Clinical implication of VEGF serum levels in cirrhotic patients with or without portal hypertension

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Serum neopterin concentrations in chronic liver disease.

Neopterin is produced by macrophages after stimulation with interferon gamma or lipopolysaccharide. Its production is increased in many infectious, autoimmune, and malignant diseases. The aim of this study was to examine whether, on the basis of neopterin as a marker, liver diseases could be classified according to aetiology and stage of disease. A cohort of 264 patients with chronic liver diseases (viral, metabolic, autoimmune, toxic) and 150 normal controls were studied; 136 of the patients had cirrhosis. Increased serum neopterin concentrations were found in 41% of all patients (controls 6.0 (2.2) nmol/l), with patients in the cirrhotic stage of disease showing higher neopterin values (mean (SD) 15.7 (23.6) nmol/ml) than those in the non-cirrhotic stage (9.9 (5.5)). There were no statistically significant differences in the serum neopterin concentrations that could be considered characteristic for different stages of disease classified according to the Child criteria. Such differences in concentrations of neopterin that were found in patients with liver diseases grouped according to underlying causes were only marginal. Serum neopterin concentrations were found to be significantly lower than in any other disease group only in patients with Wilson''s disease. The results suggest that activated macrophages participate in the development of chronic liver disease. Measurement of serum neopterin does not offer a reliable method for differentiating between various aetiologies of chronic liver diseases and does not help to predict severity of cirrhosis.     

慢性乙型肝炎患者血清甲状腺相关物质和IL-6检测及其临床意义

目的：研究慢性乙型肝炎病毒（Hepatitis B Virus,HBV）感染者血清甲状腺激素、抗甲状腺自身抗体及白细胞介素（interleukin,IL）-6水平变化及其临床意义。方法选取健康对照者18例、慢性乙型肝炎（CHB）患者65例和乙型肝炎肝硬化患者34例,应用电化学发光法分别检测并比较血清甲状腺激素水平、促甲状腺激素（TSH）、抗甲状腺相关抗体及IL-6水平。结果 CHB患者抗甲状腺过氧化物酶抗体（TPOAb）、抗甲状腺球蛋白抗体（TGAb）、抗促甲状腺激素受体抗体（TRAb）和IL-6水平分别为（9.5±5.6） KIU/L、（42.5±218.7） KIU/L、（1.5±0.7） IU/L和（6.6±12.6） pg/mL,在肝硬化患者分别为（9.5±8.6） KIU/L、（47.6±101.5） KIU/L、（2.2±1.7） IU/L和（15.8±25.5） pg/mL,均显著高于正常组[分别为（4.4±5.6） KIU/L、（7.7±18.3） KIU/L、（0.8±0.8） IU/L和（2.8±2.0） pg/mL,P〈0.05],而CHB和肝硬化患者血FT3分别为（2.4±0.5） ng/L和（2.4±0.6） ng/L,均显著低于对照组[（2.9±0.2） ng/L,P〈0.05];肝硬化患者TRAb和IL-6水平分别为（2.2±1.7） IU/L和（15.8±25.5） pg/mL,明显高于CHB患者[（1.5±0.7） IU/L和（6.6±12.6） pg/mL,P〈0.05],而TT3和TT4水平分别为（0.8±0.3） nmol/L和（5.4±1.9）nmol/L,显著低于CHB患者[（1.3±0.3） nmol/L和（8.0±2.2） nmol/L,P〈0.05]。结论联合检测慢性HBV感染者血清甲状腺激素、抗甲状腺自身抗体及IL-6水平对病情评价和预后判断有一定的临床价值。     

Clinical Significance of Serum and Urinary Neopterin Levels in Patients with Various Liver Diseases

