In this experiment, the effects of beta-cypermethrin on acute toxicity and serum GPT and GOT of crucian were studied. It was indicated that the 96hLC50 of beta-cypermethrin was 11.4 μg L-1. The crucian serum was trea...In this experiment, the effects of beta-cypermethrin on acute toxicity and serum GPT and GOT of crucian were studied. It was indicated that the 96hLC50 of beta-cypermethrin was 11.4 μg L-1. The crucian serum was treated at the levels, 0 μg L-1, 0.114 μg L-1, 0.57 μg L-1, 1.14 μg L-1 for 0 d 5 d 10 d 15 d and 20 d, respectively. The results showed that beta-cypermethrin could make great damage to crucian biochemical characteristics, and suggested that the effects of toxicant on serum GPT and GOT could be used as an index of toxicological assessment.展开更多
AIM: To evaluate the factors associated with liver function alterations after laparoscopy-assisted gastrectomy (LAG) for gastric cancer. METHODS: We collected the data of gastrectomy patients with gastric cancer and d...AIM: To evaluate the factors associated with liver function alterations after laparoscopy-assisted gastrectomy (LAG) for gastric cancer. METHODS: We collected the data of gastrectomy patients with gastric cancer and divided them into 2 groups: open gastrectomy (OG) and LAG. We also collected the data of patients with colon cancer to evaluate the effect of liver manipulations during surgery on liver function alterations. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and alkaline phosphatase were measured on the preoperative day and postoperative day 1 (POD1), POD3, POD5, and POD7. RESULTS: No changes in liver function were observed after the operation in patients with colon cancer (n = 121). However, in gastric cancer patients (n = 215), AST and ALT levels increased until POD5 compared to those in colon cancer patients and these findings were observed both in the LAG and OG without a significant difference except at POD1. The mean hepatic enzyme levels at POD1 in the LAG group were significantly higher than those in the OG group (P = 0.047 for AST and P = 0.039 for ALT). The factors associated with elevated ALT on POD1 in patients with gastric cancer were body mass index (P < 0.001), operation time (P < 0.001), intraoperative hepatic injury (P = 0.048), and ligation of an aberrant left hepatic artery (P = 0.052) but not type of operation (OG vs LAG, P = 0.094). CONCLUSION: We conclude that the liver function alteration after LAG may have been caused by direct liver manipulation or aberrant hepatic artery ligation rather than the CO2 pneumoperitoneum.展开更多
AIM: To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle-aged males with elevated alanine aminotransferase (e-ALT).METHODS: A retrospective, observational followup study ...AIM: To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle-aged males with elevated alanine aminotransferase (e-ALT).METHODS: A retrospective, observational followup study on MetS development at a 5-year interval was conducted using health examination data. Nine hundred and ninety six male employees not fulfi lling MetS criteria at screening were enrolled. Age, MetScomponents, liver enzymes, serological markers for viral hepatitis, abdominal ultrasound, insulin resistance status, lifestyles, and workplace factors were analyzed.RESULTS: The prevalence of elevated serum ALT (> 40 U/L, e-ALT) at baseline was 19.1%. There were 381 (38.3%) workers with long-term exposures to day-night rotating shift work (RSW). 14.2% of subjects developed MetS during follow-up. After 5 years, the workers with e-ALT had significantly unfavorable changes in MetS-components, and higher rates of MetS development, vs subjects with normal baseline ALT levels. Workers with both baseline e-ALT and 5-year persistent RSW (pRSW) exposure had the highest rate of MetS development. Also, e-ALT-plus-pRSW workers had a significant increase in MetS-components atfollow-up, compared with the other subgroups. After controlling for potential confounders, e-ALT-plus-pRSW workers posed a signifi cant risk for MetS development (odds ratio, 2.7; 95% confi dence interval, 1.4-5.3, vs workers without baseline e-ALT nor pRSW). CONCLUSION: We suggest that all early middle-aged male employees with e-ALT should be evaluated and managed for MetS. Particularly in terms of job arrangements, impacts of long-term RSW on MetS development should be assessed for all male employees having baseline e-ALT.展开更多
AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/...AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.展开更多
AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with no- tably elevated alanine aminotransferase (ALT). METHODS: All the inpatients with ALT levels above 10...AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with no- tably elevated alanine aminotransferase (ALT). METHODS: All the inpatients with ALT levels above 10 times upper limit of normal range (ULN) were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS: A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury (n = 46, 35.7%), DILl (n = 25, 19.4%) and malignancy (n = 21, 16.3%) were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury (14.5 5.6 ULN vs 32.5 :I: 30.7 ULN, P = 0.001). Among DILI patients, one (4%) case was classified as definite, 19 (76%) cases were clas- sified as probable and 5 (20%) as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 (92%) cases and mixed in 2 (8%). The extent of severity of liver injury was mild in 21 (84%) patients and moderate in 4 (16%). Before discharge, 10 (40%) patients were recovered and the other 15 (60%) were improved. The improved patients tended to have a higher peak ALT (808 + 348 U/L vs 623 + 118 U/L, P = 0.016) and shorter treatment duration before discharge (8 + 6 d vs 28 ~ 12 d, P = 0.008) compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 (32%) cases, followed by glucocorticoids in 6 (24%) cases. Twenty-four (96%) cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs (e.g., glycyr- rhizinate), antioxidants (e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin), polyene phospha- tidyl choline and herbal extracts (e.g., protoporphyrin disodium and silymarin). Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio (OR) 32.7, 95%CI (2.8-374.1),CONCLUSION: DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.展开更多
AIM: To determine serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy bl...AIM: To determine serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy blood donors. METHODS: This cross-sectional study was performed in 934 male blood donors, aged 18 to 68 years, who consecutively attended Tehran blood transfusion service in 2006. All participants were seronegative for HBV or HCV infections, non alcohol users, and all underwent a standard interview and anthropometric tests. Clinical and biochemical parameters including AST, ALT, and GGT activities were determined. Patients taking drugs known to cause hepatic fat deposition were excluded. For AST, ALT, and GGT variables, we used 33.33 and 66.66 percentiles, so that each of them was divided into three tertiles. RESULTS: Mean AST, ALT, and GGT activities were 25.26 ± 12.58 U/L (normal range 5-35 U/L), 33.13 ± 22.98 (normal range 5-35 U/L), and 25.11 ± 18.32 (normal range 6-37 U/L), respectively. By univariate analyses, there were significant associations between increasing AST, ALT, or GGT tertiles and age, body weight, body mass index, and waist and hip circumferences (P < 0.05). By multiple linear regression analyses, ALT was found to be positively correlated with dyslipidemia (B = 6.988, P = 0.038), whereas ALT and AST were negatively correlated with age. AST, ALT, and GGT levels had positive correlation with family history of liver disease (B = 15.763, P < 0.001), (B = 32.345, P < 0.001), (B =24.415, P < 0.001), respectively.CONCLUSION: Although we did not determine the cutoffs of the upper normal limits for AST, ALT, and GGT levels, we would suggest screening asymptomatic patients with dyslipidemia and also subjects with a family history of liver disease.展开更多
Toxic hepatitis or drug-induced liver injury encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure.The advantages of a long half-life,wide spectrum,high tissue p...Toxic hepatitis or drug-induced liver injury encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure.The advantages of a long half-life,wide spectrum,high tissue penetration rate,and a good safety profile,make ceftriaxone,a third-generation cephalosporin,a frequent choice in the treatment of childhood infections.Previous studies have reported a few cases of high aspartate aminotransferase and alanine aminotransferase levels,along with three cases of hepatitis caused by ceftriaxone.Here,we report a case of drug-induced toxic hepatitis in a patient who was treated with ceftriaxone for acute tonsillitis.展开更多
AIM: To verify the usefulness of FibroQ for predicting fi brosis in patients with chronic hepatitis C, compared with other noninvasive tests. METHODS: This retrospective cohort study included 237 consecutive patients ...AIM: To verify the usefulness of FibroQ for predicting fi brosis in patients with chronic hepatitis C, compared with other noninvasive tests. METHODS: This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ, aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to platelet ratioindex, cirrhosis discriminant score, age-platelet index (API), Pohl score, FIB-4 index, and Lok's model were calculated and compared. RESULTS: FibroQ, FIB-4, AAR, API and Lok's model results increased significantly as fibrosis advanced (analysis of variance test: P < 0.001). FibroQ trended to be superior in predicting signifi cant fi brosis score in chronic hepatitis C compared with other noninvasive tests. CONCLUSION: FibroQ is a simple and useful test for predicting signifi cant fi brosis in patients with chronic hepatitis C.展开更多
