Splanchnic and leg exchange of free fatty acids in patients with liver cirrhosis

Splanchnic and leg exchange of free fatty acids (FFA), glycerol and ketone bodies, as well as FFA turnover, were determined in the post-absorptive state in 8 patients with liver cirrhosis and in 6 healthy control subjects. The catheter technique was used together with tracer ([14C]oleate) infusion. The arterial concentrations of FFA, glycerol and ketone bodies were 2-6-fold higher in the patients than in the controls. The FFA turnover was 230% greater in the patients, while the fractional turnover was similar in the two groups. In the splanchnic region as well as in the leg, both FFA uptake and release were increased 2-4-fold in the patients. The fractional uptake of FFA was reduced in both areas, indicating that the augmented uptake was due to the high circulating FFA levels alone. The splanchnic production of ketone bodies was four times higher in the patients than in the controls (295 +/- 30 vs 87 +/- 11 mumol/min). The fraction of FFA converted to ketone bodies was greater (42 +/- 6 vs 20 +/- 5%, P less than 0.05), indicating that the accelerated ketone body production was a combined effect of raised FFA uptake and altered intrahepatic metabolism of FFA. The splanchnic production of glucose was reduced by approximately 50% in the patients, while the uptake of glycerol was augmented. The leg uptake of 3-hydroxybutyrate was increased 300% and the release of glycerol was 200% greater in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure

OBJECTIVE: In acute liver failure (ALF), urea production is severely impaired, and detoxification of ammonia by glutamine synthesis plays an important protective role. The aim of this study was to examine the effects of therapeutic high-volume plasmapheresis (HVP) on arterial concentrations and splanchnic exchange rates of ammonia, urea, and amino acids-in particular, glutamine. METHODS: A quantity of 8 L of plasma was exchanged over the course of 7 h in 11 patients with ALF after development of hepatic encephalopathy grade III-IV. Splanchnic exchange rates of ammonia, urea, and amino acids were measured by use of liver vein catheterization. RESULTS: HVP removed ammonia and glutamine at a rate of 1 micromol/min and 27 micromol/min, respectively. Arterial ammonia decreased from 160 +/- 65 to 114 +/- 50 micromol/L (p < 0.001). In contrast, arterial glutamine was only minimally changed from 1791 +/- 1655 to 1764 +/- 1875 micromol/L (NS). This implied that the rate of systemic glutamine synthesis was increased by 27 micromol/min. Splanchnic exchange rates (before vs after HVP) were as follows: for ammonia, -93 +/- 101 versus -70 +/- 80 micromol/min (NS); urea-nitrogen, 0.08 +/- 1.64 versus -0.31 +/- 0.45 mmol/min (NS); alanine, -73 +/- 151 versus 12 +/- 83 micromol/min (p < 0.05); and glutamine: 132 +/- 246 versus 186 +/- 285 micromol/min (NS), with negative values denoting release. CONCLUSIONS: Arterial ammonia decreased during HVP in patients with ALF. The data suggest that this effect of HVP could be explained by increased hepatic urea synthesis and possibly by increased glutamine synthesis in muscle tissue.     

Splanchnic metabolism of fuel substrates in acute liver failure

BACKGROUND/AIMS: This study aimed to characterize the exchange of fuel substrates in the splanchnic circulation in acute liver failure. METHODS: Liver vein catheterization was used in 22 patients with acute liver failure after development of hepatic encephalopathy grade III-IV Healthy controls, patients with cirrhosis and patients with acute on chronic liver disease were also studied. RESULTS: In acute liver failure there was splanchnic removal of glucose (0.21+/-0.44 mmol/min), release of lactate (0.34+/-0.37 mmol/min), pyruvate (0.08+/-0.06 mmol/min) and ketone bodies (0.04+/-0.02 mmol/min), while extraction of amino acids and free fatty acids was insignificant. In the acute liver failure group, a normal hepatic venous oxygen saturation (0.69+/-0.12) and normal pyruvate/lactate ratio suggested absence of hypoxia even though the acetoacetate/beta-hydroxybutyrate ratio was decreased. Only in the acute liver failure group did the measured splanchnic oxygen content difference exceed what could be accounted for even by hypothesizing complete oxidation of all extracted blood-borne fuel substrates; oxidation of endogenous substrates may be quantitatively important in this condition. CONCLUSION: Acute liver failure was associated with a state of accelerated glycolysis in the splanchnic region, leading to release of lactate in the absence of splanchnic hypoxia.     

