Prevalence of subclinical hepatic encephalopathy in cirrhotics and relationship to plasma amino acid imbalance

Neuropsychological status, as assessed by trailmaking test; plasma amino acids, and ammonia, were studied in 54 cirrhotics without clinical evidence of encephalopathy to determine the prevalence of subclinical mental dysfunction and its relationship to metabolic abnormalities. Control values for psychometric performance were established in 54 normal subjects matched for age, sex, educational level, and employment status. Of these subjects, 16 were also used as controls for fasting ammonia and plasma amino acids. Eighteen cirrhotics (33%) showed impaired performances of the psychometric test; free tryptophan and the ratio free tryptophan to neutral amino acids were increased in 37% and 62% of cases and correlated with the psychometric scores (r=0.45 andr=0.70, respectively). In eight cirrhotics with mild encephalopathy, psychometric and metabolic evaluations were repeated several times during the infusion of amino acid solutions rich in branched-chain amino acids. Again significant correlations were observed between the psychometric scores and plasma amino acids. We conclude that a considerable proportion of clinically normal cirrhotics have neuropsychological deficits. The severity of impairment may be related to the plasma amino acid imbalance, namely to an increased passage of tryptophan across the blood-brain barrier.     

Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r=0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ratio of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.A part of this work was presented at the 15th Meeting of the European Association for the Study of the Liver (EASL), Beograd, Yugoslavia, September 4–6, 1980.     

Insulin and glucagon levels in liver cirrhosis

Alterations in insulin and glucagon levels might account for the plasma amino acid imbalance of cirrhotics. In order to verify this hypothesis we evaluated basal insulin, glucagon, branched-chain amino acids, aromatic amino acids, and free tryptophan in 13 controls and 37 cirrhotics divided on the basis of their mental state; in 4 patients the hormonal and amino acid patterns were sequentially studied during various stages of encephalopathy. Glucagon is high in cirrhotics and progressively increases with the worsening of the mental state. Free tryptophan and aromatic amino acids show a similar behavior and significantly correlate with glucagon levels (r = 0.67 and r = 0.81, respectively). On the other hand insulin levels, which are high in cirrhotics without encephalopathy, fall in the presence of deep coma. Insulin did not correlate with any of the plasma amino acids considered. Our data suggest that the catabolic state associated with increased glucagon levels may account for some of the alterations in the plasma amino acid profiles of cirrhotics. Portal-systemic shunting does not seem to be the common cause of both hyperglucagonemia and hyperaminoacidemia. Decreased branched-chain amino acid levels may be related to factors different from those involved in the alterations of carbohydrate homeostasis.     

Can dietary intake influence plasma levels of amino acids in liver cirrhosis?

BACKGROUND: Modifications in plasma amino acid patterns in cirrhotics are attributed to impaired liver function, being more evident in alcoholic than in viral cirrhosis. AIM: To evaluate whether diet influences plasma amino acid concentrations in different aetiological groups of cirrhotics. PATIENTS: Study population comprised 40 patients with cirrhosis (25 virus- and 15 alcohol-related], all Child A, and 30 healthy subjects (controls). METHOD: A food frequency and quality questionnaire was utilized to determine dietary history and alcohol intake. Nutritional status was evaluated by anthropometric method. Amino acids were determined, on venous blood samples, using a specific analyzer while cysteine was evaluated by fluorescent high power liquid chromatography RESULTS: The total daily intake of calories, proteins, lipids, and carbohydrates was similar in all individuals. Food quality distinguished the cirrhotics from the controls, but not the different aetiological groups of cirrhotics. Plasma cysteine levels were significantly lower, while aromatic amino acids and methionine were significantly higher, in all cirrhotics (p<0.001 and p<0.01, respectively, versus controls). The decrease in cysteine and the increase in other amino acids were more marked in alcoholics (p<0.01). CONCLUSIONS: Ethanol intake, but not diet, further enhances the changes in plasma aromatic amino acids, methionine and cysteine induced by impaired liver function in patients with cirrhosis, suggesting a direct interference of alcohol in their metabolism.     