AIM: To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS: The Long-Evans cinnamon (LEC) rat mod- el of Wilson's disease (WD) was used to study...AIM: To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS: The Long-Evans cinnamon (LEC) rat mod- el of Wilson's disease (WD) was used to study the im- pact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults (month 5) for three months. Animals that received reduced di- etary copper (rCu) throughout their lifetime served as a control. Hepatitis-associated serum markers (alanine aminotransferase, aspartate transaminase, bilirubin) were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa), fat metabolism (Srebf1), ex- tracellular matrix (Timp1), oxidative stress (Hmox1), and the cell cycle (Cdknla) were analyzed by real-time polymerase chain reaction. RESULTS: Regardless of the time point when hCu was started, LEC rats (35/36) developed fulminant hepati- tis and died. Animals receiving rCu (36/36) remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals (477 ± 75 μg/g). With regard to start of hCu, onset of fulminant hepatitis was significantly (P 〈 0.001) earlier in adults (35±9 d) that showed pre-accumulation of liver copper as com- pared to the pup group (77±15 d). Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION: Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical threshold of liver copper which is important to trigger the course of WD.展开更多
Objective To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. Methods A total of 430 female in-patients with breast cancer of stages 0 ...Objective To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. Methods A total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011. Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis. Results Liver metastasis was more likely to occur in patients with stage Ill cancer or c-erbB-2-positive expression. Alanine aminotransferase, aspartate aminotransferase, ~/-glutamyltransferase (GGT), alkaline phosphatase, lactate dehvdrogenase (LDH), and carbohydrate antigen 1153 (CA153) levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH, GGT, and CA153 were 174 U/L, 32 U/L, and 26.48 Dg/L, respectively. The areas under the curves of LDH, GGT, and CEA were 0.795, 0.784, and 0.661, respectively, and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6% and 85.7 %, respectively. The specificity of serial tests for both pairs of enzymes was 97.7%. Conclusions Tile sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis.展开更多
AIM:To investigate the association of obesity and elevated alanine aminotransferase with insulin resistance and compare these factors with metabolic syndrome. METHODS:We enrolled a total of 1308 male workers aged from...AIM:To investigate the association of obesity and elevated alanine aminotransferase with insulin resistance and compare these factors with metabolic syndrome. METHODS:We enrolled a total of 1308 male workers aged from 22 to 63 years.Data was extracted from the workers'periodic health check-ups in hospitals.All cases were from the community of northern Taiwan. This was a cross-sectional observational study from July to September in 2004.We grouped all cases into four groups,based on the quartile of homeostasis model assessment.The top fourth quartile group was defined as the group with insulin resistance.We performed multivariate logistic regression analysis for the odds ratio of the risk factors for insulin resistance. RESULTS:Compared with metabolic syndrome,the coexistence of both factors had a 4.3-fold(95%CI: 2.7-6.8)increased risk,which was more than metabolic syndrome with a 3.6-fold(95%CI:2.6-5.0)increased risk.The two factors had a synergistic effect.The synergistic index of obesity and elevated alanine aminotransferase(ALT)was 2.1(95%CI:1.01-4.3).CONCLUSION:Obesity and elevated ALT are associatedwith insulin resistance.The effects are synergistic. Coexistence of them is better than metabolic syndrome in predicting insulin resistance.展开更多
AIM: To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus (HDV) and to identify the factors that would be predictive of the sustained viral response (SVR). METHODS: This prospectiv...AIM: To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus (HDV) and to identify the factors that would be predictive of the sustained viral response (SVR). METHODS: This prospective study was conducted in Medical Unit IV of the Liaquat University of Medi- cal and Health Sciences Hospital Jamshoro from June 2008 to September 2011. This study cohort included all patients of either sex who presented during this time with hepatitis B surface antigen positivity, hepa- titis B virus DNA 〉 20 000 IU/ml, serum glutamic py- ruvic transaminase (SGPT) 〉 2(upper limit of normal), HDV-RNA positivity with fibrosis stage ≥ 2. Informed consent was obtained from each of these individuals. Patients