gamma-GT Levels Research Articles

Synergism between smoking and alcohol consumption with respect to serum gamma‐glutamyltransferase†‡

There is increasing evidence that serum levels of the liver enzyme gamma-glutamyltransferase (gamma-GT) are an important predictor of incidence and mortality of various diseases. Apart from alcohol consumption, body mass index and smoking have been found to be associated with serum levels, but little is known about potential interactions of these factors. The aim of this study was to assess the individual and joint impact of alcohol consumption and smoking on levels of gamma-GT, with particular attention to potential differences by sex. The study was based on data of 8465 subjects aged 50 to 74 years, obtained at baseline examination of the ESTHER study, a large population-based cohort study in Germany. Exposure-outcome relationships were assessed in women and men, adjusting for potential confounders by multiple regression. In both sexes, moderate to heavy alcohol consumption (100+ g/week) was associated with 1.7-fold increased odds of elevated gamma-GT (>50 IU/L) in reference to nonsmoking alcohol abstainers, whereas smoking by itself was unrelated to gamma-GT. However, when moderate to heavy alcohol consumption was present in combination with heavy smoking, the odds ratios (95% CI) increased to 2.9 (1.1-7.6) in women and to 3.8 (2.2-6.6) in men (test for interaction between alcohol consumption and smoking: P(females) = 0.12, P(males) = 0.0017). Our results support the notion of a detrimental interaction between cigarette smoking and alcohol consumption as determinants of elevated serum gamma-GT, especially in men.

Erfolgreiche Behandlung der primären biliären Zirrhose mit Ciclosporin

Four patients (aged 35, 52, 53 and 62 years) with primary biliary cirrhosis (raised levels of gamma-GT, alkaline phosphatase and immunoglobulins, as well as of antimitochondrial antibodies) were treated with cyclosporine and methylprednisolone. Different from the regimen for immunosuppressive treatment after organ transplantation, the dosage of cyclosporine was set not according to whole-blood levels but individualized to variations in serum transaminases. An initial dose of 2-2.5 mg/kg proved to be optimal. Higher doses caused a rise in liver enzymes or bilirubin, because of toxic effects produced by the cyclosporine, which is predominantly metabolized in the liver. Optimal initial doses correlated positively with serum IgG levels. In all patients there was an improvement not only in the abnormally high levels of liver enzymes but also in their general condition. There was a marked fall in antimitochondrial antibody titres and immunoglobulin values. These findings indicate that treatment of primary biliary cirrhosis with low doses of cyclosporine and methylprednisolone is effective and low in side effects and can arrest the progression of the disease even in an advanced stage.

Prognostic analysis of pulmonary metastases from hepatocellular carcinoma

To analyze the prognostic factors for the patients with lung metastases from hepatocellular carcinoma (HCC). One hundred and five patients with lung metastases from HCC were analyzed retrospectively. We analyzed the impact factors, including the gender, age, liver function, serum AFP and gamma-GT level, the status of intrahepatic tumor and pulmonary metastases and treatment for them, the distant metastases beyond the lung, as well as the causes of death. The overall cumulative probability of survival was calculated by the Kaplan-Meier method, and the difference between the groups was compared using the Log-rank test. Univariate and multivariate analyses using the Cox-regression proportional hazard model were performed to evaluate the prognostic parameters for survival. The survival after the lung metastases was influenced by clinical parameters, such as the status and the treatment for both the intrahepatic tumor and the pulmonary lesions. The causes of death were respiratory failure due to metastatic lesions from HCC in 16 patients (20.0%), liver failure caused by the progressive intrahepatic lesions in 54 (67.5%). The mean and median survival times were 684 and 487 days after HCC diagnosis and 264 and 179 days after lung metastases, respectively. It was very important to treat the intrahepatic tumor because its worsening was still the major cause of death. The progressive treatment for pulmonary metastases may also be advised for possible prolongation of survival.

