Gamma-glutamyl Transpeptidase Levels Research Articles

Relationship between Menopausal Status and Metabolic Syndrome Components in Korean Women

Background: Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. Methods: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel Ⅲ criteria. Results: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The stro ng correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 (95% confidence interval (CI) 1.014~2.269) in perimenopausal women and OR 1.573 (95% CI 1.025~2.414) in postmenopausal women). In addition, the prevalence of metabolic syndrome increased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. Conclusion: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause. (KOREAN DIABETES J 32:243-251, 2008)

Liver function tests in patients with bacteremia.

The purpose of this study was to evaluate liver function tests as potential indicators of bacteremia. We examined 156 patients with laboratory-confirmed bacteremia (bacteremia group) and 211 bacteremia-negative patients with bacterial infections (control group). The patients of the two groups had no underlying liver diseases. For patients in the bacteremia group, we analyzed liver function tests results obtained the day when the first positive blood culture was ordered. For those in the control group, the same data were obtained on the day when the first of multiple negative blood cultures was ordered. At t-test analyses, serum levels of gamma-glutamyl transpeptidase (gamma-GT) and alkaline phosphatase (ALP) were significantly higher, and those of albumin, total cholesterol, and cholinesterase were significantly lower in the bacteremia group than in the control group. Multivariate analyses found serum cholinesterase as an independent factor with adjusted odds ratio of 0.319 (per 65 U/L, standard deviation [SD] size). Serum level of C-reactive protein (CRP), on the other hand, showed no significant difference between the two groups. Serum levels of gamma-GT, ALP, albumin, total cholesterol, and cholinesterase more rapidly altered when various bacterial infections accompanied bacteremia. Therefore, they may be useful in detecting sepsis in its early stages.

Rezidivierende Schwangerschaftscholestase und perlenschnurartige Choledocholithiasis bei einer Patientin mit Stoppcodon im ABCB4-Gen des hepatischen Phospholipidtransporters

We report the case of a 40-years-old female patient with recurrent cholestatic liver disease who presented twice with severe intrahepatic cholestasis of pregnancy and pronounced choledocholithiasis between pregnancies. Bile duct stones were removed endoscopically and a laparoscopic cholecystectomy was performed after the second pregnancy. Liver histology revealed intrahepatic cholestasis with portal inflammation and fibrosis, resembling progressive familial intrahepatic cholestasis (PFIC). Molecular genetic studies identified the heterozygous mutation c.957C > T in the ABCB4 gene encoding the hepatobiliary phospholipid transporter. This is the first report of this mutation that introduces a stop codon in an index patient with intrahepatic cholestasis of pregnancy and multiple bile duct stones. In addition, we detected the ABCB11 polymorphism V 444A, which is associated with a decreased expression of the bile salt export pump. Whereas homozygous carriers of the ABCB4 mutation develop PFIC type 3, the heterozygous ABC transporter mutations represent genetic risk factors for cholelithiasis and recurrent cholestatic hepatitis upon challenge with oral contraceptives or during pregnancy. Of note, the patient presented with normal serum gamma-glutamyltranspeptidase activities during pregnancy-associated cholestatic episodes but normal liver enzymes after delivery, whereas choledocholithiasis was associated with high gamma-glutamyl transpeptidase levels. It is unknown whether ursodeoxycholic acid prevents cholestasis or gallstones in patients with ABCB4 deficiency.

Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy

Background Intrahepatic cholestasis of pregnancy is a multifactorial disorder of pregnancy associated with a genetic background. Aim To evaluate the genetic contribution of ABCB4, MDR3 gene in the development of intrahepatic cholestasis of pregnancy in a large cohort of Italian subjects. Methods This study represents an extension of a previous multicentre-prospective study including three Italian referral centres. In all, we enrolled 96 women at the 3rd trimester of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes by standard procedures. Polymerase chain reaction was used to amplify exon 14, 15 and 16 of MDR3 gene. Results We found 3 non-synonymous heterozygous mutations in exon 14 (E528D, R549H, G536A), 1 in exon 15 (R590Q) and 2 in exon 16 (R652G, T6671). MDR3 gene variants in exons 14, 15 and 16 occurred in 7/96 of pregnant mothers with intrahepatic cholestasis of pregnancy (7.2%), and in none of 96 pregnant controls matched for age and parity. All seven patients had normal gamma-glutamyl transpeptidase, normal bilirubin, but high levels of both alanine transferase and serum bile acids. One had cholesterol biliary lithiasis. The outcome of pregnancy was normal in four cases (with vaginal delivery), while there was one fetal distress. Conclusions MDR3 mutations are responsible for the development of intrahepatic cholestasis of pregnancy in only a small percentage of Italian women. Further genetic studies are warranted, however, to clarify the role of different mutations in intrahepatic cholestasis of pregnancy.