Serum and urinary neopterin levels were measured by radioimmunoassay in 120 healthy controls, 16 asymptomatic HBsAg carriers, 12 patients with acute hepatitis, 13 with chronic inactive hepatitis, 35 with chronic active hepatitis, 46 with liver cirrhosis, 18 with hepatocellular carcinoma, and 6 with alcoholic liver disease. Serum and urinary neopterin levels were significantly higher in almost all patients than in normal subjects. Neopterin levels were highest in acute hepatitis and correlated with the results of liver function tests, but did not show this correlation in chronic liver disease. In chronic liver disease, the levels of serum neopterin in non-A non-B viral patients was significantly increased, compared with those in B viral and alcoholic patients. The rate of abnormal urinary neopterin levels in chronic liver disease was higher than the rate of abnormal serum neopterin levels, but no difference was observed between the rates of abnormal serum and urinary levels in acute hepatitis and asymptomatic HBsAg carriers. These results indicate that serum and urinary neopterin levels may be useful markers for cell-mediated immunity in liver disease, and that the immune system response in chronic liver disease may be different for different pathogens.     

乙肝肝硬化血清透明质酸与HBV DNA的相关性

目的:探讨乙肝肝硬化患者血清透明质酸与HBV DNA水平的相关性.方法:收集乙肝肝硬化患者144例,其中女性42例,男性102例,平均年龄(54.42±11.53)岁,Child pugh A级42例,Child pugh B级40例,Child pugh C级62例,采用放射免疫法检测血清透明质酸,荧光定量PCR检测血清HBV DNA水平,对血清透明质酸、血清HBV DNA水平进行统计并分析两者之间的关系.结果:随着乙肝肝硬化Child分级的加重,患者的血清透明质酸水平也增高,不同分级之间的差异有统计学意义(174.10μg/L±127.98μg/Lvs421.35μg/L±176.96μg/Lvs903.58μg/L±212.02μg/L,P<0.01).不同Childpugh分级患者的血清HBV DNA水平差异无统计学意义(P>0.05).不同Child pugh分级患者的血清HBV DNA和透明质酸水平无显著相关性(P>0.05).结论:随着患者的Child pugh分级升高,HA水平显著增高,说明HA是反映肝硬化程度的敏感指标;乙肝肝硬化患者HBV DNA与肝硬化程度无显著相关,血清透明质酸与HBV DNA水平之间也无显著相关性,因此抗病毒和抗纤维化治疗对乙肝肝硬化患者同等重要.     

Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease

OBJECTIVE: To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients. METHODS: One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Student's t-test and the non-parametric Kruskall-Wallis test (P<0.05). RESULTS: Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80 ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001), whereas they were within normal range (<0.5 ng/ml) in all patients with uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15 group A patients (46.2%) and 4/13 group E patients (30.8%), all of them cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without established bacterial infection. CONCLUSION: Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.     

病毒性肝炎患者血清新喋呤检测的临床意义

研究血清新喋呤水平与慢性病毒性肝炎、肝炎肝硬化、慢性重型肝炎和感染的关系和意义。采用ELISA法检测35例慢性乙型肝炎,26例肝炎肝硬化,35例慢性重型肝炎。其中合并感染患者共19例。研究显示慢性重型肝炎组血清新喋呤水平明显高于肝炎肝硬化组和慢性肝炎组;合并感染患者血清新喋呤高于非感染患者。新喋呤水平与TBil和TBA密切相关。病毒性肝炎患者血清新喋呤水平与肝病严重程度和感染有关,对病情判断和感染诊断有参考意义。     