were diagnosed with hepatitis D on the ba- sis of detectable viral antibodies and the presence of HDV-RNA in their serum. A liver biopsy was performed in all cases and fibrosis staging was performed in ac- cordance with the METAVIR scoring system. All eligible patients were administered peg-interferon at a weekly dosage of 1.5 μg/kg body weight for 48 wk. HDV-RNA was assayed at the end of this treatment period and again at 24 wk later. A biochemical response was de- termined by a normalization of SGPT at the end of the treatment or during follow up. The end of treatment response was defined by a HDV-RNA negative status. A sustained virological response was defined by unde- tectable serum HDV-RNA at six months after the end of treatment. RESULTS: Among the 277 patients enrolled in our present study, 238 completed a course of peg-interfer- on therapy of which 180 (75.6%) were male and 58 (24.4%) female. Biochemical responses were achieved in 122/238 (51.3%) patients. End of treatment re- sponses were achieved in 71/238 (29.8%) cases. A SVR was achieved in 70 of these patients (29.4%). A strong association was found between the SVR and the end of treatment responses (P = 0.001), biochemical responses (P = 0.001) and the degree of fibrosis (P = 0.002). CONCLUSION: Peg-interferon therapy can induce re- mission in nearly one third of patients harboring HDV.展开更多
The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver functi...The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver function(T.protein,albumin,alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase),energetic parameters(adenosine triphosphate,adenosine diphosphate,adenosine monophosphate,inorganic phosphate,total adenylate,adenylate energy charge and potential phosphate).The effect on glycolytic and glycogenolytic enzymes(glucose,glycogen,glycogen phosphorylase,pyruvate kinase and phosphofructokinase against hypoxia) was also studied.The drugs were administered 24 and 1 h prior sodium nitrite intoxication.All biochemical parameters were estimated 1 h after sodium nitrite injection.Injection of sodium nitrite(75 mg/kg,sc) produced a significant disturbance in all biochemical parameters of liver function,energetic parameters and glycolytic and glycogenolytic enzymes.Hepatic damage was confirmed by histopathological examination of the liver as compared to controls.The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination,suggesting potential protection against sodium nitrite-induced hypoxia.It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.展开更多
AIM:To formulate a noninvasive index predictive of se-verity of liver f ibrosis and activity in chronic hepatitis C.METHODS:This cross sectional study was conducted on polymerase chain reaction positive,treatment nave...AIM:To formulate a noninvasive index predictive of se-verity of liver f ibrosis and activity in chronic hepatitis C.METHODS:This cross sectional study was conducted on polymerase chain reaction positive,treatment nave patients.Fibrosis was staged on a f ive point scale from F0-F4 and activity was graded on a four point scale from A0-A3,according to the METAVIR system.Patients were divided into two overall severity groups,minimal disease(< F2 and < A2)and signif icant disease(≥ F2 or ≥ A2).Eleven markers were measured in blood.Sta-tistically,the primary outcome variable was identif ica-tion of minimal and signif icant overall disease.Indices were formulated using β regression values of different combinations of nine statistically significant factors.Diagnostic performance of these indices was assessed through receiver-operating characteristic curve analysis.RESULTS:A total of 98 patients were included and of these 46 had an overall clinically significant disease.Our f inal six marker index,Liverscore for Hepatitis C,consisted of age,alanine transaminase,gamma-gluta-myl transpeptidase,apolipoprotein A-1,alpha-2 macro-globulin and hyaluronic acid.The area under the curve was found to be 0.813.On a 0-1 scale,negative predic-tive value at a cutoff level of ≤ 0.40 was 83%,while positive predictive value at ≥ 0.80 remained 89%.Al-together,61% of the patients had these discriminative scores.CONCLUSION:This index is discriminative of minimal and significant overall liver disease in a majority of chronic hepatitis C patients and can help in clinical de-cision making.展开更多
文摘In this experiment, the effects of beta-cypermethrin on acute toxicity and serum GPT and GOT of crucian were studied. It was indicated that the 96hLC50 of beta-cypermethrin was 11.4 μg L-1. The crucian serum was treated at the levels, 0 μg L-1, 0.114 μg L-1, 0.57 μg L-1, 1.14 μg L-1 for 0 d 5 d 10 d 15 d and 20 d, respectively. The results showed that beta-cypermethrin could make great damage to crucian biochemical characteristics, and suggested that the effects of toxicant on serum GPT and GOT could be used as an index of toxicological assessment.
