Increased Serum Gamma-glutamyltransferase Research Articles

Prevalence of portal vein and splanchnic venous thrombosis in dogs with chronic hepatitis.

Alterations in haemostasis have been described in dogs and humans with chronic hepatitis. Portal vein thrombosis is a recognised complication of chronic hepatitis in humans; however, its prevalence in dogs with chronic hepatitis has not been reported. We aimed to estimate the prevalence of, and describe clinical and laboratory data of dogs with chronic hepatitis and portal vein thrombosis and splanchnic venous thrombosis. Retrospective cross-sectional study. Medical records of dogs admitted to a veterinary teaching hospital between 2009 and 2019 were reviewed. Dogs were included if chronic hepatitis was histopathologically confirmed, and if diagnostic imaging or necropsy indicated the presence of thrombosis. Clinical and laboratory data (i.e. haematology, biochemistry, coagulation panels) were recorded. Descriptive statistics were used to characterise dogs with and without thrombosis. Records from 136 dogs with chronic hepatitis were identified. Three of these dogs, 2.2% (95% confidence interval: 0.8 to 6.3%) all females, were diagnosed with portal vein thrombosis. Five dogs in total, (3.7%; 95% confidence interval: 1.6 to 8.3%), including three with portal vein thrombosis, all females, were diagnosed with splanchnic venous thrombosis. Dogs with portal vein and splanchnic venous thrombosis often had hyperbilirubinaemia, increased serum gamma-glutamyl transferase activity, and decreased plasma antithrombin 3 activity. They also had relatively high alternative Child-Pugh scores for dogs (median 6 out of 13). Portal vein and splanchnic venous thrombosis are potentially serious complications that were identified in a relatively low proportion of dogs with chronic hepatitis.

Efficacy and safety of trastuzumab emtansine in Her2 positive metastatic breast cancer: real world experience

Aim: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. Method: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. Findings: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second line therapy in 37,7% of the cases and median number of T-DM1 cycles was 9. Progression free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma glutamyl transferase (2%). Discussion: The best of our knowledge this is the largest real life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Giant liver fibrous tumours metastatic from atypical recurrent meningeal neoplasia

A 71-year-old woman presented to the emergency room of an academic hospital for biliary vomit of one week duration. Her past medical history was remarkable for a recurrent atypical meningeal neoplasia, diagnosed ten years earlier, treated with surgical excision and radiotherapy in 2008, then only with radiotherapy in2013, 2015, 2017. Blood tests revealed increased serum gamma-glutamyltransferase and alkaline phosphatase. At physical examination, hepatomegaly was noted; abdominal ultrasound revealed multiple inhomogeneous hypo-echoic hepatic lesions (the largest 11 cm in diameter).

Correlation Between miR-125b Expression and Liver Fibrosis in Patients with Chronic Hepatitis C

Objectives: The study aimed to investigate the role of miR-125b as a non-invasive biomarker in chronic hepatitis C. Methods: An observational study was conducted on 94 treatment-naive HCV-infected patients (mean age 49.8 ± 11.5 years, 59.6% females). Liver fibrosis was assessed by transient elastography (TE) and the expression of miR-125b in plasma was quantified by real-time PCR. Results: All patients were infected with HCV genotype 1b and had active viral replication, 42.6% had significant cytolysis, and 73.4% had increased serum gamma-glutamyl transferase (GGT) values. Significant fibrosis (liver stiffness measured by TE of > 7.1 kPa) was present in 61.7% of the patients. No significant associations were found between miR-125b expression and baseline HCV viral load (P = 0.56), IL28B polymorphisms (P = 0.5), alpha-fetoprotein levels (P = 0.27), and patients’ gender (P = 0.13) or age (P = 0.5). In a univariate analysis, the miR-125b expression level was significantly correlated with ALT (P = 0.001) and GGT levels (P < 0.0001). An up-regulated expression of miR-125b was found in plasma samples from patients with advanced liver fibrosis as compared to those with mild/moderate fibrosis [mean miR-125b value = 0.002 versus 0.001 (P = 0.02)]. In a multiple regression analysis, an upregulated miR-125b expression level remained independently in association only with significant fibrosis and increased GGT level (P = 0.026; R2 = 0.242). Conclusions: An up-regulated miR-125b expression might be an indicator of severe liver fibrosis in patients with chronic hepatitis C, independent of the viral replication level.

Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting.

The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located), and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9); second group (thrombus in main pulmonary artery branches; n = 71); third group (thrombus in pulmonary artery segmental branches; n = 34); and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8). Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009) and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033) remained independently associated with proximally localized thrombus in pulmonary artery. The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.

Increased serum gamma-glutamyltransferase levels are associated with ventricular instability in type 2 diabetes.

The purpose of our study is to examine the association between serum GGT levels and ventricular instability in Chinese patients with T2DM. We conducted a cross-sectional, community-based study in Nanjing, China from June to November 2011. Among 10,050 patients aged 40-79 years, we enrolled 2444 with pre-diabetes, 2496 with T2DM, and 4521 without diabetes (non-diabetes). Electrocardiograms were performed to measure the QT interval corrected for heart rate (QTc) and QT interval dispersion (QTd). Serum GGT levels, metabolic parameters, body mass index, and blood pressure were also measured. We found that there were no significant associations of increased QTc/QTd with serum GGT levels in participants with pre-existing T2DM and non-diabetes, after adjusting for age, duration of diabetes, and metabolic parameters. Even after adjustment, higher risks of QTc ≥ 440 ms/√s and QTd ≥ 58 ms were found in participants with serum GGT levels ≥49 U/L compared with those with <15 U/L in the pre-diabetes (QTc: OR 1.96, 95 % CI 1.23-2.47; QTd: OR 1.34, 95 % CI 1.07-1.94) and newly diagnosed T2DM (QTc: OR 2.01, 95 % CI 1.39-2.51; QTd: OR 1.53, 95 % CI 1.03-1.99) groups. We conclude that Increased serum GGT levels are associated with some markers of ventricular repolarization abnormalities in the early stage of T2DM.

Nitrate-induced Biochemical and Histopathological Changes in the Liver of Rats: Ameliorative Effect of Hyparrhenia hirta

ObjectiveThe present study investigated the protective role of Hyparrhenia hirta (H. hirta) against sodium nitrate (NaNO3)-induced hepatoxicity. MethodsMale Wistar rats were randomly divided into three groups: a control group and two treated groups during 50 d with NaNO3 administered either alone in drinking water or co-administered with H. hirta. ResultsNaNO3 treatment induced a significant increase in serum levels of glucose, total cholesterol and triglyceride while serum total protein level decreased significantly. Transaminases and lactate deshydrogenase activities in serum were elevated indicating hepatic cells' damage after treatment with NaNO3. The hyperbilirubinemia and the increased serum gamma glutamyl transferase activities suggested the presence of cholestasis in NaNO3 exposed rats. In parallel, a significant increase in malondialdehyde level along with a concomitant decrease in total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities were observed in the liver after NaNO3 treatment. Furthermore, nitrate caused a significant induction of DNA fragmentation. These modifications in NaNO3-treated rats corresponded histologically with hepatocellular necrosis and mononuclear cells infiltration. H. hirta supplementation showed a remarkable amelioration of the abnormalities cited above. ConclusionThe results concluded that the treatment with H. hirta had a significant role in protecting the animals from nitrate-induced liver dysfunction.

