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Transaminase
Kinds of Transaminase Terms modified by Transaminase Selected AbstractsExperimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effectJOURNAL OF DIGESTIVE DISEASES, Issue 4 2005F MAROTTA OBJECTIVE: The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. METHODS: Sprague,Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. RESULTS: Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. CONCLUSIONS: Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation. [source] HEPATITIS C AND ADDICTION: Chronic viral hepatitis is a significant contributor to the immunosenescent phenotype of parenteral drug addictionADDICTION BIOLOGY, Issue 2 2009Albert S. Reece ABSTRACT Intravenous drug addiction is known to be associated with an inordinate morbidity and mortality. As our previous report had identified an immune phenotype consistent with accelerated ageing, we wished to investigate how much of this change may have been related to chronic viral hepatitis. A total of 12 409 clinical pathology results from the period 1995,2007 were reviewed. To control for the differences in age, only patients less than 48 years of age were considered. A total of 636 substance use disorder (SUD) and 6103 non-SUD (N-SUD) patients were studied. They had comparable ages (mean ± SD 31.32 ± 6.90 versus 31.57 ± 9.23, P -value not significant), but the SUD group had more males (74.37% versus 53.20%, P < 0.001). For most of the changes examined splitting the two SUD groups into hepatitis C positive (HCV+) and hepatitis C negative (HCV,) demonstrated that the majority of the described changes were most marked in the HCV+ group. The globulins were higher in the HCV+ group and the albumin was lower and fell more markedly with age than in N-SUD or HCV, (all P < 0.001). The globulin/albumin ratio was significantly higher in HCV+ than HCV, or N-SUD (both P < 0.0001) and rose more with age. These changes were paralleled by the ESR, elevations in the CRP and lymphocyte count. Transaminases were elevated in SUD and HCV+ groups compared with N-SUD (all P < 0.02). At multivariate analysis ESR, lymphocyte count, dual hepatitis B and C seropositivity, AST and HCVAb were significant predictors of the serum globulin level and accounted for 21% of the variance. These data extend our earlier report and show that much of the immunosenescent phenotype of SUD, encompassing the known immunosuppression and the observed immunostimulation, is statistically related to chronic viral hepatitis. Important theoretical and practical management (vaccination) implications ensue. [source] The clinical features of dermatomyositis in a South Australian populationINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2 2007Vidya LIMAYE Abstract Aim:, To review the clinical features of dermatomyositis (DM) in a South Australian population. Methods:, Retrospective review of medical records of patients with biopsy-proven DM in South Australia from 1990 to 2005. Results:, There were 21 cases of biopsy-proven DM in SA (62% F, mean age 49.7 ± 18.4 years) and clinical details were available in 20 of these. Malignancy was identified in 9/20 patients; in five this followed the diagnosis of DM, with three malignancies seen within 3 months of disease onset. Three patients had a clearly defined immune insult prior to the diagnosis of DM; one patient had Mycoplasma pneumoniae infection 23 days prior to DM, two had pneumococcal and influenza vaccinations 5 and 14 days prior to the onset of DM, respectively. Two of three patients with anti-Jo-1 antibody experienced thromboembolism within 2 months of DM onset and three patients had interstitial lung disease (2 with anti-Jo-1 antibody). Creatine kinase (CK) was elevated in 15/20 cases and showed strong correlation with transaminases, and notably not with traditional inflammatory markers. Conclusions:, This retrospective review of patients with biopsy-proven DM suggests a role for infection/vaccination in triggering disease onset. A particularly strong association with malignancy was observed and it is suggested that DM may predispose to thrombosis. Transaminases, in addition to CK may be used to monitor disease activity, and traditional inflammatory markers have little role in this. [source] Should liver function tests be included in definitions of metabolic syndrome?DIABETIC MEDICINE, Issue 5 2008Evidence from the association between liver function tests, components of metabolic syndrome, prevalent cardiovascular disease Abstract Aims The definition of metabolic syndrome (MS) continues to be debated and does not include abnormal liver function tests (LFTs). This study aims to determine: (1) the association between the five ATP3 MS diagnostic components and different LFTs, and (2) the association between raised LFTs and prevalent cardiovascular disease (CVD). Methods A total of 1357 patients, without alcoholism or known liver disease, from randomly selected households from rural Victoria, Australia, attended for biomedical assessment. Receiver operating characteristic (ROC) areas under the curve (AUC) were determined for associations between the ATP3 diagnostic components, and between LFTs and ATP3 diagnostic components. Results The range of ROC AUC for ATP3 diagnostic components was 0.60,0.77. Waist had the strongest association and blood pressure the weakest. The strength of association between ATP3 diagnostic components and gamma GT (GGT) was similar (0.63,0.72), but was less for alanine transaminase and aspartate transaminase. Using the ROC-derived GGT cut-off (men 27 IU, women 20 IU), those with MS and a high GGT had more CVD than those with MS and a low GGT, and those without MS (18% vs. 10% vs. 7%, respectively; P < 0.001). Among those with MS, after adjusting for covariates, the odds ratio of CVD was 2.66 (1.18,5.96) for a high GGT compared to a low GGT. CVD was not significantly more prevalent in MS patients with a low GGT compared to non-MS patients. Conclusions We suggest that including a raised GGT in the criteria for MS could increase its predictive nature for CVD. Prospective studies are needed to confirm this finding. [source] Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis CEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Omer Dizdar Abstract Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV(+) patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels. [source] Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in miceFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009C. Girish Abstract Oxidative stress is implicated as a common pathologic mechanism contributing to the initiation and progression of hepatic damage in a variety of liver disorders. Present study attempts to evaluate the hepatoprotective activity of picroliv, curcumin and ellagic acid in comparison to silymarin using paracetamol (PCM) induced acute liver damage. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg) and was assessed by quantifying the serum enzyme activities, phenobarbitone induced sleeping time and histopathological analysis of liver tissues. The antioxidant parameters, malondialdehyde (MDA), reduced glutathione (GSH) and catalase of the liver tissue were also assessed. The herbal drugs were administered for 7 days by oral route at 50 and 100 mg/kg. PCM induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase) in serum and MDA level in liver. There was also a significant decrease in activity of GSH and catalase levels. The histopathological examination on toxic models revealed centrizonal necrosis and fatty changes. Pretreatment of mice with picroliv, curcumin and ellagic acid reversed these altered parameters towards normal values, which were compared with silymarin. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver cytochrome P450 enzymes. This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing the lipid peroxidation and augmenting the antioxidant defense system or regeneration of hepatocytes. These active phytochemicals may be developed as drugs for the treatment of liver diseases. [source] Ferulic acid, a natural protector against carbon tetrachloride-induced toxicityFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2005M. Srinivasan Abstract The present work is aimed at evaluating the protective effect of ferulic acid (FA), a naturally occurring phenolic compound on CCl4 induced toxicity. The activities of liver markers (alanine transaminase, aspartate transaminase, alkaline phosphatase, , -glutamyl transferase), lipid peroxidative index (thiobarbituric acid-reactive substances, hydroperoxides, nitric oxide, protein carbonyl content), the antioxidant status (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione) were used as biomarkers to monitor the protective role of FA. The liver marker enzymes in plasma and lipid peroxidative index in liver and kidney were increased in CCl4 -treated groups, which were decreased significantly on treatment with FA. The antioxidants, which were depleted in CCl4 -treated groups, were improved significantly by FA treatment. Administration of FA to normal rats did not produce any harmful effects. Thus our results show that FA is an effective antioxidant without any side-effects and may be a great gain in the current search for natural therapy. [source] A member of the YER057c/yjgf/Uk114 family links isoleucine biosynthesis and intact mitochondria maintenance in Saccharomyces cerevisiaeGENES TO CELLS, Issue 6 2001Jong-Myong Kim Background Two paralogs, YIL051c and YER057c, in the Saccharomyces cerevisiae genome are members of the YER057c/Yigf/Uk114 family, which is highly conserved among Eubacteria, Archaea and Eukarya. Although the molecular function of this protein family is not clear, previous studies suggest that it plays a role in the regulation of metabolic pathways and cell differentiation. Results Yil051cp is 70% identical in amino acid sequence to Yer057cp, and differs in that the former is longer by 16 amino acids containing, in part, the mitochondrial targeting signal at the N-terminus of the protein. An HA-tagged protein of Yil051cp is localized strictly in mitochondria, while that of Yer057cp is found in both cytoplasm and nucleus. Disruption of YIL051c (yil051c,) resulted in severe growth retardation in glucose medium due to isoleucine auxotroph, and no growth in glycerol medium due to the loss of mitochondria. An extract prepared from yil051c, cells showed no transaminase activity for isoleucine, while that for valine or leucine was intact. Haploid yil051c, cells newly isolated from the YIL051c/yil051c, hetero-diploids gradually lost mitochondrial DNA within 24 h in the absence of, but not in the presence of, an isoleucine. Mutants either requiring leucine (leu2,112) or isoleucine-valine (bat1,, bat2,) in a YIL051c background showed no changes in mitochondrial DNA maintenance in the absence of requirements. Conclusions Based on these results, we named Yil051c as Ibm1 (Isoleucine Biosynthesis and Mitochondria maintenance1) and concluded that: (i) Ibm1p determines the specificity of isoleucine biosynthesis, probably at the transamination step, (ii) Ibm1p is required for the maintenance of mitochondrial DNA when isoleucine is deficient, and (iii) Isoleucine compensates for the lack of Ibm1p. Taken together, Ibm1p may act as a sensor for isoleucine deficiency as well as a regulator determining the specificity for branched amino acid transaminase. [source] Inflammation and drug hepatotoxicity: Aggravation of injury or clean-up mission?,HEPATOLOGY, Issue 5 2005Hartmut Jaeschke BACKGROUND & AIMS Inflammatory mediators released by nonparenchymal inflammatory cells in the liver have been implicated in the progression of acetaminophen (APAP) hepatotoxicity. Among hepatic nonparenchymal inflammatory cells, we examined the role of the abundant natural killer (NK) cells and NK cells with T-cell receptors (NKT cells) in APAP-induced liver injury. METHODS C57BL/6 mice were administered a toxic dose of APAP intraperitoneally to cause liver injury with or without depletion of NK and NKT cells by anti-NK1.1 monoclonal antibody (MAb). Serum alanine transaminase (ALT) levels, liver histology, hepatic leukocyte accumulation, and cytokine/chemokine expression were assessed. RESULTS Compared with APAP-treated control mice, depletion of both NK and NKT cells by anti-NK1.1 significantly protected mice from APAP-induced liver injury, as evidenced by decreased serum ALT level, improved survival of mice, decreased hepatic necrosis, inhibition of messenger RNA (mRNA) expression for interferon-gamma (IFN-gamma), Fas ligand (FasL), and