Role of Ursodeoxycholic Acid in Prevention of Methotrexate-induced Liver Toxicity

Methotrexate (MTX)-induced hepatotoxicity restricts the clinical use of this immunosuppressive drug. In this study, our aim was to research the role of oxidative stress in the hepatic toxicity of MTX and the protective effect of ursodeoxycholic acid (UDCA) in this setting. Wistar type rats (n = 32) were divided into four groups; group-1 as the MTX + UDCA, group-2 as the MTX, group-3 as the UDCA, group-4 as the saline-receiving groups. The MTX + UDCA and MTX groups of rats received 50 mg/kg of UDCA administered orally; whilst physiological saline was administered orally to the MTX and saline groups and continued for the next 6 days. On the second day of the study, the MTX + UDCA and MTX groups had a single intraperitoneal dose of MTX of 20 mg/kg. The UDCA and saline groups also received similar volumes of physiological saline intraperitoneally. On the sixth day, serum samples were collected and analyzed for ALT, alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) and homogenated liver tissues were examined for reactive oxygen metabolites (ROM); luminol, lucigenin, lipid peroxygenation product malondialdehyde (MDA) and glutathione (GSH) levels. In the MTX group, serum ALT, ALP, GGT and tissue ROM levels were higher and GSH level was lower. On the histopathological examination, hepatocellular necrosis was clearly more evident in the MTX group than the MTX + UDCA group. UDCA treatment protects against MTX-induced liver toxicity. Histopathologically hepatocyte necrosis can be prevented by UDCA treatment, indicating clearly the hepatoprotective effect of this agent on MTX-induced liver injury.

Plasma Levels of Cell-Free Apoptotic DNA Ladders and Gamma-Glutamyltranspeptidase (GGT) in Diabetic Children

The plasma levels of apoptotic DNA ladders (i.e., apoptosemia) and gamma-glutamyltranspeptidase (GGT) in diabetic outpatients and rats were investigated. Apoptotic DNA ladders were detected in plasma from 26.8% of type 1 (T1) and 18.5% of type 2 (T2) diabetic children 1-20 years of age, 25.7% of hospitalized children and 35.7% of adult RA outpatients, but in only 3.5% of adult pre-op patients. Plasma from 7.7% of young streptozotocin-induced diabetic but not control rats contained apoptotic DNA ladders. Apoptosemia was detected more often in male T1 (31%) and T2 (30.8%) diabetic outpatients than in female T1 (20.8%) and T2 (15.4%) diabetic outpatients. GGT in apoptosemic plasma was significantly higher than in nonapoptosemic plasma from T1 (P = 0.001) but not T2 diabetic children. The highest amounts of apoptotic DNA were detected most often in diabetic children > or =14 years of age. In vitro study results suggest that cell-free apoptotic DNA ladders appear prior to an increase in GGT activity in serum from human blood incubated at 37 degrees C. The results suggest that 24.7% of plasma samples from diabetic children contained apoptotic DNA ladders, the incidence and amounts of apoptotic DNA ladders were higher in the older diabetic children, and GGT was elevated in apoptosemic T1 diabetic children (P = 0.01). The results indicate that "silent" apoptosemia occurs in T1 and T2 diabetic children and suggest elevated GGT in diabetic children could be due to release from apoptotic cells.