Sonographic detection and clinical studies in the spontaneous passage of bile duct calculi

Spontaneous transpapillary stone passage was found in 16 of 84 cases with sonographically detected common bile duct stones. Stone passage was confirmed by ultrasound and retrograde endoscopic cholangiography (ERC) as well as by intraoperative cholangiography and also by clinical observation. Sonographic diagnosis was demonstrated by incontestably safe documentation. 15 of 16 patients with transpapillary stone passage had right upper abdominal pain, three patients an attack of acute pancreatitis, whereas in 5 cases hyperamylasaemia was found. Decreasing levels of bilirubin , alkaline phosphatase and gamma-GT are of minor value in diagnosing a stone passage. Despite a new and more successful sonographic technique in detecting common bile duct stones, ERC remains the standard diagnostic procedure.

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.

Correlations of Laparoscopy with Histology and Laboratory Studies on Liver Diseases in Bariatric Patients

Non-alcoholic fatty liver disease is prevalent in obese patients. Liver biopsy remains the best diagnostic tool for confirmation. We evaluated the effectiveness of macroscopic parameters of laparoscopy in diagnosis of liver diseases. Moreover, correlations of laparoscopy with histology and laboratory data were also studied. From December 2004 to April 2006, 126 morbidly obese patients submitted to laparoscopic bariatric surgery at the En-Chu-Kong Hospital were prospectively studied. There were correlations of histologic steatosis with liver surface fat spot density, liver margin shape, and liver size. Histologic inflammation was related to liver color, vascularity beneath hepatic capsule, liver margin shape, liver size, and liver surface nodularity. Histologic fibrosis had relations to liver color, liver surface nodularity, liver size, varices of ligamentum teres. Spleen size was related to liver surface nodularity and spleen congestion. Relationships of laboratory data with laparoscopic findings included: aspartate transaminase (AST) level with liver size, alanine transaminase (ALT) level with liver color and liver size, albumin level with liver margin shape and liver surface fibrosis and liver size, total protein level with liver size, alkaline phosphatase (ALP) level with liver surface fibrosis, blood glucose level with liver surface nodularity and spleen size, C-peptide with liver size. Besides, there were relations of gamma-GT level with liver color, liver margin shape, liver and spleen size. Besides histology and laboratory studies, laparoscopic inspection of the abdominal cavity provides important and additional information, which contributed to the final diagnosis of chronic liver diseases and detection of possible pathology in patients.

Valoración de los modelos APRI y Forns para el diagnóstico no invasivo de fibrosis en pacientes con hepatitis C coinfectados y no coinfectados por VIH

APRI and Forns (IF) index are noninvasive models consisting of routine laboratory data for the prediction of liver fibrosis in patients with chronic hepatitis C. The aim of our study was to confirm the value of these models to predict significant fibrosis in these patients and if they may decrease the need for performing liver biopsy specimens in coinfected and HIVnon-coinfected. We included 60 patients with chronic hepatitis C and histologic data, 33 were coinfected with HIV. Mild fibrosis (F0-F1) was found in 73% patients, severe fibrosis (F3-F4) in 23% and cirrhosis in 18.3%. We calculated and compared APRI and IF with the stage of liver fibrosis. The APRI score < 0.5 or > 1.5 and IF < 4.2 or > 6.9, as predictors of mild or severe fibrosis, were only available in 53% and 49%. Neither laboratory nor APRI and IF were associated with liver fibrosis in non-coinfected patients. We only found association in HIV coinfected patients: severe fibrosis (F3-4) whit higher gammaglobulins [24.5% vs. 30% (p < 0.05)] and Gamma-GT levels [77 (46.5) vs. 32 (48.5) (p < 0.05)], and lower prothrombin time [72% vs. 91% (p < 0.05) ] and platelets.109 count [129 (40) vs. 170 (78) (p < 0.05)]; APRI was lower than 0.5 in 41.6% patients with mild fibrosis (F0-1) against none with severe (F3-4) (p < 0.05); specifity (E) of APRI < 0.5 for predicting mild fibrosis was 100%, but sensivity (S) was very low (41%), with a positive preditive value (VPP) of 100%, but a negative predictive value (VPN) also very low ( 36.3%). Our study showed that these models don t avoid the need for liver biopsies. More than a half of patients are not appropriately classified according to findings on liver biopsy and S and VPN are very low. The combination of these index with gammaglobulins, Gamma-GT, AST, ALT and platelet levels and protrombine time, only may be an approach to degree of fibrosis or inflammation liver in HIV co-infected patients.

