Cholylglycine Levels Research Articles

Effects of intrahepatic cholestasis of pregnancy on hepatic function, changes of inflammatory cytokines and fetal outcomes.

The effects of intrahepatic cholestasis of pregnancy (ICP) on hepatic function, changes of inflammatory cytokines and fetal outcomes were studied. In total, 663 pregnant women admitted to Daqing Longnan Hospital from July 2016 to December 2017 were selected. There were, 40 cases with ICP enrolled in the observation group, and 40 normal pregnant women were recruited in the normal group. They were also grouped according to hepatic function and inflammatory cytokines, with 40 cases in each group. Neonatal Apgar scores were recorded. The correlations of serum cholylglycine (CG) in pregnant women with umbilical artery systolic-to-diastolic (S/D) ratio in the third trimester of pregnancy, the alanine aminotransferase level, the high-sensitivity C-reactive protein (hs-CRP) level, neonatal Apgar score and gestational week were analyzed. The birth weight in the observation group was lighter than that in the normal group (P<0.05); the gestational week at birth was earlier than that in the normal group (P<0.05); Apgar score at birth was lower than that in the normal group (P<0.05), and the levels of inflammatory cytokines were higher than those in the control group (P<0.05). Apgar scores of newborns at birth and at 1 and 5 min after birth in the normal hepatic function and normal inflammatory cytokine groups were higher than those in the abnormal hepatic function group (P<0.05). The serum CG level in pregnant women was positively correlated with umbilical artery S/D ratio, the alanine aminotransferase level and the hs-CRP level in the third trimester of pregnancy, but negatively correlated with neonatal Apgar score and gestational week. Among patients with ICP, the higher the GG level in the body is, the higher the alanine aminotransferase, inflammatory cytokine and umbilical artery S/D ratio will be, which may cause lower neonatal Apgar score, neonatal asphyxia and premature delivery.

Optical imaging of cholylglycine by using liquid crystal droplet patterns on solid surfaces

Determining cholylglycine (CG) levels is of great importance in the detection of liver abnormalities. In this study, we present a novel liquid–crystal (LC)-based method assisted with cholylglycine hydrolase (CGH) for the optical detection of CG levels. The detection method is based on the disruption of the orientations of a nematic LC, 4-cyano-4′-pentylbiphenyl (5CB), doped with dodecyl aldehyde. Aldehyde-doped 5CB droplets were placed on pre-treated glass slides and patterned with solutions of interest. When in contact with a small drop of a CG aqueous solution, bright fan-shaped LC droplet patterns were observed under polarizing optical microscopy, indicating a planar orientation of LC at the aqueous/LC interface. However, aldehyde with short-alkyl chain couples with glycine released from the enzymatic reaction between CG and CGH forming amphiphilic Schiff bases, which display dark cross patterns of LC, suggesting a homeotropic orientation of the LC. This system may offer a highly sensitive and methodologically simple approach to determine CG levels for clinical diagnostics and commercial applications.

Study on the placental expression of MDR3 in intrahepatic cholestasis of pregnancy

目的 探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)胎盘中胆盐载体磷脂输出泵(multidrug resistance p-plycoprotein,MDR3)的表达,以及母、胎血中总胆汁酸(total bile acids,TBA)和甘胆酸(cholylglycine,CG)水平的变化;进一步分析胎盘胆盐载体对胆汁酸水平的调节作用及其与ICP的关系.方法ICP(ICP组)及正常妊娠(对照组)孕妇各20例.母血、胎儿脐静脉血中TBA、CG水平的测定分别采用放射免疫法和速率法;胎盘组织中胆盐载体MDR3 mRNA的表达采用荧光定量PCR法.结果(1) ICP组母血、脐血中的TBA、CG水平均高于对照组(P＜0.05).ICP组母血TBA水平高于脐血(25.8±16.6和8.6±5.5)μnol/L,CG水平高于脐血(3416.1±1986.0和821.8±673.2)μg/dL(P＜0.05);对照组母血和脐血TBA水平(3.4±2.5和4.4±3.3)μmol/L,CG水平(342.7±234.9和309.3±145.2)μg/dL比较,差异无统计学意义(P＞0.05).(2)ICP和正常妊娠各期胎盘组织中均有MDR3 mRNA的表达.ICP组MDR3 mRNA表达量低于对照组(0.80±0.67和162.63±334.33)拷贝/ng(P＜0.05).(3)ICP组、对照组胎盘中MDR3 mRNA表达量与母血、脐血中TBA和CG水平均无相关性(r=-0.60～0.165,P＞0.05).结论ICP胎盘胆盐载体MDR3 mRNA表达降低,可能引起ICP胎盘对胆汁酸的转运障碍、胎儿体内胆汁淤积,可能是引起ICP胎儿窘迫的原因。

