Serum immunoreactive prolyl hydroxylase in liver disease

The concentration of serum immunoreactive prolyl hydroxylase (SIRPH) was measured in thirty patients with chronic active hepatitis, thirteen with primary biliary cirrhosis, four with alcoholic or idiopathic cirrhosis, and four with acute hepatitis; the values were compared with those in twenty-three control subjects. Increases in SIRPH were found in all the groups with liver diseases, individual values being highest in primary biliary cirrhosis in which about two-thirds of patients had values more than two standard deviations above the mean value in the control subjects. No correlation was found between SIRPH and other tests of liver function or some routine laboratory tests. SIRPH may reflect some hitherto unknown of unmeasured process in the diseased hepatic cells.     

Clinical significance of serum 7S collagen in various liver diseases

Serum type IV collagen fragment (7S collagen domain) was measured in 30 controls and 152 liver disease patients with a radioimmunoassay using a polyclonal antibody to human placenta 7S collagen. The serum concentrations of 7S collagen (mean +/- SD) were 4.2 +/- 0.9 ng/mL in controls, 5.1 +/- 2.0 ng/mL in acute hepatitis, 6.5 +/- 2.5 ng/mL in chronic inactive hepatitis, 9.5 +/- 3.8 ng/mL in chronic active hepatitis, 14.4 +/- 7.5 ng/mL in liver cirrhosis, and 14.4 +/- 6.9 ng/mL in hepatocellular carcinoma. In acute hepatitis, 7S collagen was slightly increased, whereas type III procollagen N-peptide and prolyl hydroxylase were markedly increased. In chronic liver disease, 7S collagen concentrations increased with the severity of the disease, and also reflected the degree of fibrosis. The serum 7S collagen concentrations were significantly correlated with those of type III procollagen N-peptide and prolyl hydroxylase in all subjects. These results suggest that serum 7S collagen concentration is a useful diagnostic aid for determining hepatic collagen metabolism in liver diseases.     

Serum enzymes of collagen synthesis and type III procollagen amino-propeptide in Nigerian patients with sickle cell disease

Serum immunoreactive prolyl hydroxylase protein, galactosylhydroxylysyl glucosyltransferase activity and the aminoterminal propeptide of type III procollagen were measured in 20 patients with sickle cell disease and the values were compared with those in 20 apparently healthy Nigerians. The means for the two enzymes and serum aminoterminal propeptide of type III procollagen were significantly higher in the sickle cell disease patients. Significant correlations were found between the values for the two enzymes and the protein serum aminoterminal propeptide of type III procollagen within the sickle cell disease patients. The data confirm that collagen formation is found in the liver, bone and other organs of patients with this disease. The measurement of serum immunoreactive prolyl hydroxylase protein, serum galactosylhydroxylysyl glucosyltransferase activity and serum aminoterminal propeptide of type III procollagen in prospective studies might be helpful in predicting hepatic, bone or diffuse fibrogenesis in sickle cell disease.     

Three serum markers of collagen biosynthesis in Nigerians with cirrhosis and various infectious diseases

Serum immunoreactive prolyl hydroxylase protein, galactosylhydroxylysyl glucosyltransferase activity, and the aminoterminal propeptide of type III procollagen (S-Pro(III)-N-P) were measured in twenty patients with cirrhosis and ninety with various infectious diseases, and the values were compared with those in sixty apparently healthy Nigerians. The means for all three markers were elevated significantly in the patients with cirrhosis (P less than 0.001), acute viral hepatitis (P less than 0.001), amoebic liver abscess (P less than 0.001) and the early stages of Schistosoma mansoni infection (P less than 0.001 for S-Pro(III)-N-P, P less than 0.005 for the two other markers). The mean S-Pro(III)-N-P was also distinctly elevated during the early stages of Schistosoma haematobium infection (P less than 0.01) and filariasis (P less than 0.001), whereas none of the three markers was elevated during an acute attack of malaria. Significant correlations were found between the values for the three markers within the groups of patients with cirrhosis, amoebic liver abscess and schistosomiasis, the correlations for the pooled group of all patients being highly significant (P less than 0.001). The data suggest that elevated hepatic collagen formation is found not only in cirrhosis but also in several infectious diseases. The three serum markers may be useful for showing the stages of active collagen formation in various liver diseases and for predicting the development of fibrosis in acute cases if the values remain elevated.     