Splanchnic exchange of glucose, amino acids and free fatty acids in patients with chronic inflammatory bowel disease.

In order to study arterial concentrations and splanchnic exchange of substrates and hormones in patients with chronic inflammatory bowel disease three patients with Crohn's disease and four with ulcerative colitis were studied using the hepatic venous catheter technique. Systemic turnover and regional exchange of free fatty acid were evaluated using intravenous infusion of 14C-labelled oleic acid. All measurements were made in the postabsorptive, overnight fasted state. Arterial glucose concentrations were 10% lower in the patients but net splanchnic glucose output was similar in patients and controls. Glucose precursor uptake (lactate, pyruvate, and glycerol), however, was increased two to five fold in the patients. Arterial amino acid concentrations were generally reduced but net splanchnic amino acid uptake was the same in patients and controls. Arterial concentrations of free fatty acid and oleic acid as well as systemic and fractional turnover were similar in patients and controls. The patients' splanchnic uptake of oleic acid was increased more than three fold in comparison with controls. Splanchnic release of oleic acid was also augmented in the patients. Both arterial concentrations and splanchnic production of ketone bodies were raised in the patients. The proportion of splanchnic free fatty acid uptake which could be accounted for by ketone body production was significantly greater in the patients (37 +/- 4%) than the controls (20 +/- 5%, p less than 0.025). Estimated hepatic blood flow was 55% greater (p less than 0.01) in the patients as compared with the controls (1930 +/- 150 vs 1240 +/- 70 ml/min), while splanchnic oxygen uptake was similar in the two groups. From these findings it is concluded that patients with chronic inflammatory bowel disease show (1) markedly increased hepatic blood flow, reflecting an inflammatory hyperaemia in the splanchnic region, (2) a normal net splanchnic glucose output, (3) accelerated hepatic gluconeogenesis as well as ketogenesis, probably as a consequence of the altered hormonal milieau, and (4) low concentrations of most amino acids possibly because of protein malabsorption. These findings underscore the importance of adequate protein and carbohydrate administration to this patient group.     

Correlations between zinc, amino acids and ammonia in liver cirrhosis

In view of the universal metabolic importance of zinc in the organism, it was the purpose of the present work to determine the concentrations of zinc in serum, of amino acids and ammonia in plasma of patients with liver cirrhosis, and investigate that correlations might exist between these substances. The study involved 18 patients with decompensated liver cirrhosis without coma and eleven with coma. The subjects with normal livers were used as controls. While confirming known data (reduced zinc levels, imbalance of plasma amino acids, hyperammonaemia in chronic liver diseases) the findings also revealed correlations between the above substances. A negative correlations existed between zinc and ammonia. Decreases in zinc serum levels were accompanied by increases in plasma ammonia concentrations in hepatic coma (p less than 0.05). Plasma levels of amino acids did not correlate with serum zinc concentrations.     

Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure.

BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine metabolism. METHODS: The study consisted of patients with FHF (n = 16) or cirrhosis (n = 5), and healthy subjects (n = 8). Cerebral blood flow was measured by the 133Xe washout technique. Blood samples for determination of ammonia and amino acids were drawn simultaneously from the radial artery and the internal jugular bulb. RESULTS: A net cerebral ammonia uptake was only found in patients with FHF (1.62 +/- 0.79 micromol x 100 g(-1) x min(-1)). The cerebral glutamine efflux was higher in patients with FHF than in the healthy subjects and cirrhotics, -6.11 +/- 5.19 vs. -1.93 +/- 1.17 and -1.50 +/- 0.29 micromol x 100 g(-1) x min(-1), respectively (P < 0.05). Patients with FHF who subsequently died of cerebral herniation (n = 6) had higher arterial ammonia concentrations, higher cerebral ammonia uptake, and higher cerebral glutamine efflux than survivors. Intervention with short-term mechanical hyperventilation in FHF reduced the net cerebral glutamine efflux, despite an unchanged net cerebral ammonia uptake. CONCLUSIONS: Patients with FHF have an increased cerebral glutamine efflux, and short-term hyperventilation reduces this efflux. A high cerebral ammonia uptake and cerebral glutamine efflux in patients with FHF were associated with an increased risk of subsequent fatal intracranial hypertension.     

Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats.

The pathogenesis of brain edema in acute liver failure is poorly understood. We have previously shown that rats with ischemic acute liver failure (portacaval anastomosis followed by hepatic artery ligation) exhibit brain edema and intracranial hypertension, with swelling of cortical astrocytes as the most prominent neuropathological abnormality. Because ammonia has been shown to induce swelling of astrocytes in vivo and in vitro, we examined the relationship between brain ammonia, amino acids generated from ammonia metabolism and brain water content in this model. Four groups of animals were studied: rats subjected to two sham operations, rats subjected to portacaval anastomosis and a sham operation, rats subjected to a sham operation and hepatic artery ligation and rats subjected to portacaval anastomosis and hepatic artery ligation. The last group of animals was studied at three progressive stages of encephalopathy. Cortical gray matter water increased from 80.26% +/- 0.22% (sham + sham) to 82.46% +/- 0.06% (last stage of devascularization). In cerebral cortex, brain ammonia increased to a maximum of 5.4 mmol/L. Glutamine, generated in glial cells from ammonia and glutamate, increased sixfold to 24 mmol/L and remained at this level throughout all stages of encephalopathy. Alanine, which may be generated from the transamination of glutamine, increased in parallel to the increase in water (r = 0.80, n = 15). In this model of fulminant liver failure and associated brain edema, brain ammonia increases to levels associated with in vitro swelling of brain slices and glial cells. The accumulation of osmogenic aminoacids such as glutamine and alanine may contribute to the selective astrocyte swelling seen in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictive value of arterial ammonia for complications and outcome in acute liver failure

BACKGROUND AND AIMS: In acute liver failure (ALF), the brain is exposed to high levels of ammonia. Human studies defining the clinical significance of ammonia in ALF are lacking. This prospective study evaluated the relationship of arterial ammonia levels at admission to complications and survival among patients with ALF. METHODS: Eighty consecutive ALF patients admitted from March 2001 to December 2003 were followed up until death or complete recovery. All had arterial ammonia estimation at admission (enzymatic method). Logistic regression analysis was performed to identify independent predictors of mortality. RESULTS: Forty two (52.5%) patients died. Non-survivors had significantly higher median ammonia levels than survivors (174.7 v 105.0 micromol/l; p<0.001). An arterial ammonia level of > or = 124 micromol/l was found to predict mortality with 78.6% sensitivity and 76.3% specificity, and had 77.5% diagnostic accuracy. Patients with higher ammonia levels also developed more complications, including deeper encephalopathy (p = 0.055), cerebral oedema (p = 0.020), need for ventilation (p<0.001), and seizures (p = 0.006). Logistic regression analysis showed that pH, presence of cerebral oedema, and arterial ammonia at admission were independent predictors of mortality (odds ratios 6.6, 12.6, and 10.9, respectively). Incorporating these variables, a score predicting mortality risk at admission was derived: 2.53 + 2.91 ammonia + 2.41 oedema + 1.40 pH, where ammonia is scored as 0 (if <124 micromol/l) or 1 (if > or =124 micromol/l); oedema is scored as 0 (absent) or 1(present); and pH is scored as 1 (if < or =7.40) or 0 (if >7.40). Levels of partial pressure of ammonia were equally correlated with outcome. CONCLUSION: Arterial ammonia at presentation is predictive of outcome and can be used for risk stratification. Ammonia lowering therapies in patients with ALF should be evaluated.     