Plasma amino acid response to protein ingestion in patients with liver cirrhosis

The metabolic effects of a protein-rich meal were studied for 3 h in 10 controls and in 20 cirrhotic patients. After protein ingestion, blood glucose did not vary significantly. Insulin and glucagon levels rose in controls and, more markedly, in cirrhotics. Aromatic amino acids and tryptophan increased more in cirrhotics as a result of their decreased liver function. Similarly, branched-chain amino acids increased by 153 +/- 14 nmol/ml X min (mean +/- SE) in controls and by 259 +/- 27 nmol/ml X min in cirrhotics (p less than 0.02), in the presence of a markedly increased insulin response. Branched-chain amino acid metabolism mainly occurs in skeletal muscle under insulin control; in cirrhosis, it might be reduced as a consequence of insulin resistance. To support this hypothesis, the effects of the protein meal were compared with those of an oral glucose load in 15 cirrhotic patients. Branched-chain amino acid response to protein ingestion significantly correlated with blood glucose response to oral glucose (r = 0.714), and with insulin resistance during the glucose tolerance test, when assessed by the insulinogenic index (r = 0.628). Similarly, in 8 patients, increased branched-chain amino acid response also correlated with the index of tissue sensitivity to insulin obtained by means of the glucose clamp technique during continuous insulin infusion (r = -0.809). We conclude that liver cirrhosis is characterized by an abnormal branched-chain amino acid response to protein ingestion, which matches the well-known intolerance to oral glucose. Both alterations are possibly due to decreased peripheral insulin activity on substrates.     

Plasma amino acids imbalance in patients with liver disease

The venous plasma amino acid patterns have been determined in 12 normal individuals and in 71 shunted and nonshunted cirrhotics in various grades of hepatic encephalopathy. The free amino acids have been determined by an amino autoanalyzer; the total and free tryptophan have been measured by a spoctrophotofluorimetric method. In 14 instances arterial plasma amino acid patterns have been measured simultaneously. High levels of aromatic and sulfurated amino acids and low levels of branched-chain amino acids have been constantly found in all cirrhotics. Methionine, phenylalanine, valine, leucine, tyrosine, and free tryptophan showed a statistical difference between controls and all other groups. These altered patterns did not correlate either with the grade or the evolution of the coma or with the presence of the surgical anastomosis. No statistical differences were lated with the grade and evolution of the hepatic encephalopathy was free tryptophan. The molar ratios between the amino acids sharing the same transport system across the blood-brain-barrier have been considered. A very good correlation with the grade of the mental disorder was found with the ratios free tryptophan/phenylalanine-tyrosine-methionine-valine-leucine-isoleucine and free tryptophan/branched-chain amino acids.This work was supported by Grant 30.3.1971, no. 118, 500.6/Contract 72, from Ministero della Sanita. Dir. Gen. Sery. Med. Soc., Div. VI.     

Oral glucose in cirrhotics. Effects on plasma aminoacid patterns and the role of insulin and glucagon.

Changes in the plasma aminoacid (AA) profile present in hepatic encephalopathy were related to a catabolic state characterized by a reduced insulin/glucagon molar ratio (IRI/IRG). Oral glucose is able to suppress the hyperglucagonemia and further to increase the elevated insulin levels of cirrhotics leading to a rise of IRI/IRG. We evaluated the plasma AAs in ten controls and twelve cirrhotics following the ingestion of oral glucose. At 180 min we demonstrated a similar fall (about 35%) of plasma AAs both in cirrhotics and in controls, with the exception of free tryptophan, which fell more markedly in cirrhotics (about 60%), possibly secondary to the fall in plasma free fatty acids. After the oral glucose load, the levels of aromatic AAs and free tryptophan, as well as the molar ratio free tryptophan/branched-chain + aromatic AAs returned to normal in cirrhotics. High levels of both aromatic AAs and free tryptophan have been implicated in the pathogenesis of hepatic coma. Our data support the hypothesis that the administration of oral glucose might be relevant in the management of cirrhotic patients with hepatic encephalopathy, possibly improving their mental state.     

