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.     

Extracellular brain ammonia levels in association with arterial ammonia,intracranial pressure and the use of albumin dialysis devices in pigs with acute liver failure

In acute liver failure (ALF) hyperammonemia plays a mayor role in the pathogenesis of hepatic encephalopathy (HE) but does not always correlate with the severity of mental deterioration and intracranial pressure (ICP). The aim of our study was to evaluate the association with extracellular brain ammonia, ICP and the therapeutical impact of two albumin dialysis devices. ALF was induced by complete hepatectomy in 13 pigs. All pigs were monitored and treated under intensive care conditions until death. Arterial blood and cerebral microdialysis samples were collected and ICP data recorded. Additionally in 5 pigs, standard albumin dialysis and in 3 animals an albumin dialysis prototype was initiated as a tool. Arterial ammonia increased straight after hepatectomy, while extracellular brain ammonia remained on a moderate level 10 h post ALF initiation. After 16 h the brain ammonia reached arterial ammonia levels before plateauing at 1,200 μM, though the arterial ammonia continued to rise. The ICP correlated with the brain ammonia levels. No impact of the different dialysis therapies on neither blood nor brain ammonia levels was observed. In ALF the extracellular brain ammonia revealed a delayed increase compared to arterial ammonia. It correlated strongly with the ICP and could serve as a sensitive marker for HE development. Albumin dialysis did not affect blood or brain ammonia levels.     

Opportunistic infection in patients with acute liver failure

Background

Treatment with systemic corticosteroids is often used for acute liver failure (ALF), but this has increased the number of profoundly immunocompromised patients and cases of opportunistic infection.

Methods

Between January 2007 and December 2012, all patients (n = 51) referred to the Chiba University Hospital for treatment of ALF were studied. Patients with prothrombin activity of 40 % or less of the standardized values were defined as having ALF. Patient age, sex, cause of ALF, alanine aminotransferase and total bilirubin levels, prothrombin activity and total amount of corticosteroid were analyzed to determine the factors associated with the occurrence of opportunistic infection.

Results

Opportunistic infections occurred in 21.6 % (n = 11) of ALF patients. Thirty-five patients underwent systemic corticosteroid therapy, and 31.4 % of those patients showed opportunistic infections. Cytomegalovirus (n = 9, 81.8 %) and Pneumocystis jiroveci (n = 6, 54.5 %) were the microorganisms frequently suspected as the causes of opportunistic infection. In 7 (63.6 %) of the 11 cases of opportunistic infection, 2 or more species of microorganism were detected. Seven patients (63.6 %) with opportunistic infection were cured by treatment. Cox regression analysis for the patients who underwent systemic corticosteroid therapy steroid treatment revealed that age over 52 years (compared to younger patients: odds ratio = 9.62, 95 % confidence interval = 1.22–76.9) was only the predictive factor for the occurrence of opportunistic infection.

Conclusion

Opportunistic infections are not rare in ALF patients, and the appropriate diagnosis and treatment of these infections are critical during ALF treatment.     

Hyperlactatemia in patients with non-acetaminophen-related acute liver failure

AIM:To characterize hyperlactatemia in patients withnon-acetaminophen acute liver failure(ALF)in anattempt to clarify the mechanisms implicated and therole as a prognosis factor.METHODS:In the setting of liver transplantation,63consecutive patients with non-acetaminophen acute liverfailure were studied in relation to tissue oxygenation,hemodynamic and metabolic parameters.Before andafter transplantation,the number of infected patientsand outcome were registered.RESULTS:Acute ALF showed higher levels of lactatethan subacute ALF(5.4±1 mmol/L versus 2.2±0.6mmol/L,P=0.01).Oxygenation parameters were withinthe normal range.Lactate levels showed good correlationwith respiratory quotient(r=0.759,P<0.005),meanglucose administration(r=0.664,P=0.01)andencephalopathy(r=0.698,P=0.02),but not withsplanchnic arteriovenous difference in PCO2,pH and thepresence of infection(P=0.1).Portal vein lactate washigher(P<0.05)than arterial and mixed venous lactate,suggesting its production of hyperlactatemia in theintestine and spleen.The presence of infection was anindependent predictor of survival.CONCLUSION:Hyperlactatemia is not a prognosisfactor due to byproduct of the overall acceleration inglycolysis.     

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.     

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.     

Critical management decisions in patients with acute liver failure

Few admissions to the ICU present a greater clinical challenge than the patient with acute liver failure (ALF), the syndrome of abrupt loss of liver function in a previously unaffected individual. Although advances in the intensive care management of patients with ALF have improved survival, the prognosis of ALF remains poor, with a 33% mortality rate and a 25% liver transplant rate in the United States. ALF adversely affects nearly every organ system, with most deaths occurring from sepsis and subsequent multiorgan system failure, and cerebral edema, resulting in intracranial hypertension (ICH) and brainstem herniation. Unfortunately, the optimal management of ALF remains poorly defined, and practices are often based on local experience and case reports rather than on randomized, controlled clinical trials. The paramount question in any patient presenting with ALF remains defining an etiology, since specific antidotes can save lives and spare the liver. This article will consider recent advances in the assignment of an etiology, the administration of etiology-specific treatment to abate the liver injury, and the management of complications (eg, infection, cerebral edema, and the bleeding diathesis) in patients with ALF. New data on the administration of N-acetylcysteine to patients with non-acetaminophen ALF, the treatment of ICH, and assessment of the need for liver transplantation will also be presented.     

1977例急性、亚急性、慢加急性肝衰竭患者的病因与转归分析

目的 探讨急性肝衰竭(ALF)、亚急性肝衰竭(SALF)、慢加急性肝衰竭(ACLF)的病因. 方法回顾性总结1977例肝衰竭患者的临床资料,对病因、年龄、性别、转归等方面进行比较分析.结果 ALF的前三位病因是:HEV感染(33.96%)、HBV感染(13.21%)与药物性肝病(9.43%);SALF为药物性肝病(31.53%)、HEV感染(16.22%)、HBV感染(9.91%);ACLF为HBV感染(90.29%)、洒精性肝病(2.65%)、HBV与HEV重叠感染(2.26%).常见嗜肝病毒感染者占90.09%(1781例),其中单HBV感染占92.93%(1655例).在HBV感染者中(1655例),26～55岁患者占77.10%(1276例).2005-2007年酒精性肝衰竭患者39例,占酒精性病因患者的81.25%(48例);2006-2007年药物性肝衰竭共23例,占药物性病因的56.10%(41例).除药物性肝损伤外,其他病因均男性多于女性.三类肝衰竭总治愈,好转率为35.56%,HEV感染性肝衰竭的治愈,好转率高于药物性肝衰竭(x2=4.42,P<0.05),其他组间差异无统计学意义.结论 不同类型肝衰竭主要病因不同;HBV感染居肝衰竭病因之首,酒精性、药物性肝衰竭呈上升趋势;HEV感染性肝衰竭治愈、好转率相对较高.     

幽门螺杆菌感染对肝硬化患者血氨浓度的影响

探讨肝硬化患者幽门螺杆菌(Hp)感染与血氨的关系,及根除性治疗Hp对血氨的影响。84例肝硬化高血氨患者,分为Hp阳性组51例,阴性组33例。两组都给予支链氨基酸、乳果糖、基础护肝治疗两周,治疗前后分别测空腹静脉血氨。随后将Hp阳性组随机分两组,A组26例,应用三联疗法治疗一周;B组25例,奥美拉唑治疗一周,治疗结束一个月后复查血氨。发现阳性组的血氨与阴性组相比有显著差异(P＜0．01)。阳性组不同肝功能分级组血氨浓度之间有显著差异(P＜0．01);阴性组则否。Hp阴性组治疗前后血氨浓度变化差异有显著性(P＜0．01),阳性组则无显著差异。根除Hp治疗后血氨明显下降(P＜0．01),而用洛赛克治疗后血氨轻度升高,但无统计学意义。说明Hp感染与肝硬化患者血氨升高有密切相关性,根除Hp的治疗能有效降低血氨。     

急性肝衰竭患者血清炎性细胞因子水平分析

目的：探讨急性肝衰竭患者血清炎性细胞因子水平的变化。方法选择15例急性肝衰竭患者和15例健康人,采用Cytometric Bead Array法检测血清细胞因子。结果急性肝衰竭患者和健康人血清IL-2、IL-4、IL-5、IL-12p70和TNF-β水平无统计学差异;急性肝衰竭患者血清TNF-α（13.49 pg/mL）、IL-6（480.96 pg/mL）、IL-10（330.28 pg/mL）和IL-17（6.36 pg/mL）水平显著高于健康人（TNF-α为7.32 pg/mL,P=0.03;IL-6为4.64 pg/mL,P＆lt;0.01;IL-10为5.47pg/mL,P＆lt;0.01;IL-17为2.03 pg/mL,P=0.04）。结论炎性细胞因子在急性肝衰竭发病的病理过程中可能起了重要作用。     

HMGB1 cytoplasmic translocation in patients with acute liver failure

Background  

High-mobility group box 1 (HMGB1) is a late mediator of lethal systemic inflammation. Acute liver failure (ALF) has been shown to trigger systemic inflammation in clinical and animal studies. To evaluate the possibility of HMGB1 cytoplasmic translocation in ALF, we determined whether HMGB1 is released in hepatocytes and end organ in patients with liver failure/injury.     

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(<1.2 mg/dL in men,or<1.1 mg/dL in women)were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012.Thirty patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also included.Measurement of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system.The ACLF patients were followed during their hospitalization period.RESULTS:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed AKI.Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L.The baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.CONCLUSION:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.     

New-onset diabetes mellitus after liver transplantation in the patients with acute liver failure

International Journal of Diabetes in Developing Countries - To detect the frequency and possible risk factors of new-onset diabetes after liver transplantation in the patients with acute liver...