver disease, the enzymes that convert nitrogen waste into urea may be affected, leading to the accumulation of ammonia, which is toxic. This accumulation of ammonia can lead to scar tissue development, increasing the risk of disease progression. In this study, we show that fat accumulation in the liver produces a reversible reduction in the function of the enzymes that are involved in detoxification of ammonia. These data provide potential new targets for the treatment of fatty liver disease.

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“…: «…аммиак вызывает вредные морфологические и функциональные эффекты на HSCs in vitro» [36]. Та же группа авторов еще в одном исследовании отмечает «раннее увеличение аммиакаособенность неалкогольной жировой болезни печени, выбор агента для понижения аммиака позволяет уменьшить прогрессию НАЖБП и уровень фиброза» [37]. Еще одна группа авторов разработала методику определения внутрипеченочного аммиака как маркера и потенциального фактора повреждения печени при НАЖБП на доклинической стадии, они сделали вывод, что «накопление аммиака увеличивается у пациентов при НАЖБП с повышенной степенью лобулярного воспаления и гомоцистеина плазмы» [38].…”

Section: таблица постпрандиальные показатели кровотока и первичных мunclassified

Different types of hyperammonemia in clinical practice

Плотникова¹,

Сухих

2018

Med. sov.

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Hyperammonemia is a metabolic disorder, which is caused as a result of high levels of ammonia present in the blood. Hyperammonemia is related to severe liver diseases, primarily to cirrhosis in 90% of cases. Non-cirrhotic causes should be considered in the remaining 10%. The article describes various causes and clinical features of hyperammonemia related to the pre-cirrhotic stages of liver disease, especially to non-alcoholic fatty dystrophy. The authors also provide other etiologies that cause hyperammonemia of varying severity, from minimal to very severe, leading to fatal outcome. The paper provides an analysis of the efficacy of L-ornithine-L-aspartate in hyperammonemia, and the results of own original author’s pharmaceutical equivalence study of the original and generic drug L-ornithine-L-aspartate.

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Early increase in ammonia is a feature of non-alcoholic fatty liver disease and the ammonia lowering drug, ornithine phenylacetate (OCR-002) prevents progression of fibrosis in a rodent model

Cited by 5 publications

References 0 publications

Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis

Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis

Urea cycle dysregulation in non-alcoholic fatty liver disease

Different types of hyperammonemia in clinical practice

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