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.     

Upper limit of normal serum alanine and aspartate aminotransferase levels in Korea

Background and Aim: The widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN < 40 U/L) was recently challenged by several reports. Both ALT and aspartate aminotransferase (AST) are commonly used as surrogate markers of liver disease, but almost all studies of aminotransferase activity were conducted on ALT. We investigated not only ULN of ALT but also AST activity and to identify factors modulating them in healthy Korean. Methods: A cross‐sectional study of 411 240 registered blood donors in all nationwide blood banks belonging to the Korean Red Cross were conducted. ULN of ALT and AST was evaluated adjusting their age according to the national population census database. “Decision tree model” was used to identify the affecting factors of ALT and AST and optimal cut‐off points of affecting factors. Results: “ULN of ALT” was 34 U/L in men and 24 U/L in women and “ULN of AST” was 32 U/L in men and 26 U/L in women in the blood donor database. Decision tree analysis showed that ALT levels were mostly influenced by body mass index level and its critical two cut‐off points were 23.5 kg/m² and 25.8 kg/m², respectively. The most affecting factor of AST was gender. Conclusion: Upper limits of normal of ALT and AST in Koreans were lower than conventional accepted values (< 40 U/L) but higher than recently suggested values (male < 30 U/L and female < 19 U/L). Body mass index was the most determining factor for ALT and gender was the most influencing factor for AST activity.     

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.     

Large-scale population analysis reveals an extremely low threshold for "non-healthy" alanine aminotransferase that predicts diabetes mellitus

Background and Aims: Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM. Methods: We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years. Results: Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ～55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels. Conclusion: Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either ‘normal’ or ‘healthy’, with the later reflecting much lower values, above which an individual is at increased risk for DM.     

Association between serum transaminase levels and insulin resistance in euthyroid and non-diabetic adults

AimTo evaluate the association between elevated serum transaminase levels and insulin resistance (IR) in a population of healthy individuals.MethodsWe define IR with a cut-off point of homeostatic model assessment (HOMA-IR) ≥ 3.8. For aspartate aminotransferase (AST), we consider elevated values >30 U/L in women and values >36 U/L in men. For alanine aminotransferase (ALT), we consider elevated values >30 U/L in women and values >40 U/L in men. We performed a crude and adjusted generalized linear model from Poisson family with robust variance, in order to evaluate the association between elevated serum transaminase levels and IR. The associations were presented as prevalence ratio (PR) with their respective 95% confidence intervals (95% CI).ResultsWe included 261 participants in the study. The median age was 39 years (31–45) and 23.7% of the participants were men. The prevalence of elevated serum transaminase for AST and ALT were, 13.8% and 26.1%, respectively. The prevalence of IR was 34.1%. In the crude analysis we found statistical significance between elevated AST and ALT with IR (PR = 3.18; 95% CI: 2.33–4.34 and PR = 2.44; 95% CI: 1.88–3.30; respectively). However, in the multivariate analysis, the association only remained statistically significance with ALT, but lost its significance with AST, PR = 1.90; CI 95%: 1.31–2.77 and a PR = 1.23; CI 95%: 0.93–1.61; respectively.ConclusionElevated serum levels of ALT were associated with insulin resistance. ALT could be used in clinical practice as an additional tool to assess IR in apparently healthy people.     