Efficacy of Extended-Release Naltrexone in Alcohol-Dependent Patients Who Are Abstinent Before Treatment

Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation that is Food and Drug Administration-approved for the treatment of alcohol dependence in patients able to abstain from alcohol before treatment initiation. This paper presents the results of an analysis of efficacy data from a subgroup of patients with 4 days or more of voluntary abstinence before treatment initiation (n = 82) on a wide range of drinking-related outcomes. In these patients, all of whom received counseling, the rate of abstinence was severalfold higher for XR-NTX 380 mg compared with placebo: median time to first drink was 41 days versus 12 days, respectively; rate of continuous abstinence at end of the study was 32% versus 11% (P = 0.02). Extended-release naltrexone 380 mg, compared with placebo, substantially increased time to first heavy drinking event (>180 days vs 20 days; P = 0.04) and decreased the median number of any drinking days per month by 90% (0.7 vs 7.2; P = 0.005) and heavy drinking days per month by 93% (0.2 days vs 2.9 days; P = 0.007). The XR-NTX 380 mg group also had more than twice as many responders compared with placebo (70% vs 30%; P = 0.006; responder defined as having no more than 2 heavy drinking days in any consecutive 28-day period) and experienced greater improvement in gamma-glutamyl transpeptidase levels (P = 0.03). Outcomes for XR-NTX 190 mg (n = 26) were generally intermediate, demonstrating a dose-response effect. In conclusion, XR-NTX 380 mg prolonged abstinence and reduced the number of heavy drinking days and drinking days in patients who were abstinent for as few as 4 days before treatment initiation.

Hepatitis C Virus Viral Load After Conversion From Tacrolimus to Cyclosporine in Liver Transplant Patients: A Pilot Study

We assessed whether conversion from tacrolimus (TAC) to cyclosporine (CsA) was associated with a reduction in hepatitis C virus (HCV) viral load among HCV-positive liver transplant (OLT) patients. Patients and Methods Nine OLT patients with recurrent HCV have TAC and prednisone immunosuppression. None received any HCV antiviral therapy. After the last intake of TAC, the patients underwent a 12-hour area under the curve (AUC 12) measurement of both TAC and HCV viral loads. The next morning (D 0) patients were given CsA (4 mg/kg bid). At the first intake of CsA and at 1 month (M 1) later, the patients underwent AUC 12 for CsA and HCV viral loads. Biological data, including aspartate (AST) and alanine (ALT) aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), and bilirubin levels, were collected during AUC 12, and at M 1 and M 3. Results With respect to liver enzymes (AST, ALT, GGT), there was no significant difference between D 0, M 1, and M 3. Conversely, there was a significant decrease in AP between D 0 and M 3 ( P = .02), and a significant increase in total bilirubin between D 0 and M 1 ( P = .04), and between D 0 and M 3 ( P = .01). HCV viral load significantly increased by M 3 ( P = .01). At no time (D 0, M 1) was there any correlation between the AUC 12 of TAC or CsA, and between AUC 12 HCV viral load. Conclusion This pilot study found no acute or chronic anti-HCV effects from CsA that were evident within 12 hours after CsA administrations or beyond 1 month of CsA therapy, respectively.

Intraperitoneal chemotherapy with hydroxycamptothecin reduces peritoneal carcinomatosis: results of an experimental study