Selective Increases of Extracellular Brain Concentrations of Aromatic and Branched-Chain Amino Acids in Relation to Deterioration of Neurological Status in Acute (Ischemic) Liver Failure

Previous reports based on studies in brain tissue from humans and experimental animals suggest that aromatic amino acids (AAAs) and branched-chain amino acids (BCAA's) accumulate in brain in acute liver failure. In order to assess these changes in relation to the severity of neurological impairment and to the degree of hyperammonemia AAAs and BCAAs were measuredin vivo by cerebral microdialysis in frontal cortex of rats at various stages during the development of hepatic encephalopathy due to acute liver failure resulting from portacaval anastomosis followed by hepatic artery ligation. Extracellular brain concentrations of AAAs and of valine and leucine were elevated 2 to 4-fold following hepatic devascularization and these increases were significantly correlated to arterial ammonia concentration (r=0.71–0.84, p<0.05). Extracellular concentrations of tyrosine paralleled the deterioration of neurological status in acute liver failure rats. In view of their role as precursors of monoamine neurotransmitters, ammonia-induced alterations of intracellular/extracellular brain concentration ratios for AAAs could account for altered neuronal excitability and contribute to the encephalopathy characteristic of acute liver failure.     

Brain tryptophan, plasma free tryptophan and distribution of plasma neutral amino acids.

Although rat brain tryptophan is strikingly elevated following portacaval shunt, plasma total tryptophan is unchanged and plasma free tryptophan is not elevated to the same degree as brain tryptophan. Investigation of the concentrations of the neutral amino acids (phenylalanine, tyrosine, methionine, threonine, leucine, isoleucine, and valine) revealed that their distribution and the sum of their concentrations were altered following portacaval shunt, and that this pattern was similar to that seen in humans with cirrhosis of the liver. It is suggested that both the elevation in plasma free tryptophan and the decrease in the competing neutral amino acids, act together to increase the transport of tryptophan into brain when portal blood is diverted around the liver. The implications of these findings in therapy of hepatic coma is discussed.     

Effects of somatostatin on plasma ammonia and amino acid profile during fasting and after protein feeding in cirrhotic patients

The effects of somatostatin on fasting and absorptive plasma ammonia and amino acids were studied in 12 cirrhotic patients. They received a 6 h intravenous infusion of somatostatin (500 micrograms/h) or saline, starting 90 min before protein feeding. During the fasting period somatostatin significantly reduced plasma ammonia (-18%) and total tryptophan (-39%), increased plasma leucine (+19%), isoleucine (+17%), glutamine (+22%), glycine (+13%), arginine (+14%) and lysine (+12%), and prevented the significant fall of phenylalanine (-8%), tyrosine (-6%), alanine (-8%) and threonine (-9%) seen with saline. The percent changes in ammonia and glutamine concentrations were inversely correlated (r = -80; p less than 0.001) After protein ingestion, somatostatin slowed the maximal plasma increase in ammonia and alpha-nitrogens by at least two hours, but their total 5 h plasma response was not reduced, and even, in some instances, significantly increased (valine, leucine, glutamine, alanine and serine) with respect to saline. The results suggest that in fasting cirrhotics somatostatin reduces plasma ammonia, probably through an impaired intestinal ammoniogenesis from circulating precursors, and inhibits the disposal of branched chain, aromatic (except tryptophan) and gluconeogenic amino acids. Furthermore, it delays, but does not reduce, the plasma increase in nitrogen after protein ingestion.     

The role of protein metabolism in 204 liver cirrhotics with and without hepatic encephalopathy. II. Amino acids, free phenols and indoles

Toxic protein metabolites are assumed to play an important role in the multifactorial pathogenesis of hepatic encephalopathy (HE). To investigate this, we examined the serum levels of free amino acids, free phenols and indoles in 100 healthy adults, and in 124 liver cirrhotics with HE and 80 without HE. We found a significant increase in free serum phenols and indican already in liver cirrhosis without portal hypertension (PH) and HE. In stage III and IV HE large amounts of p-hydroxy-phenyl lactic acid were detected, which was not the case in cirrhotics without HE. In HE the increase in free serum phenols and indican was much higher than that of the mother substances tyrosine and tryptophan. The quotient BCAA/AAA was decreased significantly already in PH without HE. In addition to the increased formation by intestinal bacteria, a diminished oxidative capacity of the cirrhotic liver seems to be one of the main causes of the increased serum levels of toxic protein metabolites in HE.     