Hepatic collagen proline hydroxylase activity in alcoholic liver disease.

The activity of hepatic collagen proline hydroxylase was examined in biopsy samples as a factor in collagen synthesis in 77 patients with alcoholic liver disease. The urinary excretion of peptide bound hydroxyproline was also measured in most of the patients, as an index of collagen degradation. The highest activities of collagen proline hydroxylase were found in the patients with alcoholic hepatitis. Enzyme activity was markedly increased in patients with non-specific changes on liver biopsy, whereas, patients with fatty infiltration had only mild elevations, and those with inactive cirrhosis had normal enzyme activity. Urinary hydroxyproline was elevated only in patients with alcoholic hepatitis and inactive cirrhosis. Follow-up determinations in 16 patients with alcoholic hepatitis, after 4 to 5 weeks, revealed a decrease in enzyme activity, but no change in urinary hydroxyproline. We conclude that among the types of alcohol-related liver diseases, alcoholic hepatitis is associated with the greatest turnover of hepatic collagen.     

gamma-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

gamma-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum gamma-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic gamma-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There was no inhibitors or activators of liver gamma-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum gamma-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic gamma-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.     

Enzymes of collagen biosynthesis in skin and serum and dermatological diseases. II. Serum enzymes.

Serum immunoreactive prolyl hydroxylase protein and galactosylhydroxylysyl glucosyltransferase activity were measured in 54 patients wtih various dermatological diseases and compared with corresponding values in 32 control subjects. These serum enzymes were at the control level in the great majority of the patients, and no correlation was found between serum and skin enzymes, except for one weak correlation in lichen ruber planus. Some patients with psoriasis, lichen ruber planus, keloids, erythema nodosum or chronic discoid lupus erythematosus, however, did have at least one of these enzymes elevated in the serum, and a significant correlation (P less than 0.01) between the two enzymes was found in the total disease material. Thus it does seem that diseases limited only to the skin can sometimes raise these serum enzyme levels. The mean levels of serum immunoreactive prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase activity were significantly elevated (P less than 0.001) in active systemic connective tissue diseases such as systemic lupus erythematosus, scleroderma or dermatomyositis compared with the controls, and 4 out of 7 values for immunoreactive prolyl hydroxylase and 3 out of 7 for galactosylhydroxylysyl glucosyltransferase activity were above the 95% confidence limit of the controls. Since the levels of the skin enzymes were not elevated in most of these patients, however, the main sources for the elevated serum enzymes were probably tissues other than the skin.     

Enzymes of collagen synthesis and type III procollagen amino-propeptide in serum from Nigerians with chronic endomyocardial fibrosis

The hallmark of cardiac pathology in chronic African endomyocardial fibrosis is the laying down of excess collagen in the endomyocardium. Preliminary observations on the assay of enzymes of collagen synthesis and type III procollagen aminopropeptide in chronic African endomyocardial fibrosis are reported. Serum immunoreactive prolyl hydroxylase protein was elevated in 4, serum galactosyl-hydroxylysyl glucosyl transferase activity was elevated in 5, and type III procollagen aminopropeptide was also elevated in 5 patients. Cardiac cirrhosis and endomyocardial fibrosis could be responsible for the elevated values in these patients. The relative contribution of fibrosis of the myocardium to these elevated values remains to be clarified.     

血清甘胆酸水平在慢性肝病患者中的临床分析

目的探讨血清甘胆酸检测在慢性肝病患者诊断中的临床意义。方法将135例慢性肝病患者按病情程度分成慢性肝炎轻度组(32例)、中度组(18例)、重度组(8例),肝硬化组(62例),肝癌组(15例),同时选取20名健康体检者作为对照组。用放射免疫法检测各组对象血清甘胆酸的含量。结果慢性肝炎各组及肝硬化、肝癌组血清甘胆酸均高于对照组(P<0.01),血清甘胆酸水平在慢性肝炎各组患者之间差异有统计学意义(P<0.05)。结论慢性肝炎、肝硬化、肝癌患者血清甘胆酸较正常人升高,慢性肝炎患者随着病情加重血清甘胆酸升高。     

肝硬化患者血清sP-选择素与肝功能及肝纤维化的关系

[目的]探讨肝硬化患者血清可溶性粘附分子P-选择素(sP-选择素)与肝功能及肝纤维化的关系.[方法]选择75例肝硬化患者,测定sP-选择素、肝功能及Ⅳ型胶原水平.[结果]肝硬化组血清sP-选择素及Ⅳ型胶原水平均显著高于正常对照组;血清sP-选择素与肝功能、肝功能Child分级和Ⅳ型胶原水平明显相关.[结论]血清sP-选择素水平可能是临床观察肝硬化患者病变活动的重要指标.     