Postprandial serum cholylglycine in the detection of hepatotoxicity induced by antituberculous agents

Background: Measurement of bile acid levels has been proven helpful in the detection of hepatic abnormalities when routine liver function test results are normal or only slightly elevated. We compared the effectiveness of postprandial serum cholylglycine (CG), as determined by RIA, with commonly used liver function tests (SGOT, SGPT, alkaline phosphatase, gamma-glutamyl transpeptidase) in order to detect liver injury in patients receiving antituberculous agents. Method: We studied 100 patients receiving antituberculous agents. Laboratory tests were carried out before the initiation of therapy and after 1, 2, 3 and 8 weeks of treatment. The risk of hepatotoxicity in relation to age (>35 years) and/or the addition of pyrazinamide to the 6-month isoniazid–rifampin regimen was also assessed. Results: The percentage of patients with hepatic dysfunction detected by abnormal serum CG levels was significantly greater than that detected with conventional liver function tests. Neither age over 35 years nor the use of pyrazinamide was associated with a greater number of abnormalities in liver function tests. Conclusion: Postprandial serum CG by RIA proved to be a sensitive parameter for detecting hepatotoxicity by antituberculous agents.

Correlation of serum cholylglycine level with hepatic dysfunction in children with sickle cell anemia.

Hepatic dysfunction occurs commonly in children with sickle cell disease (SCD). Although the etiology is multifactorial, cholestasis is a prominent feature. Serum cholylglycine (CG) has been found to be a very sensitive indicator of cholestasis. Our objective was to determine whether CG levels are elevated in children with SCD and whether they are predictive of hepatic dysfunction. Blood samples were obtained from 97 children with SCD. Liver function tests were done and serum CG concentrations were measured. Patients were followed up for 2 years. Thirty-eight percent of the patients had an elevated CG level. During the 2 years of follow-up, 16% of the children with a previously elevated CG level developed abnormal liver function test results or required a cholecystectomy as compared with 13% with a previously normal CG level (p = 0.92). We conclude that although CG level was elevated in 38% of the patients with SCD, it did not appear to predict liver dysfunction during the ensuring 2 years.

Pruritus as a presenting symptom of chronic hepatitis C.

Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.

Mephenytoin disposition and serum bile acids as indices of hepatic function in chronic viral hepatitis.

The effect of chronic viral hepatitis on liver function may vary from none to hepatic failure. Changes in function are usually the result of impaired hepatocyte function or altered vascular flow and architecture. Conventional liver function tests usually cannot distinguish contributions from these mechanisms or indicate degree of hepatic metabolic dysfunction. An alternative approach is to measure the hepatic metabolism of a highly extracted compound whose oral clearance and systemic bioavailability are dependent on both hepatocyte function and degree of portosystemic shunt. The stereoselective metabolism of racemic mephenytoin (100 mg oral dose) was investigated in 35 patients with chronic viral hepatitis and compared with 153 healthy subjects. The mephenytoin R/S enantiomeric ratio and cumulative excretion of the 4'-hydroxymephenytoin metabolite in a 0- to 8-hour urine sample were used in addition to serum bile acid levels and pathologic examination of biopsy specimens to assess the severity of hepatic dysfunction and portosystemic shunting. The patients as a group excreted less 4'-hydroxymephenytoin and had a smaller R/S enantiomeric ratio of mephenytoin. The two measures were discriminatory between the patient groups classified by either serum cholylglycine level or pathologic examination of biopsy specimens. Combination of the two measures of mephenytoin metabolism allowed the patients to be classified into three groups: normal hepatocyte function without portosystemic shunt, normal hepatocyte function with portosystemic shunt, and low hepatocyte function with or without portosystemic shunt. This study has shown the potential usefulness of mephenytoin metabolism as a sensitive indicator of hepatic pathologic condition with an ability to discriminate between contributory alternative mechanisms.