文摘AIM: To evaluate the factors associated with liver function alterations after laparoscopy-assisted gastrectomy (LAG) for gastric cancer. METHODS: We collected the data of gastrectomy patients with gastric cancer and divided them into 2 groups: open gastrectomy (OG) and LAG. We also collected the data of patients with colon cancer to evaluate the effect of liver manipulations during surgery on liver function alterations. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and alkaline phosphatase were measured on the preoperative day and postoperative day 1 (POD1), POD3, POD5, and POD7. RESULTS: No changes in liver function were observed after the operation in patients with colon cancer (n = 121). However, in gastric cancer patients (n = 215), AST and ALT levels increased until POD5 compared to those in colon cancer patients and these findings were observed both in the LAG and OG without a significant difference except at POD1. The mean hepatic enzyme levels at POD1 in the LAG group were significantly higher than those in the OG group (P = 0.047 for AST and P = 0.039 for ALT). The factors associated with elevated ALT on POD1 in patients with gastric cancer were body mass index (P < 0.001), operation time (P < 0.001), intraoperative hepatic injury (P = 0.048), and ligation of an aberrant left hepatic artery (P = 0.052) but not type of operation (OG vs LAG, P = 0.094). CONCLUSION: We conclude that the liver function alteration after LAG may have been caused by direct liver manipulation or aberrant hepatic artery ligation rather than the CO2 pneumoperitoneum.
文摘AIM: To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle-aged males with elevated alanine aminotransferase (e-ALT).METHODS: A retrospective, observational followup study on MetS development at a 5-year interval was conducted using health examination data. Nine hundred and ninety six male employees not fulfi lling MetS criteria at screening were enrolled. Age, MetScomponents, liver enzymes, serological markers for viral hepatitis, abdominal ultrasound, insulin resistance status, lifestyles, and workplace factors were analyzed.RESULTS: The prevalence of elevated serum ALT (> 40 U/L, e-ALT) at baseline was 19.1%. There were 381 (38.3%) workers with long-term exposures to day-night rotating shift work (RSW). 14.2% of subjects developed MetS during follow-up. After 5 years, the workers with e-ALT had significantly unfavorable changes in MetS-components, and higher rates of MetS development, vs subjects with normal baseline ALT levels. Workers with both baseline e-ALT and 5-year persistent RSW (pRSW) exposure had the highest rate of MetS development. Also, e-ALT-plus-pRSW workers had a significant increase in MetS-components atfollow-up, compared with the other subgroups. After controlling for potential confounders, e-ALT-plus-pRSW workers posed a signifi cant risk for MetS development (odds ratio, 2.7; 95% confi dence interval, 1.4-5.3, vs workers without baseline e-ALT nor pRSW). CONCLUSION: We suggest that all early middle-aged male employees with e-ALT should be evaluated and managed for MetS. Particularly in terms of job arrangements, impacts of long-term RSW on MetS development should be assessed for all male employees having baseline e-ALT.
