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Alanine Transaminase (alanine + transaminase)
Kinds of Alanine Transaminase Selected AbstractsSodium Valproate in the Management of Painful Neuropathy in Type 2 Diabetes , a Randomized Placebo Controlled StudyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2003DK Kochar OBJECTIVE: To study the effectiveness and safety aspects of sodium valproate in the management of painful neuropathy in patients of type 2 diabetes mellitus. MATERIAL AND METHODS: A randomized double-blind placebo controlled trial of sodium valproate was done in type 2 diabetic patients to assess its efficacy and safety in the management of painful neuropathy. We screened 60 patients but eight patients could not complete the study; hence, the present study was done on 52 patients. Each patient was assessed by clinical examination, pain score by short form of the McGill pain questionnaire (SF-MPQ) and electrophysiological examination, which included motor and sensory nerve conduction velocity, amplitude and H-reflex initially and at the end of 1 month of treatment. RESULTS: Significant improvement was noticed in the pain score of patients receiving sodium valproate in comparison to patients receiving placebo at the end of 1 month (P < 0.05). The changes in electrophysiological data were not significant. The drug was well tolerated by all patients except one who developed a raised aspartate transaminase (AST)/alanine transaminase (ALT) level after 15 days of treatment. CONCLUSION: Sodium valproate is a well-tolerated drug and provides significant subjective improvement in painful diabetic neuropathy. These data provide a basis for future trials of longer duration in a larger group of patients. [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] 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] 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] 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] 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] 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] Clinical and virological characteristics of lamivudine resistance in chronic hepatitis B patients: A single center experienceJOURNAL OF MEDICAL VIROLOGY, Issue 3 2005Jian Sun Abstract We have investigated the characteristics of lamivudine-resistant strains in patients with chronic hepatitis B in Guangdong, China, where the predominant genotypes are B and C. Two hundred forty-seven patients treated with lamivudine in Nanfang Hospital were followed-up. Patients with hepatitis B e antigen (HBeAg) positive and hepatitis B virus (HBV)-DNA levels over 7.5,×,106 copies/ml at baseline had a shorter time to the selection of YMDD mutant (P,=,0.02 and 0.00, respectively). The detection of YMDD mutant precedes HBV-DNA breakthrough and alanine transaminase (ALT) flare in about 2 and 3 months, respectively. The ALT flare after the appearance of YMDD mutants was more evident in HBeAg positive patients than HBeAg negative patients (P,=,0.02). After emergence of YMDD mutant, the HBV-DNA level was significantly higher in genotype C patients compared with genotype B patients (P,=,0.02). No significant difference of YMDD mutant pattern was found between patients with genotype B and C. Four kinds of new mutants were found in over two patients including rtL80I, rtG172E, rtG174C, and rtG172E/rtG174C. In vitro transfection and real-time analysis showed that rtG172E, rtG174C, and rtG172E/rtG174C mutants had a decreased replication competence compared with wild type (33%, 27%, and 15% of the wild type HBV, respectively). Our result suggest that genotypic monitoring of YMDD mutant is important for the management of patients treated with lamivudine. J. Med. Virol. 75:391,398, 2005. © 2005 Wiley-Liss, Inc. [source] Synergistic antiviral effect of a combination of mouse interferon-, and interferon-, on mouse hepatitis virusJOURNAL OF MEDICAL VIROLOGY, Issue 2 2003Uichiro Fuchizaki Abstract Although interferon (IFN)-, and IFN-, have been reported to exhibit a synergistic antiviral effect through the different signaling pathways in vitro, their therapeutic efficacy is not well defined in vivo. The current study was carried out to investigate the combined antiviral effect in a model of mouse hepatitis virus Type 2 (MHV-2) infection, in which fulminant hepatitis is developed. MHV-2 was injected intraperitoneally into 4-week-old ICR mice, IFN or the vehicle was administered intramuscularly for 5 days, and the