非生物人工肝支持系统治疗肝功能衰竭的血清氨基酸谱变化

目的 分析肝功能衰竭患者接受非生物人工肝支持系统(ALSS)治疗引起的血清氨基酸谱变化,阐述非生物ALSS治疗肝功能衰竭的有效性.方法 对2009年6月至2010年8月间146例肝功能衰竭患者行非生物ALSS治疗,观察治疗前后患者血清氨基酸谱的变化情况,并对不同预后、不同肝功能衰竭类型以及处于不同肝功能衰竭时期患者的血清氨基酸水平的变化进行研究.计量资料采用配对样本的t检验.结果 非生物ALSS治疗后,血清谷氨酸和赖氨酸下降明显[(395.62±200.24)μumol/L比(260.05±169.56)μmol/L,(436.73±326.18)μmol/L比(407.12±292.01)μmol/L;t＝8.611,t＝2.659;均P＜0.01],苏氨酸、支链氨基酸/芳香族氨基酸显著上升[(1302.90±1288.70)μmol/L比(1406.70±1272.34)μmol/L,1.23±0.53比1.36±0.57;t＝2.895,t＝1.061;均P＜0.01].在预后不同的患者间、不同肝功能衰竭类型以及处于不同时期的肝功能衰竭患者间,谷氨酸、酪氨酸、精氨酸以及蛋氨酸等治疗前后差异有统计学意义.结论 非生物ALSS治疗可以改善肝功能衰竭患者血清氨基酸紊乱状况.不同肝功能衰竭分类、分期以及不同预后患者的血清氨基酸谱在非生物ALSS治疗后有显著不同的变化.

Abstract：

Objective To analyze the patterns of amino acid changes in liver failure patients treated with non-bioartificial liver support system (ALSS), and to explore the efficacy of ALSS in liver failure treatment. Methods A total of 146 liver failure patients treated with ALSS from June 2009 to August 2010 were recruited in this study. Paired blood samples were collected from every patient and serum amino acids and ammonia were tested by automatic amino acid analyzer. The changes of amino acids in patients with different prognoses, different types/phases of liver failure were evaluated.Measurement data were compared by paired t test. Results After ALSS treatment, liver failure patients experienced a significant decrease in serum glutamic acid and lysine [(395.62±200.24)μmol/Lvs (260. 05±169.56) μmol/L and (436. 73±326. 18)μmol/L vs (407. 12±292.01) μmol/L,respectively; t= 8. 611 and 2. 659, respectively; both P＜0.01)], while experienced greatly increases in threonine and branched-chain amino acids/aromatic amino acid ratio [( 1302. 90 ±1288.70) μmol/L vs (1406.70 ±1272. 34) μmol/L and 1. 23 ± 0. 53 vs 1. 36 ± 0.57, respectively; t = 2. 895 and 1. 061,respectively; both P＜0. 01)]. The changes of glutamic acid, tyrosine, arginine and methionine before and after ALSS treatment in patients with different prognoses, different types/phases of liver failure were all significantly different. Conclusions ALSS treatment could improve the serum amino acid disorder in liver failure patients. The amino acids in patients with different types/phases or different prognoses of liver failure change significantly after ALSS treatment.     

Branched-chain amino acids and muscle ammonia detoxification in cirrhosis

Branched-chain amino acids (BCAA) are used as a therapeutic nutritional supplement in patients with cirrhosis and hepatic encephalopathy (HE). During liver disease, the decreased capacity for urea synthesis and porto-systemic shunting reduce the hepatic clearance of ammonia and skeletal muscle may become the main alternative organ for ammonia detoxification. We here summarize current knowledge of muscle BCAA and ammonia metabolism with a focus on liver cirrhosis and HE. Plasma levels of BCAA are lower and muscle uptake of BCAA seems to be higher in patients with cirrhosis and hyperammonemia. BCAA metabolism may improve muscle net ammonia removal by supplying carbon skeletons for formation of alfa-ketoglutarate that combines with two ammonia molecules to become glutamine. An oral dose of BCAA enhances muscle ammonia metabolism but also transiently increases the arterial ammonia concentration, likely due to extramuscular metabolism of glutamine. We, therefore, speculate that the beneficial effect of long term intake of BCAA on HE demonstrated in clinical studies may be related to an improved muscle mass and nutritional status rather than to an ammonia lowering effect of BCAA themselves.     