Serum thyroglobulin in acute and chronic liver disease

In view of the widespread use of serum thyroglobulin determination in the follow-up of patients with differentiated thyroid carcinoma, the influence of acute and chronic liver disease on serum thyroglobulin concentration was investigated in thirty-seven consecutive patients with histologically proven alcoholic liver cirrhosis and twenty-three patients with acute non-alcoholic hepatitis. Seventy-four healthy volunteers served as controls. Serum thyroglobulin concentration was significantly elevated in cirrhosis: median 29.5 micrograms/l, (range 4.3-94.0 micrograms/l) compared to controls: median 16.0 micrograms/l, (range 4.8-89.6 micrograms/l), (P less than 0.001). Serum thyroglobulin concentration in patients with acute hepatitis: median 16.2 micrograms/l, (range 7.9-70.0 micrograms/l) was not significantly different from controls. The level of free-T3-index was significantly reduced and the level of free-T4-index was significantly elevated in both cirrhosis and hepatitis compared to controls. Serum TSH concentration was significantly elevated in cirrhosis compared to hepatitis and controls. Serum thyroglobulin levels were positively correlated to levels of free-T3-index (r = 0.35, P less than 0.05) and T3/T4-ratio (r = 0.40, P less than 0.05) but not to levels of serum TSH or free-T4-index or any of the liver function tests in any of the groups. In conclusion, our results do not clearly indicate whether the elevated serum thyroglobulin level in cirrhosis was caused by an impaired elimination and/or an increased secretion from the thyroid gland. The increase in serum thyroglobulin concentration in chronic alcoholic liver disease was not of a magnitude likely to cause misinterpretation of results obtained during the follow-up of patients with differentiated thyroid carcinoma.     

生存素在慢性肝病患者外周血中的表达

目的评价慢性肝病患者外周血生存素检测对慢性肝病的诊断价值。方法将研究对象分为原发性肝癌组、乙肝肝硬化组、慢性乙型肝炎组和正常对照组。各组采集空腹外周静脉血3 ml,通过双抗体夹心酶联免疫吸附测定法检测生存素浓度。结果原发性肝癌组、乙肝肝硬化组、慢性乙型肝炎组和正常对照组外周血生存素浓度分别为(83.70±14.45)ng/L、(70.58±9.78)ng/L、(67.90±9.14)ng/L和(65.07±7.58)ng/L。慢性乙型肝炎组与正常对照组比较,差异无统计学意义(P0.05),乙肝肝硬化组与正常对照组比较,差异有统计学意义(P0.05),原发性肝癌组外周血生存素浓度明显高于乙肝肝硬化组、慢性乙型肝炎组和正常对照组,差异有显著统计学意义(P0.01)。根据试验结果绘制受试者工作特征(ROC)曲线,原发性肝癌组ROC曲线下面积为0.82。结论外周血生存素是一种有诊断价值的评价慢性肝病的血清学指标,尤其对于原发性肝癌的诊断具有一定的价值。     

Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis

BACKGROUND/AIM: Serum levels of leptin, the adipocyte-derived hormone regulating food intake and energy expenditure in mammals, have been found to be increased in cirrhotic patients. The aim of the present study was to investigate leptin serum level in relation to anthropometric features and liver function in patients with viral chronic hepatitis or liver cirrhosis. METHODS: Serum leptin levels were determined by radioimmunoassay in 30 male and 10 female patients with chronic hepatitis, in 42 male and 10 female patients with liver cirrhosis, and in four respective control groups. Liver function was evaluated by the monoethylglycinexylidide formation test. Body mass index and body fat mass were estimated by weight, height and skinfold thickness measurements. RESULTS: Compared with controls, absolute serum leptin levels were significantly (p<0.01) lower in chronic hepatitis patients and similar in cirrhotic patients. Leptin serum levels were significantly (p<0.05) higher in cirrhotic than in chronic hepatitis patients. When expressed in relation to body fat mass, the above differences persisted; however, cirrhotic females showed significantly (p<0.05) higher serum leptin values than controls. Serum leptin values correlated negatively (p<0.01) with monoethylglycinexylidide serum values in all groups of patients. CONCLUSIONS: In patients with chronic viral liver disease, serum leptin levels tend to increase as liver function worsens. This may reflect a decline in the ability to downregulate energy expenditure as an adaptation to anorexia and/or to defective substrate utilisation due to liver disease and may negatively influence body weight homeostasis in these patients.     