chemokines including KC (Keratinocyte-derived chemokine); MIP-1 alpha (macrophage inflammatory protein-1 alpha); MCP-1 (monocyte chemoattractant protein-1); IP-10 (interferon-inducible protein); Mig (monokine induced by IFN-gamma) and decreased neutrophil accumulation in the liver. Hepatic NK and NKT cells were identified as the major source of IFN-gamma by intracellular cytokine staining. APAP induced much less liver injury in Fas-deficient (lpr) and FasL-deficient (gld) mice compared with that in wild-type mice. CONCLUSIONS NK and NKT cells play a critical role in the progression of APAP-induced liver injury by secreting IFN-gamma, modulating chemokine production and accumulation of neutrophils, and up-regulating FasL expression in the liver, all of which may promote the inflammatory response of liver innate immune system, thus contributing to the severity and progression of liver injury downstream of the metabolism of APAP and depletion of reduced glutathione (GSH) in hepatocytes. [source] Histologic and biochemical changes during the evolution of chronic rejection of liver allograftsHEPATOLOGY, Issue 3 2002Desley A. H. Neil Criteria for histologic diagnosis of chronic rejection (CR) are based on changes seen late in the disease process that are likely to be irreversible and unresponsive to treatment. Changes occurring during the evolution of CR are less clearly defined. The serial biopsy specimens, failed allografts, and biochemical profiles of 28 patients who underwent retransplantation for CR were examined with the aim of identifying histologic and biochemical features that were present during the early stages of CR. For each case, a point of acute deterioration in liver function tests (LFTs) was identified ("start time" [ST]) that subsequently progressed to graft failure. Biopsy specimens before, at the time of ("start biopsy" [SB]), and after the ST were assessed histologically, and findings were correlated with the biochemical changes. CR resulted from acute rejection (AR) that did not resolve. Centrilobular necroinflammation (CLNI) associated with an elevated aspartate transaminase (AST) level and portal tract features of AR were present at the start. Portal AR features resolved, CLNI persisted, AST level remained elevated, and bilirubin and alkaline phosphatase levels progressively increased throughout the evolution of CR. Portal tracts also showed a loss of small arterial and bile duct branches, with arterial loss occurring early and bile duct loss as a later progressive lesion. Foam cell arteriopathy was rarely seen in needle biopsy specimens. In conclusion, findings from this study may help identify patients at risk of progressing to graft loss from CR at a stage when the disease process is potentially reversible and amenable to treatment. [source] Alcohol-induced free radicals in mice: Direct toxicants or signaling molecules?HEPATOLOGY, Issue 5 2001Ming Yin Tumor necrosis factor , (TNF-,) and free radicals are produced in early alcohol-induced liver injury. Recently, pathology caused by alcohol was blocked nearly completely in tumor necrosis factor , receptor 1 (TNF-R1) knockout mice. With this model, it is now possible to evaluate whether free radicals are directly toxic or act as redox regulators of TNF-, production. Specifically, if free radicals were directly toxic, a parallel decrease in free radicals and pathology in TNF-R1 knockout mice would be predicted. If they only affect TNF-, production, radicals would be expected to remain high while pathology is diminished. Accordingly, free radical production in TNF-R1 knockout mice was studied here. The enteral alcohol delivery model used mice lacking TNF-R1 (p55) and wild-type control C57Bl/6J mice. Animals received a liquid diet continuously with either ethanol or isocaloric maltose-dextrin as control for 4 weeks. Urine ethanol levels fluctuated from 10 to 500 mg/dL in a cyclic pattern in mice receiving ethanol. Ethanol elevated liver:body weight ratios, serum alanine transaminase (ALT) levels, and pathology scores in wild-type mice. These parameters were blunted nearly completely in TNF-R1 knockout mice. Ethanol treatment increased free radical production in wild-type mice compared with animals fed a high-fat control diet. There were no differences in intensity of free radical signals regardless of the presence or absence of TNF-R1; however, pathology differed markedly between these groups. These findings are consistent with the hypothesis that free radicals act as redox signals for TNF-, production and do not directly damage cells in early alcohol-induced hepatic injury. [source] Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infectionHEPATOLOGY, Issue 3 2001Ph.D., Robert A. de Man M.D. Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.) [source] Long-term follow-up of interferon alfa treatment in chinese patients with chronic hepatitis B infection: The effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complicationsHEPATOLOGY, Issue 1 2001Man-Fung Yuen The long-term effect of interferon alfa (IFN-,) in Chinese patients with chronic hepatitis B infection is unknown. A total of 411 chronic hepatitis B patients (208 treated with IFN-, and 203 as control) were followed up for hepatitis B serology and the development of hepatoma and other cirrhosis-related complications. The hepatitis B e antigen (HBeAg) seroconversion rate in the IFN-,,treated group, though significantly greater at 6 and 24 months, was comparable with the control group on subsequent follow-up, irrespective of pretreatment alanine transaminase (ALT) levels. HBeAg seroreversion rate was higher in the IFN-, group compared with the control group (21.1% vs. 2.2%; P = .001). Loss of hepatitis B surface antigen (HBsAg) occurred in 2.4% of the IFN-,,treated patients and 0.49% of the control patients (P = NS). Around 90% of the anti-HBe,positive patients in both groups were still hepatitis B virus (HBV)-DNA,positive by polymerase chain reaction (PCR) assay. Two patients suffered from hepatic reactivation during the course of treatment. Nine (4.3%) patients in the IFN-, group and 2 (1.0%) in the control group developed complications of cirrhosis and hepatoma (P = .062). In Chinese HBsAg carriers, IFN-, was of no long-term benefit in inducing HBeAg seroconversion or in the prevention