Cholecystic adenocarcinoma and pancreatic insulinomas in a goat

A 13-year-old female Boer goat with a history of chronic arthritis and recurrent episodes of recumbency, increased serum gamma-glutamyl transferase, and complete inability to stand was submitted for necropsy. Gross changes included the presence of a white, firm, smooth, 6 cm × 4 cm × 3 cm mass that diffusely expanded and partially effaced the gall bladder and infiltrated the adjacent hepatic parenchyma. On cut surface, the mass was pale yellow and had small, irregular, dark yellow areas. Scattered through the pancreas were 2 gray, well-demarcated, soft, homogeneous, 1 cm in diameter nodules that bulged out from the capsular surface. The right femoral head had a locally extensive area of cartilage erosion. Histological and immunohistochemical evaluation of the gall bladder and pancreatic nodules revealed a primary cholecystic adenocarcinoma and multifocal insulinomas, respectively. A metastatic focus from the gall bladder neoplasm was observed infiltrating the right adrenal gland medulla. The goat also had mild pulmonary infestation by Muellerius capillaris. Primary hepatobiliary and pancreatic neoplasia is rare in goats, and to the authors' knowledge, neither cholecystic adenocarcinoma nor pancreatic insulinomas have been previously reported in this species.

Relationship between Serum Gamma-glutamyl Transferase Levels with Ascending Aortic Dilatation.

Increased serum gamma-glutamyl transferase levels (GGT) have been shown to directly promote oxidative stress. Previous studies have shown the relationship between the dilatation of the ascending aorta and oxidative stress. This study was designed to examine the relationship between serum GGT concentrations with dilatation of the ascending aorta. Ninety patients with ascending aortic dilatation and 90 age-sex-matched patients without aortic dilatation were included in the study. The patients were evaluated by a complete transthoracic echocardiographic examination including measurement of the aortic dimensions, where a diameter of 3.7 cm and above was accepted as ascending aortic dilatation. Serum GGT concentration was measured in all patients. In the group with aortic dilatation, HT frequency, serum uric acid, hs-CRP and GGT levels, the LV mass index, and the left atrial volume index were found to be higher than the control group. The logistic regression analysis showed that only HT frequency (OR:1.23, 95% CI 1.11-1.35, p value: 0.02), the LA volume index (OR: 1.34, 95% CI 1.21±1.4, p:0.005) and serum GGT levels (OR: 1.12, 95% CI 1.01±1.20, p:0.03) were found to be independent predictors. There was a significant correlation between serum GGT levels and ascending aortic diameter (r: 0.268, p<0.001). In the ROC curve analysis, AUC was 0.659 (0.580±0.738) for a 23.5 serum GGT cut-off value (64% sensitivity and 53% specificity). We found that serum GGT concentration was significantly associated with ascending aortic dilatation. Large epidemiological studies are required to correlate the findings from this study with clinical outcome.

Gamma glutamyl transferase activity

Increased serum gamma-glutamyl transferase (GGT) activity is known to be associated with atherosclerotic diseases. Thoracic aortic intima-media thickness (IMT) was reported as a marker of preclinical atherosclerosis. However, there is a lack of research directly examining the relationship between serum GGT activity and thoracic aortic IMT. Therefore, we aimed to investigate the association between serum GGT activity and thoracic aortic IMT. The study population consisted of 329patients without coronary artery disease, who underwent transesophageal echocardiography (TEE) examination for various indications from January 2011 to April 2013. GGT, high-sensitivity C-reactive protein (hs-CRP) and other biochemical markers were measured in all patients. The patients were classified into tertiles according to their GGT activities (GGTlow < 19U/l, GGTmid ≥ 19U/l < 29U/l, and GGThigh ≥ 29). The highest aortic IMT values were observed in the GGThigh group compared with the GGTmid and GGTlow groups (p < 0.05, for all). Also, aortic IMT values in the GGTmid group were higher than in the GGTlow group (p < 0.05). Multivariate regression analysis showed that GGT activity was independently associated with aortic IMT (β = 0.487, p < 0.001) hs-CRP (β = 0.282, p < 0.001), and triglyceride level (β = 0.161, p = 0.007). The higher serum GGT concentrations within the "normal" range were associated with a greater IMT of the thoracic aorta. GGT activity may be a predictor of the extent of subclinical aortic atherosclerosis assessed with thoracic aortic IMT.