肝硬化患者病情与小肠细菌过度生长变化关系探讨

目的 探讨小肠细菌过度生长（SIBO）与肝硬化病情严重程度的关系及小肠细菌生长与降钙素原、胆红素、血浆白蛋白、球蛋白的相关性。方法 纳入本科收治的47例肝硬化患者和15名健康志愿者。受试者接受乳果糖氢呼气试验（LHBT）,检测小肠细菌过度生长情况,使用全自动生化分析仪测定生化指标。采用自评表形式对肝硬化组患者症状进行评估。结果 在15名健康志愿者中检出1例（6.6%）伴小肠细菌过度生长,而在47例肝硬化患者中检出22例（46.8%）患者伴小肠细菌过度生长,显著高于正常人（P＜0.01）;肝硬化患者LHBT集值为（157.81±98.32）ppm,显著高于健康人[(38.87±16.05）ppm,P＜0.01],血清胆红素为（93.31±55.15）μmol/L,显著高于健康人[（14.78±8.12）μmol/L,P＜0.01],白蛋白为（31.74±10.37）g/L,显著低于健康人[(43.90±7.63) g/L, P＜0.01],球蛋白为（39.09±5.07）g/L,高于健康人[(35.94±2.31) g/L,P＞0.05],降钙素原为（0.10±0.07）ng/ml,显著高于健康人[(0.03±0.01) ng/ml,P＜0.01];降钙素原、胆红素、血浆白蛋白、球蛋白与LHBT集值具有相关性（r=0.895、P＜0.005,r=0.907、P＜0.005,r=-0.810、P＜0.005,r=0.755,P＜0.005）。结论 肝硬化患者SIBO发生率随肝功能损害程度的加重而增加,肝硬化SIBO患者腹胀及食欲不振更明显。降钙素原、胆红素和球蛋白分别与SIBO呈正相关,血浆白蛋白与SIBO呈负相关。     

Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications. METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically. RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13±3.94), (5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.     

Serum lysyl oxidase activity in chronic liver disease in comparison with serum levels of prolyl hydroxylase and laminin.

Lysyl oxidase was partially purified from serum by a diethylaminoethyl batch procedure in the presence of 6 mol/L urea and dialyzed against 3 mol/L KSCN. Using this method, we determined serum lysyl oxidase activity in 52 patients with liver disease and in 14 healthy controls, and we examined usefulness of serum lysyl oxidase in assessing liver fibrogenesis. For this purpose, serum lysyl oxidase activity in chronic liver disease was compared with serum levels of prolyl hydroxylase and laminin P1. As compared with controls, serum lysyl oxidase activity increased 1.6-fold in chronic persistent hepatitis, 4.4-fold in chronic active hepatitis and 11.8-fold in cirrhosis, indicating an increase in concert with the development of liver fibrosis. In hepatocellular carcinoma, the serum activity, although significantly increased, was lower than that in cirrhosis. Serum prolyl hydroxylase was significantly increased in chronic active hepatitis, in liver cirrhosis and in hepatocellular carcinoma. Serum laminin P1 was significantly increased in chronic active hepatitis, in cirrhosis and in hepatocellular carcinoma. Serum lysyl oxidase activity did not correlate significantly with serum levels of prolyl hydroxylase and laminin P1 in any subject or in any subgroup. The magnitude of the increase and the abnormal percentage of serum lysyl oxidase activity were larger than those for serum prolyl hydroxylase and laminin P1. These results suggest that serum lysyl oxidase activity is a more sensitive indicator of liver fibrosis than serum prolyl hydroxylase and laminin P1.     