antiviral effect was evaluated based on survival periods, liver histology, serum alanine transaminase (ALT) levels, and MHV-2 virus titers in the liver tissues. The animals in the group treated with a combination of IFN-, and IFN-, survived for longer periods than the groups treated with IFN-, alone and IFN-, alone (IFN-, 103 (IU/mouse)/-, 103 vs. IFN-, 103, P,<,0.005; IFN-, 103/-, 103 vs. IFN-, 103, P,<,0.001). This is consistent with the lower levels of hepatocellular necrosis and serum ALT and the decreased titers of MHV-2 virus in the liver tissues (48 hr, P,<,0.001; 72 hr, P,<,0.001). These findings indicate that a combination of IFN-, and IFN-, exhibits a synergistic antiviral effect on MHV-2 infection. The biology of MHV-2 is quite different from that of human hepatitis viruses; however, these results suggest the beneficial combined therapy of IFN-, and IFN-, for the treatment of human viral hepatitis. J. Med. Virol. 69:188,194, 2003. © 2003 Wiley-Liss, Inc. [source] Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2010Mahaboob Khan Rasool Abstract Objectives The aim of this research paper was to investigate the hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. Methods In the present study, the hepatoprotective and antioxidant effects of gallic acid were evaluated against paracetamol-induced hepatotoxicity in mice and compared with the silymarin, a standard hepatoprotective drug. The mice received a single dose of paracetamol (900 mg/kg body weight i.p.). Gallic acid (100 mg/kg body weight i.p.) and silymarin (25 mg/kg body weight i.p.) were administered 30 min after the injection of paracetamol. After 4 h, liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase) and inflammatory mediator tumour necrosis factor-alpha (TNF-,) were estimated in serum, while the lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione- S -transferase and glutathione) were determined in liver homogenate of the control and experimental mice. Key findings Increased activities of liver marker enzymes and elevated TNF-, and lipid peroxidation levels were observed in mice exposed to paracetamol (P < 0.05), whereas the antioxidant status was found to be depleted (P < 0.05) when compared with the control group. However gallic acid treatment (100 mg/kg body weight i.p.) significantly reverses (P < 0.05) the above changes by its antioxidant action compared to the control group as observed in the paracetamol-challenged mice. Conclusions The results clearly demonstrate that gallic acid possesses promising hepatoprotective effects. [source] Antioxidant effect of 2-hydroxy-4-methoxy benzoic acid on ethanol-induced hepatotoxicity in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2007Nadana Saravanan Alcoholic liver disease (ALD) is one of the most common diseases in society. A large number of studies are in progress to identify natural substances that are effective in reducing the severity of ALD. 2-Hydroxy-4-methoxy benzoic acid (HMBA), the active principle of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant in India, is expected to significantly inhibit the development of liver injury in ethanol administration. It is expected to reduce the severity of liver damage in terms of body weight, hepatic marker enzymes, oxidative stress, antioxidant status and histological changes in ethanol-induced hepatotoxic rats. Hepatotoxicity was induced by administering 20% ethanol (5 g kg,1 daily) for 60 days to male Wistar rats, which resulted in significantly decreased body weight and an increase in liver-body weight ratio. The liver marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, ,-glutamyl transpeptidase and lactate dehydrogenase were elevated. In addition, the levels of plasma, erythrocyte and hepatic thiobarbituric acid reactive substances, hydroperoxides and conjugated dienes were also elevated in ethanol-fed rats as compared with those of the experimental control rats. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C and ,-tocopherol was also observed on alcohol administration as compared with experimental control rats. HMBA was co-administered at a dose of 200 ,gkg,1 daily for the last 30 days of the experiment to rats with alcohol-induced liver injury, which significantly increased body weight, significantly decreased the liver-body weight ratio, transaminases, alkaline phosphatase, ,-glutamyl transpeptidase and lactate dehydrogenase, significantly decreased the levels of lipid peroxidative markers, significantly elevated the activity of enzymic and non-enzymic antioxidants in plasma, erythrocytes and liver and also increased levels of plasma and liver vitamin C and ,-tocopherol at the end of the experimental period as compared with untreated ethanol-administered rats. The histological changes were also in correlation with the biochemical findings. The results suggest that HMBA administration may afford protection against ethanol-induced liver injury in rats. [source] Anti-Inflammatory and Anti-Apoptotic Roles of Endothelial Cell STAT3 in Alcoholic Liver InjuryALCOHOLISM, Issue 4 2010Andrew M. Miller Background:, It is generally believed that the hepatoprotective effect of interleukin-6 (IL-6) is mediated via activation of signal transducer and activator of transcription 3 (STAT3) in hepatocytes. IL-6-deficient mice are more susceptible to alcohol-induced hepatocyte apoptosis and steatosis and elevation of serum alanine transaminase (ALT); however, whereas hepatocyte-specific STAT3 knockout mice are more susceptible to alcohol-induced hepatic steatosis, they have similar hepatocyte apoptosis and serum ALT after alcohol feeding compared with wild-type mice. This suggests that the hepatoprotective effect of IL-6 in alcoholic liver injury may be mediated via activation of STAT3-independent signals in hepatocytes, activation of STAT3 in nonparenchymal cells, or both. We have previously shown that IL-6 also activates STAT3 in sinusoidal endothelial cells (SECs). Thus, the purpose of this study was to investigate whether STAT3 in endothelial cells also plays a protective role in alcoholic liver injury. Methods:, Wild-type and endothelial cell-specific STAT3 knockout (STAT3E,/,) mice were pair-fed and fed ethanol containing diet for 4 weeks. Liver injury and inflammation were determined. Results:, Feeding mice with ethanol-containing diet for 4 weeks induced greater hepatic injury (elevation of serum ALT) and liver weight in STAT3E,/, mice than wild-type control groups. In addition, ethanol-fed STAT3E,/, mice displayed greater hepatic inflammation and substantially elevated serum and hepatic levels of IL-6 and TNF-, compared with wild-type mice. Furthermore, ethanol-fed STAT3E,/, mice displayed a greater abundance of apoptotic SECs and higher levels of serum hyaluronic acid than wild-type controls. Conclusions:, These data suggest that endothelial cell STAT3 plays important dual functions of attenuating hepatic inflammation and SEC death during alcoholic liver injury. [source] Naltrexone Decreases Heavy Drinking Rates in Smoking Cessation Treatment: An Exploratory StudyALCOHOLISM, Issue 6 2009Andrea King Background:, There is mixed support for the efficacy of the opioid antagonist naltrexone in the treatment of nicotine dependence. One potential unexplored mechanism underlying naltrexone's effects in smoking cessation may be in its ability to reduce alcohol consumption. Methods:, Alcohol consumption and liver enzyme levels (aspartate aminotransferase and alanine transaminase) were examined in a sample of 78 nonalcoholic social drinking smokers (34 naltrexone, 44 placebo) enrolled in a double-blind randomized clinical trial of naltrexone in smoking cessation. Naltrexone or placebo began 3 days prior to the quit date (25 mg daily) and continued for 8 weeks (50 mg daily). All participants received nicotine patches and behavioral counseling up through 4 weeks after the quit date. Results:, Naltrexone significantly reduced weekly heavy drinking rates. This effect was associated with greater nausea and pill taking adherence within the naltrexone group. Within heavy drinkers, naltrexone also directionally improved smoking quit rates compared with placebo. Liver enzyme levels did not differ during treatment with naltrexone compared with placebo. Conclusions:, Naltrexone may reduce the frequency of heavy drinking in nonalcoholics attempting to quit smoking. Further, naltrexone may preferentially improve smoking quit rates within heavy drinkers who smoke, and further investigation in larger sample sizes is warranted. [source] Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection,JOURNAL OF VIRAL HEPATITIS, Issue 1 2005J. D. Collier Summary., Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression. [source] Inflammatory change of fatty liver induced by intraportal low-dose lipopolysaccharide infusion deteriorates pancreatic insulin secretion in fructose-induced insulin-resistant ratsLIVER INTERNATIONAL, Issue 8 2008Po-Shiuan