丙氨酸转氨酶和天冬氨酸转氨酶是反映HBeAg阴性慢性乙型肝炎肝组织炎性分级的敏感指标

目的 分析HBeAg阴性慢性乙型肝炎(CHB)自然病程中血清ALT和AST水平,以及由相同肝实质细胞体积分摊的血清ALT和AST水平与肝组织炎症活动度分级的关系.方法 检测HBeAg阴性CHB患者肝组织病理学不同炎症活动度分级患者血清ALT和AST水平,以及相同肝实质细胞体积分摊的血清ALT和AST水平.数据经ANOVA检验.结果 145例CHB肝组织炎症活动度分级G1～G4级患者血清ALT水平分别为(35.3±29.1)、(91.6±120.4)、(111.6±116.1)和(118.0±122.1)U/L,用相同肝脏实质细胞体积分摊后的血清ALT水平分别为(54.0±45.1)、(144.2±184.9)、(191.3±204.8)和(215.1±226.5)U/L,G1级分别与G2～G4两两比较,差异有统计学意义(P＜0.05);G1～G4的AST水平分别为(35.5±29.0)、(64.9±71.7)、(96.0±81.9)和(102.8±77.0)U/L,相同肝脏实质细胞体积分摊后的血清AST水平分别为(54.3±44.6)、(102.3±107.9)、(165.2±148.7)和(189.4±145.4)U/L,G1与G3、G1与G4、G2与G3、G2与G4比较,差异有统计学意义(P＜0.05).结论 HBeAg阴性CHB自然病程中,ALT和AST均是反映肝组织炎症活动度分级严重性的较为敏感的指标.

Abstract：

Objective To investigate the relationship between serum levels of alanine aminotransferase (ALT)or aspartate aminotransferase (AST)apportioned by the same hepatic parenchyma cell volume and liver histological necroinflammation grades in HBeAg-negative chronic hepatitis B (CHB)patients.Methods A total of 145 CHB patients were divided into four groups:Gl,G2,G3 and G4 based on the liver histological necroinflammation grade.The serum ALT and AST levels were determined by automatic biochemical instrument in these four groups.Furthermore,serum ALT and AST levels were then apportioned by the same hepatic parenchyma cell volume.The data were analyzed by ANOVA.Results Mean serum ALT levels in G1,G2,G3 and G4 groups were (35.3±29.1),(91.6±120.4),(111.6± 116.1)and (118.0±122.1)U/L,respectively,and the serum ALT levels apportioned by same hepatic parenchyma cell volume were ( 54.0 ± 45.1 ),( 144.2 ± 184.9 ),(191.3± 204.8)and (215.1 ± 226.5)U/L,respectively.The pairwise comparison between G1 and other three groups all showed statistically significant difference (P＜0.05).Meanwhile,AST levels in G1 to G4 groups were (35.5± 29.0),(64.9±71.7),(96.0±81.9)and (102.8±77.0)U/L,respectively and the serum AST levels apportioned by the same hepatic parenchyma cell volume were (54.3±44.6),(102.3± 107.9),(165.2±148.7)and (189.4±145.4)U/L,respectively.The pairwise comparison between G1 and G3,G1 and G4,G2 and G3,G2 and G4 all showed statistically significant difference (P＜0.05).Conclusion Both AST and ALT levels are sensitive indicators for liver inflammation grading in HBeAg-negative CHB patients during the natural history of the disease.     

Normal serum alanine aminotransferase activity in uncomplicated obesity

AIM: To evaluate serum alanine aminotransferase (ALT) activity in a well-characterized group of uncomplicated obese subjects and its correlation with insulin resistance, plasma adiponectin, and leptin concentrations. METHODS: One hundred and five uncomplicated obese subjects (87 women, 18 men, age 34.3±9.6 years, BMI 39.9±8.3 kg/m2)were studied. Serum ALT activity was evaluated. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M index) and fasting insulin. Plasma leptin and adiponectin levels were also measured. RESULTS: Serum ALT concentration in the whole group of uncomplicated obese subjects was 17.73±6.33 U/L with none of the subjects presenting ALT levels greater than 43 U/L and only 9 (11%) women and 3 (19%) men showed ALT levels >19 and >30 U/L for women and men, respectively. No significant difference was detected in serum ALT levels between severe obese subjects (BMI >40 kg/m2) and those with BMI <40 kg/m2 (18.63±6.25 vs 17.26±6.02 U/L). ALT was significantly correlated with fasting insulin (r=0.485, P= 0.02) and triglycerides (r= 0.358, P=0.03). CONCLUSION: Serum ALT activity is practically normal in uncomplicated obese subjects, independently of their obesity degree. These findings suggest the role of obesityrelated comorbidities and not of BMI as main risk factors for elevated ALT levels in obese subjects.     