Preliminary investigations on the standardisation and quality control for the determination of ?-glutamyltranspeptidase activity in seminal plasma

The present study was designed to assess the effects of centrifugation velocity, standing time after dilution, freezing-thawing and chymotrypsin on the determination of gamma-glutamyltranspeptidase (gamma-GT) activities in seminal plasma, and to establish an instruction for the standardisation and quality control for the determination of gamma-GT within the same laboratory and among different laboratories. The gamma-GT level and sperm concentration of each of 72 samples of seminal plasma obtained by centrifugation at 1000 g for 10 min or 3000 g for 15 min were assayed. In addition, gamma-GT activities in diluted seminal plasma with different standing time and in samples with or without chymotrypsin were measured. The results showed that there was a significant difference of gamma-GT levels in seminal plasma obtained by centrifugation at different velocities (P < 0.001), and that gamma-GT activities in seminal plasma measured after standing for 30 min after dilution were notably lower than those measured immediately after dilution (P < 0.001). However, the data indicated that both chymotrypsin and freezing-thawing had no apparent effect on the determination of seminal gamma-GT. In conclusion, standing time after dilution and centrifugation velocity should be standardised, and frozen seminal plasma could serve as quality control products for the determination of gamma-GT activity among different laboratories.

Chios mastic gum modulates serum biochemical parameters in a human population

Introduction: Current research suggests that Chios mastic ( Pistacia lentiscus var. chia) possesses beneficial (antimicrobial, antioxidant, hepatoprotective) properties. This study aims to assess its effects on cardiologic and hepatic biochemical indices of human subjects. Materials and methods: Subjects ( n = 133, aged over 50) were randomly assigned to two groups, the first (high-dose group) ingesting daily 5 g of mastic powder and the second receiving daily a Chios mastic solution (low-dose group). Serum biochemical parameters were determined on a monthly basis for an 18-month (high-dose group) and a 12-month (low-dose group) follow-up period. Generalized least squares random-effects linear regression was performed. Results: The group ingesting Chios mastic powder (high-dose group) exhibited a decrease in serum total cholesterol, LDL, total cholesterol/HDL ratio, lipoprotein (a), apolipoprotein A-1, apolipoprotein B (apoB/apoA-1 ratio did not change), SGOT, SGPT and gamma-GT levels; in the second (low-dose) group, glucose levels decreased in males. Discussion: Chios mastic powder could have a hepatoprotective/cardioprotective role in vivo in humans.

Enteral refeeding syndrome after long-term total parenteral nutrition

Early enteral feeding (EF) may result in fever, elevated white blood cell count, increased serum levels of liver enzymes, and diarrhea. We name the complications "enteral refeeding syndrome", as a subtype of refeeding syndrome, because they are likely to result from long-term lack of lumen nutrition. The aim of this study was to investigate the characteristics of enteral refeeding syndrome after long-term total parenteral nutrition (TPN), and the solution for the disease. We collected the clinical data of 100 patients with gastrointestinal fistula, who were cured from Apirl 2001 to July 2002. Their fasting time, daily stool frequency, body temperature, heart rate, respiratory rate, levels of transaminases, alkaline phosphatase (AKP), and gamma-glutamylcyclotransferase (gamma-GT), white blood cell count, and systemic inflammatory reaction syndrome (SIRS) score were recorded before and 1, 3, 5, 10, and 15 days after EF. Student's t test and analysis of variance were used to analyze the data. Of the 100 patients, 56 were cured after selective resection of intestinal fistula, 15 were cured by emergency operation, and 29 recovered spontaneously. The levels of AKP and gamma-GT increased significantly on the 3rd day after EF [On the 3rd day after EF, (243.0 +/- 121.6) U/L and (177.2 +/- 109.9) U/L vs. before EF (181.5 +/- 127.5) U/L and (118.4 +/- 94.2) U/L, P < 0.05], and decreased gradually afterwards. The SIRS scores on the 1st day (1.05 +/- 1.08) and 3rd day (0.96 +/- 1.11) after EF were significantly higher than that before EF (0.72 +/- 0.84), then decreased to 0.83 +/- 0.91, 0.49 +/- 0.73 and 0.32 +/- 0.60 on the 5th, 10th and 15th days after EF. The number of patients with diarrhea at 1, 3, 5, 10 and 15 days post-EF were 31, 26, 12, 13, and 7, respectively. The longer the TPN lasts, the more severe the enteral refeeding syndrome becomes. Continuous EF is effective for the syndrome. Early enteral nutrition is useful in preventing it.