基金Supported by PHS grant DK075635 to Szabo G and McNeil Consumer Healthcare, a division of McNeil-PCC Inc. to Ward J
文摘AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.
基金Supported by Zhejiang Provincial Bureau of Education,No.200908690Zhejiang Provincial Bureau of Health,No.2012KYA090
文摘AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with no- tably elevated alanine aminotransferase (ALT). METHODS: All the inpatients with ALT levels above 10 times upper limit of normal range (ULN) were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS: A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury (n = 46, 35.7%), DILl (n = 25, 19.4%) and malignancy (n = 21, 16.3%) were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury (14.5 5.6 ULN vs 32.5 :I: 30.7 ULN, P = 0.001). Among DILI patients, one (4%) case was classified as definite, 19 (76%) cases were clas- sified as probable and 5 (20%) as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 (92%) cases and mixed in 2 (8%). The extent of severity of liver injury was mild in 21 (84%) patients and moderate in 4 (16%). Before discharge, 10 (40%) patients were recovered and the other 15 (60%) were improved. The improved patients tended to have a higher peak ALT (808 + 348 U/L vs 623 + 118 U/L, P = 0.016) and shorter treatment duration before discharge (8 + 6 d vs 28 ~ 12 d, P = 0.008) compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 (32%) cases, followed by glucocorticoids in 6 (24%) cases. Twenty-four (96%) cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs (e.g., glycyr- rhizinate), antioxidants (e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin), polyene phospha- tidyl choline and herbal extracts (e.g., protoporphyrin disodium and silymarin). Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio (OR) 32.7, 95%CI (2.8-374.1),CONCLUSION: DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.
文摘AIM: To determine serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy blood donors. METHODS: This cross-sectional study was performed in 934 male blood donors, aged 18 to 68 years, who consecutively attended Tehran blood transfusion service in 2006. All participants were seronegative for HBV or HCV infections, non alcohol users, and all underwent a standard interview and anthropometric tests. Clinical and biochemical parameters including AST, ALT, and GGT activities were determined. Patients taking drugs known to cause hepatic fat deposition were excluded. For AST, ALT, and GGT variables, we used 33.33 and 66.66 percentiles, so that each of them was divided into three tertiles. RESULTS: Mean AST, ALT, and GGT activities were 25.26 ± 12.58 U/L (normal range 5-35 U/L), 33.13 ± 22.98 (normal range 5-35 U/L), and 25.11 ± 18.32 (normal range 6-37 U/L), respectively. By univariate analyses, there were significant associations between increasing AST, ALT, or GGT tertiles and age, body weight, body mass index, and waist and hip circumferences (P < 0.05). By multiple linear regression analyses, ALT was found to be positively correlated with dyslipidemia (B = 6.988, P = 0.038), whereas ALT and AST were negatively correlated with age. AST, ALT, and GGT levels had positive correlation with family history of liver disease (B = 15.763, P < 0.001), (B = 32.345, P < 0.001), (B =24.415, P < 0.001), respectively.CONCLUSION: Although we did not determine the cutoffs of the upper normal limits for AST, ALT, and GGT levels, we would suggest screening asymptomatic patients with dyslipidemia and also subjects with a family history of liver disease.
文摘Toxic hepatitis or drug-induced liver injury encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure.The advantages of a long half-life,wide spectrum,high tissue penetration rate,and a good safety profile,make ceftriaxone,a third-generation cephalosporin,a frequent choice in the treatment of childhood infections.Previous studies have reported a few cases of high aspartate aminotransferase and alanine aminotransferase levels,along with three cases of hepatitis caused by ceftriaxone.Here,we report a case of drug-induced toxic hepatitis in a patient who was treated with ceftriaxone for acute tonsillitis.
