Asparaginase-associated hyperammonemia.

Asparaginase is an essential drug in the treatment of acute lymphoblastic leukemia, and discontinuation of asparaginase therapy due to clinical toxicity or silent inactivation may lead to reduced event-free survival. Common toxicities include hypersensitivity reactions, acute pancreatitis, thrombosis, hepatotoxicity, and hyperlipidemia. In addition, several small case series have described asparaginase-associated hyperammonemia, the true frequency and clinical importance of which, both short- and long-term, remain unclear.

Cirrhosis epidemiology in Denmark 1998-2022, and 2030 forecast.

Background & Aims: The incidence of cirrhosis resulting from alcohol-related liver disease (ALD) is decreasing in Denmark, whereas the incidence of obesity is increasing, driving an increase in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to perform an up-to-date study of the epidemiology of cirrhosis in Denmark, including etiologies, and a forecast through to 2030.

Methods: We identified all patients diagnosed with cirrhosis between 1998 and 2022, categorized into ALD and non-ALD cirrhosis, in nationwide Danish healthcare registries.

Cirrhosis and Faecal microbiota Transplantation (ChiFT) protocol: a Danish multicentre, randomised, placebo-controlled trial in patients with decompensated liver cirrhosis.

Introduction: Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.

Delta in Denmark: prevalence of hepatitis delta virus infection.

Hepatitis delta virus (HDV) infection has an aggressive disease course and is the most difficult to treat of the human hepatitis viruses. In Denmark, as in many countries, the national prevalence of HDV has not been established. Based on diagnoses and laboratory test results in national healthcare registries, we estimated that the prevalence of current HDV infection amongst patients with chronic hepatitis B was 3.

Down the road towards hepatic encephalopathy. Urea synthesis - the liver workhorse of nitrogen metabolism.

Urea synthesis is an irreversible, essential for maintenance of health and life, and highly regulated liver function with a very high capacity for production of the end-product urea-nitrogen. The set-point of urea synthesis in relation to its overall substrate, the prevailing blood concentration of L-α-amino acids, contributes to determine whole-body nitrogen balance and the size and composition of the plasma free amino acid pool. Ammonia is definitively eliminated from the body by urea synthesis.

Down the road towards hepatic encephalopathy. The elusive ammonia- what determines the arterial concentration?

Elevated arterial ammonia is associated with several complications of liver disease as it predicts mortality for in-patients and decompensation, hospitalization and death in out-patients with cirrhosis. In this review, our aim was to estimate how the individual organs contribute to arterial ammonia based on published data from human studies. The brain removes ammonia from arterial blood in a concentration-dependent fashion.

Hyperammonaemic encephalopathy due to non-functioning urea cycle as a complication to gastric bypass surgery.

Hyperammonaemic encephalopathy in the absence of liver failure is a major diagnostic challenge. A rare cause is as a complication to previous gastric bypass surgery, a condition reported to be associated with high mortality. In this case report, we present the exhaustive diagnostic work-up and clinical reversal of deep and recurrent hyperammonaemic encephalopathy in a patient with previous gastric bypass surgery.

Blood ammonia concentration measurement - effects of sampling site and cirrhosis during induced hyperammonaemia.

Background: Ammonia is implicated in hepatic encephalopathy (HE) and prognostic in cirrhosis. Venous ammonia concentration, yielding similar correlation with HE grades as arterial, has become the preferred practise but comparative data are limited.

Aim: To quantify effect of sampling site on ammonia concentration in healthy persons and patients with cirrhosis.

Hepatic encephalopathy as a result of ammonia-induced increase in GABAergic tone with secondary reduced brain energy metabolism.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by liver insufficiency and/or portosystemic shunting. HE is mostly episodic and as such reversible. Hyperammonemia clearly plays a key role in the pathophysiology, but the precise detrimental events in the brain leading to HE remain equivocal.

The FGL-1/LAG-3 Axis is Associated With Disease Course in Alcohol-associated Hepatitis: A Preliminary Report.

Background: Alcohol-associated hepatitis (AH) has a short-term mortality rate of up to 40% primarily related to impaired hepatocyte regeneration and uncontrolled liver inflammation. The acute phase protein fibrinogen-like protein 1 (FGL-1) produced by hepatocytes stimulates hepatocyte proliferation by autocrine signaling. FGL-1 also is a ligand for the inhibitory T cell receptor lymphocyte activation gene 3 (LAG-3).