Impact of liver steatosis on the antiviral response in the hepatitis C virus‐associated chronic hepatitis

Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center. One hundred and twelve patients with histologically proven CHC were treated with Peg INF-alpha 2a 180 microg a week subcutaneously for 48 weeks plus ribavirin 1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded according to Brunt et al. Forty-six out of 112 patients (41.1%) were sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented with LS at histology; in this group, there were 24 patients (33.3%) with SVR compared with 22 (55%) of the non-steatosis group (chi(2)=6.5, P<0.02). Variables associated with the steatosis group were: higher serum levels of AST (P<0.04), alanine aminotransferase (P<0.02), gamma-GT (P<0.004), genotype 3a (P<0.03) and severity of histology (staging P<0.05) but at multiple linear regression analysis only genotype 3a and staging were significantly associated with LS. In the SVR group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03, respectively) compared with non-responders; moreover, genotype 1 was more frequent in the NR group, while genotype 3 was more frequent in the SVR group. At histology, grading and staging were also lower in the SVR group. Multiple logistic regression showed that only the grade of steatosis and genotype 3a were the variables independently associated with SVR. This study showed a frequency of LS on the higher side of the range so far reported in the literature and confirmed that it negatively influences response to therapy. Genotype1 was confirmed to be the most frequent type in our area. It is more frequent in patients with mild-moderate steatosis and seems to condition therapeutic response negatively, together with BMI and age. In contrast, genotype 3a is more frequent in patients with severe steatosis, but is a favorable predictor of successful therapy.

Antiangiogenic effect of Lygodium flexuosum against N-nitrosodiethylamine-induced hepatotoxicity in rats

The antiangiogenic effect of Lygodium flexuosum extract was evaluated in Wistar rats intoxicated with N-nitrosodiethylamine (NDEA) in preventive and curative models. In preventive groups, NDEA was administered for 20 weeks. Daily doses of L. flexuosumn-hexane extract (200mg/kg) started 1 week before the onset of NDEA intoxication and continued for 20 weeks. In curative animals, NDEA was administered for 20 weeks followed by treatment with the n-hexane extract of L. flexuosum for 28 days. Rats intoxicated with NDEA had elevated levels of serum gamma-GT, AST, ALT, LDH levels and hepatic MDA and decreased levels of hepatic GSH. When treated with L. flexuosum extract had normal levels of gamma-GT, AST, ALT, LDH levels, hepatic MDA and GSH. NDEA administered rat liver showed an overexpressed levels of angiopoietins 1 (Ang-1) and 2 (Ang-2) and its receptor Tie-2 mRNA. L. flexuosum extract treatment significantly (p<or=0.05) reduced the levels of Ang-1 and Ang-2 and Tie-2 in rat livers evidenced by RT-PCR. Immunohistochemical analysis showed that vascular endothelial growth factor (VEGF) was overexpressed and localized around periportal area of liver sections intoxicated with NDEA and its overexpression was effectively reduced by the treatment with L. flexuosum extract. Histopathological observations also substantiated NDEA-induced hepatotoxicity and the effect was significantly (p<or=0.05) reduced by L. flexuosum extract treatment. Thus, L. flexuosum extract at a dose of 200mg/kg effectively reversed the hepatotoxicity induced by N-nitrosodiethylamine in both experimental models.

