Supplementation of alanine improves biomass accumulation and lipid production of Chlorella pyrenoidosa by increasing the respiratory and metabolic processes

The function of exogenous alanine(Ala)in regulating biomass accumulation,lipid production,photosynthesis,and respiration in Chlorella pyrenoidosa was studied.Result shows that the supplementation of Ala increased C.pyrenoidosa biomass and lipid production in an 8-d batch culture.The concentration of 10 mmol/L of Ala was optimum and increased the microalgal cell biomass and lipid content by 39.3%and 21.4%,respectively,compared with that in the control(0-mmol/L Ala).Ala supplementation reduced photosynthetic activity while boosting respiratory activity and pyruvate levels,indicating that C.pyrenoidosa used exogenous Ala for biomass accumulation through the respiratory metabolic process.The accelerated respiratory metabolism due to Ala supplementation elevated the substrate pool and improved the lipogenic gene expression,promoting lipid production at last.This study provided a novel method for increasing biomass accumulation and lipid production and elucidated the role of Ala in regulating lipid production.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients

BACKGROUND The clinical and histological features of chronic hepatitis B(CHB)patients who fall into the"grey zone(GZ)"and do not fit into conventional natural phases are unclear.AIM To explore the impact of varying the threshold of alanine aminotransferase(ALT)levels in identifying significant liver injury among GZ patients.METHODS This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy.The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines.GZ CHB patients were classified into four groups:GZ-A(HBeAg positive,normal ALT levels,and HBV DNA≤10^(7) IU/mL),GZ-B(HBeAg positive,elevated ALT levels,and HBV DNA<10^(4) or>10^(7) IU/mL),GZC(HBeAg negative,normal ALT levels,and HBV DNA≥2000 IU/mL),and GZ-D(HBeAg negative,elevated ALT levels,and HBV DNA≤2000 IU/mL).Significant hepatic injury(SHI)was defined as the presence of notable liver inflammation(≥G2)and/or significant fibrosis(≥S2).RESULTS The results showed that 50.22%of patients were classified as GZ,and 63.7%of GZ patients developed SHI.The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria(35 U/L for men and 25 U/L for women)can more accurately identify patients with significant liver damage in the GZ phases.In total,the proportion of patients with ALT≤40 U/L who required antiviral therapy was 64.86%[(221+294)/794].When we lowered the ALT treatment threshold to the new criteria(30 U/L for men and 19 U/L for women),the same outcome was revealed,and the proportion of patients with ALT≤40 U/L who required antiviral therapy was 75.44%[(401+198)/794].Additionally,the proportion of SHI was 49.1%in patients under 30 years old and increased to 55.3%in patients over 30 years old(P=0.136).CONCLUSION These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.

Lower alanine aminotransferase levels are associated with increased all-cause and cardiovascular mortality in nonalcoholic fatty liver patients

BACKGROUND Serum alanine aminotransferase(ALT) levels are often considered a marker to evaluate liver disease and its severity.AIM To investigate the association between ALT levels and all-cause and cause-specific mortality in patients with nonalcoholic fatty liver disease(NAFLD).METHODS The Third National Health and Nutrition Examination Survey(NHANES-Ⅲ) from 1988 to 1994 and NHANES-Ⅲ-related mortality data from 2019 onward were used to obtain the necessary data for the study. NAFLD was defined as hepatic steatosis, as diagnosed by ultrasound, with no other liver diseases. ALT levels were categorized into four groups according to the different recommended upper limits of normal(ULN) in men and women: < 0.5 ULN, 0.5-1 ULN, 1-2 ULN, and ≥ 2 ULN. The hazard ratios for all-cause mortality and cause-specific mortality were analyzed using the Cox proportional hazard model.RESULTS Multivariate logistic regression analysis demonstrated that the odds ratio of NAFLD correlated positively with increased serum ALT levels. In patients with NAFLD, all-cause mortality and cardiovascular mortality were the highest when ALT was < 0.5 ULN, yet cancer-related mortality was the highest when ALT was ≥ 2 ULN. The same results could be found in both men and women. Univariate analysis showed that severe NAFLD with normal ALT levels had the highest allcause and cause-specific mortality, but the difference was not statistically significant after adjustment for age and multivariate factors.CONCLUSION The risk of NAFLD was positively correlated with ALT level, but all-cause and cardiovascular mortality were the highest when ALT was < 0.5 ULN. Regardless of the severity of NAFLD, normal or lower ALT levels were associated with higher mortality than elevated ALT levels. Clinicians should be aware that high ALT levels indicate liver injury, but low ALT levels are associated with a higher risk of death.