血清精氨酸代琥珀酸裂解酶的测定在肝病诊断中的意义

目的探讨血清精氨酸代琥珀酸裂解酶（ASL）对肝病的诊断效能。方法测定291例肝病患者、247例非肝病患者和32名健康对照血清ASL和ALT、AST、GGT、LDH、ALP活性及TBil浓度；其中31例肝病患者进行了病理组织学检查。结果ROC曲线显示ASL对判断肝病的敏感度为100．0％，特异性为91．1％（分界值=8．0U／L）；ALT和AST的敏感度为97．60%和83．8％，特异性仅分别为24．7％和28．3％（分界值=40．0U／L）。ASL在不同肝病的变化情况是肝癌〉急性肝炎〉肝硬化〉慢性肝炎；ASL浓度[（86．9±26．5）u／L]与肝病理组织学炎症活动度计分（9．83±3．36）呈正相关（r=0．417，P=0．019）。结论ASL诊断肝病的敏感度、特异性优于AST和ALT，是肝病诊断的有用指标。     

The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease

OBJECTIVE: The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is often greater than 2:1 in alcoholic hepatitis. The purpose of this study was to determine whether this ratio may be used to distinguish nonalcoholic steatohepatitis (NASH) from alcoholic liver disease. METHODS: Patients with NASH were matched with controls with alcoholic liver disease based on age, gender, and date of diagnosis. The diagnosis of alcoholic liver disease was based on exclusion of other causes and a significant history of alcohol consumption. The diagnosis of nonalcoholic steatohepatitis was based on exclusion of other causes of liver disease and a liver biopsy showing > 10% steatosis and inflammation. The two sided Student t test was used for statistical analysis. RESULTS: From 1990 to 1996, 70 patients with NASH were matched with 70 subjects with alcoholic liver disease. Patients with NASH had a mean AST to ALT ratio of 0.9 (range 0.3-2.8, median 0.7) and subjects with alcoholic liver disease a mean ratio of 2.6 (range 1.1-11.2, median 2.0). The mean AST levels were 66 U/L and 152 U/L, and the mean ALT levels 91 U/L and 70 U/L, in the nonalcoholic steatohepatitis and alcoholic liver disease groups, respectively. Although the absolute aminotransferase levels were significantly different in the two groups (p < 0.05), the greatest difference was observed in the AST to ALT ratio (p < 0.000001). Subset analysis of patients with NASH revealed mean AST to ALT ratios of 0.7, 0.9, and 1.4 for subjects with no fibrosis, mild fibrosis, or cirrhosis, respectively. The differences among these ratios were statistically significant (p < 0.05). CONCLUSIONS: The AST to ALT ratio appears to be a useful index for distinguishing nonalcoholic steatohepatitis from alcoholic liver disease. Although values < 1 suggest NASH, a ratio of > or = 2 is strongly suggestive of alcoholic liver disease.     

Lower baseline ALT cut-off values and HBV DNA levels better differentiate HBeAg（-） chronic hepatitis B patients from inactive chronic carriers

AIM： To determine whether new cut-off values for aianine aminotransferase （ALT） and baseline hepatitis B virus （HBV） DNA levels better differentiate HBeAg（-） chronic hepatitis B （CriB） patients from inactive chronic carriers.
METHODS： Ninety-one patients [32 HBeAg（＋） CriB, 19 inactive carriers and 40 HBeAg（-） CriB] were followed up for 2 years and were tested for HBV DNA levels by a PCR-based assay. ALT was tested twice during the last 6 mo using new cut-off values： ULN （upper limit of normal） 30 IU/L for males, 19 IU/L for females. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were calculated by discriminant analysis.
RESULTS： When using the revised ALT cut-off values, the lowest optimal HBV DNA level that differentiated HBeAg（-） CHB patients from inactive carriers was 50000 copies/mL. The diagnostic accuracy of HBV DNA to determine inactive carriers with a cut-off of 50000 copies/mL was similar to the previously recommended cut-off of 100000 copies/mL （91%）. HBV DNA levels were lower than the cut-off value in 95% of inactive carriers and in 28% of HBeAg（-） CHB patients. With ALT 〈 30 IU/L in men and 〈 19 IU/L in women and HBV DNA levels 〈 100000 copies/mL, the risk of CHB is 5%. On the other hand, if ALT values were 〉 30 IU in men and 〉 19 IU in women and baseline HBV DNA levels were 〉 100000 copies/mL, the risk is 86%.
CONCLUSION： New cut-off values for ALT together with HBV DNA levels proposed by AASLD （American Association for the Study of Liver Diseases） and NIH （National Institute of Health） consensus seem appropriate to characterize inactive carriers.     

