Human Albumin Infusion in Liver Cirrhosis and Overt Hepatic Encephalopathy (HACHE): an Invesitgator-initiated, Open-label, Multicenter, Randomized Controlled Trial

Hepatic encephalopathy (HE), a severe complication of decompensated cirrhosis, is characterized as neurocognitive dysfunction. Emerging evidence suggests the potential role of human albumin infusion for the treatment of HE, but its optimal dosage remains undefined. Therefore, the investigators planned a randomized controlled trial (RCT) to compare the efficacy of human albumin infusion at different dosages in in patients with liver cirrhosis and overt HE.

Start Date01 May 2025

Sponsor / Collaborator

The General Hospital of Shenyang Military Region

NCT05920213

/ Not yet recruitingPhase 4IIT

HELP Trial: Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy

The goal of this clinical trial is to compare the efficacy of L-ornithine L-aspartate and Polyethylene Glycol in Cirrhotic Patients with Overt Hepatic Encephalopathy.
Participants will be asked to fill out a few questions on proforma that will obtain demographic information as well as information relating to the patient's health. Treatments that they will receive after inclusion in the study, will be the standard treatment (Lactulose) along with additional medication as part of our research (LOLA or Polyethylene glycol).

Start Date01 Oct 2023

Sponsor / Collaborator

Jinnah Post Graduate Medical Centre

NCT05778461

/ Not yet recruitingNot ApplicableIIT

Efficacy of L-ornithine L-aspartate and Therapeutic Plasma Exchange Versus Plasma Exchange Alone in Lowering Ammonia and Improving Outcomes in Pediatric Acute Liver Failure: A Randomized Controlled Trial

Pediatric acute liver failure (PALF) is associated with very high mortality and morbidity with native liver survival varying between 21 to 75%.Hyperammonemia manifesting as hepatic encephalopathy and causing cerebral edema isresponsible for poor neurological outcome in ALF. Ammonia lowering measures have led to improvement in HE and higher native liver survival. L-ornithine L-aspartate (LOLA), a salt of natural amino-acids ornithine and aspartate, is an importantammonia scavenging drug. It acts as a substrate for urea cycle in liver and also converts ammonia to glutamine in perivenous hepatocytes as well as in the muscles.This drug has been shown to reduce ammonia and improve hepatic encephalopathy in cirrhoticadults.However, the issue with this drug is that the glutamine formed can reconvert to ammonia by the action of glutaminase, possibly, the reason why it failed to show decrease in ammonia and improvement in native liver survival in a randomized controlled trial in adult ALF. In western countries, ornithine phenylacetate has been used where ornithine converts ammonia to glutamine and phenylacetate then binds to this glutamine to form phenylacetylgutamine and eliminates it. Therapeutic plasma exchange (TPE), both high volume and standard volume has been shown to improve native liver survival in adults with ALF and is the standard of care in management of ALF and a grade 1 recommendation by all eminent liver societies.TPE leads to decreased ammonia. Although rate of ammonia formation is multiple times higher than rate of ammonia removal by plasmapheresis, this ammonia reduction is an indirect effect of glutamine removal by TPE. Glutamine, thus, acts as a reservoir for clearance of ammonia (in muscles and perivenous hepatocytes).In contrast to adults, the response to therapeutic plasma exchange has not been as encouraging inchildren, yet, most centers continue to use it based on recommendations in adults. Based on the knowledge that LOLA converts ammonia to glutamine and TPE clears glutamine from plasma, the investigators hypothesize that LOLA would act in synergestic way with TPE to lower ammonia levels, resulting in improvement in HE and better native liver survival in pediatric ALF. The goal of this clinical trial is to compare L-ornithine L-aspartate and therapeutic plasma exchange versus plasma exchange alone in lowering ammonia and improving outcomes in patients with pediatric acute liver failure.

