Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy

BACKGROUND/AIMS: To compare venous, arterial and partial pressure of ammonia (pNH(3)) in 27 consecutive cirrhotics with hepatic encephalopathy, 15 cirrhotics without hepatic encephalopathy and nine controls; to reevaluate all parameters after the improvement of encephalopathy. METHODS: Patients were studied by clinical examination and psychometric testing. pNH(3) was calculated from arterial ammonia and pH. RESULTS: In patients with encephalopathy, each form of ammonia was higher than in both controls and patients without encephalopathy. The correlation with the severity of hepatic encephalopathy was similar for venous (r=0.72), arterial ammonia (r=0.76) and pNH(3) (r=0.75). The sensitivity and specificity of each variable in correctly classifying the patients as having or not having hepatic encephalopathy was also similar. Each form of ammonia decreased after the resolution or amelioration of symptoms. However, even in the 17 patients with complete resolution of hepatic encephalopathy, all three ammonia determinations resulted unchanged or increased in some patients. CONCLUSIONS: Despite the significant correlation between pNH(3) and hepatic encephalopathy, our study suggests that neither pNH(3) nor arterial ammonia are, from a clinical point of view, more useful than venous ammonia: all three determinations being limited both for the diagnosis of hepatic encephalopathy and for the clinical management of the patients.     

Partial pressure of ammonia versus ammonia in hepatic encephalopathy

Ammonia is considered the major pathogenetic factor of cerebral dysfunction in hepatic failure. The correlation between total plasma ammonia and the severity of hepatic encephalopathy (HE), however, is variable. Because ammonia that is present in gaseous form readily enters the brain, the correlation with the grade of HE of the pH-dependent partial pressure of gaseous ammonia (pNH(3)) could be better than that of total arterial ammonia levels. To test this hypothesis, 56 cirrhotic patients with acute episodes of clinical HE (median age, 54 years; range, 21-75) were studied by clinical examination and by long-latency median-nerve sensory-evoked potentials (SEPs) N70 peak, an objective and sensitive electrophysiological measure of HE. pNH(3) was calculated from arterial blood according to published methods. The clinical grade of HE correlated (P <.001) with both pNH(3) and total ammonia, but correlation was stronger with pNH(3) (r =.79 vs.69, P =.01). A similar correlation was found for N70 peak latency (r =.71 with pNH(3) vs.64 with total ammonia, respectively, P =.08). In summary, arterial pNH(3) correlates more closely than total ammonia with the degree of clinical and electrophysiological abnormalities in HE. These findings support the ammonia hypothesis of HE and suggest that pNH(3) might be superior to total ammonia in the pathophysiological evaluation of HE.     

Lactic acidosis in fulminant hepatic failure. Some aspects of pathogenesis and prognosis

To obtain further evidence of tissue hypoxia in fulminant hepatic failure, we have measured the mixed venous lactate concentration and the acid-base status of 32 patients at the time of their admission, in grade III or IV encephalopathy. The mixed venous lactate was elevated in 26 of the 32 patients (median 5.0 mmol/l, range 0.8-21.1 mmol/l), and, in 17 patients, this was associated with evidence of a metabolic acidosis. Mixed venous lactate levels correlated inversely with the mean arterial pressure (r = 0.56, P less than 0.005), systemic vascular resistance (r = 0.62, P less than 0.001) and the oxygen extraction ratio (r = 0.44, P less than 0.02). The 17 patients with a raised mixed venous lactate and metabolic acidosis had a significantly reduced systemic vascular resistance and oxygen extraction ratio compared with the other 15 (median systemic vascular resistances 944 and 1710 dyne X s/cm5/m2, respectively, P less than 0.05, median oxygen extraction ratios 19 and 23%, respectively, P less than 0.05). Survival was markedly reduced in the patients with hyperlactataemia and a metabolic acidosis, and only one out of the 17 survived compared with 12 of the remaining 15, P = 0.0002. These results suggest that lactic acid accumulation may be in part the consequence of tissue hypoxia that develops as a result of arteriovenous shunting, reflected in the reduction in systemic vascular resistance. This tissue hypoxia may occur despite apparently adequate systemic blood pressure, flow and oxygenation.     

Hepatic arterial pulsatility index in cirrhosis: correlation with portal pressure.

BACKGROUND/AIMS: Determination of the pulsatility index by means of duplex sonography provides the opportunity to evaluate the vascular resistance of the hepatic artery noninvasively. The aim of this study was to investigate the relationship between the hepatic arterial pulsatility index and the hepatic venous pressure gradient in cirrhosis. METHODS: In 50 patients with cirrhosis, hepatic venous pressure gradient was determined in the fasting state. Immediately thereafter, hepatic arterial pulsatility index and portal blood flow velocity were measured by duplex sonography with no knowledge of hepatic venous pressure values. In addition, the duplex parameters were determined in 20 controls. RESULTS: Hepatic arterial pulsatility index was significantly higher in patients with cirrhosis than in controls (0.92+/-0.1 vs. 1.14+/-0.18; p<0.001) and directly correlated with the hepatic venous pressure gradient (r = 0.7; p<0.001). Furthermore, weak correlations were found between hepatic arterial pulsatility index and Child-Pugh score (r = 0.49; p<0.01) and between portal blood flow velocity and hepatic venous pressure gradient (r = -0.48; p<0.01). CONCLUSION: In cirrhosis the hepatic arterial vascular resistance seems to increase parallel to the rise of the portal pressure. Therefore, duplex sonographic determination of the hepatic arterial pulsatility index may contribute to the noninvasive evaluation of portal hypertension.     

Amino acid challenge in patients with cirrhosis: a model for the assessment of treatments for hepatic encephalopathy.

BACKGROUND/AIMS: To mimic episodic hepatic encephalopathy after gastrointestinal bleeding under controlled conditions, cirrhotic patients were challenged with an amino acid mixture of comparable composition to haemoglobin. METHODS: Basal EEG, psychometric score (HE test), reaction times and venous blood ammonia were recorded. Following a 54 or 108 gm oral amino acid challenge, blood ammonia levels and EEG were recorded at 30-min intervals, and psychometric testing was repeated at 180 min. Ten controls (57 +/- 2) and 31 cirrhotics (52 +/- 2) of which 21 were Child's grade A or B and 10 grade C underwent the challenge. Nine had a transjugular intrahepatic porta-systemic shunt in situ. RESULTS: Seventeen patients had abnormal baseline HE scores. Basal blood ammonia and reaction time A were significantly greater in patients (52 +/- 5 micromol/l and 478 +/- 20 ms, respectively) than controls (19 +/- 2 micromol/l and 372 +/- 14 ms) (P < 0.001). Following the challenge, in patients with advanced liver disease (Child's grade B and C) the slowing of reaction time A (+85 +/- 38 and +71 +/- 31 ms, respectively; P < 0.03) and EEG (ratio of slow to fast wave activity +0.31 +/- 0.12 and +0.58 +/- 0.19; P < 0.02) were significantly greater than in controls (-3.3 +/- 8 ms and 0.00 +/- 0.03, respectively). Patients with an abnormal basal HE score had the most pronounced changes (reaction time A +110 +/- 39 ms, P < 0.01, EEG +0.52 +/- 13, P < 0.01, respectively). The change in EEG ratio correlated with the dose of amino acid administered (r = 0.96; P < 0.008). CONCLUSION: The amino acid challenge constitutes a reproducible human model of episodic, Type C hepatic encephalopathy unaffected by the complications usually encountered in clinical practice.     

Effects of isosorbide dinitrate on portal hypertension in alcoholic cirrhosis

It has recently been reported that vasodilators lower portal pressure in patients with cirrhosis. This effect, however, is not definitively proven. The effect of isosorbide dinitrate (5 mg sublingually) on splanchnic and systemic hemodynamics was investigated in 13 patients with alcoholic cirrhosis and portal hypertension. The administration of isosorbide dinitrate reduced hepatic venous pressure gradient by 34% (P less than 0.001), mean arterial pressure by 30% (P less than 0.001), cardiac index by 17% (P less than 0.001) and systemic vascular resistance by 11% (P = 0.05). Hepatic blood flow was not affected by the treatment. Significant correlations were found between the decrease in hepatic venous pressure gradient and that of cardiac index (P less than 0.05) and mean arterial pressure (P less than 0.05). These data indicate that isosorbide dinitrate lowers portal pressure in patients with cirrhosis. Decrease in cardiac output, rise in splanchnic arterial vascular resistance and decrease in porto-hepatic resistance seem to participate in determining the effect.     

Predictors of nonresponse to lactulose for minimal hepatic encephalopathy in patients with cirrhosis

Background/Aims: Minimal hepatic encephalopathy (MHE) impairs health‐related quality of life and predicts overt hepatic encephalopathy (HE) in cirrhotic patients. Lactulose is effective in the treatment of MHE. However, not all patients respond to lactulose. We evaluated predictors of nonresponse to lactulose. Patients and methods: Consecutive 110 cirrhotic patients without HE were evaluated for MHE by psychometry, P300 auditory event‐related potential (P300ERP), venous ammonia and critical flicker frequency (CFF). MHE was diagnosed by abnormal psychometry and P300ERP (>2 SD). MHE patients were treated with lactulose for 1 month. Response was defined by normalization of the abnormal test parameters (both psychometric tests and P300ERP). Results: Sixty patients (54.5%) were diagnosed as having MHE: 17/39 (44%) in Child's A, 21/42 (50%) Child's B and 22/29 (76%) in Child's C. There was a significant difference between Child's C's vs Child's A's and B's (P<0.05). Abnormal psychometric tests and abnormal P300ERP were seen in 74 (67%) and 74 (67%) patients respectively. Of 60 patients with MHE, after treatment, psychometry remained abnormal in 22 (36.6%) and P300ERP in 21 (35%) patients. CFF was<38 Hz in 34 (57%) and 11 (18%) patients, respectively, before and after treatment in MHE patients. There was a significant difference between the baseline serum sodium level (134.7±2.6 vs 131.1±2.2 mmol/L, P=0.001) and the venous ammonia level (76.6±20.7 vs 113.4±22.8 μmol/L, P=0.001) between responders vs nonresponders. Receiver operating characteristic analysis was performed to identify the cutoff for venous ammonia [cutoff 93.5 mmol/L, area under the curve (AUC) 0.892 (0.814–0.970)] and for the serum sodium level [cutoff 132.5 mmol/L, AUC 0.874 (0.779–0.998)]. Taking a cutoff of 93.5 mmol/L for ammonia patient had a sensitivity of 88.5% and a specificity of 79.4%, respectively, and a cutoff of 132.5 mmol/L for serum sodium patient had a sensitivity of 76.5% and a specificity of 88.5% for nonresponse to lactulose. On univariate analysis and multivariate analysis, serum sodium and venous ammonia were the only two parameters associated with nonresponse to lactulose. Conclusion: The prevalence of MHE was 55% and MHE improved in 57% patients with lactulose. Baseline low serum sodium and high venous ammonia were highly predictive of nonresponse to lactulose therapy.     

氨甲酰磷酸合成酶-Ⅰ和鸟氨酸氨基甲酰转移酶与肝性脑病的关系

目的 探讨血清氨甲酰磷酸合成酶Ⅰ(CPS-Ⅰ)和鸟氨酸氨基甲酰转移酶(OCT)在肝性脑病(HE)发生中的作用.方法 2008年1月-2009年12月在我院住院的120例肝硬化患者,其中HE患者25例,非肝性脑病(非HE)患者95例.对照组为我院健康体检正常者60例.收集研究对象的血清和血浆,采用酶联免疫吸附试验方法测定血清CPS-Ⅰ、OCT,VITROS-250干化学分析仪测定血氨.分析HE组、非HE组、对照组CPS-Ⅰ和OCT水平;分析肝硬化患者CPS-Ⅰ、OCT与肝功能及血氨的相关性;分析CPS-Ⅰ、OCT水平与肝硬化患者Child-Pugh分级之间的相关性.应用SPSS15.0软件进行数据分析,采用x2和t检验,计量资料两组间比较采用成组t检验,多组间的比较采用方差分析、q检验,两变量相关分析采用Pearson相关分析法.结果 HE组血清CPS-Ⅰ、OCT水平分别为(143.3±48.5)U/L和(297.0±102.6)×10 U/L,非HE组分别为(180.3±51.5)U/L和(351.8±109.0)×10 U/L,t值分别为2.53和2.78,P值均＜0.01;HE组、非HE组血清CPS-Ⅰ、OCT水平均低于正常对照组,t值分别为3.21、4.16和2.12、3.15,P值均＜0.05.CPS-Ⅰ与OCT相关性好,r=0.946,P＜0.05;CPS-Ⅰ、OCT与ALT、AST呈负相关,r值分别为-0.284、-0.239、-0.303、-0.322,P值均＜0.05.肝硬化患者CPS-Ⅰ、OCT水平和Child分级密切相关,F值分别为10.13,20.28,P值均＜0.01.结论 肝硬化患者CPS-Ⅰ和OCT活性影响血氨水平,CPS-Ⅰ和OCT与肝性脑病的发生密切相关.     

Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration

Cerebral edema leading to cerebral herniation (CH) is a common cause of death in acute liver failure (ALF). Animal studies have related ammonia with this complication. During liver failure, hepatic ammonia removal can be expected to determine the arterial ammonia level. In patients with ALF, we examined the hypotheses that high arterial ammonia is related to later death by CH, and that impaired removal in the hepatic circulation is related to high arterial ammonia. Twenty-two patients with ALF were studied retrospectively. In addition, prospective studies with liver vein catheterization were performed after development of hepatic encephalopathy (HE) in 22 patients with ALF and 9 with acute on chronic liver disease (AOCLD). Cerebral arterial-venous ammonia difference was studied in 13 patients with ALF. In all patients with ALF (n = 44), those who developed CH (n = 14) had higher arterial plasma ammonia than the non-CH (n = 30) patients (230 +/- 58 vs. 118 +/- 48 micromol/L; P <. 001). In contrast, galactose elimination capacity, bilirubin, creatinine, and prothrombin time were not different (NS). Cerebral arterial-venous differences increased with increasing arterial ammonia (P <.001). Arterial plasma ammonia was lower than hepatic venous in ALF (148 +/- 73 vs. 203 +/- 108 micromol/L; P <.001). In contrast, arterial plasma ammonia was higher than hepatic venous in patients with AOCLD (91 +/- 26 vs. 66 +/- 18 micromol/L; P <.05). Net ammonia release from the hepatic-splanchnic region was 6.5 +/- 6. 4 mmol/h in ALF, and arterial ammonia increased with increasing release. In contrast, there was a net hepatic-splanchnic removal of ammonia (2.8 +/- 3.3 mmol/h) in patients with AOCLD. We interpret these data that in ALF in humans, vast amounts of ammonia escape hepatic metabolism, leading to high arterial ammonia concentrations, which in turn is associated with increased cerebral ammonia uptake and CH.     

乳果糖治疗肝性脑病和亚临床肝性脑病149例临床观察

目的 进一步评估乳果糖对肝硬化肝性脑病和亚临床肝性脑病的疗效。方法 观察乳果糖治疗前后患者的精神状态、扑翼状震颤、脑电图、静脉血氨浓度和数字连接试验的改善情况。结果 乳果糖对肝性脑病组的脑病表现总有效率达96.5％,治疗前后静脉血氨浓度和数字连接试验的改善均有非常显著性差异(P<0.01);亚临床肝性脑病组治疗前后血氨有非常显著性差异(P<0.01),数字连接试验有显著性差异(P<0.05)。在乳果糖治疗观察期间,无一例亚临床肝性脑病患者发展为肝性脑病。结论 乳果糖适合于肝硬化肝性脑病和亚临床肝性脑病患者长期服用,可作为预防和治疗肝性脑病的常规用药。     

急性食管胃底静脉曲张破裂出血行急诊经颈静脉肝内门体分流术后发生肝性脑病的危险因素分析

目的 通过临床结果分析了解急性食管胃底静脉曲张破裂出血行急诊经颈静脉肝内门体分流术(TIPS)术后肝性脑病(HE)的危险因素。方法 回顾性分析2013年1月-2018年12月因失代偿期肝硬化伴急性食管胃底静脉曲张破裂出血在苏州大学附属第一医院接受内镜或者药物治疗失败,72 h内行覆膜支架TIPS治疗的93例患者的临床资料。根据术后发生HE情况分为HE组(n=36)和非HE组(n=57)。收集患者术前临床资料,包括性别、年龄、病因、合并症,血生化指标包括WBC、PLT、红细胞比积、TBil、AST、Alb、血清肌酐、PT等,根据实测值分别计算每位患者MELD评分,记录TIPS支架植入前测得的肝静脉锲压与游离压,肝静脉压力梯度(HVPG)为两者的差值。计量资料两组间比较采用t检验或Mann-Whitney U检验;计数资料两组间比较采用χ^2检验。二分类变量logistic回归分析TIPS术后患者的预后危险因素。结果 术后HE发病率为38.710%,两组间术前MELD评分[(13.000±3.189)分vs(11.684±2.068)分,t=2.068,P=0.043]、HVPG[(24.908±5.317) mm Hg vs (22.597±4.928) mm Hg,t=2.100,P=0.039]差异均有统计学意义。进一步HE分级显示0~1级17例(47.222%),2级9例(25.000%),3级6例(16.667%),4级4例(11.111%)。逐步logistic回归分析发现,MELD评分[比值比(OR)=0.803,95%可信区间(95%CI): 0.679~0.948,P=0.010)和HVPG(OR=0.896,95%CI: 0.816~0.984,P=0.022)是TIPS术后HE发病的独立危险因素。结论 急性食管胃底静脉曲张破裂出血行急诊TIPS术后HE发生率高,术前MELD评分和HVPG可预测TIPS术后HE发生风险。     

Splanchnic and leg exchange of amino acids and ammonia in acute liver failure

BACKGROUND & AIMS: In patients with acute liver failure, hyperammonemia is associated with cerebral herniation. We examined the splanchnic and leg exchange of amino acids, urea, and ammonia in such patients. METHODS: Bedside liver vein catheterization was used in 22 patients after development of hepatic encephalopathy grades III-IV. Femoral venous blood was sampled in 7 of these patients. RESULTS: Arterial amino acid concentration (8.1 +/- 4.1 mmol/L) was increased 4-fold above normal. Glutamine (2.4 +/- 1.8 mmol/L) and alanine (0.57 +/- 0.35 mmol/L) were by far the predominant amino acids exchanged in the splanchnic and leg circulation. In the splanchnic circulation, there was a net uptake of glutamine (241 +/- 353 micromol/min) and ammonia and alanine were released in an almost 1:1 stoichiometry (r(2) = 0.47; P < 0.001). In the leg, ammonia and alanine were removed and glutamine released. The leg ammonia concentration difference was correlated to that of glutamine (r(2) = 0.80; P = 0.008) and alanine (r(2) = 0.67; P = 0.03). CONCLUSIONS: Splanchnic metabolism of glutamine in combination with decreased hepatic function was responsible for the splanchnic release of ammonia and alanine. These processes were reversed in skeletal muscle. Stimulation of skeletal muscle metabolism of ammonia could be a important target for future treatment of patients with acute liver failure.     

Portal hypertension and ascites in acute hepatitis: clinical, hemodynamic and histological correlations

We attempted to ascertain the mechanism of portal hypertension and ascites complicating acute hepatitis in 66 patients who underwent transvenous liver biopsy and measurement of hepatic venous pressure gradient. Increase in hepatic venous pressure gradient was related to the severity of acute hepatitis, as indicated by the significant correlation between the values for hepatic venous pressure gradient and serum bilirubin, serum albumin or coagulation factor V, and by its higher value in patients with, than in patients without, encephalopathy. Hepatic venous pressure gradient was higher in patients with, than in patients without, ascites (12.5 +/- 3.4 vs. 8.4 +/- 3.6 mmHg, respectively; p less than 0.001). No ascites was clinically detectable in the patients in whom hepatic venous pressure gradient was below 6 mmHg. We tested the hypothesis that sinusoidal collapse due to liver cell dropout was a major factor in portal hypertension. Semiautomatic determination of the fractional area of sinusoidal collapse on chromotrope-stained sections and automatic measurement of Sirius red-stained collagen fiber density were performed. Hepatic venous pressure gradient significantly correlated with fractional sinusoidal collapse area (r = 0.61, p less than 0.001) and with Sirius red-stained collagen fiber density (r = 0.43, p less than 0.01). We conclude that portal hypertension in the course of acute hepatitis is related to the severity of liver damage and is a major factor in the development of ascites. Portal hypertension is mainly determined by intrahepatic vascular space being reduced by the collapse of sinusoids.     

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.     

Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy

Aim: The objective of this systematic review and meta‐analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. Methods: Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure was improvement in hepatic encephalopathy. Results were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I². Results: Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly improved hepatic encephalopathy (RR = 1.40, 95% CI = 1.05–1.86, I² = 5%). Probiotics decreased arterial ammonia (weighted mean difference 15.95; 95% CI = 26.72–3.28; I² = 68%), but not venous ammonia (weighted mean difference 5.23; 95% CI = 21.77–11.30; I² = 89%). Treatment with probiotics or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04–2.57; I² = 59%). Regression analysis showed evidence of small‐study effects. Conclusion: The present meta‐analysis suggests that probiotics may be an effective treatment of hepatic encephalopathy, though rigorous evaluation in standardized, randomized, clinical trial with clinically relevant outcomes is still needed.     

Effect of graded hypoxia on hepatic tissue oxygenation measured by near infrared spectroscopy.

BACKGROUND/AIMS: In liver transplantation ischaemia-reperfusion injury of the graft reduces hepatic tissue oxygenation which has prognostic value for patient survival. Near infrared spectroscopy (NIRS) can measure extracellular (haemoglobin oxygenation) and intracellular tissue oxygenation (cytochrome oxidase oxidation). However, it has not been validated for measuring hepatic tissue oxygenation in an experimental model with graded hypoxia. METHODS: New Zealand White rabbits (2.9+/-0.3 kg, n=9) underwent laparotomy for liver exposure. Heart rate, blood pressure, temperature, arterial blood pH and blood gas partial pressures were monitored during the experiments. Near infrared spectroscopy probes were placed on the liver surface to record continuously hepatic oxyhaemoglobin, deoxyhaemoglobin and cytochrome oxidase oxidation. Graded hypoxia was achieved by stepwise reduction of the inspired oxygen from 15 to 4%. During recovery from hypoxia 30% oxygen was administered. RESULTS: There was an immediate reduction of hepatic oxyhaemoglobin with hypoxia and a simultaneous increase of hepatic deoxyhaemoglobin. Hepatic oxyhaemoglobin showed a positive correlation with arterial oxygen pressure (r=0.77, p<0.001). Hepatic deoxyhaemoglobin showed a negative correlation with arterial oxygen pressure (r=-0.75, p<0.001). Hepatic cytochrome oxidase decreased significantly with an inspired oxygen of 10% or less and showed a positive correlation with arterial oxygen pressure (r= 0.90, p<0.001). CONCLUSIONS: Near infrared spectroscopy is an effective method for monitoring hepatic extracellular and intracellular tissue oxygenation.     

FibroScan~实施受控衰减参数检测肝脂肪变的影响因素及应用价值分析

目的探讨FibroScan~实施受控衰减参数(controlled attenuation parameter,CAP)无创定量检测肝脂肪变的影响因素及应用价值。方法纳入非酒精性脂肪性肝病患者46例,慢性乙型肝炎并肝脂肪变患者31例。以肝活检为"金标准"评价肝脂肪含量,其中肝脂肪变分级S0:5%;S1:5%~33%;S2:34%~66%;S3:66%。使用FibroScan-502机型及M探头对所有研究对象进行CAP值测定。分析CAP值与肝脂肪含量、人体学指标及生化学指标的相关性。结果肝脂肪变处于S0、S1、S2、S3的患者分别有12例、29例、31例、5例。CAP值随着肝脂肪变分级增加而增大,各级肝脂肪变患者CAP值差异具有统计学意义(χ~2=36.990,P=0.000),相邻两级间CAP值差异均具有统计学意义(均P0.05);Spearman相关分析表明,CAP值与体质指数(BMI)(r=0.368,P=0.001)、腰围(r=0.298,P=0.008)、肝脂肪变分级(r=0.696,P=0.000)呈正相关,与年龄(r=-0.335,P=0.003)呈负相关。当控制了肝脂肪变分级后,偏相关分析显示,CAP值仍与BMI(r=0.242,P=0.035)、腰围(r=0.243,P=0.034)呈正相关,与年龄(r=-0.142,P=0.222)的相关关系消失;多元逐步回归分析显示,仅肝脂肪变分级是肝脏CAP值的独立影响因素;受试者工作特征曲线分析发现,CAP诊断肝脂肪变程度≥5%、≥34%、≥67%的曲线下面积分别为0.891(P=0.000)、0.862(P=0.000)、0.889(P=0.004),最佳临界值分别为279、318、332 dB/m。结论 FibroScan~实施CAP无创定量检测肝脂肪变具有较好的应用价值,肝脂肪变分级是肝脏CAP值的独立影响因素。     

The effect of augmenting portal venous inflow on intrahepatic pressure and resistance in the isolated perfused porcine liver

BACKGROUND/AIMS: The literature regarding the relationship between portal venous flow and pressure is controversial. The aim of this study was to examine the effects of doubling portal venous inflow on hepatic hemodynamics. METHODOLOGY: Portal venous pressure, intrahepatic portal venous resistance, hepatic arterial pressure and intrahepatic arterial resistance were assessed during basal portal venous inflow (756 +/- 142 mL/min; mean +/- SD) and enhanced portal venous inflow (1512 +/- 284 mL/min) in an isolated perfused normal porcine liver model (n = 6). Hepatic arterial flow was maintained constant throughout the experiments. RESULTS: During the period of enhanced portal venous flow there was an increase in: portal venous pressure (from 9 +/- 2 to 22 +/- 7 mm Hg, P = 0.0076); the difference between portal venous and hepatic venous pressures (from 2 +/- 2 to 10 +/- 5 mm Hg; P = 0.0289); hepatic arterial pressure (from 84 +/- 9 to 151 +/- 33 mm Hg, P = 0.0019); and intrahepatic arterial resistance (from 0.3488 +/- 0.0637 to 0.6387 +/- 0.2020, P = 0.0046). CONCLUSIONS: The increases in hepatic artery pressure and intrahepatic arterial resistance are a result of the hepatic arterial 'buffer response', a phenomenon not previously demonstrated in vitro. The magnitude of the observed changes in portal venous and hepatic venous pressure leads to the conclusion that, in the porcine liver, the intrahepatic venous resistance sites react by constricting to increases in portal venous inflow.     

Relationships between plasma atrial natriuretic peptide concentrations and hemodynamics and hematocrit in patients with cirrhosis.

We studied the relationships in 29 patients with cirrhosis between pulmonary arterial atrial natriuretic peptide concentrations and the following: systemic and splanchnic hemodynamics, the hematocrit, arterial oxyhemoglobin saturation, oxygen tension and the severity of cirrhosis. Plasma atrial natriuretic peptide concentrations ranged from 21 to 208 pg/ml and averaged 78 +/- 8 pg/ml (mean +/- S.E.M.). Simple regression analysis showed significant correlations between plasma atrial natriuretic peptide concentration and the following: hematocrit, mean pulmonary arterial pressure, wedged hepatic venous pressure, free hepatic venous pressure, pulmonary wedged pressure and serum bilirubin concentrations. No significant correlations were found between plasma atrial natriuretic peptide concentrations and all other hemodynamic values, arterial oxyhemoglobin saturation and oxygen tension. Multiple stepwise regression analysis showed that the hematocrit, mean pulmonary arterial pressure and wedged hepatic venous pressure were significant and independent predictors of pulmonary artery plasma atrial natriuretic peptide concentrations (R2 = 0.69). Partial regression coefficients were -0.74 (p less than 0.001), 0.61 (p less than 0.001) and 0.44 (p less than 0.05) for the hematocrit, the mean pulmonary arterial pressure and the wedged hepatic venous pressure, respectively. In conclusion, in patients with cirrhosis, increased plasma atrial natriuretic peptide concentrations were related to the degree of hemodilution, increased pulmonary arterial pressure and the degree of portal hypertension. Plasma atrial natriuretic peptide concentrations were not influenced by the arterial oxygenation levels.     

High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study

Large spontaneous portal-systemic shunts have been occasionally described in patients with cirrhosis. This study was undertaken to assess the prevalence of portal-systemic shunts in patients with cirrhosis with recurrent or persistent hepatic encephalopathy (HE) as compared with patients with cirrhosis without HE. Fourteen patients with cirrhosis with recurrent or persistent HE (cases) and 14 patients with cirrhosis without previous or present signs of overt HE matching for age and degree of liver failure (controls) were studied. Each patient underwent neurological assessment and cerebral magnetic resonance (MR) imaging to exclude organic neurological pathological conditions. HE evaluation included psychometric performance (Trail-Making Test A), electroencephalogram (EEG), mental status examination and grading, arterial, venous, and partial pressure of ammonia determination. The presence of portal-systemic shunts was assessed by portal venous phase multidetector-row spiral computed tomography (CT). Large spontaneous portal-systemic shunts were detected in 10 patients with HE and in only 2 patients without HE (71% vs. 14%; chi square = 9.16; df = 1.0; P = .002). The patients with HE presented ascites (P = .002) and medium/large esophageal varices (P = .02) less frequently than the control group. In conclusion, our study suggests that large spontaneous shunts may often sustain the chronicity of HE; the presence of large shunts should be sought in patients with cirrhosis with recurrent or persistent HE.