Effects of insulin-like growth factor-I administration on in vivo regulation of urea synthesis in normal subjects and patients with cirrhosis.

Background: The anabolic effects of insulin-like growth factor-I (IGF-I) may involve a decrease of hepatic nitrogen (N) clearance, but this has never been studied in humans. Patients with cirrhosis have low levels of IGF-I and might benefit from IGF-I therapy. Conversely, a possible decrease in hepatic N clearance by IGF-I could increase the risk of hepatic encephalopathy.

Age-dependency of galactose elimination capacity in healthy children and children with chronic liver disease.

Objective: Galactose elimination capacity (GEC) is used as a quantitative measure of liver metabolic function with prognostic value in adults with acute and chronic liver failure. Almost no data are available regarding GEC in children, however. This study thus aims to meet the previously unmet clinical need for age-related data on GEC in children.

Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotrophins in obese children.

Objective: Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis.

Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure.

Background: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.

Aim: To examine whether paracetamol-induced acute liver failure increases long-term mortality.

Methods: We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984-2004.

Unchanged capacity of urea synthesis during acute phase response in rats.

Background: The acute phase response presents a catabolic event related to increased waste of amino-N via hepatic urea synthesis despite an increased need for amino-N incorporation into acute phase proteins. In our previous studies, tumour necrosis factor-α (TNF-α) acutely up-regulated the in vivo capacity of urea-nitrogen synthesis (CUNS) in rats before the hepatic acute phase response was established. To extend these observations, this study aimed to clarify the regulation of N elimination via urea during the later stages of the acute phase response.

Insulin sensitivity and body composition in cirrhosis: changes after TIPS.

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production.

Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine.

Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia.

Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study.

Unlabelled: The clinical course of alcoholic cirrhosis, a condition with a high mortality, has not been well described. We examined prevalence, risk, chronology, and mortality associated with three complications of cirrhosis: ascites, variceal bleeding, and hepatic encephalopathy. We followed a population-based cohort of 466 Danish patients diagnosed with alcoholic cirrhosis in 1993-2005, starting from the date of hospital diagnosis and ending in August 2006.

No oxygen delivery limitation in hepatic encephalopathy.

Hepatic encephalopathy is a condition of reduced brain functioning in which both blood flow and brain energy metabolism declined. It is not known whether blood flow or metabolism is the primary limiting factor of brain function in this condition. We used calculations of mitochondrial oxygen tension to choose between cause and effect in three groups of volunteers, including healthy control subjects (HC), patients with cirrhosis of the liver without hepatic encephalopathy (CL), and patients with cirrhosis with acute hepatic encephalopathy.

Tumor necrosis factor-alpha acutely up-regulates urea synthesis in vivo in rats--a hepatic component of inflammatory catabolism?

Background: Catabolism is a serious problem in patients with active inflammation. The tissue nitrogen (N) depletion is related to increased hepatic capacity for elimination of N via conversion of amino-N into urea-N. This is caused by the inflammatory process, but the mediators responsible are unknown.

Body composition changes after transjugular intrahepatic portosystemic shunt in patients with cirrhosis.

Aim: To investigate the effect of transjugular intrahepatic porto-systemic shunt (TIPS) on malnutrition in portal hypertensive cirrhotic patients.

Methods: Twenty-one patients with liver cirrhosis and clinical indications for TIPS insertion were investigated before and 1, 4, 12, 52 wk after TIPS. For each patient we assayed body composition parameters [dry lean mass, fat mass, total body water (TBW)], routine liver and kidney function tests, and free fatty acids (FFA).

Ascites from patients with alcoholic liver cirrhosis contains higher IGF-I bioactivity than serum.

Objective: Patients with liver cirrhosis have diminished hepatic IGF-I generation, resulting in low circulating levels, whereas data on IGF-I in ascites are sparse. Therefore, we compared the IGF-system in serum and ascites from cirrhotic patients.

Design And Patients: The study comprised 43 patients (12 females) with ascites and liver function of 58 +/- 10% of normal.

The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study.

Background: Despite its biologic plausibility, the association between liver function and mortality of patients with chronic liver disease is not well supported by data. Therefore, we examined whether the galactose elimination capacity (GEC), a physiological measure of the total metabolic capacity of the liver, was associated with mortality in a large cohort of patients with newly-diagnosed cirrhosis.

Methods: By combining data from a GEC database with data from healthcare registries we identified cirrhosis patients with a GEC test at the time of cirrhosis diagnosis in 1992-2005.