Serum amino acids in hepatic encephalopathy--effects of branched chain amino acid infusion on serum aminogram

Encephalopathic patients with cirrhosis of the liver consistently showed elevated levels of the aromatic amino acids, phenylalanine, tyrosine and free tryptophan as well as methionine in serum, whereas levels of the branched chain amino acids, valine, leucine and isoleucine, were depressed. Comatose patients with fulminant hepatitis had markedly elevated levels of all amino acids, the results being greatly different from those of cirrhotic patients. Molar ratios of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) decreased both in cirrhotics with and without encephalopathy and in cases with fulminant hepatitis. Infusion of a commercially available L-amino acid solution in a cirrhotic patient induced a strikingly abnormal aminogram documented in hepatic encephalopathy. Therefore, effects of branched chain amino acid infusion on the deranged amino acid pattern were primarily studied for the purpose of improvement in hepatic encephalopathy by normalization of serum amino acid patterns. Elevated levels of the aromatic amino acids and methionine could be apparently depressed in a cirrhotic patient by this type of infusion but not in a case of fulminant hepatitis probably because of the poor utilization of these amino acids in severely impaired liver.     

Gestational Ethanol Consumption on Tissue Amino Acid Levels: Decreased Free Histidine and Tryptophan in Fetal Tissues with Concomitant Increase in Urinary Histamine Excretion

The effects of ethanol consumption during pregnancy on maternal, placental, and fetal tissue amino acid levels and metabolism were investigated. Pregnant Sprague-Dawley rats were given 35% ethanol-calorie liquid diet, ad libitum, from gestation day 7 to 21. Control rats were pair-fed with isocaloric sucrose substituted for ethanol. Ethanol consumption decreased fetal body weight and increased placental weight. Twenty-four amino acids were determined in six tissues (maternal plasma and liver, placenta, fetal plasma, liver, and brain) by HPLC with orthophthalaldehyde derivatization. The effects of ethanol on free amino acid levels differed from tissue to tissue. In general, ethanol affected more amino acids in maternal plasma, fetal plasma, and liver. Maternal liver, placenta, and fetal brain amino acids were more resistant to ethanol effect. Two essential amino acids, histidine and tryptophan, were consistently decreased in fetal tissues by maternal ethanol consumption. The values (ethanol vs. control, nmole/ml or g, mean +/- SEM, N = 20) of fetal plasma, liver, and brain for histidine were 51.8 +/- 6.0 vs. 85.3 +/- 4.5 (p = 0.001), 269.0 +/- 26.4 vs. 503.7 +/- 47.3 (p = 0.0004), and 117.9 +/- 7.7 vs. 154.6 +/- 8.7 (p = 0.0055), respectively; and for tryptophan were 105.7 +/- 3.1 vs. 132.2 +/- 4.1 (p = 0.0001), 128.8 +/- 3.7 vs. 144.3 +/- 6.0 (p = 0.0407), and 83.4 +/- 7.2 vs. 103.6 +/- 3.2 (p = 0.0198), respectively. Histidine was also decreased in placenta by ethanol (138.1 +/- 6.6 vs. 189.1 +/- 11.8 nmole/g, p = 0.0014).(ABSTRACT TRUNCATED AT 250 WORDS)     

Albumin dialysis has a favorable effect on amino acid profile in hepatic encephalopathy

According to one popular theory, hepatic encephalopathy (HE) is partly caused by an imbalance in plasma amino acid levels. The Fischer's ratio between branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) correlates with the degree of HE; the lower Fischer's ratio, the higher the grade of HE. Extra-corporeal liver support systems, like MARS(R)-albumin dialysis (Molecular Adsorbents Recirculating System), can improve HE. The MARS(R) system uses a hyperosmolar albumin circuit to remove both water-soluble and albumin-bound substances. Plasma levels of neuroactive amino acids were analyzed in 82 consecutive patients with life-threatening liver failure admitted to our ICU. All patients fulfilled our indications for MARS treatment and most also fulfilled the criteria for liver transplantation (LTx). In patients with acute liver failure (ALF), as compared to those with acute decompensation of chronic liver failure (AcOChr), levels of leucine and isoleucine were significantly higher before MARS(R) treatment. In all patients, before MARS(R) treatment the higher the grade of HE grade the lower was the Fischer's ratio and higher were the levels of inhibitory neuroactive amino acids. During MARS(R) treatments the Fischer's ratio increased, and the grade of HE decreased. The increase in Fischer's ratio was mainly due to the decrease in AAAs. The plasma levels of neuroactive amino acids, methionine, glutamine, glutamate, histidine and taurine decreased during MARS(R)-treatment. In this study MARS(R)-albumin dialysis had a favorable effect on the plasma amino acid profile of patients with HE.     