We studied the efficacy and safety of intraperitoneal chemotherapy with hydroxycamptothecin (HCPT) for the treatment of peritoneal carcinomatosis in animal model. Highly metastatic human hepatocellular carcinoma (HCC) cell line HCCLM3 was injected into the peritoneal cavity of 30 nude mice to construct a model of intraperitoneal carcinomatosis, which were randomized into a treatment group and a control group of 15 mice in each group. The former received intraperitoneal injections of HCPT at the dose of 2 mg/kg body weight for 7 days every other week, on weeks 2, 4 and 6; and the latter received the same dose schedule treatment of 0.9% sodium chloride solution. The mice were observed for 8 weeks. Body weight changes, intraperitoneal carcinomatosis, hematological and biochemical parameters were evaluated. On day 56, 14 mice in the treatment group were still alive, compared against 5 in the control group, and the mean survival time was 55 +/- 1 days [95% confidence interval (CI) 54-57 days] versus 43 +/- 4 days (95% CI 34-51 days) (P = 0.002). The tumor weight in the treatment group (0.8 +/- 0.8 g) was significantly smaller than the control group (2.0 +/- 0.8 g) (P = 0.00028). No bloody ascites or diffuse peritoneal carcinomatosis were observed in the treatment group, as compared with 4 mice (26.7%) that developed bloody ascites and 6 mice (40%) which developed diffuse peritoneal carcinomatosis in the control group (P < 0.001). The treatment group had a significantly lower peripheral white blood cell count [(3.18 +/- 1.72) x 10(9) l(-1)] than the control group [(5.08 +/- 2.03) x 10(9 )l(-1)] (P < 0.05), significantly lower serum alpha fetoprotein level (101.22 +/- 20.12 microg/l) than the control group (244.87 +/- 30.24 microg/l) (P < 0.05), and significantly lower serum gamma glutamyl transpeptidase level (12.45 +/- 2.26 U/l) than the control group (20.75 +/- 3.87 U/l) (P < 0.05). No obvious treatment related toxicities were observed. Intraperitoneal injection of HCPT could inhibit tumor progression, reduce the extent of peritoneal carcinomatosis and improve survival of tumor bearing mice.

Glucose Abnormalities Are an Independent Risk Factor for Nonresponse to Antiviral Treatment in Chronic Hepatitis C

The influence of glucose abnormalities on the efficacy of antiviral treatment is unknown. This study investigated whether glucose abnormalities (impaired fasting glucose and type 2 diabetes) influence the response to antiviral therapy with interferon plus ribavirin in patients with chronic hepatitis C. A total of 178 treatment-naïve patients with chronic hepatitis C treated with combination therapy were retrospectively studied. SVR was assessed after completing treatment. Fasting plasmatic glucose was measured prior to therapy. Compared with nonresponders (N = 111), patients with SVR (N = 67) had lower plasma glucose (94.1 +/- 12.7 vs 104.4 +/- 25.8 mg/dL, P= 0.001) and a lower prevalence of glucose abnormalities (24.24%vs 44.14%, P= 0.012). The SVR rate was 45.13% in patients with normoglycemia (N = 113), 28.26% in patients with impaired fasting glucose (N = 46), and 15.78% in type 2 diabetic patients (N = 19) (P < 0.001). Multivariate logistic regression identified genotype 1 (OR 1.55, 95% CI 1.01-2.41, P= 0.05), gamma-glutamyltranspeptidase level (OR 6.41, 95% CI 1.86-22.07, P= 0.003), and presence of glucose abnormalities (OR 2.33, 95% CI 1.04-5.20, P= 0.039) as being independently associated with the absence of an SVR. In addition, patients with glucose abnormalities (N = 65) showed a lower virological response rate when compared with a subgroup of normoglycemic patients (N = 65) matched for sex, age, and liver fibrosis (24.6%vs 44.6%, P= 0.001). Glucose abnormalities are an independent predictor of poor virological response to combined therapy in hepatitis C virus infected patients.

A large-scale, multicentre, double-blind trial of ursodeoxycholic acid in patients with chronic hepatitis C

Background:Combined pegylated interferon and ribavirin has improved chronic hepatitis C (CH-C) therapy; however, sustained virological response is achieved in only about half of the patients with a 1b genotype infection....

Ultracentrifugation of Serum Samples Allows Detection of Hepatitis C Virus RNA in Patients with Occult Hepatitis C