of hepatoma and other cirrhosis-related complications. [source] Pathophysiologic importance of E- and L-selectin for neutrophil-induced liver injury during endotoxemia in miceHEPATOLOGY, Issue 5 2000Judy A. Lawson Neutrophils can cause parenchymal cell injury in the liver during ischemia-reperfusion and endotoxemia. Neutrophils relevant for the injury accumulate in sinusoids, transmigrate, and adhere to hepatocytes. To investigate the role of E- and L-selectin in this process, C3Heb/FeJ mice were treated with 700 mg/kg galactosamine and 100 ,g/kg endotoxin (Gal/ET). Immunogold labeling verified the expression of E-selectin on sinusoidal endothelial cells 4 hours after Gal/ET injection. In addition, Gal/ET caused up-regulation of Mac-1 (CD11b/CD18) and shedding of L-selectin from circulating neutrophils. Gal/ET induced hepatic neutrophil accumulation (422 ± 32 polymorphonuclear leukocytes [PMN]/50 high power fields [HPF]) and severe liver injury (plasma alanine transaminase [ALT] activities: 4,120 ± 960 U/L; necrosis: 44 ± 3%) at 7 hours. Treatment with an anti,E-selectin antibody (3 mg/kg, intravenously) at the time of Gal/ET administration did not significantly affect hepatic neutrophil accumulation and localization. However, the anti,E-selectin antibody significantly attenuated liver injury as indicated by reduced ALT levels (,84%) and 43% less necrotic hepatocytes. In contrast, animals treated with an anti,L-selectin antibody or L-selectin gene knock out mice were not protected against Gal/ET-induced liver injury. However, E-, L-, and P-selectin triple knock out mice showed significantly reduced liver injury after Gal/ET treatment as indicated by lower ALT levels (,65%) and reduced necrosis (,68%). Previous studies showed that circulating neutrophils of E-selectin,overexpressing mice are primed and activated similar to neutrophils adhering to E-selectin in vitro. Therefore, we conclude that blocking E-selectin or eliminating this gene may have protected against Gal/ET-induced liver injury in vivoby inhibiting the full activation of neutrophils during the transmigration process. [source] Incubation phase of acute hepatitis B in man: Dynamic of cellular immune mechanismsHEPATOLOGY, Issue 5 2000George J.M. Webster After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV-specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV-DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct ex vivo quantification of HBV-specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus-specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease. [source] Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in KoreaHEPATOLOGY, Issue 4 2000Byung-Cheol Song It has been suggested that hepatitis B e antigen (HBeAg) seroconversion after lamivudine therapy is durable in Caucasians with chronic hepatitis B (CHB). However, little is known whether it is also durable in endemic areas of hepatitis B virus (HBV) infection. We evaluated the posttreatment durability of lamivudine-induced HBeAg seroconversion and the predictive factors for relapse in Korean patients with CHB. We retrospectively analyzed 98 HBeAg-positive patients with CHB who were treated with lamivudine between August 1996 and December 1997. Lamivudine was given at a dose of 150 mg per day. After HBeAg seroconversion, lamivudine was continued for an additional 2 to 4 months, and posttreatment monitoring continued for up to 24 months. HBeAg seroconversion was achieved in 34 of the 98 patients (34.7%). The mean duration of treatment in these seroconverters was 9.3 ± 3.0 months. During the follow-up period, the cumulative relapse rates at 1 year and 2 years posttreatment were 37.5% and 49.2%, respectively. Most relapses were accompanied by elevation of serum alanine transaminase (94%) and reappearance of HBeAg (81%). Pretreatment serum HBV DNA levels and the duration of additional lamivudine therapy after HBeAg seroconversion were 2 independent predictive factors for posttreatment relapse. In conclusion, lamivudine-induced HBeAg seroconversion was not durable in this endemic area. And the duration of additional lamivudine therapy after HBeAg seroconversion significantly affected the posttreatment relapse. Further studies are needed to determine the duration of lamivudine and to elucidate the cause of high relapse after HBeAg seroconversion in endemic areas of HBV. [source] Prednisolone Priming Enhances Th1 Response and Efficacy of Subsequent Lamivudine Therapy in Patients With Chronic Hepatitis BHEPATOLOGY, Issue 3 2000Yun-Fan Liaw M.D. Asian lamivudine trial has shown that hepatitis B e antigen (HBeAg) seroconversion rate during 1 year of lamivudine therapy was only 16% but was 64% in the subgroup of patients with a pretherapy serum alanine transaminase (ALT) level over 5 times the upper limit of normal (ULN). To test whether ALT rebound following corticosteroid priming enhances response to lamivudine therapy, a pilot study was conducted in 30 patients with ALT levels less than 5× ULN (43-169; N < 36 U/L). They received 30 mg of prednisolone daily for 3 weeks, 15 mg daily for 1 week, no treatment for 2 weeks, and then 150 mg of lamivudine daily for 9 months. Complete response (CR) was defined as ALT normalization with HBV-DNA seroclearance and HBeAg seroconversion. Peripheral blood mononuclear cell proliferation and cytokine secretion in response to recombinant HBV core antigen were serially assayed in 7 patients during priming and after withdrawal of prednisolone. Clinical rebound with an ALT over 5× ULN was observed in 20 patients (67%). Of these 20, 12 (60%) showed CR as compared with 1 (10%) of the 10 patients without significant ALT rebound (P < .002). The HBeAg seroconversion sustained in 70% of the patients 3 to 6 months after the end of lamivudine therapy. Immunological assays revealed that the responders showed Th1 dominant response and higher stimulation index to prednisolone priming. No serious side effect was encountered. These results suggest that corticosteroid priming induced immune/ALT rebound greatly enhances response to lamivudine therapy in chronic hepatitis B. Confirmation by randomized controlled trial is needed. [source] Estrogen is involved in early alcohol-induced liver injury in a rat enteral feeding modelHEPATOLOGY, Issue 1 2000Ming Yin The aim