Hsieh Abstract Background: This study tested whether subacute inflammatory change of fatty liver induced by portal endotoxaemia is detrimental to pancreatic insulin secretion in fructose-fed rats (FFRs) with fatty liver. Methods: Rats were randomly assigned into two groups with a regular or fructose-enriched diet for 8 weeks. Rats, after fructose feeding for 4 weeks, were further divided into three subgroups: on fructose diet alone, on fructose diet combined with intraportal saline or lipopolysaccharide (LPS) infusion (n=8 per group) for the next 4 weeks. In another set of experiments, the liver and pancreatic tissues were obtained for histological examination in these four groups. Pancreatic insulin secretion was evaluated by in vivo hyperglycaemic clamp study. Results: Fasting plasma insulin concentrations and homoeostasis model assessment-insulin resistance, an insulin resistance score, were significantly increased in FFRs but failed to change in rats with LPS treatment. The 4-week intraportal LPS infusion significantly increased circulating aspartate transaminase, alanine transaminase and C-reactive protein levels but did not alter endotoxin levels in FFRs. The increased white blood cell count was also noted in rats after intraportal LPS infusion for 2 and 4 weeks. The attenuated first-phase and second-phase insulin responses in FFRs shown in hyperglycaemic clamp were further deteriorated in those with intraportal LPS infusion. Increased histopathological scores of liver and pancreas shown in FFRs were further increased in those combined with portal endotoxaemia. Conclusion: This study demonstrates that the chronic subacute inflammatory change of fatty liver induced by mild portal endotoxaemia could deteriorate insulin secretion in a rodent model of metabolic syndrome and fatty liver. [source] Clinical significance and evolution of core promoter and precore mutations in HBeAg-positive patients with HBV genotype B and C: a longitudinal studyLIVER INTERNATIONAL, Issue 6 2007Chien-Hung Chen Abstract Background/Aims: The aims of this longitudinal study were to investigate whether the clinical outcome and evolution of core promoter and precore mutations were different during hepatitis B e antigen (HBeAg) seroconversion between hepatitis B virus (HBV) genotypes B and C in HBeAg-positive patients with chronic hepatitis B. Patients and Methods: The core promoter and precore sequences were determined from serial sera of 156 HBeAg-positive patients with chronic HBV infection. Results: In HBV genotype C, the T1762/A1764 mutant was detected earlier than the A1896 mutant, and the frequency was significantly higher than in HBV genotype Ba over the entire follow-up period. In HBV genotype Ba, A1896 was found earlier than the T1762/A1764 mutant, and the frequency was significantly higher than in genotype C only before HBeAg seroconversion, and the A1896 mutant played an important role in HBeAg seroconversion in HBV genotype Ba. In addition, the T1846 variant was an independent factor associated with HBeAg seroconversion. Furthermore, HBV genotype C was associated with the development of G or C1753 and T1766/A1768 mutations, and the reactivation of hepatitis after HBeAg seroconversion. Based on Cox's regression analysis, the significant risk factors of liver cirrhosis were older age at entry [hazard ratio (HR)=1.085, 95% confidence interval (CI)=1.036,1.136, P=0.001], alanine transaminase (ALT) >80 U/l (HR=3.48, 95% CI=1.37,8.86, P=0.009), and the T1762/A1764 mutant (HR=5.54, 95% CI=2.18,14.08, P<0.001). Conclusions: Our study showed that different HBV genotypes were associated with various mutations in the core promoter and precore regions during HBeAg seroconversion. T1762/A1764 mutation could be useful in predicting clinical outcomes in HBeAg-positive patients with HBV infection. [source] Plasma transforming growth factor-,1 level and efficacy of ,-tocopherol in patients with non-alcoholic steatohepatitis: a pilot studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2001T. Hasegawa Background: Non-alcoholic steatohepatitis is a distinct entity, characterized by fatty change, lobular inflammation and fibrosis of the liver. Some cases of non-alcoholic steatohepatitis progress to cirrhosis, but it is not easy to distinguish this disease from non-alcoholic fatty liver by non-invasive examinations. No proven therapy for non-alcoholic steatohepatitis exists. Transforming growth factor-,1 is implicated in the development