Hepatic oxidant injury and glutathione depletion during total parenteral nutrition in weanling rats.

Hepatobiliary dysfunction occurs commonly in infants on prolonged parenteral nutrition alimentation; however, the underlying mechanisms causing liver injury are poorly understood. We postulated that oxidant stress played a significant role in parenteral nutrition-induced liver abnormalities and tested this hypothesis in a rat model. Weanling male rats received 8 days of total parenteral nutrition (TPN) through a central venous catheter (TPN group), pair feeding of rat chow and placement of a central venous catheter (sham group), or ad libitum feedings of rat chow (control group). After 8 days of TPN, serum alanine aminotransferase and cholylglycine levels were elevated, hepatocellular steatosis was present, hepatic mitochondria had dilated intracristal spaces, and lipid peroxidation of mitochondria was increased compared with sham and control groups. Hepatic glutathione levels decreased to 16% of control values after 5 days of TPN; this was followed by mitochondrial lipid peroxidation and elevated serum cholylglycine levels after 8 days of TPN. Sham and control rats showed no evidence of mitochondrial lipid peroxidation or liver injury after 8 days. Removal of metabisulfate from TPN solutions and addition of cysteine HCl or choline had no major effect on these findings. Bacterial translocation was not increased in TPN rats. These data suggest that glutathione depletion and oxidant stress are important factors in the pathogenesis of TPN-induced liver abnormalities in the weanling rats.

Cholylglycine serum levels in cirrhosis

Objective: To evaluate the usefulness of the measurement of fasting serum levels of cholylglycine in patients with cirrhosis and to compare these with standard liver tests. Method: Serum levels of cholylglycine were measured by radioimmunoassay in 82 patients with cirrhosis who also underwent a complete clinical and laboratory evaluation. Results: Of the patients, 86.6% (68% with Child’s class A cirrhosis, 87% with B and 97% with C; (P = 0.015) had increased cholylglycine serum levels. There were many significant correlations between cholylglycine and other liver tests. We also found a significant association with several clinical parameters characteristic of advanced liver disease. The severity of cirrhosis also correlated with cholylglycine serum levels (P = 0.008). Bile acid levels were found to be the most sensitive of the liver tests studied. Conclusions: Raised cholylglycine serum levels are associated with liver dysfunction. Measurement of fasting cholylglycine levels could be useful as a marker of severity in the evaluation and follow-up of cirrhotic patients, and could be applied along with other commonly used liver tests. © Current Science Ltd.

A correlative study on serum cholylglycine levels in hepatobiliary disease.

The serum cholylglycine (CG), alanine aminotransferase (ALT) and total bilirubin levels were studied in 210 patients with hepatobiliary disease and in 70 healthy subjects. Serum CG concentrations in all the hepatobiliary diseases were found to be significantly higher than those of their controls. Patients with abnormal increases in ALT and bilirubin levels also showed raised CG concentrations; however, some patients with normal ALT and bilirubin levels, still had markedly elevated CG values. Patients with hepatic cirrhosis had high serum CG levels, followed, in descending order, by chronic active hepatitis and chronic persistent hepatitis. In the cholecystitis and cholelithiasis cases, their CG levels were significantly higher than those of the controls but lower than the values in hepatic disease patients; however, more cholecystitis cases had abnormally high serum bilirubin levels than CG. The results also show that serum CG concentrations vary in the different hepatobiliary diseases, and that serial CG measurements are more sensitive than measuring ALT and bilirubin levels in the diagnosis of hepatic diseases. Serum CG can be used as an index for evaluating the activity of chronic hepatitis; it can also be employed as a diagnostic tool in cholecystitis and cholelithiasis.

Effect of dietary lipid and vitamin E on mitochondrial lipid peroxidation and hepatic injury in the bile duct-ligated rat.