Incidence and prognosis of cholangiocarcinoma in Danish patients with and without inflammatory bowel disease: a national cohort study, 1978-2003.

Patients with inflammatory bowel disease (IBD) are at increased risk of cholangiocarcinoma (CC), but quantitative data are scant. Furthermore, little is known about the impact of IBD on CC occurrence and prognosis. Based on nationwide population-based registries we compared the incidence and survival of CC patients with and without IBD from 1978 to 2003.

Socioeconomic status and survival of cirrhosis patients: a Danish nationwide cohort study.

Background: Low socioeconomic status is a risk factor for liver cirrhosis, but it is unknown whether it is a prognostic factor after cirrhosis diagnosis. We examined whether marital status, employment, and personal income were associated with the survival of cirrhosis patients.

Methods: Using registry-data we conducted a population-based cohort study of 1,765 Danish cirrhosis patients diagnosed in 1999-2001 at age 45-59 years.

The IGF system after insertion of a transjugular intrahepatic porto-systemic shunt in patients with liver cirrhosis.

Objective: Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) into patients with liver cirrhosis usually induces a gain in body cell mass. Changes in the IGF system in favor of anabolism may be involved. We, therefore measured blood concentrations of the components of the IGF system in cirrhosis patients before and after elective TIPS.

Increased energy expenditure and glucose oxidation during acute nontraumatic skin pain in humans.

Background And Objective: Tissue injury is accompanied by pain and results in increased energy expenditure, which may promote catabolism. The extent to which pain contributes to this sequence of events is not known.

Methods: In a cross-over design, 10 healthy volunteers were examined on three occasions; first, during self-controlled nontraumatic electrical painful stimulus to the abdominal skin, maintaining an intensity of 8 on the visual analogue scale (0-10).

Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.

Objectives: Growth hormone (GH) reduces the catabolic side effects of steroid treatment via effects on the amino-nitrogen metabolism. Ipamorelin is a synthetic peptide with GH releasing properties. We wished to study the metabolic effects of Ipamorelin and GH on selected hepatic measures of alpha-amino-nitrogen conversion during steroid-induced catabolism.

Effects of lipopolysaccharide endotoxin on the insulin-like growth factor I system in rats with cirrhosis.

Background: Patients with liver cirrhosis have disturbances in the insulin-like growth factor I (IGF-I) system that favour insulin resistance and catabolism. High morbidity and mortality of such patients from infections may be related to further aggravation of this problem but human data are controversial. Here, the effect of lipopolysaccharide (LPS) endotoxin on the IGF system was studied in rats with cirrhosis.

Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study.

Objectives: It is known that liver disease can cause an imbalance in the coagulation system, but available data on liver disease and risk of venous thromboembolism are conflicting. We examined the risk of venous thromboembolism in patients hospitalized with liver diseases.

Methods: We conducted a nationwide Danish case-control study of incident cases of venous thromboembolism from 1980 to 2005 using population-based data from the National Registry of Patients, and from the Civil Registration System.

Role of nonalcoholic fatty liver disease in the development of insulin resistance and diabetes.

Nonalcoholic fatty liver disease (NAFLD) is a common disease that is usually accompanied by insulin resistance (IR). Whether or how NAFLD and IR are temporally and mechanistically related is controversial. Recent studies focus on their epidemiology, the importance of dietary fat, the role of adipocytokines and the sterol regulatory element-binding protein-1c.

Metabolic fate of isoleucine in a rat model of hepatic encephalopathy and in cultured neural cells exposed to ammonia.

Hepatic encephalopathy is a severe neuropathological condition arising secondary to liver failure. The pathogenesis is not well understood; however, hyperammonemia is considered to be one causative factor. Hyperammonemia has been suggested to inhibit tricarboxylic acid (TCA) cycle activity, thus affecting energy metabolism.

Low cerebral oxygen consumption and blood flow in patients with cirrhosis and an acute episode of hepatic encephalopathy.

Background & Aims: It is unclear whether patients with hepatic encephalopathy (HE) have disturbed brain oxygen metabolism and blood flow.

Methods: We measured cerebral oxygen metabolism rate (CMRO(2)) by using (15)O-oxygen positron emission tomography (PET); and cerebral blood flow (CBF) by using (15)O-water PET in 6 patients with liver cirrhosis and an acute episode of overt HE, 6 cirrhotic patients without HE, and 7 healthy subjects.

Results: Neither whole-brain CMRO(2) nor CBF differed significantly between cirrhotic patients without HE and healthy subjects, but were both significantly reduced in cirrhotic patients with HE (P < .