非生物人工肝支持系统治疗肝功能衰竭的血清氨基酸谱变化

Objective To analyze the patterns of amino acid changes in liver failure patients treated with non-bioartificial liver support system (ALSS), and to explore the efficacy of ALSS in liver failure treatment. Methods A total of 146 liver failure patients treated with ALSS from June 2009 to August 2010 were recruited in this study. Paired blood samples were collected from every patient and serum amino acids and ammonia were tested by automatic amino acid analyzer. The changes of amino acids in patients with different prognoses, different types/phases of liver failure were evaluated.Measurement data were compared by paired t test. Results After ALSS treatment, liver failure patients experienced a significant decrease in serum glutamic acid and lysine [(395.62±200.24)μmol/Lvs (260. 05±169.56) μmol/L and (436. 73±326. 18)μmol/L vs (407. 12±292.01) μmol/L,respectively; t= 8. 611 and 2. 659, respectively; both P＜0.01)], while experienced greatly increases in threonine and branched-chain amino acids/aromatic amino acid ratio [( 1302. 90 ±1288.70) μmol/L vs (1406.70 ±1272. 34) μmol/L and 1. 23 ± 0. 53 vs 1. 36 ± 0.57, respectively; t = 2. 895 and 1. 061,respectively; both P＜0. 01)]. The changes of glutamic acid, tyrosine, arginine and methionine before and after ALSS treatment in patients with different prognoses, different types/phases of liver failure were all significantly different. Conclusions ALSS treatment could improve the serum amino acid disorder in liver failure patients. The amino acids in patients with different types/phases or different prognoses of liver failure change significantly after ALSS treatment.     

非生物人工肝支持系统治疗肝功能衰竭的血清氨基酸谱变化

Objective To analyze the patterns of amino acid changes in liver failure patients treated with non-bioartificial liver support system (ALSS), and to explore the efficacy of ALSS in liver failure treatment. Methods A total of 146 liver failure patients treated with ALSS from June 2009 to August 2010 were recruited in this study. Paired blood samples were collected from every patient and serum amino acids and ammonia were tested by automatic amino acid analyzer. The changes of amino acids in patients with different prognoses, different types/phases of liver failure were evaluated.Measurement data were compared by paired t test. Results After ALSS treatment, liver failure patients experienced a significant decrease in serum glutamic acid and lysine [(395.62±200.24)μmol/Lvs (260. 05±169.56) μmol/L and (436. 73±326. 18)μmol/L vs (407. 12±292.01) μmol/L,respectively; t= 8. 611 and 2. 659, respectively; both P＜0.01)], while experienced greatly increases in threonine and branched-chain amino acids/aromatic amino acid ratio [( 1302. 90 ±1288.70) μmol/L vs (1406.70 ±1272. 34) μmol/L and 1. 23 ± 0. 53 vs 1. 36 ± 0.57, respectively; t = 2. 895 and 1. 061,respectively; both P＜0. 01)]. The changes of glutamic acid, tyrosine, arginine and methionine before and after ALSS treatment in patients with different prognoses, different types/phases of liver failure were all significantly different. Conclusions ALSS treatment could improve the serum amino acid disorder in liver failure patients. The amino acids in patients with different types/phases or different prognoses of liver failure change significantly after ALSS treatment.     

Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure

High circulating ammonia concentrations are common in patients with acute liver failure (ALF) and are associated with hepatic encephalopathy (HE) and intracranial hypertension (ICH). Other risk factors are poorly characterized. We evaluated the relation of the admission arterial ammonia concentration and other clinical variables with the development of HE and ICH. Arterial ammonia was measured on admission to the intensive care unit in 257 patients; 165 had ALF and severe HE, and there were 3 control groups: acute hepatic dysfunction without severe HE (n = 50), chronic liver disease (n = 33), and elective surgery (n = 9). Variables associated with ICH and HE were investigated with regression analysis. Ammonia was higher in ALF patients than controls. An independent risk factor for the development of severe HE and ICH, a level greater than 100 mumol/L predicted the onset of severe HE with 70% accuracy. The model for end-stage liver disease (MELD) score was also independently predictive of HE, and its combination with ammonia increased specificity and accuracy. ICH developed in 55% of ALF patients with a level greater than 200 mumol/L, although this threshold failed to identify most cases. After admission, ammonia levels remained high in those developing ICH and fell in those who did not. Youth, a requirement for vasopressors, and renal replacement therapy were additional independent risk factors. Conclusion: Ammonia is an independent risk factor for the development of both HE and ICH. Additional MELD scoring improved the prediction of HE. Factors other than ammonia also appear important in the pathogenesis of ICH. Ammonia measurements could form part of risk stratification for HE and ICH, identifying patients for ammonia-lowering therapies and invasive monitoring.     