Occult hepatitis C virus (HCV) infection of patients with abnormal liver function tests of unknown origin who are anti-HCV and serum HCV RNA negative but who have HCV RNA in the liver has been described. As HCV replicates in the liver cells of these patients, it could be that the amount of circulating viral particles is under the detection limit of the most sensitive techniques. To prove this hypothesis, serum samples from 106 patients with occult HCV infection were analyzed. Two milliliters of serum was ultracentrifuged over a 10% sucrose cushion for 17 h at 100,000 x g(av), where av means average, and HCV RNA detection was performed by strand-specific real-time PCR. Out of the 106 patients, 62 (58.5%) had detectable serum HCV RNA levels after ultracentrifugation, with a median load of 70.5 copies/ml (range, 18 to 192). Iodixanol density gradient studies revealed that HCV RNA was positive at densities of 1.03 to 1.04 and from 1.08 to 1.19 g/ml, which were very similar to those found in the sera of patients with classical chronic HCV infection. Antigenomic HCV RNA was found in the livers of 56 of 62 (90.3%) patients with detectable serum HCV RNA levels after ultracentrifugation, compared to 27 of 44 (61.4%) negative patients (P < 0.001). No differences in the median loads of antigenomic HCV RNA between patients with an those without serum HCV RNA (4.5 x 10(4) [range, 7.9 x 10(2) to 1.0 x 10(6)] versus 2.3 x 10(4) [range, 4.0 x 10(2) to 2.2 x 10(5)]) were found. Alanine aminotransferase and gamma-glutamyl transpeptidase levels, liver necroinflammatory activity, and fibrosis did not differ between both groups. In conclusion, HCV RNA can be detected in the sera of patients with occult HCV infection after circulating viral particles are concentrated by ultracentrifugation.

50 Years Ago in The Journal of Pediatrics: Neonatal hepatitis in siblings

Peterman MG. J Pediatr 1957;50:315-20 In 1957, M. G. Peterman reported two sets of siblings presenting in the neonatal period with cholestasis. With the limited available therapy, there was progression of disease leading to death. Common to all the cases was the presence of giant cell transformation of liver cells on post-mortem examination resulting in the diagnosis of neonatal hepatitis. Peterman described the diagnosis as a “general all-inclusive term, probably as satisfactory as any,” recognizing that the etiology was ill-defined. Over the last 50 years, cases of familial neonatal cholestasis have served as models to elucidate hepatic physiology, to identify specific genetic and molecular defects, and to expand the differential diagnosis of intrahepatic cholestasis presenting in the newborn period. This, in turn, has lead to improved diagnostic and therapeutic modalities. Many of the known genetic forms of intrahepatic cholestasis fall into broad categories of defects in embryogenesis, bile acid metabolism, and canalicular transport. Other causes of intrahepatic cholestasis include multi-organ disorders, metabolic diseases, and other clinically definable syndromes.1Balistreri W.F. Bezerra J.A. Whatever happened to “neonatal hepatitis”?.Clinics in Liver Disease. 2006; 10: 27-33Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar Evaluation of infants presenting with conjugated hyperbilirubinemia has evolved to include recognition of the immature physiology of the newborn liver, evaluation for infection and metabolic disease, radiographic study of the biliary anatomy, and differentiation of intrahepatic cholestatic syndromes through a combination of clinical features, serum bile acid level, serum gamma glutamyl transpeptidase level, and liver biopsy. Diagnostic studies of the future include development of a gene chip, biomarkers of genetic defects, and targeted testing of molecular defects. Continued understanding of liver physiology and molecular pathophysiology of cholestatic disease has resulted in therapy to reduce symptoms, improve nutritional status, and delay progression of disease. These measures encompass medical therapy as well as surgical intervention including liver transplantation. The goal, however, should be to avoid the need for liver transplantation by defining and treating the underlying disease. Despite the progress over the last 50 years in diagnosis and treatment of neonatal hepatitis, approximately 15% of patients continue to be diagnosed with idiopathic disease.1Balistreri W.F. Bezerra J.A. Whatever happened to “neonatal hepatitis”?.Clinics in Liver Disease. 2006; 10: 27-33Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar Clearer definition of phenotype, precise nomenclature of known diseases, and multi-center registries will be critical in improving diagnostic and treatment strategies in those with defined disease and in understanding the etiology of disease in those yet undiagnosed cases.