基金Supported by Clinical Study Project XMRP, No. CMRPG 690081, from Chiayi Chang Gung Memorial Hospital
文摘AIM: To verify the usefulness of FibroQ for predicting fi brosis in patients with chronic hepatitis C, compared with other noninvasive tests. METHODS: This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ, aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to platelet ratioindex, cirrhosis discriminant score, age-platelet index (API), Pohl score, FIB-4 index, and Lok's model were calculated and compared. RESULTS: FibroQ, FIB-4, AAR, API and Lok's model results increased significantly as fibrosis advanced (analysis of variance test: P < 0.001). FibroQ trended to be superior in predicting signifi cant fi brosis score in chronic hepatitis C compared with other noninvasive tests. CONCLUSION: FibroQ is a simple and useful test for predicting signifi cant fi brosis in patients with chronic hepatitis C.
基金Supported by Deutsche Forschungsgemeinschaft, SCHM 964/10-1Innovative Medizinische Forschung, Münster
文摘AIM: To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS: The Long-Evans cinnamon (LEC) rat mod- el of Wilson's disease (WD) was used to study the im- pact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults (month 5) for three months. Animals that received reduced di- etary copper (rCu) throughout their lifetime served as a control. Hepatitis-associated serum markers (alanine aminotransferase, aspartate transaminase, bilirubin) were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa), fat metabolism (Srebf1), ex- tracellular matrix (Timp1), oxidative stress (Hmox1), and the cell cycle (Cdknla) were analyzed by real-time polymerase chain reaction. RESULTS: Regardless of the time point when hCu was started, LEC rats (35/36) developed fulminant hepati- tis and died. Animals receiving rCu (36/36) remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals (477 ± 75 μg/g). With regard to start of hCu, onset of fulminant hepatitis was significantly (P 〈 0.001) earlier in adults (35±9 d) that showed pre-accumulation of liver copper as com- pared to the pup group (77±15 d). Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION: Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical threshold of liver copper which is important to trigger the course of WD.
文摘Objective To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. Methods A total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011. Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis. Results Liver metastasis was more likely to occur in patients with stage Ill cancer or c-erbB-2-positive expression. Alanine aminotransferase, aspartate aminotransferase, ~/-glutamyltransferase (GGT), alkaline phosphatase, lactate dehvdrogenase (LDH), and carbohydrate antigen 1153 (CA153) levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH, GGT, and CA153 were 174 U/L, 32 U/L, and 26.48 Dg/L, respectively. The areas under the curves of LDH, GGT, and CEA were 0.795, 0.784, and 0.661, respectively, and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6% and 85.7 %, respectively. The specificity of serial tests for both pairs of enzymes was 97.7%. Conclusions Tile sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis.
文摘AIM:To investigate the association of obesity and elevated alanine aminotransferase with insulin resistance and compare these factors with metabolic syndrome. METHODS:We enrolled a total of 1308 male workers aged from 22 to 63 years.Data was extracted from the workers'periodic health check-ups in hospitals.All cases were from the community of northern Taiwan. This was a cross-sectional observational study from July to September in 2004.We grouped all cases into four groups,based on the quartile of homeostasis model assessment.The top fourth quartile group was defined as the group with insulin resistance.We performed multivariate logistic regression analysis for the odds ratio of the risk factors for insulin resistance. RESULTS:Compared with metabolic syndrome,the coexistence of both factors had a 4.3-fold(95%CI: 2.7-6.8)increased risk,which was more than metabolic syndrome with a 3.6-fold(95%CI:2.6-5.0)increased risk.The two factors had a synergistic effect.The synergistic index of obesity and elevated alanine aminotransferase(ALT)was 2.1(95%CI:1.01-4.3).CONCLUSION:Obesity and elevated ALT are associatedwith insulin resistance.The effects are synergistic. Coexistence of them is better than metabolic syndrome in predicting insulin resistance.