Start Date15 Mar 2023

Sponsor / Collaborator

Institute of Liver & Biliary Sciences

100 Clinical Results associated with Ornithine aspartate

100 Translational Medicine associated with Ornithine aspartate

100 Patents (Medical) associated with Ornithine aspartate

359

Literatures (Medical) associated with Ornithine aspartate

01 Dec 2025·Current Neurology and Neuroscience Reports

Hepatic Encephalopathy: Current Thoughts on Pathophysiology and Management

Review

Author: Pan, Kausik ; Chakravarty, Ambar ; Sen, Barun Kumar

PURPOSE OF REVIEWThis review highlights the causes, types and clinical staging of hepatic encephalopathy (HE). Current concepts on the probable pathogenetic mechanisms and currently practiced therapeutic options are discussed.RECENT FINDINGSHE may be covert and overt. Also known as minimal HE. Covert HE, where there are behavioral abnormalities and impairment in activities of daily living with intact sensorium. The pathophysiology of HE remains poorly understood. There is disturbance of the urea cycle due to liver disease leading to increased production of ammonia. The ammonium ion enters the astrocytes along with glutamate (converted to glutamine by ammonia) and myo-inositol, thereby increasing the osmolality of the astrocytic cytoplasm. This osmotic gradient results in accumulation of water inside the astrocytes resulting in cerebral edema and increase in brain volume. Additionally, current research has noted the role of cerebral oxidative/nitrosative stress and the synergistic effects of increased cerebral ammonia and alteration in neurotransmitters, neurometabolites, and cortical excitability due to systemic inflammation. In advanced liver disease with systemic infection or inflammation, neuroinflammatory processes play significant role in the development of HE. Inflammatory cytokines like TNF-α, IL-6, IL-17 in presence of hyperammonemia have been found to induce neurotoxicity of ammonia by passing through the blood brain barrier and causing enlarged/swollen pale astrocytes, resulting in HE. Disrupted enterohepatic circulation in end stage liver disease also causes elevation of bile acids which induces neuroinflammation. Manganese and zinc play as co-factors of enzymatic reaction. These metal deposition causes multiple psychomotor symptoms observed in HE. The gut environment has a major impact on brain function in patients with HE. Toxins such as ammonia and inflammatory cytokines produced by this impaired intestinal flora access the circulation through porto-systemic anastomoses and exacerbate or precipitate HE. Finally, as a result of recurrent cerebral edema from astrocytic dysfunction and neuroinflammation, permanent neurodegeneration occurs with cognitive decline and motor disturbances, especially parkinsonian features and gait disturbances. This is the stage of chronic hepatic encephalopathy. Currently L-ornithine L-aspartate (LOLA) is being used to lower the ammonia level by stimulating the urea cycle. HE comprises a broad spectrum of neurological and/or psychiatric abnormalities caused by hepatic insufficiency and/or portal-systemic shunting in the absence of any other causes of brain dysfunction. HE may be caused or precipitated by several factors like infections, intoxications and drugs. The encephalopathic features may be covert or overt. The pathogenetic mechanisms for HE may be different. In the presence of liver disease, HE primarily results from disturbed urea cycle with hyperammonemia causing astrocytic swelling and cerebral edema. Porto-systemic anastomoses with intact liver function can cause HE by allowing ammonia and other toxins produced by the gut microbial flora and allowing these to bypass detoxification by the liver and exposing the brain to their harmful effects. Principles of therapy are twofold. First protecting the liver and the brain from gut generated ammonia and other toxins by ensuring smooth bowel function and avoiding stagnation with the use of osmotic laxatives like lactulose or lactitol and also reducing the gut microbial load with use of anti-bacterials/bacteriophages like neomycin and rifaximin along with metronidazole. Second, reducing the already generated cerebral edema by use of mannitol and appropriate ventilatory support. Currently L-ornithine L-aspartate (LOLA) is being used to reduce the ammonia load to the liver. LOLA is a stable compound formed from two amino acids. L-ornithine plays a crucial role in stimulating the urea cycle, leading to a reduction in ammonia levels. Both L-ornithine and L-aspartate serve as substrates for the enzyme glutamate transaminase, and their administration results in elevated glutamate concentrations. Ammonia is subsequently utilized in the conversion of glutamate to glutamine through the action of glutamine synthetase. Finally in resistant cases the use of liver transplant needs to be considered. Alternatively extracorporeal liver assist devices may be used like Molecular Adsorbent Recirculating System (MARS) or Single-Pass Albumin Dialysis (SPAD).

27 Jan 2025·Irish medical journal

Unusual Presentation of Confusion: Hyperammonaemic Hepatic Encephalopathy Due to Intrahepatic Portosystemic Venous Shunt.