of this study was to investigate whether reduction in blood estrogen by removal of the ovaries would decrease the sensitivity of female rats to early alcohol-induced liver injury using an enteral ethanol feeding model, and if so, whether estrogen replacement would compensate. Livers from ovariectomized rats with or without estrogen replacement after 4 weeks of continuous ethanol exposure were compared with nonovariectomized rats in the presence or absence of ethanol. Ethanol increased serum alanine transaminase (ALT) levels from 30 ± 6 to 64 ± 7 U/L. This effect was blocked by ovariectomy (31 ± 7) and totally reversed by estrogen replacement (110 ± 23). Ethanol increased liver weight and fat accumulation, an effect that was minimized by ovariectomy and reversed partially by estrogen replacement. Infiltrating leukocytes were increased 6.7-fold by ethanol, an effect that was blunted significantly by ovariectomy and reversed by estrogen replacement. Likewise, a similar pattern of changes was observed in the number of necrotic hepatocytes. Blood endotoxin and hepatic levels of CD14 messenger RNA (mRNA) and protein were increased by ethanol. This effect was blocked in ovariectomized rats and elevated by estrogen replacement. Moreover, Kupffer cells isolated from ethanol-treated rats with estrogen replacement produced more tumor necrosis factor , (TNF-,) than those from control and ovariectomized rats. It is concluded, therefore, that the sensitivity of rat liver to alcohol-induced injury is directly related to estrogen, which increases endotoxin in the blood and CD14 expression in the liver, leading to increased TNF-, production. [source] Antituberculosis drug-related liver dysfunction in chronic hepatitis B infectionHEPATOLOGY, Issue 1 2000Wai-Man Wong Liver toxicity is a common side effect of antituberculosis (anti-TB) drugs. We studied the differences in liver dysfunction observed during anti-TB treatment between hepatitis B virus carriers (HBV) and noncarriers. Three hundred twenty-four patients on anti-TB drugs were recruited and followed up for 1 year. Forty-three patients with HBV and 276 non-HBV patients were included for analysis. Liver function tests and viral markers were monitored monthly. Liver biopsy was requested whenever the alanine transaminase (ALT) was persistently abnormal. Eighty-six HBV carriers who were not given anti-TB drugs were chosen as a second control and evaluated prospectively. The incidence of liver dysfunction was significantly higher in HBV carriers given anti-TB drugs (34.9%) when compared to noncarriers (9.4%, P < .001) and with HBV carriers not given anti-TB drugs (8.1%, P < .001). For patients given anti-TB drugs, HBV carriers who developed liver dysfunction were younger (P = .011) and had more severe liver injury compared with noncarriers (P = .008). By multiple logistic regression analysis, age (P = .002) and hepatitis B infection (P < .001) were the only 2 significant risk factors for hepatotoxicity related to anti-TB therapy. [source] Alanine transaminase rather than abdominal ultrasound alone is an important investigation to justify cholecystectomy in patients presenting with acute pancreatitisHPB, Issue 5 2010Kerry Anderson Abstract Objectives:, The aims of this study were to investigate the predictive value of an elevated level of alanine transaminase (ALT) for biliary acute pancreatitis (AP) and to reconsider the role of abdominal ultrasound (AUS). Methods:, All patients admitted to Christchurch Public Hospital with AP between July 2005 and December 2008 were identified from a prospectively collected database. Peak ALT within 48 h of presentation was recorded. Aetiology was determined on the basis of history, AUS and other relevant investigations. Results:, A total of 543 patients met the inclusion criteria. Patients with biliary AP had significantly higher median (range) ALT than those with non-biliary causes (200 units/l [63,421 units/l] vs. 33 units/l [18,84 units/l]; P < 0.001). An ALT level of >300 units/l had a sensitivity of 36%, specificity of 94%, positive predictive value of 87% and positive likelihood ratio of 5.6 for gallstones. An elevated ALT and negative AUS had a probability of 21,80% for gallstones. Conclusions:, An elevated ALT strongly supports a diagnosis of gallstones in AP. Abdominal ultrasound effectively confirms this diagnosis; however, a negative ultrasound in the presence of a raised ALT does not exclude gallstones. In some patients consideration could be given to proceeding to laparoscopic cholecystectomy based on ALT alone. [source] Preoperative determinants of common bile duct stones during laparoscopic cholecystectomyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2008A. J. Sheen Summary Introduction:, The aim of this study is to determine whether there are any clinical or biochemical predictors of common bile duct (CBD) stones in patients undergoing laparoscopic cholecystectomy. Methods:, A prospective database of nearly 1000 laparoscopic cholecystectomies performed under the care of a single surgeon with a standardised technique between 1999 and 2006, was analysed. Clinical presentation, ultrasound and immediate preoperative biochemical results as well as the operative cholangiogram findings were reviewed. Routine cholangiography was attempted in most patients and the primary outcome variable was the detection of bile duct stones. The data was analysed using chi-squared test for categorical variables. The significant variables on univariate analysis were further characterised to identify the independent predictors of bile duct stones using a logistic regression model (significance p < 0.05). Results:, A total of 757 of 988 patients (77%) underwent cholangiography. Male-to-female ratio was 1 : 3 with a median age of 54 years (range: 17,93). Ten per cent of patients had bile duct stones identified on cholangiography. On univariate analysis, jaundice (p = 0.019), cholangitis (p < 0.001), alanine transaminase > 100 (p = 0.024), alkaline phosphatase (ALP) > 350 (p < 0.001) and CBD > 10 mm (p = 0.01) were significant markers for predicting bile duct stones. Bilirubin > 30 (×2 normal) was found not to be significant (p = 0.145). On a logistic regression model, ALP > 350 and/or cholangitis were found to be independent predictive factors of CBD