Gamma Glutamyltranspeptidase Activity and Viral Hepatitis in Dialysis Population

Numerous investigations have reported that viral hepatitis is associated with significant hepatocellular damage, as expressed by raised aminotransferases in serum, in dialysis population. However, scarce information exists on the activity of gamma glutamyltranspeptidase (GGTP) in dialysis patients with infection by hepatotropic viruses. We measured serum GGTP values in a large cohort (n=757) of patients receiving long-term dialysis; healthy controls were also included. The relationship between GGTP values and a series of demographic, clinical, and biochemical parameters was analyzed. Serum GGTP levels were tested by spectrophotometry. A subset (n=333) of dialysis patients was tested by molecular technology (branched-chain DNA (bDNA) assay) to evaluate the relationship between serum GGTP and HCV viremia. A subgroup (n=78) of dialysis patients was analyzed by an ultrasound scan of gallbladder and biliary tract to assess the presence of gallstone disease. Multivariate analyses were made using regression models; serum GGTP values were included as a dependent variable. The usefulness of serum GGTP levels in detecting HBsAg and anti-HCV positivity was evaluated using receiver operating characteristics (ROC) curve analysis. Univariate analysis showed that serum GGTP levels were significantly higher in HBsAg positive and/or anti-HCV positive patients than in HBsAg negative/anti-HCV negative patients on dialysis; 85.1+/-184.1 versus 25.86+/-23.9 IU/l (P=0.0001). The frequency of raised GGTP levels was 22.2% (41/184) among dialysis patients with chronic viral hepatitis. Multivariate analysis showed a significant and independent association between serum GGTP values and positive HBsAg (P=0.005) and anti-HCV antibody (P=0.0001) status. Mean GGTP values were significantly higher in study patients than controls, 32.32+/-60.02 versus 23.5+/-16.92 IU/L (P=0.01); however, no significant difference with regard to GGTP between study and healthy cohorts persisted after correction for age, gender, race, and viral markers. No relationship between gallstone disease and serum GGTP was found (NS). An independent and significant association (P=0.0291) between raised GGTP levels and detectable HCV RNA in serum was noted among patients tested by biology molecular techniques. ROC technology demonstrated that GGTP was equally useful for detecting HBV (P=0.0004) and HCV (P=0.0005) among dialysis patients. We found an independent and significant association between serum GGTP values and HBsAg and/or anti-HCV antibody in dialysis population. Twenty-two percent of dialysis patients with chronic viral hepatitis had elevated GGTP. No difference in GGTP between HBsAg- negative/anti-HCV- negative dialysis patients and healthy individuals was found. Routine testing for serum GGTP levels to assess liver disease induced by hepatotropic viruses or other agents in dialysis population is suggested.

Characterization of overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis according to antimitochondrial antibodies status

Codification of variant forms between Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) has not been definitively standardized. The aim of this study was to compare among 102 consecutive patients, 2 subsets of overlap syndrome (OS, N=21) with and without antimitochondrial antibody (AMA) to two groups of patients with typical PBC (N=43) or AIH (N=38). OS was defined by the presence in the same patient of at least 2 of 3 accepted criteria of PBC and AIH. Twelve patients with OS were AMA negative and 9 were AMA positive. A lower level of alanine transaminase (139+/-48 vs 269+/-154 IU/L, P<0.05) and a trend towards a higher level of alkaline phosphatase or gamma-glutamyl transpeptidase was observed in OS without AMA than in OS with AMA (693+/-200 vs 544+/-124 IU/L; 370+/-66 vs 241+/-77 IU/L, respectively). All AMA-negative patients with OS had antinuclear and/or anti-smooth muscle antibodies. OS without AMA differed from those with AMA in that they had more severe bile duct damage including destructive cholangitis (P<0.05), ductopenia (P<0.05), ductular hyperplasia (P<0.05) and a higher METAVIR fibrosis score (2.5+/-0.3 vs 1.3+/-0.3, P<0.05). The response to therapy was not different between PBC, AIH and OS. According to the presence of AMA, 2 homogeneous subgroups of patients with overlap syndrome between PBC and AIH may be identified. AMA status affects clinical presentation and liver disease severity of OS.