Selective nuclear factor κ‐B inhibitors, pyrolidium dithiocarbamate and sulfasalazine, prevent the nephrotoxicity induced by gentamicin

To investigate the effect of selective nuclear factor kappa-B (NFkappa-B) inhibitors, pyrolidium dithiocarbamate (PD) and sulfasalazine (SZ) on renal tubular necrosis and inducible nitric oxide synthase (iNOS) and NFkappa-B expression induced by gentamicin in rats. In all, 48 adult male Sprague-Dawley rats were divided into six equal groups; group 1, control; group 2, injected with gentamicin for 10 days (100 mg/kg/day, intraperitoneal, i.p.); group 3, injected with gentamicin plus PD (100 mg/kg/day, i.p.); group 4, injected with gentamicin plus SZ (75 mg/kg/day, i.p.); group 5, injected with gentamicin plus distilled water (vehicle for PD); and group 6, injected with gentamicin plus ammonium hydroxide (75 mg/day, 1 m, vehicle for SZ) for 10 days. At 24 h after the last injection, rats were killed and the renal cortex separated from the medulla. A small sample was fixed in formaldehyde solution for histological and immunohistochemical examination. Blood samples were also taken to assess the serum levels of urea, creatinine, Na(+), K(+) and gamma-glutamyl transpeptidase (GT). Crude extracts of the cortex were used to determine reduced glutathione (GSH-Px), NO and malondialdehyde (MDA). Immunohistochemically, iNOS and the active subunit of NFkappaB, P65, were evaluated using mouse monoclonal antibodies. On haematoxylin and eosin staining, compared with the controls rats, gentamicin caused widespread tubular necrosis (grade 3 and 4) but in group 3 and 4 there was a marked reduction in the extent of tubular damage. Immunohistochemically there was more marked staining for iNOS and P65 expression in rats given gentamicin than in the control and group 3 and 4 (P < 0.001). In groups 3 and 4 iNOS and P65 expression were significantly less than in rats given only gentamicin. There was no significant difference in serum levels of Na(+), K(+), blood urea nitrogen and creatinine. Compared with control rats, gentamicin caused hyperproteinuria, a marked increase in levels of serum gamma-GT, MDA and NO, and a decrease in GSH-Px (P < 0.001). These results indicate that gentamicin induces iNOS expression through activation of NFkappa-B (P65). It is possible to prevent gentamicin-induced nephrotoxicity using selective NFkappa-B inhibitors.

Establishment of a rat model of alcoholic liver fibrosis induced by complex factors

To establish a model of alcoholic liver fibrosis (ALF) in rats induced by complex factors. Forty-seven healthy male rats were divided into three groups: normal control group (n=12), minor CCl4 group (n=12) and complex factors group (n=27). The rats in the complex factors group were fed a complex diet including alcohol, corn oil and pyrazole, and administered with intraperitoneal injection of minor CCl4 to induce ALF. During induction process, the histopathological changes of liver tissue and the values of liver-to-body weight ratio were both observed regularly. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (gamma-GT) in these three groups were all examined at the 12th week of the induction process. At the 12th week of the induction process, the model of ALF induced by complex factors was successfully established in rats, and the histopathological presentations showed alcoholic fatty liver, hepatitis and liver fibrosis in a sequence along with the induction process. The value of liver-to-body weight ratio and the serum levels of ALT, AST and gamma-GT of rats in the complex factors group were all significantly different from those in the other two groups. It is a steady and effective way to induce ALF in rats with complex diet and minor CCI4 injection.

Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome

To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gamma-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). In the cholestasis group, serum TBIL, DBIL, ALT, gamma-GT, TBA, IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, gamma-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-alpha levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, gamma-GT, TBA, IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01 or 140.57 +/- 70.32 vs 79.06 +/- 35.25, P < 0.05), while biliary TBIL, DBIL, gamma-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-alpha levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, gamma-GT, IL-6 and TNF-alpha levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-alpha levels in the cholestasis group were higher than those in the hepatitis group. Biliary IL-6 and TNF-alpha were found to be more significantly increased than serum IL-6 and TNF-alpha in IHS (P < 0.01). The biliary IL-6 and TNF-alpha levels were positively correlated with serum DBIL, TBA and gamma-GT levels in IHS subjects. Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-alpha levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.

HCV liver infection and liver steatosis: evidence for indirect mechanisms in genotype 3?