基金Supported by Hepatitis Prevention and Control Program Sindh,Pakistan Chief Minister's initiative,a government organization provided peg-interferon treatment to patients for 48 wk free of cost
文摘AIM: To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus (HDV) and to identify the factors that would be predictive of the sustained viral response (SVR). METHODS: This prospective study was conducted in Medical Unit IV of the Liaquat University of Medi- cal and Health Sciences Hospital Jamshoro from June 2008 to September 2011. This study cohort included all patients of either sex who presented during this time with hepatitis B surface antigen positivity, hepa- titis B virus DNA 〉 20 000 IU/ml, serum glutamic py- ruvic transaminase (SGPT) 〉 2(upper limit of normal), HDV-RNA positivity with fibrosis stage ≥ 2. Informed consent was obtained from each of these individuals. Patients were diagnosed with hepatitis D on the ba- sis of detectable viral antibodies and the presence of HDV-RNA in their serum. A liver biopsy was performed in all cases and fibrosis staging was performed in ac- cordance with the METAVIR scoring system. All eligible patients were administered peg-interferon at a weekly dosage of 1.5 μg/kg body weight for 48 wk. HDV-RNA was assayed at the end of this treatment period and again at 24 wk later. A biochemical response was de- termined by a normalization of SGPT at the end of the treatment or during follow up. The end of treatment response was defined by a HDV-RNA negative status. A sustained virological response was defined by unde- tectable serum HDV-RNA at six months after the end of treatment. RESULTS: Among the 277 patients enrolled in our present study, 238 completed a course of peg-interfer- on therapy of which 180 (75.6%) were male and 58 (24.4%) female. Biochemical responses were achieved in 122/238 (51.3%) patients. End of treatment re- sponses were achieved in 71/238 (29.8%) cases. A SVR was achieved in 70 of these patients (29.4%). A strong association was found between the SVR and the end of treatment responses (P = 0.001), biochemical responses (P = 0.001) and the degree of fibrosis (P = 0.002). CONCLUSION: Peg-interferon therapy can induce re- mission in nearly one third of patients harboring HDV.
文摘The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver function(T.protein,albumin,alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase),energetic parameters(adenosine triphosphate,adenosine diphosphate,adenosine monophosphate,inorganic phosphate,total adenylate,adenylate energy charge and potential phosphate).The effect on glycolytic and glycogenolytic enzymes(glucose,glycogen,glycogen phosphorylase,pyruvate kinase and phosphofructokinase against hypoxia) was also studied.The drugs were administered 24 and 1 h prior sodium nitrite intoxication.All biochemical parameters were estimated 1 h after sodium nitrite injection.Injection of sodium nitrite(75 mg/kg,sc) produced a significant disturbance in all biochemical parameters of liver function,energetic parameters and glycolytic and glycogenolytic enzymes.Hepatic damage was confirmed by histopathological examination of the liver as compared to controls.The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination,suggesting potential protection against sodium nitrite-induced hypoxia.It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.
基金Supported by Ziauddin University,Karachi and Pakistan Medical Research Council,Islamabad
文摘AIM:To formulate a noninvasive index predictive of se-verity of liver f ibrosis and activity in chronic hepatitis C.METHODS:This cross sectional study was conducted on polymerase chain reaction positive,treatment nave patients.Fibrosis was staged on a f ive point scale from F0-F4 and activity was graded on a four point scale from A0-A3,according to the METAVIR system.Patients were divided into two overall severity groups,minimal disease(< F2 and < A2)and signif icant disease(≥ F2 or ≥ A2).Eleven markers were measured in blood.Sta-tistically,the primary outcome variable was identif ica-tion of minimal and signif icant overall disease.Indices were formulated using β regression values of different combinations of nine statistically significant factors.Diagnostic performance of these indices was assessed through receiver-operating characteristic curve analysis.RESULTS:A total of 98 patients were included and of these 46 had an overall clinically significant disease.Our f inal six marker index,Liverscore for Hepatitis C,consisted of age,alanine transaminase,gamma-gluta-myl transpeptidase,apolipoprotein A-1,alpha-2 macro-globulin and hyaluronic acid.The area under the curve was found to be 0.813.On a 0-1 scale,negative predic-tive value at a cutoff level of ≤ 0.40 was 83%,while positive predictive value at ≥ 0.80 remained 89%.Al-together,61% of the patients had these discriminative scores.CONCLUSION:This index is discriminative of minimal and significant overall liver disease in a majority of chronic hepatitis C patients and can help in clinical de-cision making.