Long-term results of liver resection for hepatocellular carcinoma in noncirrhotic liver

Hepatocellular carcinoma (HCC) is among the most common malignant neoplasms worldwide. Only few data on HCC in noncirrhotic livers without viral hepatitis in Western countries are available. The purpose of this study was to define the outcomes and potential prognostic factors associated with survival after hepatic resection in patients with HCC in the absence of liver cirrhosis and hepatitis B or C infection. From January 2000 to September 2010, 148 patients without liver cirrhosis and without extrahepatic metastases underwent curative hepatic resection for HCC at the Surgical Department of the Charité, Campus Virchow Klinikum. The outcomes of these patients were retrospectively reviewed. Patients with cirrhosis or severe fibrosis, fibrolamellar HCC, and those positive for hepatitis B or C were excluded. The cumulative 1-, 3-, 5-, and 7-year survival rates were 75.4%, 54.7%, 38.9%, and 31.8%, respectively. The 1-, 3-, 5-, and 7-year disease-free survival rates were 60.3%, 38.0%, 29.1%, and 18.1%, respectively. In the multivariate analysis, cumulative survival was decreased by patient age, increased operative time, increased preoperative serum gamma-glutamyl transferase (GGT), and tumor stage. In the subgroup with unifocal neoplasms, N0 and R0 status, tumor size >10 cm, and tumor differentiation were highly predictive of lesser survival. Unfavorable survival was observed in patients with multifocal neoplasms, tumor size >10 cm, and/or poor tumor differentiation. The current TNM staging system is stratified for survival and recurrence. Extension of the current TNM staging system by grading and more exact differentiation of tumor size may increase its prognostic accuracy for predicting outcome. Preoperative increased serum GGT level could be a new poor prognostic factor.

Serum Gamma-Glutamyltransferase and the Risk of Hyperuricemia: A 6-Year Prospective Study in Japanese Men

We conducted a longitudinal study to investigate whether increased serum gamma-glutamyltransferase independently predicts subsequent development of hyperuricemia. The study participants included 3,310 Japanese men without hyperuricemia, aged 20-54 years. The participants had annual heath examinations for 6 years to assess incident hyperuricemia (defined as serum uric acid>416.4 μmol/l and/or taking medication for hyperuricemia). The risk of incident hyperuricemia was compared in participants grouped according to their baseline serum gamma-glutamyltransferase level. During follow-up, there were 529 incident cases of hyperuricemia. A positive, dose-response relationship was observed between serum gamma-glutamyltransferase and the risk of incident hyperuricemia. The hazard ratios (95% confidence intervals) for hyperuricemia, compared with a serum gamma-glutamyltransferase level ≤19 U/l, were 1.32 (1.05-1.67) for 20-39 U/l, 1.28 (0.90-1.83) for 40-59 U/l, 1.56 (0.98-2.47) for 60-79 U/l, and 1.57 (1.02-2.41) for ≥80 U/l after adjustment for baseline serum uric acid, creatinine, total cholesterol, and glycated hemoglobin levels, ln(serum alanine aminotransferase), age, systolic blood pressure, medications for hypertension, hypercholesterolemia, and diabetes, body mass index, and smoking and exercise habits. A similar positive relationship was observed regardless of the presence or absence of alcohol drinking, obesity, metabolic disorders (any combination of hypertension, hypercholesterolemia and/or diabetes), or clinically high serum aminotransferases, without evidence of a significant interaction between increased serum gamma-glutamyltransferase and risk factors for incident hyperuricemia. These findings indicate that increased serum gamma-glutamyltransferase is an independent predictor of subsequent development of hyperuricemia.