Diagnostic value of FIB-4, aspartate aminotransferaseto-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index(APRI), and liver stiffness measurement(LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase(PNALT).METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase(PIALT1) group [alanine transaminase(ALT) within 1-2 × upper limit of normal value(ULN)], and 64 in PIALT2 group(ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81%(16/95), 32.56%(28/86), and 45.31%(28/64), and moderate liverfibrosis of 24.2%(23/95), 33.72%(29/86), and 43.75%(28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group(P < 0.05). No significant difference was found in the areas under the curve(AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group(P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference(P > 0.05) was found in AUCs for all comparisons(P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI(P < 0.05).CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

Interactions and Biological Activity of Rare Earth Perchlorate Complexes with Alanine and Imidazole

The interactions of nine rare earth perchlorate complexes with alanine and imidazole were studied in methanol. The general formulae of these compounds are RE(Ala) 2Im(ClO 4) 3· n H 2O(RE=Ce, Pr, Nd, Sm, Eu, Gd, Tb, Yb) and La(Ala) 3Im(ClO 4) 3·H 2O, respectively. The composition and structure of the prepared compounds were determined by the chemical analysis, elemental analysis, IR spectroscopy, UV, FS spectroscopy, X ray powder diffraction, 1H NMR and solubility. The thermal decomposition processes of these complexes were studied on the basis of TG DTG. The preliminary bioassay shows that the compounds have a remarkable bacteriostasis effect on nine varieties of microbe.

Alanine racemase is essential for the growth and interspecies competitiveness of Streptococcus mutans

D-alanine （D-Ala） is an essential amino acid that has a key role in bacterial unique enzyme that interconverts L-alanine and D-alanine in most bacteria, antimicrobial drug development. Streptococcus mutans is a major causative cell wall synthesis. Alanine racemase （Air） is a making this enzyme a potential target for factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Air in S. mutans. We constructed air mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that air deletion was lethal to S. mutans. A minimal supplement of D-Ala （150 pg.mL- 1） was required for the optimal growth of the air mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the air mutant strain. We also determined the compromised competitiveness of the air mutant strain relative to the wild-type S. mutans against other oral streptococci （S. sanguinis or S. gordonil~, demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of air to the growth and competitiveness of S. mutans, Air may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.

Elevated alanine aminotransferase activity is not associated with dyslipidemias,but related to insulin resistance and higher disease grades in non-diabetic non-alcoholic fatty liver disease

Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into analysis.Exclusion criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid therapy.ALT levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for women.Results:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations.Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT levels.Conclusions:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before.By excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations.Further studies are needed to confirm our results.

Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B

AIM To explore the effect of alanine aminotransferase(ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B(CHB) patients. METHODS A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT(ALT ≤ 40), slightly elevated ALT(40 < ALT ≤ 80) and elevated ALT(ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis(stages S2-4), including the aspartate aminotransferase(AST)-to-platelet(PLT) ratio index(APRI), fibrosis index based on 4 factors(FIB-4), King's score, Forns index and gamma-glutamyl transpeptidase(GGT)-to-PLT ratio(GPR), were evaluated for each group. RESULTS Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L(range 0.705-0.755) and 40 < ALT ≤ 80 U/L(range 0.726-0.79) than for patients with ALT > 80 U/L(range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L(range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L(range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L(range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT.CONCLUSION ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these noninvasive tests.