Branched-chain amino acids in sepsis and hepatic failure

The pathophysiologic mechanisms for the metabolism of hepatic failure and severe sepsis are complex, and in many ways similar. The similarities concern abnormalities in peripheral and hepatic protein metabolism. The ability of enteral and parenteral solutions containing increased amounts of branched-chain amino acids to ameliorate many of the derangements observed in these disease states relates to this shared pathophysiology.     

Branched-chain amino acids in liver diseases

Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.     

Free amino acids in congestive heart failure

Free amino acids were quantitatively analyzed in cardiac muscle and plasma of dogs with chronic congestive heart failure produced by progressive pulmonary artery stenosis. Right ventricular systolic pressure increased from 32 to 89 mmHg and right ventricular end diastolic pressure from 3 to 15 mmHg following chronic constriction of the pulmonary artery. The ratio of right to left ventricular weight approximately doubled (30% vs. 63%) while percent dry weight (21%) did not change in failing hearts. The concentration of plasma and left ventricular amino acids were the same in control and experimental animals. The total free amino acid pool of the failing right ventricle appeared to increase and a significant alteration was seen in methionine concentration (0.111 ± 0.047 vs. 0.523 ± 0.081 μmol/g dry weight). A large change was found in the concentration of taurine (2-aminoethanesulfonic acid) in right ventricles (32.8 ± 3.4 vs. 126 ± 10 μmol/g dry weight) while the same compound was not altered in left ventricles. Myocardial free amino acid metabolism, as judged by endogenous concentrations, was not greatly influenced by chronic heart failure although failing right ventricles seemed to have an expanded pool. Specifically, the large increase in taurine concentration, which was confined to the failing right ventricle, may have functional significance since this compound has been linked to cellular calcium ion movement.     

Usefulness of exchange transfusion in acute liver failure due to severe falciparum malaria

Acute hepatic failure is a rare and serious complication of severe falciparum malaria. The management of uncomplicated falciparum malaria comprises of specific antimalarial drugs and supportive therapy. In a few patients who are critically ill because of severe falciparum malaria and heavy parasitaemia, exchange transfusion has been used. We describe a young male Saudi patient who presented with a 2-day history of fever, jaundice, and confusion. On examination he was deeply jaundiced, confused, and irritable. There were no signs of chronic liver disease. His laboratory workup revealed a markedly raised direct hyperbilirubinaemia and transaminases with prolonged prothrombin time. His serology was negative for HbsAg, HBc IgM, anti-HCV, HAV IgM, HEV IgM, and IgG. He was initially treated with parenteral quinine and other supportive treatment, without any improvement of his clinical and laboratory parameters. At this stage he was treated with whole blood exchange transfusion. He slowly improved, with complete normalization of his liver function tests and prothrombin time.     

Therapeutic plasma exchange in liver failure

The multi-organ failure syndrome associated with acute and acute-on-chronic liver failure (ACLF) is thought to be mediated by overwhelming systemic inflammation triggered by both microbial and non-microbial factors. Therapeutic plasma exchange (TPE) has been proven to be an efficacious therapy in autoimmune conditions and altered immunity, with more recent data supporting its use in the management of liver failure. Few therapies have been shown to improve survival in critically ill patients with liver failure who are not expected to survive until liver transplantation (LT), who are ineligible for LT or who have no access to LT. TPE has been shown to reduce the levels of inflammatory cytokines, modulate adaptive immunity with the potential to lessen the susceptibility to infections, and reduce the levels of albumin-bound and water-bound toxins in liver failure. In patients with acute liver failure, high volume TPE has been shown to reduce the vasopressor requirement and improve survival, particularly in patients not eligible for LT. Standard volume TPE has also been shown to reduce mortality in certain sub-populations of patients with ACLF. TPE may be most favorably employed as a bridge to LT in patients with ACLF. In this review, we discuss the efficacy and technical considerations of TPE in both acute and acute-on-chronic liver failure.     

血浆置换治疗对急性肝衰竭患者血清炎性细胞因子水平的影响

不少研究证实急性肝衰竭及伴随的多器官功能衰竭与体内多种炎性细胞因子的异常升高密切相关。如何降低炎性细胞因子水平,调节机体免疫状态成为治疗急性肝衰竭的重要措施之一。常规内科药物治疗较难有效清除体内蓄积的毒性物质、降低炎性细胞因子水平。人工肝支持治疗是近年发展迅速的终末期肝病的非内科治疗手段。[第一段]