Serum gamma-glutamyltransferase level is associated with serum superoxide dismutase activity and metabolic syndrome in a Japanese population

Serum gamma-glutamyltransferase level has attracted considerable attention as a predictor of various conditions, such as cardiovascular disease and cancer. Although the mechanism that links the serum gamma-glutamyltransferase level to these diseases is not fully understood, one explanation is that gamma-glutamyltransferase may be closely related to oxidative stress. We conducted a large cross-sectional study to evaluate the relationship between serum gamma-glutamyltransferase and oxidative stress. We examined anti-oxidative stress activity and accumulation of oxidative stress in serum obtained from 2907 subjects who underwent a complete health check-up. We used serum total superoxide dismutase activity as an index of anti-oxidative stress activity. Superoxide dismutase is one of the most important intracellular and extracellular defense systems against superoxide, but the relationship between serum superoxide dismutase activity and the serum gamma-glutamyltransferase level is unclear. The serum gamma-glutamyltransferase level was negatively correlated with serum superoxide dismutase activity, a correlation that was observed even within the normal range. A subgroup analysis stratified by the amount of alcohol consumed also showed a similar correlation. In contrast, the serum gamma-glutamyltransferase level was positively correlated with serum lipid peroxide level, even in the normal range. Furthermore, an increased serum gamma-glutamyltransferase level was significantly associated with the progression of metabolic syndrome and carotid artery intima-media thickness. The serum gamma-glutamyltransferase level, even in the normal range, was significantly associated with anti-oxidative stress activity, the accumulation of oxidative stress, metabolic syndrome, and atherosclerosis. Measuring the serum gamma-glutamyltransferase level is simple and inexpensive, and this level can be used as a sensitive marker of oxidative stress and metabolic syndrome.

Increased serum gamma-glutamyltransferase activity in patients with metabolic syndrome

Accumulating data indicate that serum gamma-glutamyltransferase (GGT) activity represents a true marker of atherosclerotic cardiovascular disease and has prognostic importance. In this study, we sought to evaluate serum GGT activity in patients with metabolic syndrome (MetS). We enrolled 232 patients (mean age 60.4 years) from our outpatient cardiology clinic, 117 with and 115 without MetS (control group) as defined by the ATP-III criteria. The results of serum liver function tests including serum GGT and C-reactive protein (CRP) levels were compared between the two groups. The two groups were similar with regard to age, sex, smoking, and family history of coronary artery disease (p>0.05). The prevalences of hypertension and dyslipidemia were significantly higher in patients with MetS. Compared with controls, patients with MetS had significantly higher serum GGT [(median 21, interquartile range (16-33) vs. 19 (14-26) U/l; p=0.008] and C-reactive protein levels [6.2 (3.6-9.4) vs. 5.0 (3.1-7.0) U/l; p=0.044]. A high GGT activity (>40 U/l) was determined in 14.5% of the patients with MetS and in 4.4% of the control subjects (p=0.012). Serum GGT level showed significant correlations with MetS (r=0.24, p=0.001), CRP (r=0.20, p=0.003), triglyceride (r=0.18, p=0.006), HDL cholesterol (r=-0.19, p=0.004), aspartate aminotransferase (r=0.15, p=0.02), alanine aminotransferase (r=0.32, p=0.001), and alkaline phosphatase (r=0.16, p=0.01). This significant association continued only for MetS (β=-0.25, p=0.03), HDL cholesterol (β=-0.18, p=0.03), and alkaline phosphatase (β=0.17, p=0.01) in multivariate regression analysis. Our findings suggest that patients with MetS have higher serum GGT and CRP levels compared with controls. This increased GGT level might be a marker of increased oxidative stress and premature atherosclerosis.

What is your diagnosis? Biopsy impression smear of a hepatic mass in a yearling Thoroughbred filly