Disease progression in chronic hepatitis C patients with normal alanine aminotransferase levels

AIM:To investigate whether the disease progression of chronic hepatitis C patients with normal alanine aminotransferase(ALT) levels differs by ALT levels.METHODS:A total of 232 chronic hepatitis C patients with normal ALT(< 40 IU/L) were analyzed.The patients were divided into "high-normal" and "low-normal" ALT groups after determining the best predictive cutoff level associated with disease progression for each gender.The incidence of disease progression,as defined by the occurrence of an increase of ≥ 2 points in the Child-Pugh score,spontaneous bacterial peritonitis,bleeding gastric or esophageal varices,hepatic encephalopathy,the development of hepatocellular carcinoma,or death related to liver disease,were compared between the two groups.RESULTS:Baseline serum ALT levels were associatedwith disease progression for both genders.The best predictive cutoff baseline serum ALT level for disease progression was 26 IU/L in males and 23 IU/L in females.The mean annual disease progression rate was 1.2% and 3.9% for male patients with baseline ALT levels ≤ 25 IU/L(low-normal) and > 26 IU/L(highnormal),respectively(P = 0.043),and it was 1.4% and 4.8% for female patients with baseline ALT levels ≤ 22 IU/L(low-normal) and > 23 IU/L(high-normal),respectively(P = 0.023).ALT levels fluctuated during the follow-up period.During the follow-up,more patients with "high-normal" ALT levels at baseline experienced ALT elevation(> 41 IU/L) than did patients with "lownormal" ALT levels at baseline(47.7% vs 27.9%,P = 0.002).The 5 year cumulative incidence of disease progression was significantly lower in patients with persistently "low-normal" ALT levels than "high-normal" ALT levels or those who exhibited an ALT elevation > 41 U/L during the follow-up period(0%,8.3% and 34.3%,P < 0.001).CONCLUSION:A "high normal" ALT level in chronic hepatitis C patients was associated with disease progression,suggesting that the currently accepted normal threshold of serum ALT should be lowered.

Explanation of Theoretical Mechanism of Isomerization of L-Alanine Conformation for Experimental Results

B3LYP/6-31＋＋G＊＊ method was applied to investigate the mechanism of alanine isomerization.12 minima and 22 transition states were obtained after optimization and several paths of isomerization were found.It is found that intramolecular single-bond rotation and proton transfer might lead to isomerization.The energy barrier of C–N bond rotation was lower than 2.52 kcal·mol 1,while the energy barrier ranges of the rotation of C–C and C–O were separately 0.43~ 7.01 and 4.69~12.19 kcal·mol 1,and the minimum energy barrier of proton transfer was 30.76 kcal·mol 1.The most probable isomerization path and mechanism for the two most stable conformations was discussed to find that the highest energy barrier to be crossed in this path was 11.87 kcal·mol 1.In order to understand the microscopic nature why only 4 conformations were detected in the experiment,thermodynamic properties of all conformations at the experimental temperature of 391 K was calculated.It is found that conformations XII,XI,X and IX can only unidirectionally convert into conformations rapidly with low energy and vanish immediately.The other conformations were distributed according to Maxwell-Boltzman＇s law,and the distribution probabilities of conformations I,II,III,IV,V,VI,VII and VIII were respectively 27.2%,26.5%,25.8%,6.4%,5.2%,4.8%,2.5% and 1.6%.Conformations I,II and III with bigger probability and stronger absorption peak were easy to detect in the experiment.Conformation IV had a relatively smaller probability（6.4%） and weak absorption peak which,however,could also be identified.The other conformations had too small probability to identify in the spectrum.

Postoperative day one serum alanine aminotransferase does not predict patient morbidity and mortality after elective liver resection in non-cirrhotic patients

ABSTRACT： Serum aminotransferases have been used as surrogate markers for liver ischemia-reperfusion injury that follows liver surgery. Some studies have suggested that rises in serum alanine aminotransferase （ALT） correlate with patient outcome after liver resection. We assessed whether postoperative day 1 （POD 1） ALT could be used to predict patient morbidity and mortality following liver resection. We reviewed our prospectively held database and included consecutive adult patients undergoing elective liver resection in our institution between January 2013 and December 2014. Primary outcome assessed was correlation of POD 1 ALT with patient＇s morbidity and mortality. We also assessed whether concurrent radiofrequency ablation, neoadjuvant chemotherapy and use of the Pringle maneuver significantly affected the level of POD 1 ALT. A total of 110 liver resections were included in the study. The overall in-hospital patient morbidity and mortality were 31.8% and 0.9%, respectively. The median level of POD 1 ALT was 275 IU/L. No correlation was found between POD 1 serum ALT levels and patient morbidity after elective liver resection, whilst correlation with mortality was not possible because ofthe low number of mortalities. Patients undergoing concurrent radiofrequency ablation were noted to have an increased level of POD 1 serum ALT but not those given neoadjuvant chemotherapy and those in whom the Pringle maneuver was used. Our study demonstrates POD 1 serum ALT does not correlate with patient morbidity after elective liver resection.