Studies on serum immunoreactive prolyl 4-hydroxylase in liver diseases--its elevation both in hepatocellular damage and cholestatic diseases

The concentration of serum immunoreactive prolyl 4-hydroxylase (S-IRPH) was determined in patients with various liver diseases by the radioimmunoassay developed previously. S-IRPH values were elevated in acute hepatitis (p less than 0.01), hepatocellular carcinoma (p less than 0.05), metastatic liver neoplasm (p less than 0.01) and cholestatic diseases (p less than 0.001), but no significant elevation was seen in chronic hepatitis or liver cirrhosis. The mean value of S-IRPH was highest in cholestatic diseases, and next highest in acute hepatitis. In addition to acute hepatitis, S-IRPH was increased in other conditions of hepatocellular damage such as exacerbation of chronic hepatitis or immediately after transcatheter arterial embolization of hepatocellular carcinoma. In cases of hepatocellular damage S-IRPH varied concurrent with cytoplasmic enzyme (AST, ALT and LDH) levels and in cases of cholestatic diseases with biliary enzyme (Al-P and gamma GTP) levels. These properties appear to be unique among serum enzymes. The characteristics of S-IRPH were considered to be related to its unique subcellular localization within the cell, ie the membrane of rough endoplasmic reticulum.     

自身免疫性肝病相关自身免疫性抗体的特征分析及临床应用价值

目的：观察自身免疫性肝病（AILD）相关自身免疫性抗体的特征分析及临床应用价值。方法：临床纳入自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）以及病毒性肝炎患者作为研究对象,并选取健康体检者作为对照。检测每组患者的相关自身免疫指标。结果：AIH患者血清ANA阳性率明显高于PBC、病毒性肝炎以及对照组（P〈0．05）。PBC患者血PBC患者血清AMA阳性率显著高于AIH组（P〈0．05）。血清ANA在AIH以及PBC患者中均以高低度（1：1000）为主。结论：每种AILD均伴有其特征性的自身抗体,对各种类型的慢性肝病常规进行自身抗体检测对于诊断和鉴别AILD有重要的临床意义。     

慢性肝炎患者乙型肝炎病毒复制与肝纤维化标志物的关系

目的研究慢性乙型肝炎（下称乙肝）患者血清乙肝病毒（HBV）复制水平与肝纤维化血清标志物的关系。方法选择150例临床确诊为慢性乙肝的50例早期肝硬化患者，采用荧光定量聚合酶链反应（FQ-PCR）检测血清HBVDNA水平，放射免疫法和酶免疫法检测肝纤维化血清标志物（透明质酸、层黏连蛋白、Ⅲ型前胶原和Ⅳ型胶原），对血清HBVDNA水平与肝纤维化标志物的关系进行分析，并与100例无肝硬化患者血清HBVDNA及肝纤维化标志物水平进行比较。结果慢性乙肝患者血清HBVDNA水平与肝纤维化标志物的关系无统计学意义（P〉0．05），早期肝硬化患者血清肝纤维化标志物水平显著高于无肝硬化患者，但HBVDNA水平却低于无肝硬化患者（P〈0．05）。结论慢性乙肝患者血清HBVDNA水平与肝纤维化标志物水平无显著相关性。     

Serum type III procollagen peptide as a non-invasive marker of liver damage during infancy and childhood in extrahepatic biliary atresia, idiopathic hepatitis of infancy and alpha 1 antitrypsin deficiency

To evaluate the role of serum procollagen III peptide as a non-invasive marker of liver damage and prognosis in hepatobiliary disorders of infancy, we have measured its concentration at presentation and serially in 30 infants with extrahepatic biliary atresia, 22 with idiopathic hepatitis of infancy, 10 with alpha 1 antitrypsin deficiency and 105 age-matched controls. Raised procollagen III peptide concentrations occurred in 51% of patients at presentation and 59% at follow up but were not related to the type of liver disease or the severity of liver damage, as assessed either by standard biochemical tests of liver function, serum glycocholic acid, semiquantitative assessment of 11 histopathological features or hepatic prolyl hydroxylase activity. Serum procollagen III peptide concentrations also gave no guide to prognosis. Although the factors determining serum procollagen III peptide concentrations in hepatobiliary disorders of infancy are unknown at the present time, we suggest that changes in growth rate may be of major importance in determining the significance of serum procollagen III peptide concentrations in infants and children.     