Correlation of HBV DNA levels in serum and liver of chronic hepatitis B patients with cirrhosis

AIM: We sought to evaluate whether serum HBV DNA levels correlates with the liver free HBV DNA levels in chronic hepatitis B. METHODS: Thirty-three consecutive chronic hepatitis B patients with cirrhosis were included in this study. Twenty cases had detectable serum HBV DNA (> 1.8 pg/ml). All had detectable free liver HBV DNA. RESULTS: There was a strong correlation between the serum and liver HBV DNA levels (P = 0.0018, r = 0.717). Thirteen cases had undetectable serum HBV DNA. Among them, six cases still had detectable liver free HBV DNA. Eight cases were HBeAg-positive. Among them, seven cases were positive for both serum and liver HBV DNA, and one case was negative for both serum and liver HBV DNA. Twenty-five cases were HBeAg-negative and anti-HBe-positive. Among them, 13 cases were positive for serum HBV DNA, and 19 cases were positive for liver HBV DNA. No significant difference was noted for positivity of serum HBV DNA or liver free HBV DNA between HBeAg-positive and HBeAg-negative groups. The level of serum HBV DNA(491 +/- 772 pg/ml versus 203 +/- 447 pg/ml, p = 0.07) and liver free HBV DNA (33 +/- 81 pg/microg versus 6 +/- 15 pg/microg, p = 0.13) was also not statistically different. CONCLUSION: In conclusion, serum HBV DNA levels is strongly correlated with liver HBV DNA levels in chronic hepatitis B with cirrhosis. Liver free HBV DNA can still be detected in about half of the cirrhotic patients with undetectable serum HBV DNA. Serum HBeAg is not a good predictor of serum or liver HBV DNA levels in cirrhotic patients.     

Adenosine deaminase isoenzymes and neopterin in liver cirrhosis

The aim of this study was to define the pattern of neopterin and ADA isoenzymes in liver cirrhosis. A total of 117 patients with liver cirrhosis were included. Serum levels of ADA were assayed in the presence and absence of a specific inhibitor for ADA1. Serum neopterin was measured using a competitive enzyme-linked immunosorbent assay. The grade of liver insufficiency was assessed according to the Child-Pugh classification and the monoethylglycinexylidide test. Serum ADA, ADA1, ADA2 and neopterin were higher in cirrhotic patients than in control subjects. A stepwise increase in serum ADA level was observed with increasing severity of liver cirrhosis. The probability of ADA2 being greater than the mean was approximately 2.5 times higher (2.48, CI 95%: 1.36-4.52) in patients with liver cirrhosis due to hepatitis C virus (HCV) infection than in those patients with cirrhosis of a different etiology. No correlation was found between ADA2 and neopterin. Our data show that liver insufficiency and HCV infection increase the serum levels of ADA and its major isoenzyme ADA2. Furthermore, ADA isoenzyme determination adds no value to total ADA value. The absence of a correlation between ADA2 and neopterin suggests that different physiologic processes are involved in their increase.     

Metabolic bone disease of liver cirrhosis: Is it parallel to the clinical severity of cirrhosis?

Metabolic bone disease has long been recognized in chronic liver disease, especially cholestatic or alcoholic liver diseases. The aim of the present study was to investigate the prevalence and severity of osteodystrophy in cirrhotic men and the correlation of its incidence with the clinical severity of cirrhosis in an endemic area of post-necrotic hepatitis. We measured serum levels of osteocalcin, 25-hydroxyvitamin D, parathyroid hormone mid-molecule, calcium and testosterone in 74 cirrhotic men (Child-Pugh's classification grade A n= 30, B n= 21 and C n= 23) and 16 healthy controls. Standard X-rays and bone mineral densities of lumbar spine were performed in 30 patients with post-necrotic cirrhosis and 10 healthy controls. Serum levels of osteocalcin, parathyroid hormone and testosterone were significantly lower in patients with cirrhosis than in controls. Changes paralleling an increased severity of cirrhosis were found in the serum levels of 25–hydroxyvitamin D and testosterone, but not in the serum levels of osteocalcin and parathyroid hormone. The lumbar bone mineral density was significantly lower in patients with post-necrotic cirrhosis than in controls (0.97 ± 0.13 vs 1.07±0.12 g/cm², P<0.05) and was correlated with serum 25–hydroxyvitamin D levels (r = 0.467; P<0.005). There was no correlation between the bone mineral density and serum osteocalcin or the clinical severity of cirrhosis. The prevalence of spinal osteoporosis, as defined by a lumbar bone mineral density greater than two standard deviations below the mean value of the controls, was 20% in cirrhotic patients compared with 10% in controls. Two (6.7%) patients (both grade C) had spinal compression fractures compared with none in the control group. In conclusion, serum osteocalcin and lumbar bone mineral density were significantly lower in cirrhotic men than in controls. However, they were not correlated with each other or the clinical severity of cirrhosis.     