The CIRrhotic Ascites Severity (CIRAS) model predicts hepatic hydrothorax at all stages of ascites.

Background: Hepatic hydrothorax (HH) is a rare but severe manifestation of cirrhotic ascites. Whether HH development relates to ascites severity is uncertain and simple clinical models to predict HH from all stages of ascites are missing. The recently published CIRrhotic Ascites Severity (CIRAS) model using only ascites-related variables may serve this purpose.

Glucagon Resistance in Individuals With Obesity and Hepatic Steatosis Can Be Measured Using the GLUSENTIC Test and Index.

Increased plasma levels of glucagon (hyperglucagonemia) promote diabetes development but are also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance toward amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated.

Cerebral Aspects of Portal Hypertension: Hepatic Encephalopathy.

Portal hypertension has cerebral consequences via its causes and complications, namely hepatic encephalopathy (HE), a common and devastating brain disturbance caused by liver insufficiency and portosystemic shunting. The pathogenesis involves hyperammonemia and systemic inflammation. Symptoms are disturbed personality and reduced attention.

Cognitive dysfunction in early experimental metabolic dysfunction-associated steatotic liver disease is associated with systemic inflammation and neuroinflammation.

Background & Aims: Cognitive dysfunction is an increasingly recognised manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanistic link remains unclear. The aim of this study was to investigate the hypothesis that experimental MASLD leads to cognitive dysfunction via systemic inflammation and neuroinflammation.

Methods: Twenty male Sprague Dawley rats were randomised to a high-fat high-cholesterol (HFHC) diet to induce MASLD, or a standard diet (n = 10/group), for 16 weeks.

Post-Transjugular Intrahepatic Portosystemic Shunt (TIPS) Hepatic Encephalopathy-A Review of the Past Decade's Literature Focusing on Incidence, Risk Factors, and Prophylaxis.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension and its' complications in liver cirrhosis, yet the development of hepatic encephalopathy (HE) remains a significant concern. This review covers the reported incidence, risk factors, and management strategies for post-TIPS HE over the past decade. Incidence varies widely (7-61%), with factors like age, liver function, hyponatremia, and spontaneous portosystemic shunts influencing risk.

Distribution of non-ceruloplasmin-bound copper after i.v. Cu injection studied with PET/CT in patients with Wilson disease.

Background & Aims: In Wilson disease (WD), copper accumulation and increased non-ceruloplasmin-bound copper in plasma lead to liver and brain pathology. To better understand the fate of non-ceruloplasmin-bound copper, we used PET/CT to examine the whole-body distribution of intravenously injected 64-copper (Cu).

Methods: Eight patients with WD, five heterozygotes, and nine healthy controls were examined by dynamic PET/CT for 90 min and static PET/CT up to 20 h after injection.

Role of ammonia in NAFLD: An unusual suspect.

Mechanistically, the symptomatology and disease progression of non-alcoholic fatty liver disease (NAFLD) remain poorly understood, which makes therapeutic progress difficult. In this review, we focus on the potential importance of decreased urea cycle activity as a pathogenic mechanism. Urea synthesis is an exclusive hepatic function and is the body's only on-demand and definitive pathway to remove toxic ammonia.

The prevalence and risk factors for cognitive impairment in obesity and NAFLD.

Background: Severe obesity may be accompanied by cognitive dysfunction and NAFLD, but the associations remain unclear. We describe the prevalence and features of cognitive dysfunction and examine the associations between cognitive dysfunction and the presence and severity of NAFLD, and the associations between cognitive dysfunction and signs of other obesity-related comorbidities and neuronal damage.

Methods: A cross-sectional study of patients with a body mass index of 35 kg/m2 underwent evaluation for bariatric surgery.

Non-Selective Beta-Blockers and Risk of Sepsis in Patients with Cirrhosis and Ascites: Results from a Large Observational Study.

Background And Aims: Previous studies have not been able to determine whether non-selective beta-blockers (NSBB) reduce the risk of sepsis in cirrhosis. We aimed to examine this question with data from 1198 patients with cirrhosis and ascites included in clinical studies of satavaptan, a vasopressin receptor antagonist with no effect on infection risk.

Methods: Risk of sepsis was estimated for NSBB users vs nonusers.