Clinical significance of serum glutathione reductase in various clinical conditions, especially in liver diseases.

Serum glutathione reductase activity was measured in various conditions including acute hepatitis, chronic hepatitis, liver cirrhosis, malignant neoplastic diseases, and obstructive jaundice. A statistically significant elevation of the enzyme activity was found in all of these clinical conditions above normal value, especially in patients with acute hepatitis, some liver cancer, and malignant biliary obstruction. Comparison with other liver function tests showed the existence of statistically significant correlations of serum glutathione reductase with SGOT, SGPT and alkaline phosphatase in acute hepatitis, and with alkaline phosphatase in cirrhosis. In parenchymatous liver disease, serial determination was found to be important. High values in obstructive jaundice suggest the malignant obstruction.     

Elevated level of serum Mn-superoxide dismutase in patients with primary biliary cirrhosis: possible involvement of free radicals in the pathogenesis in primary biliary cirrhosis.

Serum Mn-superoxide dismutase (Mn-SOD) was determined in patients with various liver diseases including 31 patients with primary biliary cirrhosis (PBC), 46 with hepatocellular carcinoma (HCC), 17 with liver cirrhosis (LC), 23 with chronic hepatitis (CH) and 12 patients with obstructive jaundice with an enzyme-linked immunosorbent assay using a specific monoclonal antibody. The serum level in patients with PBC (407 +/- 35 ng/ml, mean +/- SEM; n = 31) was significantly increased (p less than 0.01) compared with those of other liver diseases. Mn-SOD level did not correlate with total bilirubin level, gamma-glutamyl transpeptidase activity, alkaline phosphatase activity, alanine aminotransferase activity, IgM, or with ceruloplasmin level in the sera of the patients. When the patients with PBC were histologically subdivided into four groups according to Scheuer's classification (Scheuer PJ. Primary biliary cirrhosis. In: Scheuer PJ, ed. Liver biopsy interpretation. 3rd ed. London: Bailliere Tindall, 1980:47-56), a high level of serum Mn-SOD was noticed in the early stage as well as in the advanced stage of the disease. Immunoblot analysis confirmed the reactivity and specificity of the monoclonal antibody to the enzyme protein in the patients' sera. Immunostaining of a liver biopsy specimen from the patients with PBC revealed increased expression of the enzyme protein in damaged epithelial cells of interlobular bile ducts, bile ductules, and degenerated hepatocytes. These data suggested that free radicals including superoxide anion are possibly involved in the pathogenesis of the disease and Mn-SOD may play some role in a protection against the superoxide anion.     

Biochemical study of fibrosis in the rat liver in biliary obstruction.

In an attempt to study the collagen formation in the liver occurring in association with obstructive jaundice, the authors carried out an experiment with liver slices from common bile duct-ligated rats. Hepatic collagen was fractionated into the neutral soluble, acid soluble and insoluble fractions, and the hydroxyproline synthesis rate of each fraction was measured using 14C-proline. Determination was also made for hexosamine content in the same liver tissue. The hydroxyproline content of hepatic collagen increased as biliary obstruction was prolonged, particularly from the 4th week, which is the transitional period of liver histology into biliary cirrhosis. The hexosamine content of hepatic collagen showed a similar tendency. The neutral soluble, acid soluble and insoluble collagen fractions all increased as biliary obstruction was prolonged. The collagenosynthetic activity of the neutral soluble fraction, attained a peak in 1 to 2 weeks of biliary obstruction, which indicates that collagen fibers are formed actively in the early stage of jaundice, although there is only a slight increase in the absolute amount of fibers developed then. Serum monoamine oxidase level tended to be parallel to collagenosynthetic activity but not to collagen content.     