血清蛋白电泳、免疫球蛋白及其轻链测定对肝病患者的临床意义

目的探讨血清中免疫球蛋白和轻链测定以及血清蛋白电泳在肝病患者中的临床应用价值。方法用免疫散射比浊法在特定蛋白分析仪上检测92例肝病患者(包括急性肝炎患者28例、慢性肝炎患者33例、肝硬化患者31例)及45例健康者血清中免疫球蛋白IgG、IgA、IgM以及κ轻链和λ轻链的水平;用琼脂糖凝胶电泳法对所有样本进行血清蛋白电泳检测。结果与对照组相比,急性肝炎组以IgM升高为主,差异有统计学意义(P<0.05);两组κ轻链和λ轻链水平比较,差异无统计学意义(P>0.05)。急性肝炎组和肝硬化组IgG、IgA水平均高于对照组,差异有统计学意义(P<0.05);两组κ轻链和λ轻链水平分别与对照组比较,差异均有统计学意义(P<0.05)。血清蛋白电泳结果显示,急性肝炎组与对照组相比,两组γ区球蛋白含量比较,差异无统计学意义(P>0.05);慢性肝炎组和肝硬化组γ区球蛋白含量与对照组比较,差异有统计学意义(P<0.05)。结论血清中免疫球蛋白及其轻链的含量与肝脏疾病密切相关,慢性肝炎肝硬化患者血清蛋白电泳呈现典型的多克隆增殖图谱。血清蛋白电泳、免疫球蛋白和轻链水平的测定可作为肝脏功能监测的辅助指标。     

Serum xanthine oxidase in human liver disease

OBJECTIVES: High concentrations of serum xanthine oxidase (XO) have been reported during human liver disease and hepatocyte injury in experimental settings. However, it is unclear whether this elevation reflects hepatocyte necrosis or has a different meaning. METHODS: The serum level of XO in 64 patients with chronic liver disease (17 patients with cirrhosis, 30 with chronic hepatitis, and 17 with cholestatic disorders) and in 12 control subjects was determined by a competitive ELISA. Conventional serum markers of liver damage were assessed in all patients, and grading and staging were scored in the chronic hepatitis group according to Knodell. RESULTS: The XO serum levels were significantly higher in the patients than in the controls. The differences were also significant when controls were compared to patients with chronic hepatitis and cholestatic disorders separately, but not when compared to the cirrhosis group. Patients with cholestatic disorders had XO values higher than those of patients with cirrhosis or chronic hepatitis. XO levels did not correlate with stage and grade in chronic hepatitis group. We found a weak but significant positive correlation in patients between XO serum level and gamma-glutamyl transpeptidase (r = 0.37). This correlation was stronger when chronic hepatitis (r = 0.42) and, especially cholestatic disorders (r = 0.71), were separately tested, but was absent in the cirrhosis group. The XO values positively correlated with alkaline phosphatase in patients with cholestatic disorders. A level of serum XO >32 microg/ml specifically identified cholestatic disorders in our study population. CONCLUSIONS: A marked elevation of serum XO in patients with chronic liver disease seems to reflect the presence of cholestasis. No correlation between XO levels and histological or serum evidence of hepatocyte necrosis was found in these patients.     