Alanine and aspartate aminotransferase and glutamine-cycling pathway:Their roles in pathogenesis of metabolic syndrome

Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major challenge.Interestingly,Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts.The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk,and observed that metabolic risk factors such as obesity,insulin resistance(IR),high blood pressure,and dyslipidemia were associated with several metabolites,including branched-chain amino acids,other hydrophobic amino acids,tryptophan breakdown products,and nucleotide metabolites.In addition,the authors found a significant association of IR traits with glutamine,glutamate and the glutamineto-glutamate ratio.These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk.We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions.We discuss here the critical role of the "liver metabolism" in the pathogenesis of the MS and IR,and postulate that before fatty liver develops,abnormal levels of liver enzymes,such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver.

Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease

Objective:To investigate the relationship between alanine aminotransferase (ALT) levels and metabolic syndrome (MS) in nonalcoholic fatty liver disease (NAFLD). Methods: A total of 26527 subjects who received medical health checkup in our hospital from January 2005 to July 2007 were enrolled in the study. The diagnosis of fatty liver was based on ultrasound imaging. MS was defined according to the criteria of the Adult Treatment Panel III. ALT, triglyceride (TG), high density lipo-protein cholesterol (HDL-c), fasting plasma glucose (FPG), height, weight, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in each subject to analyze the relationship between MS and ALT activity. Results: (1) The prevalence of NAFLD in men (30.94%) was significantly higher than that in women (15.65%); (2) The incidence of MS in NAFLD (33.83%) was significantly greater than that in non-NAFLD (10.62%); (3) Of the 6470 subjects with NAFLD, in the age-adjusted partial correlation analysis, there were statistically significant correlations between the ALT levels and most metabolic risk factors in each sex (P<0.01), except that ALT levels had no correlation with HDL-c in women. Moreover, in the multiple stepwise regression analysis, SBP lost its significance, and WC, body mass index (BMI), age, DBP, TG and FPG were independently associated with ALT levels in both sexes (P<0.05). HDL-c remained significant and was independently related to ALT levels in men; (4) ALT levels were significantly higher in subjects with MS compared to those without MS (P<0.001). Mean ALT levels increased with the number of MS components in each sex (P<0.05 for trend). Conclusion: We found a strong rela-tionship between ALT levels and MS in NAFLD and revealed that the cluster of MS components might be the predictor for ALT elevations.

Serum γ-glutamyltransferase,alanine aminotransferase,and aspartate aminotransferase activity in Iranian healthy blood donor men

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.

Non-ALT biomarkers for markedly abnormal liver histology among Chinese persistently normal alanine aminotransferase-chronic hepatitis B patients

AIM To determine incidence and clinical biomarkers of marked necroinflammation and fibrosis characteristics among chronic hepatitis B(CHB) patients with persistently normal alanine aminotransferase(PNALT).METHODS Liver biopsy was performed on 115 CHB patients with PNALT. Necroinflammation and fibrosis were graded by the Knodell histologic activity index and the Ishak fibrosis score, respectively. Correlations between the available clinical parameters and necroinflammation and fibrosis were analysed.RESULTS Marked necroinflammation(Knodell activity index ≥ 7) and fibrosis(Ishak fibrosis score ≥ 3) were found in 36.5% and 15.5% of CHB patients with PNALT, respectively. Following a univariate logistic regression analysis, multiple logistic regression analysis indicated that aspartate transaminase(AST)(AUROC = 0.852, cut-off value = 22.5 U/L) serves as an independent predictor of notable liver inflammation, while platelet(PLT) count(AUROC = 0.905, cut-off value = 171.5 ×109/m L) and gamma-glutamyl transpeptidase(GGT)(AUROC = 0.909, cut-off value = 21.5 U/L) level serve as independent predictors of notable liver fibrosis.CONCLUSION A considerable proportion of marked histological abnormalities existed in our cohort, who will benefit from optimal therapeutic strategies administered according to predictive indication by AST, PLT and GGT levels.