血清铁 铁蛋白及转铁蛋白联合检测在肝脏疾病中的应用

目的探讨肝病患者铁代谢相关血清学指标的临床诊断意义及铁在肝损伤过程中的作用。方法采用全自动生化分析仪分别对52例慢性乙型肝炎患者,47例肝硬化患者,34例肝细胞癌患者和30例健康对照者进行血清Fe水平检测;采用电化学发光仪对慢性乙型肝炎患者、肝硬化和肝细胞癌患者及30例健康对照者进行血清铁蛋白及转铁蛋白检测。结果慢性乙型肝炎患者、肝硬化患者血清铁、铁蛋白水平均高于健康对照组(P<0.05);肝细胞癌患者铁蛋白、转铁蛋白及血清铁水平明显高于慢性乙型肝炎患者及肝硬化患者;与健康对照组比较差异有统计学意义(P<0.05)。肝病患者血清铁、铁蛋白和转铁蛋白与肝功能常用检测指标具有相关性。结论血清铁、铁蛋白和转铁蛋白可作为肝脏疾病诊断的重要参考指标,对疾病的判断和预后有重要的意义。     

Fibro Scan 与超声检查诊断肝纤维化的异同性及关联性

【目的】探讨FibroScan检查（FS检查）与超声检查（US检查）在诊断慢性肝病患者肝纤维化的异同性和相关性。【方法】选取2014年1月至2015年5月在院诊治的慢性肝病患者382例作为研究对象,其中慢性乙型肝炎（HBV ）感染260例,慢性丙型肝炎82例,原发性胆汁性肝硬化40例。分别采用FS检查和U S检查两种方法对肝脏、脾脏等器官及其血管分布等进行测定,并采用Spearman相关性分析、多重线性回归分析对各项检测指标,特别是FS检查的肝硬度值（FS值）,进行相关性分析。【结果】US检查结果显示,慢性乙型肝炎患者、慢性丙型肝炎患者、原发性胆汁性肝硬化患者的肝左叶厚度、肝右叶厚度、门静脉内径、肝脏血管走形、胆囊疾病及脂肪肝发病率等差异无统计学意义（ P ＞00．5）;三组患者的FS值分别为（95．74±94．91）kPa、（163．38±113．58）kPa、（276．87±186．77）kPa ,三组患者间差异无统计学意义（ P ＞00．5）,各组间两两比较差异均有统计学意义（ P ＜00．5）;原发性胆汁性肝硬化患者肝脏表面光滑度、肝脏回声状况差于慢性乙型肝炎患者和慢性丙型肝炎患者,肝硬化发生率明显高于后两组患者（ P ＜00．5）;FS值与肝左叶厚度、门静脉内径、肝脏表面光滑度、肝脏回声、肝脏血管走形、肝硬化等成正相关（ P ＜00．1）,与胆囊疾病发生率呈负相关（ P ＜00．1）;FS值与超声检测结果的回归性分析显示,肝脏表面光滑度、肝左叶厚径和门静脉内径,各个偏回归系数差异均有统计学意义（ P ＜00．5）。【结论】FS检查与US检查具有较好的相关性,在临床工作中结合US和Fibroscan检查结果进行综合分析,能更好对肝病患者肝纤维化程度做出准确评估,更好的指导临床治疗。     

乙肝相关性肝病患者幽门螺杆菌感染的研究

目的研究慢性乙型肝炎(乙肝)、乙肝肝硬化、乙肝后肝癌等肝病患者幽门螺杆菌(Hp)感染情况。方法收集慢性乙肝、乙肝肝硬化、乙肝后肝癌等肝脏疾病患者273例,日期正常体检人群60例,采用免疫层析法检测患者血清中抗Hp抗体(Hp-IgG),定量PCR检测HBV DNA。结果乙肝相关性肝病患者Hp感染率73.3%,正常体检人群为40.0%,2组比较差异有统计学意义(P<0.01);慢性乙肝、乙肝肝硬化、乙肝后肝癌3组患者Hp感染率分别为62.7%、77.0%、79.7%,后二者Hp明显高于慢性乙肝患者(P<0.05);按病毒载量分级,HBV DNA阴性组Hp感染率低于HBV DNA阳性组,而阳性组按低、中、高分组,各组间Hp感染率分别为69.4%、65.0%、66.1%(P>0.05);乙肝肝硬化患者按Child-push分级后,A、B、C各级之间的Hp感染率分别为51.9%、63.4%、65.6%(P>0.05)。结论 Hp感染可能参与乙肝肝病患者肝脏损伤,显示Hp具有肝细胞毒性作用;肝硬化、肝癌感染率高于慢性乙型肝炎,提示Hp感染与慢性肝病疾病进展和肝癌的发生有一定相关性。