• Humans
• Child
• Hepatic Encephalopathy/etiology
• Tumor Necrosis Factor-alpha
• Interleukin-6
• Biomarkers
• Cytokines

• Humans
• Ammonia
• Liver Cirrhosis/diagnosis
• Fibrosis
• Prognosis
• Hepatic Encephalopathy

• MR/V006657/1 Medical Research Council
• MR/V006757/1 Medical Research Council

• Ammonia/metabolism
• Automobile Driving
• Hepatic Encephalopathy/diagnosis
• Hepatic Encephalopathy/metabolism
• Hepatic Encephalopathy/physiopathology
• Hepatic Encephalopathy/therapy
• Humans
• Nutritional Support
• Patient Reported Outcome Measures
• Prognosis
• Societies, Medical

Increased blood ammonia (NH₃) is an important causative factor in hepatic encephalopathy, and clinical treatment of hepatic encephalopathy is focused on lowering NH₃. Ammonia is a central element in intraorgan nitrogen (N) transport, and modeling the factors that determine blood-NH₃ concentration is complicated by the need to account for a variety of reactions carried out in multiple organs. This review presents a detailed quantitative analysis of the major factors determining blood-NH₃ homeostasis – the N metabolism of urea, NH₃, and amino acids by the liver, gastrointestinal system, muscle, kidney, and brain – with the ultimate goal of creating a model that allows for prediction of blood-NH₃ concentration. Although enormous amounts of NH₃ are produced during normal liver amino-acid metabolism, this NH₃ is completely captured by the urea cycle and does not contribute to blood NH₃. While some systemic NH₃ derives from renal and muscle metabolism, the primary site of blood-NH₃ production is the gastrointestinal tract, as evidenced by portal vein-NH₃ concentrations that are about three times that of systemic blood. Three mechanisms, in order of quantitative importance, release NH₃ in the gut: 1) hydrolysis of urea by bacterial urease, 2) bacterial protein deamination, and 3) intestinal mucosal glutamine metabolism. Although the colon is conventionally assumed to be the major site of gut-NH₃ production, evidence is reviewed that indicates that the stomach (via Helicobacter pylori metabolism) and small intestine and may be of greater importance. In healthy subjects, most of this gut NH₃ is removed by the liver before reaching the systemic circulation. Using a quantitative model, loss of this “first-pass metabolism” due to portal collateral circulation can account for the hyperammonemia observed in chronic liver disease, and there is usually no need to implicate hepatocyte malfunction. In contrast, in acute hepatic necrosis, hyperammonemia results from damaged hepatocytes. Although muscle-NH₃ uptake is normally negligible, it can become important in severe hyperammonemia. The NH₃-lowering actions of intestinal antibiotics (rifaximin) and lactulose are discussed in detail, with particular emphasis on the seeming lack of importance of the frequently emphasized acidifying action of lactulose in the colon.

• ammonia
• cirrhosis
• encephalopathy
• glutamate
• glutamine
• lactulose
• shunt
• urea
• urease

• Ammonia
• blood
• breath
• diagnostics

AIM: To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC).

METHODS: The subjects included 35 patients with AL-LC (34 men, 1 woman; mean age, 58.9 ± 10.7 years; median age, 61 years; range: 37-76 years). All patients were enrolled in this study after obtaining written informed consent. Liver function was measured with tests measuring albumin (Alb), prothrombin time (PT), brain natriuretic peptide (BNP), branched amino acid and tyrosine ratio (BTR), branched chain amino acid (BCAA), tyrosine, ammonia (NH₃), cholinesterase (ChE), immunoreactive insulin (IRI), total bile acid (TBA), and the retention rate of indocyanine green 15 min after administration (ICG R15). Hepatic blood flow, hepatic arterial tissue blood flow (HATBF), portal venous tissue blood flow (PVTBF), and total hepatic tissue blood flow (THTBF) were simultaneously calculated using xenon computed tomography.

RESULTS: PVTBF, HATBF and THTBF were 30.2 ± 10.4, 20.0 ± 10.7, and 50.3 ± 14.9 mL/100 mL/min, respectively. Alb, PT, BNP, BTR, BCAA, tyrosine, NH₃, ChE, IRI, TBA, and ICG R15 were 3.50 ± 0.50 g/dL, 72.0% ± 11.5%, 63.2 ± 56.7 pg/mL, 4.06 ± 1.24, 437.5 ± 89.4 μmol/L, 117.7 ± 32.8 μmol/L, 59.4 ± 22.7 μg/dL, 161.0 ± 70.8 IU/L, 12.8 ± 5.0 μg/dL, 68.0 ± 51.8 μmol/L, and 28.6% ± 13.5%, respectively. PVTBF showed a significant negative correlation with ICG R15 (r = -0.468, P <0.01). No significant correlation was seen between ICG 15R, HATBF and THTBF. There was a significant correlation between PVTBF and Alb (r = 0.2499, P < 0.05), and NH₃ tended to have an inverse correlation with PVTBF (r = -0.2428, P = 0.0894). There were also many significant correlations between ICG R15 and liver function parameters, including Alb, NH3, PT, BNP, TBA, BCAA, and tyrosine (r = -0.2156, P < 0.05; r = 0.4318, P < 0.01; r = 0.4140, P < 0.01; r = 0.3610, P < 0.05; r = 0.5085, P < 0.001; r = 0.4496, P < 0.01; and r = 0.4740, P < 0.05, respectively).

CONCLUSION: Our investigation showed that there is a close correlation between liver function and hepatic blood flow.

• Alcoholic liver cirrhosis
• Hepatic tissue blood flow
• Liver function
• Indocyanine green
• Xenon computed tomography

• Adult
• Aged
• Biomarkers/blood
• Female
• Humans
• Liver/blood supply
• Liver/metabolism
• Liver/pathology
• Liver/physiopathology
• Liver Circulation
• Liver Cirrhosis, Alcoholic/blood
• Liver Cirrhosis, Alcoholic/diagnosis
• Liver Cirrhosis, Alcoholic/physiopathology
• Liver Function Tests
• Male
• Middle Aged
• Predictive Value of Tests