of liver fibrosis, and is inhibited by ,-tocopherol (vitamin E) in the liver. Therefore, in this study, the significance of the measurement of the level of plasma transforming growth factor-,1 and the effect of ,-tocopherol on the clinical course of non-alcoholic steatohepatitis were investigated. Methods: Twelve patients with non-alcoholic steatohepatitis and 10 patients with non-alcoholic fatty liver, with a diagnosis confirmed by liver biopsy, were studied. None of the patients had a history of alcohol abuse, habitual medicine or malignant or inflammatory diseases. All patients were negative for hepatitis B, C and G virus. Patients were given dietary instruction for 6 months, and then ,-tocopherol (300 mg/day) was given for 1 year. Blood chemistries, measurement of plasma transforming growth factor-,1 level and liver biopsies were undertaken before and after the 1-year ,-tocopherol treatment. Results: The serum alanine transaminase level decreased in non-alcoholic fatty liver patients, but not in non-alcoholic steatohepatitis patients, after 6 months of dietary therapy. Although the serum alanine transaminase level in non-alcoholic steatohepatitis patients was reduced during the 1-year ,-tocopherol treatment, ,-tocopherol had no effect on the serum alanine transaminase level in non-alcoholic fatty liver patients. The histological findings, such as steatosis, inflammation and fibrosis, of the non-alcoholic steatohepatitis patients were improved after ,-tocopherol treatment. The plasma transforming growth factor-,1 level in non-alcoholic steatohepatitis patients was significantly elevated compared with that in non-alcoholic fatty liver patients and healthy controls, and decreased, accompanied by an improvement in serum alanine transaminase level, with ,-tocopherol treatment. Conclusions: lOur data suggest that the measurement of the level of plasma transforming growth factor-,1 represents a possible method of distinguishing between non-alcoholic steatohepatitis and non-alcoholic fatty liver. Long-term ,-tocopherol treatment may be safe and effective for non-alcoholic steatohepatitis. A randomized, controlled, double-blind trial is needed to confirm the full potential of ,-tocopherol in the management of non-alcoholic steatohepatitis. [source] Rheumatoid arthritis, alcohol, leflunomide and methotrexate.MUSCULOSKELETAL CARE, Issue 4 2008Can changes to the BSR guidelines for leflunomide, methotrexate on alcohol consumption be justified? Introduction:,The summary of product characteristics for leflunomide and methotrexate recommend avoiding alcohol. By contrast, the latest British Society for Rheumatology (BSR) guidelines suggest that alcohol should be ,well within national limits'. A postal survey was performed of rheumatoid arthritis (RA) patients to address their alcohol consumption, and assess whether this influenced any rise in alanine transaminase (ALT) levels while on leflunomide or methotrexate. Methods:,RA patients commenced on methotrexate or leflunomide within the preceding two years were identified using the departmental database. A total of 200 patients on methotrexate or leflunomide were sent questionnaires covering demographics, disease details, duration of disease-modifying anti-rheumatic drug (DMARD) use, previous medical and drug history, alcohol advice recalled, and alcohol consumption while on the drug. ALT levels at drug commencement and the highest level on the drug were recorded. Results:,Replies were received from 69.5% of methotrexate and 57.5% of leflunomide patients. 68.6% of patients recalled receiving alcohol advice. 55.8% of leflunomide patients did not drink alcohol prior to taking the DMARD, compared with 39.4% of methotrexate patients. 27.7% of leflunomide patients continued to drink alcohol compared with 64.3% on methotrexate. For both drugs, no patterns emerged to suggest that baseline or highest ALT levels were influenced by higher levels of alcohol consumption. Discussion:,No differences were found with either methotrexate or leflunomide for self-reported alcohol consumption influencing ALT levels. It is appropriate to give similar alcohol advice to patients beginning therapy with either methotrexate or leflunomide. This research has not found any evidence to contradict the relaxation of advice on alcohol consumption with methotrexate and leflunomide in the updated BSR guidelines. Copyright © 2008 John Wiley & Sons, Ltd. 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