Hepatitis C virus (HCV) infection is associated with the appearance of liver steatosis. To search for a correlation between the number of HCV infected hepatocytes and the presence, amount and distribution of steatosis. A total of 124 frozen liver biopsies from HCV patients (genotype 3 = 21) were studied. HCV-antigens were detected on frozen liver sections using a four steps immunoperoxidase technique. Steatosis was graded by haematoxilin-eosin counterstaining on a serial section. Steatosis was detected in 82 of 124 (66.1%) patients without differences between different genotypes. Uric acid, body mass index, gammaGT levels significantly correlated with steatosis in non-3 (P < 0.01, P < 0.05, P < 0.01, respectively) but not in genotype 3 patients. HCV-antigens were detected in 95 of 124 (76.6%) cases. A positive correlation between steatosis and the number of infected hepatocytes was observed only in genotype 3 patients (P = 0.06). In most cases the number of cells with steatosis greatly outnumbered that of HCV infected cells. We confirm a possible role of the virus in the genesis of steatosis in HCV genotype 3 infected patients; however, as steatosis do not appear to be directly related to the presence of HCV-antigens within single hepatocytes, an indirect, possibly cytokine mediated, mechanism might be operative.

Cardiac hepatopathy before and after heart transplantation

Chronic cardiac hepatopathy is a common entity in patients evaluated for heart transplantation (HTX). Hepatic injury is caused by severe heart failure resulting from prolonged recurrent congestion and/or impaired arterial perfusion. No data are available on the reversibility of cardiac hepatopathy in patients undergoing HTX. Data of 56 consecutive adult patients undergoing HTX during 2000-02 at the University Hospital of Innsbruck were analysed retrospectively. The following parameters were evaluated at the time of listing and 3, 6 and 12 months after HTX. Plasma levels of gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (AP), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and total plasma protein. When listed for HTX, only 12% of all patients analysed had physiological values throughout the seven laboratory parameters assessed. Elevated levels of gamma-GT, AP, bilirubin, AST, ALT, LDH and total plasma protein were detected in 66.6%, 29%, 50%, 16.7%, 10%, 40% and 18% of all patients respectively. Accordingly, median plasma levels of gamma-GT, bilirubin and LDH were elevated, whereas the mean plasma level of AP was at the upper normal range. In contrast, median plasma level of AST and mean plasma levels of ALT and total plasma protein were within the normal range: gamma-GT (median, 109.0; range, 634.0 U/l; n = 36), AP (mean, 120.2 +/- 78.9 U/l; n = 29), bilirubin (median, 1.3; range, 16.1 mg/dl; n = 32), LDH (median, 226.0; range, 2355.0 U/l; n = 33), AST (median, 29.0; range, 145.0 U/l; n = 36), ALT (mean, 28.3 +/- 20.8 U/l; n = 36) and total plasma protein (mean, 7.2 +/- 1.1 g/dl; n = 25). Within 3 months after HTX, elevated parameters except LDH significantly ameliorated: gamma-GT (median, 59.0; range, 1160.0 U/l; P = 0.011), AP (92.2 +/- 75.2 U/l; P = 0.016), bilirubin (median, 0.9; range, 8.1 mg/dl; P = 0.004), LDH slightly increased (median, 281.0; range, 543.0 U/l; P = 0.039), but there was a delayed improvement of this parameter after 6 and 12 months post-HTX. End-stage heart failure is characterized by a cholestatic liver enzyme profile with elevated plasma levels of gamma-GT and bilirubin. These parameters significantly improve within 3 months after HTX. Therefore, chronic cardiac hepatopathy seems to be a benign, potentially reversible disease.