A 1-year-old Thoroughbred filly was presented to the Cornell University Hospital for Animals with a 10-day history of fever, diarrhea, inappetance, and hypodipsia. Clinical pathology abnormalities found by the referring veterinarian included erythrocytosis, hyperproteinemia, and increased serum gamma-glutamyltransferase and lactate dehydrogenase activities. At Cornell University, the laboratory abnormalities were confirmed and also included thrombocytosis and hypoglycemia. Erythrocytosis persisted despite vigorous fluid therapy. Ultrasound examination revealed an extremely enlarged liver with abnormal echogenicity and a 21 x 25-cm hepatic mass with varied echogenicity. Imprints of an ultrasound-guided biopsy of the mass revealed a neoplastic epithelial population of uncertain origin, although the cells did not resemble hepatocytes. Together with the presenting signs, signalment, ultrasonographic findings, and persistent erythrocytosis, the cytologic findings were considered to be most consistent with hepatoblastoma. Histopathologic examination of the mass at necropsy confirmed the diagnosis and findings also included bone marrow erythroid hyperplasia. Serum erythropoietin concentration was 28.0 mU/mL (reference interval 1.0-11.8 mU/mL), supporting erythropoietin production by the tumor and secondary inappropriate erythrocytosis. To our knowledge, this report is the first to document secondary erythrocytosis with increased erythropoietin concentration in a horse with hepatoblastoma, and also the first to describe the cytopathologic features of this rare tumor.

Is Serum Gamma-Glutamyltransferase a Biomarker of Xenobiotics, Which Are Conjugated by Glutathione?

A meta-analysis of 10 prospective cohort studies,1 including our own,2 reported that serum γ-glutamyltransferase (GGT) predicted incident vascular events. This meta-analysis posed one important, but unsolved question: why does serum GGT predict incident vascular events? In addition to vascular events, serum GGT predicts various important clinical outcomes including type 2 diabetes, metabolic syndrome, and renal problems.3–5 Serum GGT has traditionally been used as a marker of alcohol consumption; however, alcohol consumption cannot explain the disease relationships with serum GGT because these associations have been observed among nondrinkers as well as drinkers. The other prevailing interpretations are that serum GGT predicts clinical outcomes as a marker of nonalcoholic fatty liver disease (NAFLD) or oxidative stress.6–8 Although both of these explanations have some merit, each also has problems. Although not clearly stated in many of the reports,1–5 most associations of serum GGT with clinical outcomes were dose-response relations within the normal range of serum GGT; we submit that this aspect of the association is critical to interpretation. First, even though NAFLD may partially explain the associations among subjects with a relatively high serum GGT activity and NAFLD can present even among subjects with low normal serum GGT, NAFLD is unlikely to fully explain the graded associations with clinical outcomes which were observed among subjects with serum GGT in the low part of its normal range, less than 20 or 30 U/L. However, it is worthwhile to note that serum GGT may be a predictor of the future risk of NAFLD. In a prospective study by our group,9 serum GGT within its normal range strongly predicted the future risk of chronic elevation of serum alanine aminotransferase (ALT), but serum ALT within its normal range did not predict the future risk of chronic elevation of serum GGT. The …

Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene

Low phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations and low biliary phospholipid concentration with symptomatic and recurring cholelithiasis. This syndrome is infrequent and corresponds to a peculiar small subgroup of patients with symptomatic gallstone disease. The patients with the LPAC syndrome present typically with the following main features: age less than 40 years at onset of symptoms, recurrence of biliary symptoms after cholecystectomy, intrahepatic hyperechoic foci or sludge or microlithiasis along the biliary tree. Defect in ABCB4 function causes the production of bile with low phospholipid content, increased lithogenicity and high detergent properties leading to bile duct luminal membrane injuries and resulting in cholestasis with increased serum gamma-glutamyltransferase (GGT) activity. Intrahepatic gallstones may be evidenced by ultrasonography (US), computing tomography (CT) abdominal scan or magnetic resonance cholangiopancreatography, intrahepatic hyperechogenic foci along the biliary tree may be evidenced by US, and hepatic bile composition (phospholipids) may be determined by duodenoscopy. In all cases where the ABCB4 genotyping confirms the diagnosis of LPAC syndrome in young adults, long-term curative or prophylactic therapy with ursodeoxycholic acid (UDCA) should be initiated early to prevent the occurrence or recurrence of the syndrome and its complications. Cholecystectomy is indicated in the case of symptomatic gallstones. Biliary drainage or partial hepatectomy may be indicated in the case of symptomatic intrahepatic bile duct dilatations filled with gallstones. Patients with end-stage liver disease may be candidates for liver transplantation.