To assess whether lipid peroxidation of hepatic mitochondria is associated with cholestatic hepatic injury we examined the effect of bile duct ligation (BDL) versus sham surgery on mitochondrial lipids of rats maintained on one of seven diets. Diets included vitamin E-deficient (E-) and vitamin E-sufficient (E+) combined with normal lipid (11.9% calories as stripped corn oil), high lipid (35% calories as stripped corn oil), or n-3 fatty acid (fish oil) supplementation. Rats were killed 17 days after surgery, mitochondria were isolated by differential centrifugation, and lipid-conjugated dienes and thiobarbituric acid-reacting substances (TBARS) were measured in mitochondrial lipids as indices of lipid peroxidation. BDL resulted in significant increases in lipid peroxidation in all dietary groups. The E- high lipid diets (with either corn oil or fish oil) were associated with higher lipid peroxide and serum bilirubin values in BDL rats compared to the normal lipid diets. Fish oil supplementation did not ameliorate cholestatic or oxidative injury. Serum alanine aminotransferase, bilirubin, alkaline phosphatase, and cholylglycine levels correlated significantly with levels of mitochondrial conjugated dienes and TBARS. These data suggest that free radical stress occurs during BDL in the rat and may result in mitochondrial lipid peroxidation, and that diets high in lipid may increase free radical damage to hepatic mitochondria. The role of free radicals in cholestatic hepatic injury requires further investigation.

Prognostic significance of cholestatic alcoholic hepatitis

Tissue cholestasis is a histologic feature in some patients with alcoholic liver disease, but its significance is unknown. We studied prospectively the clinical, laboratory, and histologic findings of 306 chronic male alcoholics in whom liver tissue was available. Tissue cholestasis permitted identification of two groups: group I, absent or mild cholestasis (239 patients), and group II, moderate to severe cholestasis (67 patients). Statistical evaluation was performed by Student's t test and regression analyses. In patients with tissue cholestasis, 97% had elevated serum cholylglycine levels, while only 61% had significant jaundice (serum bilirubin greater than 5 mg/dl). In patients without tissue cholestasis, 66% had elevated serum cholylglycine and 13.5% jaundice. Highly significant statistical correlations (P less than 0.0001) were found between cholestasis and malnutrition, prothrombin time, AST, alkaline phosphatase, bilirubin, Maddrey's discriminant function, serum cholylglycine level, albumin, and histologic severity score. In group I, 54% survived 60 months versus 22% in group II (P less than 0.0001). Highly significant statistical correlations (P less than 0.0001) were noted between serum cholylglycine levels and the parameters enumerated earlier, but not with survival. We conclude that tissue cholestasis is a highly significant prognostic indicator of outcome in alcoholic hepatitis and is more consistently associated with bile salt retention than jaundice.

Liver involvement in human schistosomiasis mansoni. Assessment by immunological and biochemical markers.

In 20 patients with hepatic or hepatosplenic schistosomiasis and 82 individuals infected with S. mansoni, but without liver enlargement, serum parameters reflecting the fibrotic process and hemodynamic alterations as well as immunomodulation were examined. Included as controls were 35 age- and sex-matched healthy individuals from the study region in Northeast Brazil. Peripheral blood cholylglycine levels in patients with hepatomegaly, reflecting the spillover of portal blood into the systemic circulation, were elevated 12-fold over values of patients without liver involvement. Procollagen-III-peptide, a cleavage product of collagen synthesis, was elevated in patients with hepatomegaly (P less than 0.001) but normal in uncomplicated cases. Immunomodulation was assessed by in vivo delayed hypersensitivity to recall antigens and by serum beta 2-microglobulin and neopterin, substances released in the context of lymphocyte activation. Neopterin, predominantly a macrophage product, was elevated most strikingly in hepatomegalic cases (P less than 0.001). The possible interrelation between altered immune responses and excess fibrogenesis is discussed.

Bile Salt Malabsorption in Pancreatic Insufficiency Secondary to Alcoholic Pancreatitis

Twenty patients with exocrine pancreatic insufficiency secondary to alcohol abuse were studied for the presence of bile salt malabsorption. Fecal bile salts and fecal fat excretion were determined in 15 patients receiving pancreatic enzyme therapy, not receiving enzyme therapy, and on a regimen of pancreatic enzymes plus cimetidine. Serum bile salt levels were measured during fasting and postprandial conditions both during enzyme therapy and after it was stopped in 8 cases. In addition, 5 patients underwent [14C]cholylglycine breath testing during and after discontinuation of enzyme therapy. The fecal bile salt excretion varied between 610 and 3460 mg/day in the untreated patients. Treatment with pancreatic enzymes was associated with significant (p less than 0.05) reduction in fecal bile salt and fecal fat excretion. Cimetidine therapy in addition to enzyme therapy further reduced steatorrhea but failed to alter bile salt excretion significantly. Serum cholylglycine level showed significant (p less than 0.05) postprandial increase in patients receiving enzyme therapy, suggesting improved bile salt absorption. These data suggest a wide range of bile salt malabsorption in alcoholic patients with pancreatic insufficiency, which improves with pancreatic enzyme therapy.

Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis

We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 μmol/L at 15 weeks' pregnancy to 0.6 μmol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p < 0.005), median concentrations of CG remained well within the normal range (0–1.5 μmol/L). However, 10% of the group showed markedly elevated serum CG concentrations at 30 weeks' pregnancy, and the CG level in this group continued to rise during the third trimester. Pruritus was significantly more common in the group with elevated CG concentrations (48%) than in the group with normal CG levels (20%) (p < 0.005). Serum CG was a much more sensitive predictor of pruritus during pregnancy than other biochemical liver tests. Elevated CG levels were found more commonly in Mediterranean and Asian patients than patients of other ethnic origins (p < 0.025). No statistically significant associations were found between elevated CG concentrations and maternal age, number of previous pregnancies, pruritus during previous pregnancies, contraceptive-induced cholestasis, and fetal maturity. We conclude (a) that obstetric cholestasis is probably much more common than previously suspected and (b) that consideration should be given to the measurement of serum bile acids in all pregnant individuals with unexplained pruritus.

Serum bile acid in the evaluation of colchicine treatment of carbon tetrachloride-induced liver injury

The usefulness of measuring serum-conjugated bile acid concentrations by radioimmunoassay in colchicine-modified carbon tetrachloride-induced liver lesions in rats was assessed by comparing the concentrations with the results of some routinely employed liver function tests such as serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and serum total protein. The serum cholylglycine levels were significantly ( P < 0.003) raised along with the serum aspartate transaminase ( P < 0.01) and alanine transaminase ( P < 0.01) activity levels in the carbon tetrachloride-treated group of rats when compared with the group treated with carbon tetrachloride plus colchicine. Colchicine prevented the increase in serum cholylglycine, aspartate transaminase, alanine transaminase, and alkaline phosphatase induced by carbon tetrachloride but had no effect on serum total protein levels. This study suggests that radioimmunoassay of serum cholyglycine is a sensitive and specific indicator of liver injury and it is a useful tool in monitoring the treatment provided.

Radioimmunoassay of serum conjugated cholic acid in hepatic murine schistosomiasis

Cholylglycine levels were measured by radioimmunoassay in sera from 10 control CFI female mice and 22 CFI female mice experimentally infected with Schistosoma mansoni. Cholylglycine was significantly elevated in sera of all but one of the chronically infected animals. Serum aspartate transaminase was within normal limits in all the infected animals; while five infected mice had elevated serum alkaline phosphatase and all these five also had high levels of serum Cholylglycine. Marked hepatic histopathological changes were demonstrated in all the infected animals. The data suggest that serum Cholylglycine is a highly sensitive index for hepatic dysfunction in chronic hepatic schistosomiasis mansoni.

Diagnostic value of serum cholylglycine radioimmunoassay in chronic asymptomatic HBsAg carriers.

The correlation between histological liver abnormalities and fasting serum cholylglycine levels was investigated in 75 chronic asymptomatic HBsAg carriers with normal conventional liver tests, to clarify whether serum CG radioimmunoassay could help in distinguishing the carriers with histological liver damage from those with normal histological findings. Mean (+/- SEM) fasting serum CG levels were 11.6 +/- 1.5 micrograms/dl in 56 carriers with normal liver histology, 14.6 +/- 4.2 micrograms/dl in 16 subjects with CPH and 95.6 +/- 54 micrograms/dl in three carriers with CAH. The incidence of abnormal values (greater than 40 micrograms/dl) among carriers with CAH (66%) was significantly higher than in the other two groups (1.8 and 12.5%, respectively). It is concluded that, among chronic asymptomatic HBsAg carriers with normal conventional liver tests, those who show abnormal serum CG levels are likely to have severe histological damage. This justifies the inclusion of CG radioimmunoassay in the routine follow-up of these subjects. The occurrence of false-positive and false-negative results must be considered if the test is used as an aid in the selection of patients for liver biopsy.