Article

Author: McCluskey, P ; Ntlholang, O ; Yousif, M ; Magee, C

PresentationA 75-year-old man presented to the emergency department with a 5-week history of confusion, daytime somnolence, and fatigue. His physical examination was unremarkable.DiagnosisInvestigations initially showed deranged Liver function tests. Extensive investigations were done following that including CT brain, MRI brain, septic screen, Arterial blood gas, and Lumbar puncture, which were all inconclusive. An Electroencephalogram was suggestive of Encephalopathy. His Ammonia level was high (123). Triphasic CT liver, revealed Intrahepatic portosystemic venous shunt and was diagnosed with hyperammonaemic hepatic encephalopathy due to Intrahepatic portosystemic venous shunt.TreatmentManagement included the commencement of Lactulose, Rifaximin, and L-ornithine L-aspartate (LOLA). An IR-guided embolisation of the porto-venous shunt was performed. At two-month review, the patient reported no further episodes of confusion.DiscussionIntrahepatic portosystemic venous shunts should be considered in the differential diagnosis of patients presenting with confusion or other unexplained neurological symptoms, especially in the presence of liver dysfunction. Early diagnosis and appropriate management are crucial for favourable outcomes.

01 Dec 2024·Journal of Pharmaceutical and Biomedical Analysis

Identification by HSQC and quantification by qHNMR innovate pharmaceutical amino acid analysis

Article

Author: Ray, G Joseph ; Kleps, Robert A ; Rebollar-Ramos, Daniela ; Lankin, David C ; Lehtivarjo, Juuso ; Niemitz, Matthias ; Pauli, Guido F ; Chen, Shao-Nong ; Korhonen, Samuli-Petrus

This study introduces a new NMR-based methodology for identification (ID) and quantification (purity, strength) assays of widely used amino acids. A detailed analysis of four amino acids and their available salts was performed with both a high-field (600 MHz) and a benchtop (60 MHz) NMR instrument. To assess sensitivity constraints, samples for ¹H NMR analysis were initially prepared using only 10 mg of analyte and 1 mg of maleic acid (MA) as an internal calibrant (IC) and secondary chemical shift reference. The characteristic dispersion of the peak patterns indicating the presence or absence of a counterion (mostly chloride) was conserved at both high and low-field strength instruments, showing that the underlying NMR spectroscopic parameters, i.e., chemical shifts and coupling constants, are independent of the magnetic field strength. However, as the verbal descriptions of ¹H NMR spectra are challenging in the context of reference materials and pharmaceutical monographs, an alternative method for the identification (ID) of amino acids is proposed that uses ¹³C NMR patterns from multiplicity-edited HSQC (ed-HSQC), which are both compound-specific and straightforward to document. For ed-HSQC measurements, the sample amount was increased to 30 mg of the analyte and several acquisition parameters were tested, including t₁ increments used in the pulse program, number of scans, and repetition time. Excellent congruence with deviations <0.1 ppm was achieved for the ¹³C chemical shifts from 1D ¹³C NMR spectra (150 MHz) vs. those extracted from ed-HSQC (15 MHz traces). Finally, all samples of amino acid candidate reference materials were quantified by ¹H qNMR (abs-qHNMR) at both 600 and 60 MHz. At high field, both IC and relative quantitations were performed, however, with the low-field instrument, only the IC method was used. The results showed that the analyzed reference material candidates were generally highly pure compounds. To achieve adequately low levels of uncertainty for such high-purity materials, the sample amounts were increased to 100 mg of analytes and 10 mg of the IC and replicates were analyzed for selected amino acids.

News (Medical) associated with Ornithine aspartate

08 Mar 2021

·www.biospace.com

Winhealth Pharma and Merz Collaborate on Hepa-Merz® to benefit patients with liver disease in China