Quantitation of HCV RNA in liver of patients with chronic hepatitis C

BACKGROUND/AIMS: Liver HCV RNA has been quantitated in few studies and the feasibility and the role of this parameter in the evaluation of patients with chronic HCV hepatitis still warrant study. Our aim was to determine the concentrations of HCV RNA in the liver of chronic HCV patients and to correlate the results with serum viral load. We also studied the relation of levels of HCV RNA in the liver with serum aminotransferases levels and with the presence of cirrhosis. METHODS: Twenty patients (14 males, aged 28 to 61 years) were studied. Twelve were infected by HCV type 1, six by type 3 and one by type 5. Percutaneous liver biopsy samples were obtained from 14 patients, and the remainder from liver explant in patients undergoing OLT. Twelve had chronic hepatitis and eight cirrhosis. HCV RNA levels were determined by bDNA. RESULTS: HCV RNA levels below the detection limit were found in one liver and in five serum samples. HCV RNA (mean +/- SD) was 2.1 x 10(8) +/- 2.2 x 10(8) Eq/gm in the liver and 94 x 10(5) +/- 93 x 10(5) Eq/mL in serum, with a significant correlation between these values (r = 0.89; P < 0.0001). Serum HCV RNA levels were significantly lower (P = 0.001) in cirrhotic than in chronic hepatitis patients, while the groups did not differ in liver HCV RNA levels. No correlation was observed between liver or serum HCV RNA and serum ALT or AST. CONCLUSIONS: Quantitation of HCV RNA is possible even in small liver samples. Although average levels are more than one log higher than those observed in serum, hepatic concentrations correlate with those observed in serum. The application of this technology to monitoring antiviral therapy and understanding the pathogenesis of the disease remains to be determined.     

Serum hyaluronan--a non-invasive test for diagnosing liver cirrhosis

INTRODUCTION: Hyaluronan is a glucosaminoglycan synthesized by the mesenchymal cells and degraded by hepatic sinusoidal endothelial cells by a specific receptor-mediated process. Elevated levels are associated with the sinusoidal capillarization that is seen in cirrhosis. METHODOLOGY: Serum hyaluronan was measured, using a radiometric assay (Pharmacia, Sweden) in 221 patients with biopsy-proven chronic liver disease of a variety of aetiologies (alcohol n = 70, autoimmune chronic active hepatitis n = 23, primary biliary cirrhosis n = 17, hepatitis C n = 69, cryptogenic n = 15, various n = 27). All patients were fasted, and their liver function tests, full blood count, prothrombin time and Child-Pugh score were assessed at the time of the liver biopsy. RESULTS: Hyaluronan levels (microg/l) were significantly higher in patients with liver cirrhosis (cirrhosis n = 127, mean 440, 95% CI 367-515) (P < 0.0001) compared with hepatic fibrosis (n = 23, mean 144, 95% CI 69-190), chronic hepatitis (n = 60, mean 63, 95% CI 37-91) and fatty liver (n = 11, mean 107, 95% CI 37-177). Within the cirrhotic population, there was no significant difference in hyaluronan levels between different aetiologies, but hyaluronan level increased proportionally to the severity of cirrhosis. Overall, a hyaluronan level > 100 microg/l had a 78% specificity and 83% sensitivity for diagnosing cirrhosis, while the specificity was increased to 96% for all patients with hyaluronan levels > 300 microg/l. The highest specificity and sensitivity were seen at a cut-off value of 100 microg/l in patients with alcohol-associated liver disease (89%, 87%) and hepatitis C (93%, 72%) respectively. Within patient cohorts, there was a significant correlation (P < 0.01) between hyaluronan and albumin, platelet count and bilirubin, but not with alanine aminotransferase. CONCLUSION: Measurement of fasted serum hyaluronan reliably differentiated cirrhotic from non-cirrhotic liver disease and can be regarded as a useful test in the diagnosis of liver cirrhosis, particularly when a liver biopsy is contraindicated.