stones (odds ratio 6.1). Conclusions:, If a policy of routine intra-operative cholangiography is not adopted, a history of cholangitis or a raised ALP immediately preoperatively should lead to a high suspicion of CBD stones. [source] Insulin resistance phenotypes and coronary artery disease in a native Pakistani cohortINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2008A. S. Wierzbicki Summary Objective:, To determine the relationship between insulin resistance (IR) and atheroma burden in Pakistanis. Methods:, A prospective case,control study of 400 patients selected for the presence/absence of angiographic disease. Coronary atheroma burden was quantified and IR and cardiovascular risk factors were measured. Results:, The patients were divided into two groups by QuickI score. Waist circumference (90 ± 10 vs. 90 ± 9 cm; p = 0.7) was similar but the groups differed in body mass index (26.5 ± 3.7 vs. 24.2 ± 3.5 kg/m2; p < 0.001) and waist:hip ratio (0.94 ± 0.09 vs. 0.90 ± 0.06; p < 0.001). Lipid parameters showed similar high-density lipoprotein cholesterol (HDL-C) (0.77 ± 0.23 vs. 0.82 ± 0.22 mmol/l; p = 0.1) differences in triglycerides [1.32 (0.08,3.98) vs. 1.12 (0.37,3.61) mmol/l; p = 0.01], but no difference in low-density lipoprotein cholesterol (LDL-C) (2.75 ± 1.00 vs. 2.90 ± 0.94 mmol/l; p = 0.14). In insulin-resistant patients C-reactive protein (CRP) [6.8 (0.3,175.1) vs. 3.9 (0.2,57.9) mg/l: p < 0.001], sialic acid (82 ± 14 vs. 77 ± 15 mg/l; p < 0.001) aspartate transaminase [24 (7,171) vs. 21 (7,83) IU/l; p < 0.001] and gamma-glutamyl transferase [27 (8,482) vs. 21 (7,168) IU/l; p = 0.005] levels were increased. In insulin-resistant patients (n = 187), coronary artery disease (CAD) burden correlated (r = 0.55) with age (, = 1.62; p < 0.001), HDL-C (, = ,53.2; p < 0.001), lipoprotein (a) (, = 11.4; p = 0.007), smoking (, = 7.98; p = 0.004), CRP (, = 6.06; p = 0.03) and QuickI index (, = ,146; p = 0.04). In contrast in insulin-sensitive patients (n = 178) CAD burden (r = 0.46) correlated with LDL-C (, = 10.0; p = 0.02), CRP (, = 7.13; p = 0.03), HDL-C (, = ,38.1; p = 0.03), and weakly with age (, = 0.73; p = 0.07) and smoking (, = 5.52; p = 0.09). Conclusions:, Indian Asians show a dichotomous insulin-resistance phenotype. Atheroma is associated with low HDL-C and inflammation associated in all but LDL-C is a factor in the insulin sensitive in contrast to age and extent of IR in the insulin resistant. [source] Lactate levels in Asian patients with type 2 diabetes mellitus on metformin and its association with dose of metformin and renal functionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2007Vivien C. C. Lim Summary Aim:, Our aims are to discover the average fasting plasma lactate level (FPL) in Asian patients with type 2 diabetes mellitus on metformin, with or without renal impairment and whether FPL is associated with the total daily dose of metformin (Tmet) and the degree of renal impairment in these patients. Methods:, We conducted an observational cross-sectional study of Asian patients with type 2 diabetes, using measurements of FPL levels and glomerular filtration rate (GFR) calculated, using the abbreviated modification of diet in renal disease (MDRD) formula. The association between FPL, Tmet, GFR and other potential predictors was analysed. Results:, A total of 97 subjects were recruited from our diabetes centre between July 2005 and February 2006. Sixty (61.9%) of the subjects were males; 69 (71.1%) Chinese, 21 (21.6%) Malays and 6 (6.2%) Indians. The mean (SD) age was 58.8 years (10.7) and the mean body mass index was 27.1 kg/m2 (5.3). The mean FPL was 1.8 mmol/l (0.9) with 20 (20.6%) of subjects having an FPL beyond the upper limit of our reference range of 2.2 mmol/l. The mean FPL (two SE) of subjects with Tmet of , 1000, 1001,2000 and > 2000 mg were 1.7 mmol/l (0.2), 1.6 mmol/l (0.2) and 2.1 mmol/l (0.5) respectively, (p = 0.119). The mean FPL of subjects with GFR of < 60, 60,90 and > 90 ml/min/1.73 m2 was 1.7 mmol/l (0.3), 1.8 mmol/l (0.3) and 1.8 mmol/l (0.4) respectively, p = 0.757. Among the potential predictors analysed, aspartate transaminase (p = 0.001) was found to be significantly associated with FPL. Conclusions:, Our study shows no correlation between Tmet and GFR with FPL in Asian type 2 diabetic patients on metformin. [source] Dermatomyositis presenting as panniculitisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2000Yen-Yu Chao MD A 44-year-old obese woman was transferred to our clinic with a diagnosis of panniculitis. Examination showed multiple, indurated, erythematous, painful nodules and plaques distributed on the shoulders, back, forechest, abdomen, buttock, and bilateral thighs. These skin lesions appeared 2 months previously, measured 5,8 cm, and were tender on palpation. No obvious inducing factor was traced. The lesions seemed unresponsive to treatment with nonsteroidal anti-inflammatory drugs (ibuprofen, 400 mg three times a day) as similar lesions appeared in subsequent visits. Progressive proximal muscle weakness was found 1 month later. She was then admitted via the emergency room because of extensive painful skin plaques and abdominal pain. Diffuse erythematous to violaceous swelling of the face, neck, and shoulder was noted at about the same time ( Fig. 1). A skin biopsy specimen from the nodular lesion showed poikilomatous epidermal changes ( Fig. 2), and marked mononuclear cell infiltration in the dermis and subcutaneous fat ( Fig. 3). Dermatomyositis was considered as the diffuse violaceous facial erythema could be a form of heliotrope eruption, but Gottron's papule was not found. At admission, serum creatinine phosphokinase (CPK) was mildly elevated (436 IU/L; normal range, 20,170 IU/L), but serum asparagine transaminase (AST) and lactate dehydrogenase (LDH) levels were within normal limits (36 IU/L; normal, 11,47 IU/L; and 108 IU/L; normal, 90,280 IU/L, respectively). Antinuclear antibody was 1 : 80 positive with an atypical speckled pattern. Muscle strength was weakest during the first 2 days, about grade 3 by the Medical Research Council (MRC) of Great Britain scale. Gower's sign was positive. An electromyogram showed myopathic changes and a nerve conduction velocity study was normal. Serum enzymes were elevated further on the third day: AST, 55 IU/L; CPK, 783 IU/L with 100% MM form. The diagnosis of dermatomyositis was established. As for the work-up result, anti-dsDNA antibody, anti-ENA antibody, and anti-Jo1 antibody were negative. Tumor marker screen (,-HCG, AFP, CEA, and CA-125), was negative, and rhinolaryngopharyngoscope examination and gynecologic sonography were normal. Figure 1. Diffuse erythematous swelling with subtle violaceous hue extending from the temporal area to the cheeks, neck, and shoulders. The crusted lip ulcers of herpes simplex were also noted Figure 2. Basketweave hyperkeratosis, mild acanthosis, subtle vacuolar degeneration of the basal cells, and melanin incontinence (hematoxylin and eosin, ×400) Figure 3. Heavy mononuclear cells infiltrated in the subcutaneous fat tissue (hematoxylin and eosin, ×100) Pancreatitis was initially suspected because of epigastric pain and tenderness, elevated serum lipase (382 U/L; normal, 23,200 U/L), and amylase (145 U/L; normal, 35,118 U/L). No evidence of pancreatitis could be found in abdominal sonography and abdominal computed tomography (CT), however. The epigastric pain and tenderness subsided soon after admission and the serum pancreatic enzyme level declined on the second day (amylase 69 U/L; lipase, 276 U/L). The patient was then diagnosed with dermatomyositis and treated with prednisolone (120 mg/day). CPK dropped dramatically from 3286 IU/L the day before treatment to 1197 IU/L 3 days after. Panniculitis lessened and the muscle power improved after 1 week of treatment. The disease activity fluctuated even with treatment with prednisolone and the patient often felt listless and weak. The muscle weakness sometimes deteriorated to affect the patient's mobility. Facial erythema and panniculitis-like lesions were found during the worse times. Methotrexate and azathioprine were then added (7.5 mg and 250 mg per week, respectively), but CPK was still mildly elevated (189 IU/L), and the patient still felt ill. Human immune globulin (5%, 500 mL per day, 5 days per month) intravenous infusion was initiated thereafter. There was a dramatic response. Full muscle strength was retained and CPK was within the normal range in the following 6 months with only immune globulin therapy. [source] The protective effect of N -acetylcysteine against cyclosporine A-induced hepatotoxicity in ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2008Hasan Kaya Abstract The immunosuppressive agent cyclosporine A (CsA) has been reported to exert measurable hepatotoxic effects. One of the causes leading to hepatotoxicity is thought to be reactive oxygen radical formation. The aim of this study was to investigate the effects of N -acetylcysteine (NAC) treatment on CsA-induced hepatic damage by both analysing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), aspartate aminotransferase (AST) and alanine transaminase (ALT) activities with malondialdehyde (MDA) and nitric oxide (NO) levels, and using an histological approach. CsA administration produced a decrease in hepatic SOD activity, and co-administration of NAC with CsA resulted in an increase in SOD activity. MDA and NO levels increased in the CsA group and NAC treatment prevented those increases. A significant elevation in serum AST and ALT activities was observed in the CsA group, and when NAC and CsA were co-administered, the activities of AST and ALT were close to the control levels. CsA treatment caused evident morphological alterations. Control rats showed no abnormality in the cytoarchitecture of the hepatic parenchyma. The co-administration of NAC with CsA showed no signs of alteration and the morphological pattern was almost similar to the control group. In conclusion, CsA induced liver injury and NAC treatment prevented the toxic side effects induced by CsA administration through the antioxidant and radical scavenging effects of NAC. Copyright © 2007 John Wiley & Sons, Ltd. [source] Modulatory potential of ellagic acid, a natural plant polyphenol on altered lipid profile and lipid peroxidation status during alcohol-induced toxicity: A pathohistological studyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2008Nagarajan Devipriya Abstract Polyphenol-rich dietary foodstuffs, consumed as an integral part of vegetables, fruits, and beverages have attracted attention due to their antioxidant and anticancer properties. Ellagic acid (EA), a polyphenolic compound widely distributed in fruits and nuts, has been reported to scavenge free radicals and inhibit lipid peroxidation. Chronic consumption of alcohol potentially results in serious illness including hepatitis, fatty liver, hypertriglyceridemia, and cirrhosis. A little is known about the influence of EA on alcohol toxicity in vivo. Accordingly, in the present study, we have evaluated the protective effects of EA on lipid peroxidation and lipid levels during alcohol-induced toxicity in experimental rats. Forty female albino Wistar rats, which were weighing between 150,170 g were used for the study. The toxicity was induced by administration of 20% alcohol orally (7.9 g/kg body wt.) for 45 days. Rats were treated with EA at three different doses (30, 60, and 90 mg/kg body wt.) via intragastric intubations together with alcohol. At the end of experimental duration, liver marker enzymes (i.e., aspartate transaminase, alanine transaminase), lipid peroxidative indices (i.e., thiobarbituriacid reactive substances and hydroperoxides) in plasma, and lipid levels (i.e., cholesterol, free fatty acids, triglycerides and phospholipids) in tissues were analyzed to evaluate the antiperoxidative and antilipidemic effects of EA. Liver marker enzymes, lipid peroxidative indices, and lipid levels, i.e., cholesterol, triglycerides and free fatty acids, were significantly increased whereas phospholipid levels were significantly decreased in the alcohol-administered group. EA treatment resulted in positive modulation of marker enzymes, peroxidative indices, and lipid levels. EA at the dose of 60 mg/kg body wt. was found to be more effective when compared to the other two doses. Histological changes observed were also inconsistent with the biochemical parameters. Our study suggests that EA exerts beneficial effects at the dosage of 60 mg/kg body wt. against alcohol-induced damage, and it can be used as a potential drug for the treatment of alcohol-abuse ailments in the near future. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:101,112, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20226 [source] Sonographic assessment of fatty liver infiltration using the measurement of para- and perirenal fat thicknessJOURNAL OF CLINICAL ULTRASOUND, Issue 9 2010Satsuki Kawasaki MD Abstract Purpose Usefulness of abdominal ultrasonography for quantitative estimation of fatty liver by measurement of para- and perirenal sonographic fat thickness (UFT) was investigated. Methods Study subjects were 286 patients hospitalized for the treatment of diabetes. These subjects underwent blood chemistry studies, abdominal ultrasonography, and CT. On sonography, the thickness of combined para- and perirenal fat was measured between the kidney and the inner aspect of the abdominal musculature. Measurements on both sides were averaged as the UFT. Fatty liver infiltration was graded on a scale of grade 0 to 3: 0, none; 1, mild; 2, moderate; and 3, severe. With abdominal CT, the ratio of CT attenuation value of the liver to that of the spleen (L/S ratio) was measured. Results A positive correlation was found between UFT and FL grade or between UFT and L/S ratio (p < 0.0001). Positive correlations were also found between UFT and glutamic pyruvic transaminase (p < 0.05), or cholinesterase (p < 0.0001). Conclusion Measurement of UFT is a useful method for the quantification of fatty liver as well as for the quantification of visceral fat. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010 [source] Effects on acid-base balance, methaemoglobinemia and nitrogen excretion of European eel after exposure to elevated ambient nitriteJOURNAL OF FISH BIOLOGY, Issue 3 2002C.-Y. Huang Haemoglobin, methaemoglobin, blood nitrite concentration and acid-base balance were measured in European eel Anguilla anguilla following exposure to 0 (control), 0·142, 0·356, 0·751 and l·549 mM nitrite in fresh water for 24 h. Blood GOT (glutamate oxaloacetate transaminase) and GPT (glutamate pyruvate transaminase) activities and whole animal ammonia-N and urea-N excretions were also measured. Blood nitrite, methaemoglobin, PO2 (oxygen partial pressure), GOT, and whole animal ammonia-N excretion and urea-N excretion increased directly with increasing ambient nitrite concentrations, whereas blood pH, PCO2, and HCO,3 were inversely related to ambient nitrite concentration. An accumulation of nitrite in the blood of A. anguilla following 24 h exposure to elevated ambient nitrite as low as 0·751 mM increased its blood methaemoglobin, PO2, GOT and nitrogen excretion, but decreased its PCO2 (carbon dioxide partial pressure), HCO,3 and functional haemoglobin. [source] Oxidative-inflammatory damage in cirrhosis: Effect of vitamin E and a fermented papaya preparationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2007Francesco Marotta Abstract Background and Aim:, Oxidative DNA damage occurs as an early event in hepatitis C virus (HCV) infection and is an indication of the potential for carcinogenesis. The aim of this study was to test a novel antioxidant/immunomodulator in patients with HCV-related cirrhosis. Methods:, The study group consisted of 50 patients with HCV-related cirrhosis with transaminase values less than twofold increased (alanine aminotransferase [ALT] < 80 IU/L). Patients underwent a standardized food-vitamin composition assessment and were assessed for dietary intake, nutritional status and iron level. Patients were randomly allocated into two groups and then given either ,-tocopherol 900 IU/day or 9 g/day of a fermented papaya preparation (FPP, Immun-Age, Osato Research Institute, Gifu, Japan) at bedtime for 6 months. Ten healthy subjects served as controls. Patients were checked monthly for: routine tests, redox status (reduced glutathione, glutathione peroxidase, oxidized glutathione, malondialdehyde), plasma ,-tocopherol, 8-hydroxy-deoxy-guanidine (8-OHdG) level in circulating leukocyte DNA and serum levels of cytokines. Results:, Patients with cirrhosis showed a significant imbalance of redox status (low antioxidants/high oxidative stress markers) (P < 0.005 vs controls). Neither treatment regimen affected transaminases as a whole. However, vitamin E supplementation almost normalized ALT only in the limited vitamin-E-deficient subgroup. A significant improvement of redox status was obtained by both regimens. However, only FPP significantly decreased 8-OHdG and the improvement of cytokine balance with FPP was significantly better than with vitamin E treatment (P < 0.05). Conclusions:, Although the present data seem to suggest a potential supportive role of antioxidants/immunomodulators as FPP in HCV patients, more studies are needed to substantiate their effect on the natural history of the disease. [source] Restriction of dietary calories, fat and iron improves non-alcoholic fatty liver diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2007Mika Yamamoto Abstract Background:, The pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear. Recent studies suggested that oxidative stress plays an important role in the mechanism of NASH. Excessive accumulation of iron in the liver causes oxidative stress. The aim of the present study was to evaluate the grade of hepatic iron accumulation and the therapeutic response to restriction of calories, fat and iron in patients with non-alcoholic fatty liver disease (NAFLD). Methods:, Twenty-seven NAFLD patients were enrolled. The patients were categorized into two groups: 17 patients with NASH and 10 with simple steatosis. Twelve NAFLD patients (NASH, n = 9; simple steatosis, n = 3) were given a dietary prescription including restriction of energy, fat and iron. Results:, Positive iron staining was observed in 71% and 50% of patients with NASH and simple steatosis, respectively. The average energy intake, fat energy fraction and iron intake decreased significantly 6 months after the beginning of the diet in all patients. In addition, the levels of serum transaminase and ferritin were significantly decreased. Conclusion:, Dietary restriction of calories, fat and iron improved NAFLD. Reduced serum ferritin levels appear to reduce oxidative stress in the liver. [source] | ||||||||||||||||||||||||||||||||||||||||||||||