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

AIM:To identify the proportion,causes and the nature of drug-induced liver injury(DILI) in patients with notably elevated alanine aminotransferase(ALT).METHODS:All the inpatients with ALT levels above 10 times upper limit of normal range(ULN) were retrospectively 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 elevations were examined for each patient,including biliary abnormality,viral hepatitis,hemodynamic injury,malignancy,DILI or undetermined and other causes.All suspected DILI cases were causality assessed using the 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 > 10 ULN were identified.Hemodynamic injury(n = 46,35.7%),DILI(n = 25,19.4%) and malignancy(n = 21,16.3%) were the top three causes of liver injury.Peak ALT values were lower in DILI patients than in patients with hemodynamic injury(14.5 ± 5.6 ULN vs 32.5 ± 30.7 ULN,P = 0.001).Among DILI patients,one(4%) case was classified as definite,19(76%) cases were classified as probable and 5(20%) as possible according to the CIOMS scale.A hepatocellular pattern was observed 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 DILI.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 DILI with at least one adjunctive drug.Agents for treatment of DILI included anti-inflammatory drugs(e.g.,glycyrrhizinate),antioxidants(e.g.,glutathione,ademetionine 1,4-butanedisulfonate and tiopronin),polyene phosphatidyl choline and herbal extracts(e.g.,protoporphyrin disodium and silymarin).Diagnosis of DILI 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 surgical wards had a higher risk of missed diagnosis in discharge letter [odds ratio(OR) 32.7,95%CI(2.8-374.1),CONCLUSION:DILI is mostly caused by use of antibacterials and glucocorticoids,and constitutes about one fifth of hospitalized patients with ALT > 10 ULN.DILI is underdiagnosed frequently.

A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan

AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan.METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females).RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7,2%, the prevalence revealing a statistically significant decrease with increasing population age (P＜0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P＜0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference,presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66)but this was not so for females (OR = 1.09, 95%CI:0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI:1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI:1.03-2.52) were significantly related to elevated serum ALT levels only for females.CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study.(c)2005 The WJG Press and Elsevier Ihc. All rights reserved.

A better parameter in predicting insulin resistance:Obesity plus elevated alanine aminotransferase

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.

Persistent alanine aminotransferase elevation among the general Iranian population: Prevalence and causes

AIM: To determine the prevalence and causes of persistently elevated alanine aminotransferase (ALT) levels among the general population in northern Iran. METHODS: A total of 2292 (1376 female, aged 18-75 year), were selected by systematic clustered random sampling from the cities and villages of Gonbad and Kalaleh in Golestan Province and invited to participate in the study. A comprehensive history regarding alcohol drinking and medication was taken. Body mass index (BMI), viral markers and ALT levels were measured. If ALT level was ≥ 40 U/L, it was rechecked twice within 6 mo. Those with ≥ 2 times elevation of ALT were considered as having persistently elevated ALT level. Non-alcoholic fatty liver disease (NAFLD) was diagnosed based on evidence of fatty liver upon sonography and excluding other etiology. RESULTS: A total of 2049 (1351 female) patients participated in the study, 162 (7.9%) had elevated ALT level at the first measurement. Persistently elevated ALT level was detected in 64 (3.1%) participants, with51 (79.6%) with no obvious etiology, six (9.3%) with Hepatitis B, four (6.2%) with Hepatitis C virus (HCV) infection and three (4.6%) with alcoholic hepatitis. The prevalence of NAFLD and alcoholic hepatitis was 2.04% (42 patients) and 0.1% (three), respectively. There was correlation between NAFLD and male gender, overweight, diabetes and living in an urban area [odds ratio = 3.03 (95% CI: 1.6-5.72), 4.21 (95% CI: 1.83-9.68), 2.86 (95% CI: 1.05-7.79) and 2.04 (95% CI: 1.00-4.16) respectively]. CONCLUSION: NAFLD is the most common cause of persistently elevated serum ALT level among the general population of Iran.