HANG ZHOU, China, March 8, 2021 /PRNewswire/ -- On Feb. 26th, 2021, Hongkong Winhealth Pharma Group Co., Ltd (hereinafter referred to as "Winhealth Pharma") signed a strategic cooperation agreement with Merz Pharmaceuticals GmbH (hereinafter referred to as "Merz"). The strategic cooperation between the two parties marks the obtainment of Winhealth Pharma for the exclusive commercial rights of Hepa-Merz® (L-ornithine L-aspartate, an important product under Merz' product portfolio) in China. About L-ornithine L-aspartate and hepatic encephalopathy (HE) L-ornithine L-aspartate (LOLA) is a stable salt of two amino acids that stimulates ammonia detoxification by increasing urea synthesis in the liver and muscle, thereby reducing the blood ammonia content in the brain which causes hepatic encephalopathy in cirrhotic patients. Hepa-Merz® Infusion concentrate (HMI) from Merz is the only imported LOLA in the Chinese market. Hepatic encephalopathy (HE) is a specific neurological symptom of liver cirrhosis and a common cause for hospitalization of patients. Hepatic encephalopathy has an impact on patient's quality of life and marks the poor prognosis indicator for patients with liver cirrhosis. According to domestic data, the incidence of mild hepatic encephalopathy (MHE) in liver cirrhosis is 38.8-85.0%. L-ornithine L-aspartate (Hepa-Merz®) infusion particularly proved to be effective in preventing the development of hepatic encephalopathy in those cirrhotic patients with acute emergency complications (e.g. variceal bleeding). Hepa-Merz® contributes therefore to the improvement of economic and social burden in cirrhotic patients. Stefan Brinkmann, Managing Director of Merz Therapeutics, emphasized: "At Merz Therapeutics, it is our mission to bring better outcomes to more patients. We are very pleased and proud about the new contract between Winhealth Pharma and Merz, as it will allow patients with liver disease in China to receive an effective and beneficial treatment to ease their burden." Mr. Jack Wang, Chairman and CEO of Winhealth Pharma, pointed out: "It is exciting to reach cooperation with Merz again. This is another brand-new milestone since the first cooperation on Contractubex® in 2017, which will accelerate the promotion of the product portfolio layout of hepatobiliary digestive line in the mature pharmaceutical business of Winhealth Pharma. Meanwhile, based on the established strategic partnership, the two parties will further deepen cooperation and integrate the advantages of both sides, so that Hepa-Merz® can better benefit domestic patients with hepatic encephalopathy and meet the needs of more unmet patients." About Merz Merz Therapeutics, a business of Merz Pharmaceuticals GmbH, is headquartered in Frankfurt, Germany and is represented in more than 90 countries. Merz Pharmaceuticals GmbH is part of the Merz Group, a privately held, family-owned company that has dedicated more than 110 years to developing innovations that serve unmet patient and customer needs. About Winhealth Pharma Winhealth Pharma is a commercial-stage biopharmaceutical company aiming at fulfilling severely unmet or underserved medical needs for patients with rare diseases and other critical medical conditions in China and surrounding regions. Since its inception, Winhealth has been committed to sourcing, developing, and commercializing innovative therapies from leading biotech and pharmaceutical companies worldwide.

Collaborate

100 Deals associated with Ornithine aspartate

External Link

KEGG	Wiki	ATC	Drug Bank
D08303	Ornithine aspartate	A05	-

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hyperammonemia	China	Merz Pharma GmbH & Co. KGaA	04 Aug 2000
Hepatic Encephalopathy	Germany	Merz Pharma GmbH & Co. KGaA	01 Jan 1969

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatic Encephalopathy	Preclinical	North America	-	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


UEGW2015	Not Applicable	Hepatic Encephalopathy	126	Lactulose	yzcstabuep(xbrourcjml) = lcvqfsraac mhlkmwcyzv (zpvsxrjluw ) View more	Negative	01 Oct 2015
				Rifaximin	yzcstabuep(xbrourcjml) = gozxmpcnmk mhlkmwcyzv (zpvsxrjluw ) View more
ASCO2013	Not Applicable	Mycoses	413	Hepa systems (HEPA filters)	txcboazhfv(qzlrjhduxu) = kdruqkdlon lcogmiinfl (wqztydunxt )	-	20 May 2013
NCT00470314 (Pubmed \| Gastroenterology)	Phase 2	Liver Failure, Acute	201	Placebo	(dnkjyedavy) = ifpwbztglp fyqkeepoax (gbhknjjlbl )	Negative	01 Jun 2009
				L-ornithine L-aspartate (LOLA)	(dnkjyedavy) = kolzwhwrxi fyqkeepoax (gbhknjjlbl )

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis