Altered energy metabolism and oxidative injury following endotoxemia in rats with normal or cirrhotic livers

The release of oxygen-derived free radicals has been implicated in endotoxin-mediated hepatic injury. The effect of hepatic lipid peroxidation on tissue energy reserves in the livers of normal and cirrhotic rats was studied following administraton ofE. coli endotoxin. Before endotoxin injection, the basal hepatic energy charge was lower and levels of hepatic malondialdehyde (MDA) and total glutathione (GSH) higher in cirrhotic rats than in normal rats. Virtually identical levels of blood endotoxin were obtained in the two groups 24h after injection of LD50 doses of endotoxin (20 mg/kg and 1 mg/kg in normal and cirrhotic rats, respectively). Hepatic energy charge, tissue blood flow, GSH and glutathione peroxidase (GPX) were consistently or transiently decreased up to 24h after the injection of endotoxin in both normal and cirrhotic rats. MDA, significantly increased in normal rats 1 h after injection of endotoxin, returned to normal levels 3–12 h after endotoxin administration, but was again elevated at 24 h. Cirrhotic rats did not show any significant change in MDA following endotoxin injection. In normal rats, endotoxin appears to trigger the liberation of free radicals accelerating depletion of hepatic energy reserves, over and above the effect of decreased hepatic blood flow. In contrast, increased lipid peroxidation was not detected in cirrhotic rats despite GSH and GPX consumption during endotoxemia (indicating oxygen radical generation). Cirrhotic livers were apparently protected against oxygen radical injury by higher levels of endogenous GSH and GPX. Reduced hepatic blood flow may be mainly responsible for the alteration in energy metabolism of the cirrhotic liver.     

Pleomorphism of hepatic regeneration

The pleomorphism of hepatic regeneration was studied in acute liver injury and partial hepatectomy of rats. Increases in 3H-thymidine incorporation into the liver DNA fraction and in liver ornithine decarboxylase (ODC) activity were observed similarly in acute liver injury and following a two-thirds partial hepatectomy in normal rats. However, the increase in serum AFP levels was significant only in carbon tetrachloride (CCl4)-treated rats, and the portal-peripheral vein difference in plasma glucagon concentrations was great only in rats that underwent a partial hepatectomy. The weight of the remaining liver increased rapidly following a 67% hepatectomy in normal rats, but not in cirrhotic rats, of which three of five died within 6 days. Increases in liver prostaglandin E levels, 14C-orotate incorporation into the liver RNA fraction and hepatic ODC activity were observed up to 10 h following a partial hepatectomy of normal liver but not after similar removal of cirrhotic liver. Three kinds of hepatic regeneration, i.e., normal and pathologic regeneration following surgical removal of either normal or injured liver and repair of liver damage following chemically induced liver deficiency, were proposed from the observations.     

Glucose overload and hepatic energy metabolism after resection of the cirrhotic liver in rats.

The effect of glucose hyperalimentation on energy metabolism in the cirrhotic rat liver after 70% hepatectomy was studied. After resection, rats received either 30 kcal/kg per day (group I) or 200 kcal/kg per day (group II) of glucose for 48 h. In both groups, hepatic mitochondrial ATP synthesis was accelerated when palmitic acid was used as substrate and suppressed when pyruvate was used. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose. Hepatic energy charge was within normal limits in group I, but decreased significantly in group II after hepatectomy. An abundance of glucose in the early postoperative period, therefore, caused a hepatic energy derangement by suppressing fatty acids utilization; this suppression was corroborated by the findings of lower immunoreactive glucagon and non-esterified fatty-acid concentrations in group II. To determine optimal glucose administration, the predicted value of glucose disposal rate (GDR) was calculated after an intravenous glucose tolerance test. GDR decreased significantly after hepatectomy and did not increase appreciably even with a large dose of insulin administration. These results suggest that glucose administration should be tailored to the GDR values after resection of the cirrhotic liver.     

Effect of hepatic artery embolization on the adenylate energy charge level and the redox state of the cirrhotic liver

Hepatic energy charge ((ATP + 1/2ADP)/(ATP + ADP + AMP)) and arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate) were measured after hepatic artery embolization in carbon-tetrachloride-induced cirrhotic rats. In normal livers, energy charge slightly decreased at 3 h and returned to normal levels at 6 h. By contrast, in cirrhotic livers, energy charge was drastically decreased at 3 h after embolization and was not completely recovered at 6 h. Blood ketone body ratio, reflecting hepatic mitochondrial redox (NAD+/NADH) state, also decreased at 3 h after embolization in both groups, and its recovery was not observed in cirrhotic group at 6 h.     

Mitochondrial function of isolated rat hepatocytes from normal and cirrhotic liver

Mitochondrial fractions were obtained from purely isolated hepatocytes of the normal and cirrhotic livers. Mitochondrial function of isolated hepatocytes was evaluated to compare between those from the normal and those from the cirrhotic livers in addition to the evaluation of the mitochondrial function of the normal and cirrhotic liver tissues. Respiratory control, ADP/O ratio and ATP synthesis were significantly lower in the cirrhotic liver tissue than those in the normal liver tissue. However, the mitochondrial function of isolated hepatocytes showed no difference between normal and cirrhotic groups. By electron microscopic examination, debris was more observed in the mitochondrial fractions from the normal and cirrhotic tissues compared to those from hepatocytes. However, no difference of the shape and size of the mitochondria was seen between the fraction from hepatocytes and that from the tissue in each group. These results suggest that as far as hepatocyte itself is concerned, the cirrhotic liver preserves the sufficient function as well as the normal liver.     

A new experimental model of specific liver hypoxia using membrane oxygenator

The present study introduces a new experimental canine model of hepatic arterial deoxygenation using a membrane oxygenator to investigate the influence of hepatic arterial hypoxia on hepatic hemodynamics and energy metabolism. Eighteen mongrel dogs weighing 10 kg each were randomly divided into three groups: group A served as a control (118.0±9.0 mmHg of hepatic arterial O₂ content), group B as a moderately deoxygenated group (40 mmHg of hepatic arterial O₂ content), and group C as a severely deoxygenated group (25 mmHg of hepatic arterial O₂ content). Deoxygenation was achieved by perfusion of a gas mixture of O₂ and N₂ through the membrane oxygenator, which was interposed between the femoral artery and the proper hepatic artery, for 60 min. In group C, hypoxia decreased the mean systemic arterial blood pressure and hepatic arterial blood flow. Arterial blood ketone body ratio (AKBR=acetoacetate/3-hydroxybutyrate), which reflects the hepatic mitochondrial redox state, rapidly decreased prior to the significant increase of glutamate oxaloacetate transminase, glutamate pyruvate transminase, and lactate dehydrogenase after the initiation of hypoxia. Hepatic arterial deoxygenation to 25 mmHg for 60 min induced injury to hepatic hemodynamics, resulting in the deterioration of systemic hemodynamics even after the termination of liver hypoxia. This in vivo temporal hepatic arterial hypoxic model without alteration of inflow volume might be useful for investigating the mechanism of hypoxic injury and the critical point of liver hypoxia on hepatic and/or systemic hemodynamics and liver viability.     

Appearance of a cathodic band in the electrophoretogram of blood creatine kinase isoenzyme-MM fraction during hypoxia in rats

In electrophoretograms of creatine kinase (CK; EC 2.7.3.2) in patients' blood, a band, presumably of mitochondrial origin, is occasionally observed on the cathodic side of the CK-MM fraction. We studied the implications of this phenomenon in rats exposed to hypoxic conditions. In the hypoxic cardiac muscle, the proportions of CK-MB and CK-MM were not significantly different from controls, but that of the mitochondrial CK was lower. In the corresponding blood, the cathodic mitochondrial CK band appeared, but disappeared as the animals recovered from hypoxia. The CK-MB isoenzyme was increased in the blood of the control rats, as obtained by heart puncture, but no mitochondrial fraction was detected. We believe that changes in myocardial mitochondria during hypoxia are related to the appearance of the cathodic band. Cytoplasmic CK-MB, unlike mitochondrial CK, markedly increased in the rats' blood during the recovery stage rather than during the hypoxia.     

Alternations of liver pathophysiology in experimental hepatic failure treated by two forms of plasma purification procedure

Plasma cross-circulation which resembles plasma exchange and plasma perfusion over charcoal and resin adsorbents were carried out using rats with galactosamine (GalN)-induced hepatic failure to investigate the effects of those plasma purification procedures on damaged liver function. Twenty-four hr after the injection of GalN, the plasma treatment procedures were performed at a plasma flow rate of 0.1 ml/min for 6 hr. Forty-eight hr after the injection of GalN, ATP synthesis in liver mitochondrial function, and ATP and total adenine nucleotide contents in the liver, which were markedly reduced by the GalN administration, were increased by both plasma cross-circulation and plasma perfusion over adsorbents. These results suggest that both plasma purification procedures improve the deterioration of mitochondrial phosphorylation activity and produce an augmented high energy status in the liver. In the histological study of the liver, volume ratio of hepatic parenchyma in the GalN-treated liver to that in the normal liver was significantly higher in rats treated with plasma perfusion than those with sham-perfusion. An efficient removal of the hepatotoxic metabolites from the plasma, therefore, decelerates the progress of GalN induced-liver tissue necrosis, if rats with GalN-induced hepatic failure are treated in an early stage.     

Ammonia and glutamine metabolism in human liver slices: new aspects on the pathogenesis of hyperammonaemia in chronic liver disease

Ammonia and glutamine metabolism was studied in slices from normal, fatty and cirrhotic human livers. The liver disease was evaluated by histological examination. With respect to ammonia removal, urea and glutamine synthesis in human liver represent low and high affinity systems with k0.5(NH4+) values of 3.6 and 0.11 mM, respectively. Compared with normal control livers, cirrhotic livers showed a decreased glutamine synthesis from NH4Cl by about 80%. The same was true for urea synthesis. Conversely, flux through hepatic glutaminase was increased in cirrhosis 4-6-fold. These changes in hepatic glutamine and ammonia metabolism were observed regardless of whether reference was made to liver wet weight, DNA or protein content. Acetazolamide inhibited urea synthesis in cirrhotic liver slices by about 50%, indicating that mitochondrial carbonic anhydrase is required for urea synthesis also in cirrhosis. There was a significant correlation between the in-vitro determined capacity for urea synthesis from NH4Cl and the in-vivo determined plasma bicarbonate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Methylprednisolone inhibits low-flow hypoxia-induced mitochondrial dysfunction in isolated perfused rat liver

OBJECTIVE: To investigate the mechanism by which methylprednisolone protects the liver from hypoxia-induced injury. DESIGN: Prospective control study using the isolated rat liver. SETTING: Animal research facility. SUBJECTS: Male, fasted, pathogen-free Sprague-Dawley rats. INTERVENTIONS: Low-flow hypoxia was produced by reducing afferent perfusate pressure from 10 to 2.5 cm H(2)O; isolated livers were portally perfused for 2 hrs. MEASUREMENTS AND MAIN RESULTS: We measured mitochondrial membrane potential and hydrogen peroxide production by imaging rhodamine 123 and 2'-7'-dichlorofluorescein fluorescence, respectively. Leakage of mitochondrial enzymes was also monitored by assaying mitochondrial aspartate aminotransferase activity in the outflow perfusate, and the radical-scavenging effect of methylprednisolone was assessed by measuring luminol-dependent hydrogen peroxide chemiluminescence. Apoptosis in liver cells was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling. Rhodamine 123 fluorescence was significantly diminished in the hypoxic liver, especially in the region of the terminal hepatic venules, which is indicative of membrane depolarization in the mitochondria in those areas. Hypoxia-induced mitochondrial dysfunction was indicated by leakage of aspartate aminotransferase into the outflow perfusate, and increased 2'-7'-dichlorofluorescein fluorescence indicated increased hydrogen peroxide levels, particularly in the midzone. Pretreatment with 30, 10, or 3 mg/kg of methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization and enzyme leakage, although hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected. CONCLUSIONS: Methylprednisolone does not protect the liver from hypoxia-induced injury by suppressing hydrogen peroxide production. Instead, the beneficial effect of methylprednisolone seems to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.     

Significance of prednisolone administration for hepatic mitochondrial function of the rat with biliary obstruction

Mitochondrial respiratory function of the liver is disturbed in biliary obstruction, especially in that caused by tumours in the hepatobiliary system. This study aimed to clarify whether a glucocorticoid, prednisolone succinate, is effective to improve the reduced mitochondrial function of the rat liver in obstructive jaundice. Five doses of 5 mg/kg or 25 mg/kg prednisolone succinate were administered at 5 consecutive days to the rats after 1, 3 or 6 weeks of biliary obstruction and to the rats without obstruction, and the hepatic mitochondrial function and contents of cytochromes of these rats were investigated. With 25 mg/kg prednisolone, hepatic mitochondrial function was improved in rats with biliary obstruction of 3- or 6-weeks duration as compared with the prednisolone-untreated group. Compensatory increase or recuperation of the once decreased cytochrome A(+a3) and/or turnover number of phosphorylation was also observed in 25 mg/kg group. Hepatic mitochondrial function of obstruction-free animals was rather impaired by treatment with 25 mg/kg prednisolone. In 5 mg/kg group, above mentioned effects were scarcely observed. It was concluded that the hepatic mitochondrial function in animals with prolonged biliary obstruction, as same as in animals with short-term obstruction, can be improved by the administration of adequately large amounts of prednisolone.     

Effect of cyclosporine on oxidative phosphorylation and adenylate energy charge of regenerating rat liver

The effect of cyclosporin A (CyA) on regenerating liver was investigated in subtotal hepatectomized rats treated with CyA in terms of mitochondrial phosphorylative activity, hepatic energy charge, and serum bilirubin levels. In the CyA-treated hepatectomized group, the energy charge decreased from normal control value of 0.857 to 0.782 at 6 h after hepatectomy. The decreased energy charge, however, gradually increased and returned to 0.842 at 48 h after hepatectomy with no significant changes being observed between CyA-treated and untreated hepatectomized groups. Phosphorylation rate in the CyA-untreated group increased to 142% of the normal control at 24 h and then decreased to 114% at 48 h after hepatectomy. By contrast, phosphorylation rate in the CyA-treated group increased to 144% of the normal control at 24 h, but remained at the high value of 132% (P less than 0.01; compared to the CyA-untreated group) even at 48 h after hepatectomy. Serum total bilirubin levels in the CyA-treated group were significantly higher than those in the CyA-untreated group during all experimental periods. We conclude that CyA does not exert a direct detrimental effect on mitochondrial function and that, despite the marked hyperbilirubinemia induced by CyA, the mitochondrial phosphorylative activity increases adaptively to provide sufficient energy for enhanced ATP-utilizing reactions in an early process of liver regeneration.     

Significance of activation of reticuloendothelial function after hepatectomy in cirrhotic rats

Effect of hepatectomy on the prognosis of cirrhotic rats prepared by oral administration of thioacetamide was studied from the standpoint of the reticuloendothelial function and energy metabolism of the liver. OK-432, a streptococcal preparation, was used to activate reticuloendothelial functions. Administration of OK-432 to cirrhotic rats prior to 70% hepatectomy significantly prevented the elevation of serum GOT, GPT and LDH, the prolongation of blood coagulation and the decrease of serum complement level. Hepatic ATP synthesis and RNA content were significantly increase by the use of OK-432. These findings suggest that activation of reticuloendothelial functions at the time of massive hepatectomy in cirrhotic rats may diminish hepatic injury, maintain serum complement level, and improve protein synthesis of the liver.     

Effects of high hepatic acetaldehyde level following simultaneous administration of ethanol and cyanamide on liver function in rats

Extremely high concentrations of hepatic acetaldehyde were induced in rats by the intragastric administration of ethanol and cyanamide, an aldehyde dehydrogenase inhibitor; and these high levels were maintained for 4 weeks. Liver function tests, including mitochondrial ornithine carbamoyltransferase (OCT) and GOT activities, were within normal limits, and no increase in either hepatic triglyceride or collagen contents was observed. These results suggest that hepatotoxic effects of ethanol are not derived from the high acetaldehyde levels in the liver.     

Improvement of portal hypertension and hepatic blood flow in cirrhotic rats by oestrogen

BACKGROUND: In this study, we investigated the effects of oestrogen on nitric oxide synthase activity and nitric oxide production using the cirrhotic rat liver. MATERIAL AND METHODS: Cirrhosis was induced by dimethylnitrosamine. Estradiol valerate was subcutaneously injected twice at week 4 after dimethylnitrosamine treatment. Furthermore, subcutaneous injection of an oestrogen receptor antagonist, ICI-182.780, was performed 2 days before administration of estradiol valerate. Portal pressure and hepatic blood flow were measured. Nitric oxide synthase activity was assessed by l-citrulline generation. Sinusoidal endothelial cells were isolated from the cirrhotic rat liver and cultured. The cells were incubated with estradiol and/or ICI-182.780 for 24 h. Images for nitric oxide in sinusoidal endothelial cells were obtained using diaminofluorescein-2 diacetate. RESULTS: Cirrhotic rats treated with estradiol valerate showed a significant decrease in portal pressure and a significant increase in hepatic blood flow compared with those of control cirrhosis rats. However, in cirrhotic rats treated with ICI-182.780, the reduction of portal pressure and elevation of hepatic blood flow were completely inhibited. In cirrhotic rats treated with estradiol valerate, nitric oxide synthase activity was increased compared with that in control cirrhotic rats. The fluorescent level of intracellular nitric oxide in estradiol-stimulated, cultured, sinusoidal endothelial cells was higher than that in nontreated sinusoidal endothelial cells. CONCLUSIONS: The present study indicated that oestrogen plays an important role in the enhancement of nitric oxide production in sinusoidal endothelial cells of cirrhotic liver and reduces the portal pressure in cirrhotic rats.     

Changes in concentrations of respiratory components and cytochrome oxidase activity in mitochondria obtained from carbon tetrachloride-induced cirrhotic rat liver

1. Changes in the concentrations of respiratory components, phosphorylative activity, the cytochrome oxidase activity of mitochondria and the hepatic adenylate energy charge level (in situ) were studied in cirrhotic rat liver induced by carbon tetrachloride (CCl4). 2. In the cirrhotic liver mitochondria, concentrations of cytochrome a(+a3), cytochrome b, coenzyme Q9 and coenzyme Q10 increased significantly to 2.44 +/- 0.02 x 10(-10) (mean +/- SE), 1.37 +/- 0.05 x 10(-10), 25.57 +/- 0.47 x 10(-10) and 5.39 +/- 0.26 x 10(-10) mol/mg of mitochondrial protein, respectively, compared with 1.83 +/- 0.03 x 10(-10), 1.22 +/- 0.02 x 10(-10), 16.24 +/- 0.39 x 10(-10) and 1.81 +/- 0.07 x 10(-10) in normal rats [P less than 0.001 for cytochrome a(+a3), coenzyme Q9 and coenzyme Q10, and P less than 0.01 for cytochrome b]. 3. Concentrations of flavoprotein and pyridine nucleotides decreased significantly to 13.33 +/- 0.14 x 10(-10) and 45.68 +/- 1.59 x 10(-10) mol/mg of mitochondrial protein, respectively, compared with 14.79 +/- 0.33 x 10(-10) and 86.26 +/- 1.83 x 10(-10) in normal rats (P less than 0.001). There was no significant difference in the concentration of cytochrome c(+c1). 4. Cytochrome oxidase activity per unit of cytochrome a(+a3) increased significantly to 67.43 +/- 1.71 atoms O s-1 mol-1, compared with 55.77 +/- 1.16 in normal rats (P less than 0.001). By contrast, phosphorylative activity per unit of cytochrome a(+a3) decreased significantly in the cirrhotic liver to 10.40 +/- 0.36 s-1 compared with 13.43 +/- 0.49 in normal rats (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Liver transduction with a simian virus 40 vector encoding insulin-like growth factor I reduces hepatic damage and the development of liver cirrhosis

Liver transplantation is the only treatment for advanced liver cirrhosis. Therapies halting the progression of the disease are urgently needed. Administration of recombinant insulin-like growth factor-I (rIGF-I) induces hepatoprotective effects in experimental cirrhosis. Therefore, we analyzed the efficacy of a recombinant simian virus 40 vector (rSV40) encoding IGF-I (rSVIGF-I) to prevent cirrhosis progression. First, transgene expression was evaluated in mice injected with rSV40 encoding luciferase, which showed long-term hepatic expression of the transgene. Interestingly, luciferase expression increased significantly in CCl(4)-damaged livers and upon IGF-I administration, thus liver injury and IGF-I expression from rSVIGF-I should favor transgene expression. rSVIGF-I therapeutic efficacy was studied in rats where liver cirrhosis was induced by CCl(4) inhalation during 36 weeks. At the end of the study, the hepatic levels of IGF-I and IGF-binding protein 3 were higher in rSVIGF-I-treated rats than in control cirrhotic animals. Cirrhotic rats treated with rSVIGF-I had reduced serum bilirubin, transaminases and liver fibrosis scores and increased hepatic expression of hepatocyte growth factor and STAT3alpha as compared to cirrhotic animals. Furthermore, cirrhotic animals showed testis atrophy and altered spermatogenesis, whereas testicular size and histology were normal in cirrhotic rats that received rSVIGF-I. Therefore, rSV40-mediated sustained expression of IGF-I in the liver slowed cirrhosis progression.     

Acute oxygen supplementation restores markers of hepatocyte energy status and hypoxia in cirrhotic rats

The oxygen limitation hypothesis states that hepatocyte hypoxia is the mechanism determining metabolic restriction in the cirrhotic liver. Therefore we studied markers of hepatocyte energy state and cellular hypoxia in livers of normal and cirrhotic rats before and after oxygen supplementation. Rats with carbon tetrachloride-induced cirrhosis and procedural control rats were exposed to either room air or a hyperoxic gas mixture for 1 h immediately before freeze clamping and perchloric acid extraction of liver tissue. Extracts were assessed by (31)P NMR and enzymatic assays. Livers from cirrhotic rats breathing room air showed a reduced ratio of ATP/ADP, an increased ratio of inorganic phosphate/ATP, and a trend toward an increased ratio of lactate/pyruvate compared with procedural control livers (ATP/ADP 1.73 +/- 0.35 versus 2.68 +/- 0.61, P <.05; P(i)/ATP 2.74 +/- 0.48 versus 1.56 +/- 0.26, P <.05; lactate/pyruvate 29.3 +/- 6.4 versus 22.5 +/- 7.4, P =.18). After supplementation with oxygen for 1 h, these ratios in cirrhotic livers approached control values. A variety of other metabolic markers affected by cirrhosis showed variable trends toward normal in response to oxygen supplementation, whereas minor trends toward an increase in ATP levels in control animals suggest the possibility of marginal oxygen limitation in normal livers. The data are consistent with the hypothesis that hepatocytes in cirrhotic livers have normal metabolic capacity but are constrained by a deficit in oxygen supply. Interventions aimed at increasing oxygen supply to the liver may have both short- and long-term therapeutic value in the management of cirrhosis.     

实时灰阶超声造影对肝硬化定量诊断的初步探讨

目的利用新型超声造影剂及匹配成像技术观察肝硬化患者的肝动脉、门静脉以及肝脏实质的灌注规律,探讨对肝硬化定量化诊断的意义.方法 26例经手术或穿刺证实为肝硬化的患者入选本研究,另8例无任何肝脏病史或肝病临床表现者作为正常肝对照组,采用第二代超声造影剂SonoVue以及Technos DU6 CnTi实时超声造影成像技术,行实时灰阶超声造影检查.造影剂注射方法分两种:其中11肝硬化患者及8例正常肝者采用慢注法,另15例肝硬化患者采用团注法.结果慢注法肝硬化的门静脉显影时间与肝实质增强峰值时间均较正常肝显著延长(39.36±11.89) s vs (30.00±6.76) s,(60.91±15.67) s vs (41.13±6.49) s,P<0.05;肝动脉显影时间、达峰值时间以及门静脉达峰值时间均与正常组无显著差异.团注法的肝动脉、门静脉平均显影时间,达峰值时间以及肝实质增强峰值时间均比慢注法提前,分别为(14.80±4.96) s,(26.67±6.92) s,(22.80±5.87) s, (33.87±6.06) s, (35.93±9.71) s;除肝动脉时相外,余各时相均有显著性差异,P<0.05.本组肝硬化患者的上述时相均与患者的Child-Paugh分级无相关性.结论本研究初步结果显示利用造影超声有助于肝硬化的诊断,但各时相显示时间界值,还应以不同的推注方法而定,尚有待临床进一步对照研究.