Amino Acid Concentrations in Plasma and Erythrocytes in Aregeneratory and Haemolytic Anaemias

The concentrations of unbound amino acids in erythrocytes and in plasma from 7 normal individuals, 11 patients with various types of aregeneratory anaemia, and 4 patients with hereditary haemolytic anaemias were determined on a Technicon Amino Acid Analyzer (Perry et al 1970). Most amino acids were normally found in higher concentrations in plasma than intracellularly. Cystine, methionine and tryptophan were almost exclusively present in plasma. Aspartic acid, however, was mainly found in erythrocytes, and glutathione only in erythrocytes. Glutamic acid and ornithine were more concentrated in the cells, while glycine and asparagine showed approximately the same concentrations in erythrocytes as in plasma. In the patients, plasma amino acids showed little deviations from normal, but in the erythrocytes there were striking changes. Erythrocyte glutamic acid concentrations were moderately to markedly elevated in all patients studied, and glycine concentrations in 13 out of 15 patients. In addition, the following amino acids were increased intracellularly in more than one patient: glutamine (8 patients), serine (7), asparagine (5), threonine (4), taurine (3), alanine (2), valine (2), ornithine (2), lysine (2), citrulline (2). Aspartic acid was decreased in erythrocytes from 4 patients with aregeneratory and 1 with haemolytic anaemia.     

维持性血液透析患者血浆游离氨基酸检测的临床意义

目的　对维持血液透析患者的血浆游离氨基酸进行测定和分析。方法　用氨基酸自动分析仪测定 15例血透患者在一次透析前后的血浆氨基酸谱。结果　血透患者在透析前的必需氨基酸除苯丙氨酸外均较正常对照组降低 ,其中以缬氨酸、亮氨酸和组氨酸下降为显著 ;非必需氨基酸中精氨酸、甘氨酸和鸟氨酸明显升高 ;酪氨酸/苯丙氨酸和丝氨酸 /甘氨酸的比值较对照组明显降低。患者在一次透析后的必需和非必需氨基酸均低于透析前水平。结论　血透患者氨基酸异常的原因可能与蛋白质摄入不足、尿毒症毒性物质和酸中毒等有关     

Elevated plasma ammonia level in hepatic cirrhosis: role of glucagon

Elevated plasma ammonia level in hepatic cirrhosis has been attributed to a lack of conversion of enteric ammonia into urea or to its entry into systemic circulation via portasystemic shunting, or to both. It is exaggerated by excessive protein intake. Because hyperglucagonemia is well documented in cirrhosis and a protein meal is an effective glucagon secretagogue, plasma glucose, insulin, glucagon, and ammonia levels were determined in 50 cirrhotic patients after an overnight fast. Effects of a protein meal were also assessed in 20 of these patients. Plasma glucose was normal and remained unaltered after a protein meal. Insulin, glucagon, and ammonia levels were elevated, but only in patients with advanced liver dysfunction. Ammonia levels correlated significantly with glucagon (r = 0.61, p less than 0.001), but not with insulin or glucose levels. Insulin and glucagon levels rose after a protein meal in all patients and controls; whereas a significant rise in the ammonia level occurred only in decompensated cirrhotics. Elevation of the ammonia level was significantly correlated with fasting glucagon (r = 0.54, p less than 0.05), as well as with glucagon response (r = 0.65, p less than 0.01), but not with basal insulin or insulin response. Furthermore, the rise in ammonia level occurred too early to be accounted for by enteric generation. Finally, direct effects of glucagon administration on plasma glucose and serum ammonia were examined in 15 cirrhotic patients. Glucose response was significantly blunted in cirrhotic patients as compared with normal subjects, whereas serum ammonia rose promptly but only in cirrhotics, with maximum rise being noted in cirrhotic patients with advanced liver dysfunction. This study, therefore, suggests that hyperglucagonemia may contribute significantly to hyperammonemia in hepatic cirrhosis.     