Severity of ultrasonographic liver steatosis and metabolic syndrome in Korean men and women

To evaluate the association between the severity of liver steatosis and metabolic syndrome in apparently healthy Korean adults. We examined 1 022 men and women, aged 30-79 years, who participated in a health screening test. A standard interview, anthropometrics, biochemical studies, and abdominal ultrasonography were conducted for each participant. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III, with a modification for the waist circumference cut-off level. The severity of liver steatosis was evaluated using liver ultrasonography, and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (gamma-GT) levels were determined. Ultrasonographic liver steatosis was strongly associated with metabolic syndrome and common metabolic abnormalities. Compared with people without steatosis, people with mild, moderate, and severe steatosis had adjusted odds ratios for metabolic syndrome of 1.72 (95%CI, 1.01-2.94), 2.89 (1.75-4.76) and 3.53 (1.25-9.98) in men, and 2.86 (1.64-5.01), 3.19 (1.80-5.65) and 3.70 (0.82-16.73) in women, respectively. The serum AST level was not associated with metabolic syndrome. The serum ALT and gamma-GT levels were significantly associated with metabolic syndrome in men but not in women. The occurrence of metabolic syndrome shows a stronger association with the severity of ultrasonographic steatosis than with the serum liver enzyme levels. The degree of fatty infiltration detected on ultrasonography can be used as an indicator of liver dysfunction attributable to metabolic abnormalities.

Exogenous melatonin enhances bile flow and ATP levels after cold storage and reperfusion in rat liver: implications for liver transplantation

Although the use of melatonin in the transplantation field has been suggested, it has not been previously tested in a liver cold-storage model. We used a rat liver model to study (a) the dose-dependent effect of melatonin on bile production, and (b) the potential of melatonin to improve liver function after cold-storage. Male Wistar rats were perfused with Krebs-Henseleit bicarbonate buffer (KHB) at 37 degrees C without or with 25, 50, 100 and 200 microM melatonin. Each dose of melatonin stimulated bile production. For cold-storage studies, livers were flushed with either University of Wisconsin (UW) or Celsior solution and stored for 20 hr at 4 degrees C. Reperfusion (120 min) was performed with KHB at 37 degrees C. In subsequent studies, 100 microM melatonin were added to the perfusate during the reperfusion period. ATP and melatonin levels in the tissue were measured. Bile analysis was performed by measuring melatonin, bilirubin and gamma-glutamyl transpeptidase (gamma-GT) levels in the fluid. A dose-dependent increase in bile secretion, associated with an enhanced melatonin and bilirubin levels in the bile were observed. Also, tissue levels of melatonin increased in a dose-dependent manner. When melatonin was added during the reperfusion period, bile production and bile bilirubin levels increased both with UW and Celsior solutions. The analysis of gamma-GT in the bile showed an increase in the Celsior-preserved liver and the addition of melatonin to the perfusate reduced this effect. Tissue ATP levels were higher when melatonin was added to the perfusion medium. Higher levels of melatonin in bile than in tissue were found. In conclusion, we demonstrate that melatonin improves significantly the restoration of liver function after cold-storage and reperfusion.

Effects of melatonin on carbon tetrachloride-induced changes in rat serum

Carbon tetrachloride (CCl4) is a volatile organic chemical, which causes tissue damage, especially to the liver and kidney. In experimental animals it has been shown to be carcinogenic. This study was designed to evaluate the effects of exogenous melatonin administration on the CCl4-induced changes of some biochemical parameters in rat blood. Twenty-four male Wistar rats were randomly divided into three equal groups: Control, CCl4 and CCl4 plus melatonin (CCl4+MEL). Rats in CCl4 group were injected subcutaneously with CCl4 0.5 ml/kg in olive oil while rats in CCl4+MEL group were injected with CCl4 (0.5 ml/kg) plus melatonin (25 mg/kg in 10% ethanol) every other day for one month. Control rats were treated with olive oil. Serum urea, creatinine, total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and conjugated bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (gamma-GT), total iron, and magnesium levels were determined. Serum AST, ALT, total and conjugated bilirubin, ALP, gamma-GT, and total iron levels were significantly higher in CCl4-treated rats than in the controls, while urea, total protein, and albumin levels were significantly lower. Melatonin treatment did not cause a significantly change in serum urea, total protein, and albumin levels. However, the elevations in AST, ALT, total and conjugated bilirubin, ALP, gamma-GT, and total iron levels induced by CCl4 injections were significantly reduced by melatonin. On the other hand, melatonin administration significantly decreased serum magnesium levels. These results indicate that melatonin could be a protective agent against the CCl4 toxicity in rats, most likely through its antioxidant and free radical scavenger effects.