Association of Working Conditions and Lifestyle with Increased Serum Gamma-Glutamyltransferase: A Follow-up Study

This study investigated the association of working conditions and lifestyle with the development of increased serum gamma-glutamyltransferase (GGT) in Japanese workers. A follow-up study was carried out on workers of a telecommunication enterprise who received their first annual health check-up between 1992 and 1996, when they were between 40 and 54 years of age. Workers who had high serum GGT (> or =60 IU/L in males, > or =30 IU/L in females), a past history of disease, or current illness at their first check-up were excluded from the analysis. In total, the study included 15,586 workers. The association between working conditions and lifestyle and development of increased serum GGT (> or =60 IU/L in males, > or =30 IU/L in females) was investigated by pooled logistic regression analyses. In males, body mass index, consumption of alcohol (<2 times/week, 2-5 times/week, >5 times/week), smoking (<20 cigarettes/day, > or =20 cigarettes/day), rarely taking three meals a day, marked preference for salty meals, and little preference for vegetables were positively associated with the development of increased serum GGT. Preferences for fatty meals (marked, moderate) were negatively associated with the development of increased serum GGT. In females, age and BMI were positively associated with the development of increased serum GGT. Applying a new statistical analysis to this retrospective cohort study of 5 years, we revealed the health influences of alcohol consumption, smoking and eating habits on increased serum GGT. On the other hand, this study indicated that shift work or other working conditions are not significant risk factors for increased serum GGT.

Role of gamma-glutamyl transferase activity in patients with chronic hepatitis C virus infection.

Increased serum gamma-glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV-infected carriers. Patients with a liver biopsy presenting anti-HCV and HCV-RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the chi2 test and multivariate logistic regression analysis. Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Initially, age >40 years (P=0.007), elevated ALT (P=0.01), grading of inflammatory activity (P=0.004) and staging of fibrosis (P<0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P=0.01) and staging 3 and 4 fibrosis (P=0.01) remained independently associated with elevated GGT level. A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C.

Chronic effects of moniliformin in broiler and turkeys fed dietary treatments to market age.

Floor pen studies were conducted, with broilers from 1 to 7 wk of age and with turkeys from 1 to 14 wk of age, to evaluate the chronic effects of moniliformin (M). Fusarium fujikuroi (M-1214) culture material was added to typical corn-soybean basal diets to supply 0, 25, or 50 mg M/kg diet (broilers) or 0, 12.5, 25, 37.5, or 50 mg M/kg diet (turkeys). Compared with controls, chicks fed diets containing 50 mg M/kg consumed more feed, had lower body weight gain, were less efficient in converting feed to body weight gain, and had increased relative heart and proventriculus weights. Chicks fed the diet containing 50 mg M/kg also had significantly higher mortality and decreased mean corpuscular volumes compared with controls. Broilers fed 25 and 50 mg M/kg also had increased serum gamma glutamyltransferase activities. Feed intake, body weight gain, and feed conversion of turkeys fed dietary M were not affected. At 6 and 14 wk, turkeys fed 25, 37.5, or 50 mg M/kg diet had increased (P < 0.05) relative heart weights when compared with controls. At week 14, turkeys fed diets containing 37.5 or 50 mg M/kg also had increased (P < 0.05) relative liver weights compared with turkeys fed 0, 12.5, or 25 mg M/kg diet. Lesions, observed only in the hearts of broilers and turkeys fed 50 mg M/kg, were loss of cardiomyocyte cross striations, increased cardiomyocyte nuclear size, and an increased number of cardiomyocyte mitotic figures (turkeys only). Results indicate that > or = 37.5 mg M/kg is hepatoxic and > or = 25 mg M/kg is cardiotoxic to turkeys and 50 mg M/kg diet is toxic to broilers fed to market age.