Ethanol consumption, amino acid and glutathione blood levels in patients with and without chronic liver disease

BACKGROUND: Ethanol abuse and liver cirrhosis cause a reduction of glutathione blood levels; liver cirrhosis induces an alteration of the plasma amino acid pattern. We evaluated whether or not ethanol abuse affects amino acid levels, particularly those that are involved in metabolizing glutathione in the plasma and erythrocytes of chronic alcohol abusers with or without liver cirrhosis. METHODS. We studied 10 chronic alcohol abusers without liver cirrhosis, 10 with alcoholic cirrhosis, 10 affected by hepatitis C virus-related cirrhosis, and 10 healthy subjects. Glutathione, y-glutamyl-cysteine, and cysteine were determined by fluorescent HPLC, glutamic acid, glycine, and other free amino acids by cation exchange chromatography both in the plasma and erythrocytes of all studied subjects. RESULTS AND CONCLUSIONS: In both alcoholics and cirrhotics, we found a significant increase of plasma-aromatic amino acid and methionine levels, whereas glutathione was significantly reduced. The erythrocytes of these patients showed a significant increase of cysteine, glutamic acid, and glycine; gamma-glutamylcysteine was normal; and glutathione and other free amino acids were significantly decreased. Data suggest that, independent of liver cirrhosis, ethanol abuse affects the metabolism of amino acids and glutathione in both the plasma and the erythrocytes.     

Impaired insulin-mediated amino acid plasma disappearance in non-alcoholic fatty liver disease: a feature of insulin resistance

BACKGROUND AND AIM: Insulin resistance is a main feature, and possibly a pathogenic factor, of non-alcoholic fatty liver disease. It is usually measured on glucose metabolism; the effects on amino acid regulation have never been assessed. In particular, no data are available on insulin-dependent branched-chain amino acid metabolism, which is under insulin control. MATERIALS AND METHODS: We measured amino acid disappearance from plasma during an euglycemic glucose clamp in 39 biopsy-proven non-alcoholic fatty liver disease patients and in ten control subjects. A primed-constant infusion of insulin (constant rate, 40 mU/m2 per min for 2 h) was used to raise plasma insulin to approximately 100 mU/l. Euglycemia was maintained by a variable glucose infusion, a measure of tissue insulin sensitivity. Plasma amino acids were assayed during the clamp after ninhidrin derivatization. RESULTS: Fasting plasma amino acids were similar in the two groups. Steady-state insulin levels were significantly higher in non-alcoholic fatty liver disease patients, whereas tissue sensitivity to insulin was reduced by 50%. The plasma disappearance of branched-chain amino acids, as well as the disappearance of the sum of glutamine and glutamate and that of serine were significantly reduced in non-alcoholic fatty liver disease. Differences were maintained after adjustment for steady-state insulin, and correlated with reduced tissue sensitivity to glucose. CONCLUSION: Insulin resistance in non-alcoholic fatty liver disease patients also affects amino acid metabolism, especially for amino acids involved in peripheral muscle nitrogen exchange. The metabolic effects of altered protein/amino acid metabolism must be considered.     

肝炎后肝硬化病人血浆氨基酸和整体蛋白质更新速率的研究

目的用稳定性检索标记的１５Ｎ－甘氨酸和１３Ｃ－亮氨酸双示踪技术研究肝炎后肝硬化病人血浆氨基酸和整体蛋白质更新速率。方法１１例正常人和１９例肝硬化加入（１２例代偿期，７例失代偿期）恒速静滴６小时示踪剂后测定血浆中标记氨基酸水平，并计算血浆中氨基酸和整体蛋白质的更新速率，合成速率和分解速率。结果肝硬化时血浆氨基酸和蛋白顶的更新速率，合成和分解速率均明显加快，分解速率大于合成速率，此现象在失代偿期尤为明显。结论肝硬化时机体氨基酸和蛋白质代谢处于高流量状态，分解速率明显高于合成速率，处于负氮平衡状态。