Effect of the Inducer of Interleukin‐6 (ME3738) on Rat Liver Treated With Ethanol

Recently, ME3738, a derivative of soyasapogenol B, was developed as an inducer of interleukin (IL)-6. It has been demonstrated that ME3738 is stimulate to produce IL-6 and that it protects against concanavalin A-induced liver failure. It has also been reported that IL-6 prevents alcoholic fatty liver in mice. These results suggest that ME3738 may prevent alcoholic liver injury. In the present study, we investigated whether ME3738 prevents fatty liver in ethanol-fed rats. Twenty-four male rats were fed with liquid diets containing ethanol or carbohydrates for 8 weeks. Liquid diets were prepared with or without ME3738 (0.8 mg/mL). Liver sections were stained for histology and IL-6 expression. Fatty changes of liver were classified into 4 grades: 0, 1+, 2+, and 3+. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), triglyceride, total cholesterol, and IL-6 were measured, as was hepatic ATP content. The extent of fatty degeneration in ethanol-fed rats was significantly greater (p=0.023) than that in controls. Fatty changes in rats fed ethanol containing ME3738 decreased, but were not significantly different from those in rats fed ethanol. Immunohistochemical staining of IL-6 was observed in perivenular hepatocytes of all rats, with its intensity becoming stronger in the order of controls, controls containing ME3738, ethanol, and ethanol-containing ME3738-fed rats. Plasma levels of AST and ALT in rats fed ethanol were significantly higher than those in controls. In rats fed ethanol-containing ME3738, these levels decreased to those of control-fed rats, but were not significantly different from those in rats fed ethanol. Plasma IL-6 was not detected in any rats. Hepatic ATP content in rats fed ethanol was significantly (p<0.05) lower than that in control-fed rats; however, in rats fed ethanol-containing ME3738, it increased to that in control-fed rats. Oral administration of ME3738, inducer of IL-6 may prevent the development of fatty liver caused by chronic ethanol consumption.

Influence of the level of γ-glutamyltranspeptidase activity on the response of poorly and moderately differentiated rhabdomyosarcoma cell lines to all-trans-retinoic acid

Differentiation therapy with retinoic acid has been considered a potential approach for treating rhabdomyosarcoma. Analysis of retinoids as differentiating agents for rhabdomyosarcoma is, however, rendered incomplete by the fact that some rhabdomyosarcoma cell lines are retinoic acid resistant. Therefore, the aim of the present work was to study the effect of all-trans-retinoic acid on two rat tumour cell lines, derived from the same rhabdomyosarcoma tumour model (i.e. the moderately differentiated low metastatic F21 cell line and the poorly differentiated high metastatic S4MH cell line), to discover how degree of differentiation and glutathione metabolism influence response to this retinoic acid derivative. We observed that whereas in the S4MH cell line all-trans-retinoic acid induced a significant inhibition of tumorigenic potential, in F21 cells all-trans-retinoic acid enhanced tumour growth and only at a higher dose was there a slight antiproliferative effect. These effects were in consonance with the activity level of gamma-glutamyltranspeptidase, which was significantly increased in F21 cells, but not in S4MH cells, in response to the all-trans-retinoic acid-induced increase in reactive oxygen species. The pro-tumour effect observed in F21 cells was reversed by adding buthionine sulphoximide, a specific cellular glutathione-depleting agent, to the all-trans-retinoic acid treatment. This combination produced a decrease in gamma-glutamyltranspeptidase activity, and an increase in oxidative stress and apoptosis. Our findings suggest that the response to all-trans-retinoic-acid of the tumour cell lines studied is influenced by the strong relationship between intracellular glutathione content, gamma-glutamyltranspeptidase activity and degree of differentiation of the rhabdomyosarcoma cell line, and that this relationship should be taken into account when identifying 'retinoid-sensitive' tumours.

Viral and Host Factors Associated with Steatosis in Iranian Patients with Chronic Hepatitis C

Purpose: Evaluation of the frequency of steatosis in Iranian patients with CHC and also the association of various viral and host factors with steatosis in these patients.We also evaluated the association of severity of fibrosis and steatosis in this group of patients. Methods: In this cross-sectional analytical study 80 treatment naive chronic hepatitis c patients who were referred to Taleghani hospital, Tehran from 2004 to 2006 were included with non-probability convenient sampling. Patients' liver biopsy samples were evaluated by two expert hepatopathologists. We divided patients into two groups based on pathology report: group A, without significant steatosis (steatosis in <5% of hepatocytes) and group B, with significant steatosis (steatosis in >5% of hepatocytes). Age, gender, BMI, lipid profile, FBS, LFT, HCV-genotype, HCV-RNA viral load and liver fibrosis stage were determined and compared in two groups. HCV genotyping was analysed by PCR-RFLP method. Results: Fourty two (52.5%) out of 80 patients had steatosis.There was no significant difference between the mean age or sex distribution of patients with or without steatosis. BMI, mean viral load and serum levels of cholesterol, triglyceride, gloucose, and gamma-glutamyl transpeptidase of steatosis group was significantly higher than non steatosis group (p < 0.05). Mean score of fibrosis was 2.17 ± 0.91 and 1.63 ± 1.02 in patient with and without steatosis, respectively (p= 0.015). The frequency of patients with genotype 1 in the group without steatosis was significantly higher than the group with steatosis (p= 0.003), while the frequency of patients with genotype 3 in the group with steatosis was significantly higher than the group without steatosis (p <0.0001). The mean viral load in patients with genotype3 infection with steatosis was significantly higher than patients with genotype 3 infection without steatosis (p= 0.009). The mean viral load in patients with genotype 1 infection with steatosis was not significantly different from patients with genotype 1 infection without steatosis (p= 0.565). Conclusions: Infection with genotype 3 hepatitis c virus particularly if associated with high HCV-RNA level is associated with significant steatosis. But steatosis in patients infected with genotype 1 virus is associated with abnormal metabolic host factors than viral factors. Presence of steatosis is associated with more severe fibrosis in chronic hepatitis c.

Increased Serum Ferritin Concentrations and Liver Enzyme Activities in Patients with Metabolic Syndrome

Emerging scientific evidence suggests that increases in body iron represent a risk factor for the development of metabolic syndrome and diabetes. The aim of our study was to determine the body iron stores in patients with metabolic syndrome, and to evaluate the potential relationship of iron overload with specific features of the metabolic syndrome, such as fatty liver. A total of 490 individuals were enrolled. The diagnosis of metabolic syndrome was based on National Cholesterol Education Program-Adult Treatment Panel III (ATPIII) criteria. The metabolic syndrome group was consisted of 185 patients having three or more criteria, whereas individuals with less than three criteria constituted the control group. Metabolic syndrome patients displayed higher ferritin concentration as compared to control individuals. Ferritin levels were positively correlated with insulin concentration, as well as with Homeostasis Model Assessment (HOMA) index values. Multiple regression analysis revealed that ferritin was the most important independent determinant of insulin resistance indices. Patients with metabolic syndrome also exhibited increased concentrations of alanine aminotransferase and gamma-glutamyltranspeptidase compared to controls. Multiple regression analysis revealed that ferritin concentration was the most important determinant of gamma-glutamyltranspeptidase levels. Patients with the metabolic syndrome exhibit an increase in body iron stores as well as elevated concentrations of liver enzymes compared to the individuals who do not fulfill the criteria for the diagnosis of this syndrome. Our data support a direct role of increased body iron in the pathogenesis of insulin resistance, whereas iron overload may also contribute to the development of specific features of the metabolic syndrome, such as fatty liver.

Maternal Lamotrigine Treatment and Elevated Neonatal Gamma-Glutamyl Transpeptidase

Lamotrigine is an antiepileptic drug with a low adverse-effect profile. This report describes an infant born to an epileptic mother treated with lamotrigine, who had a highly elevated gamma-glutamyl transpeptidase level after birth. There was no other clinical or biochemical evidence of liver or bile duct dysfunction. Infant serum level of lamotrigine, which crosses the placenta, was within therapeutic limits. Gamma-glutamyl transpeptidase levels declined slowly during the following months. We suggest that, in the absence of additional markers of tissue damage, the infant's gamma-glutamyl transpeptidase elevation was caused by maternal intake of lamotrigine. Liver function tests should be monitored in infants of lamotrigine treated mothers, as enzyme elevation might still suggest liver damage.