Upper limits of normal for alanine aminotransferase activity in the United States population

Alanine aminotransferase (ALT) is an important test for liver disease, yet there is no generally accepted upper limit of normal (ULN) in the United States. Furthermore, the ability of ALT to differentiate persons with and without liver disease is uncertain. We examined cut-offs for ALT for their ability to discriminate between persons with positive hepatitis C virus (HCV) RNA and those at low risk for liver injury in the U.S. population. Among adult participants in the 1999-2008 U.S. National Health and Nutrition Examination Survey, 259 were positive for serum HCV RNA and 3,747 were at low risk for liver injury (i.e., negative HCV RNA and hepatitis B surface antigen, low alcohol consumption, no evidence of diabetes, and normal body mass index and waist circumference). Serum ALT activity was measured centrally. Maximum correct classification was achieved at ALT = 29 IU/L for men (88% sensitivity, 83% specificity) and 22 IU/L (89% sensitivity, 82% specificity) for women. The cut-off for 95% sensitivity was an ALT = 24 IU/L (70% specificity) for men and 18 IU/L (63% specificity) for women. The cut-off for 95% specificity was ALT = 44 IU/L (64% sensitivity) for men and 32 IU/L (59% sensitivity) for women. The area under the curve was 0.929 for men and 0.915 for women. If the cut-offs with the best correct classification were applied to the entire population, 36.4% of men and 28.3% of women would have had abnormal ALT. CONCLUSION: ALT discriminates persons infected with HCV from those at low risk of liver disease, but would be considered elevated in a large proportion of the U.S. population.     

Alanine aminotransferase cut-off values for blood donor screening using the new International Federation of Clinical Chemistry reference method at 37 degrees C

BACKGROUND AND OBJECTIVES: Serum alanine aminotransferase (ALT) determination is recommended, or even required by law, in the screening of blood donors in many countries, and donors with an increased catalytic activity of ALT are excluded from blood donation. In most countries, the ALT cut-off value for blood donor screening for men and women is twice the upper limit of the normal range. The introduction, in 2002, of the new International Federation of Clinical Chemistry (IFCC) reference method, performed at 37 degrees C, required new ALT reference values to be established for healthy individuals and a new cut-off point to be determined for blood donor screening. MATERIALS AND METHODS: We compared ALT values of donor blood units using the previous German standard method, which measures ALT values at 25 degrees C, and the new IFCC reference procedure, where ALT levels are measured at 37 degrees C. RESULTS: We found a linear correlation between the ALT values obtained by the method at 25 degrees C and the new IFCC reference method (37 degrees C) (r = 0.983), and a gender- and age-independent ratio of 0.523. Using this ratio we calculated the new ALT cut-off for blood donations and now propose a new upper limit of 132 U/l (2.20 microkat/l) for men and 86 U/l (1.43 microkat/l) for women. Only 220 of 151 678 blood donations collected over a period of 5 years showed an ALT value higher than the cut-off. None were hepatitis C virus (HCV) positive in serological or nucleic acid amplification technology (NAT) assays. Only 0.006% of all blood donations were positive for antibody to HCV and thus excluded. CONCLUSIONS: With the implementation of the new IFCC reference method for ALT determination at 37 degrees C, we propose a new ALT cut-off for blood donor screening, which, for men, is about three times the upper limit of the normal range and for women about 2.5 times. Our results show that a lower cut-off would probably not yield a higher safety of blood products in terms of detecting viral infections, but would result in a loss of approximately 0.75% of suitable blood donors.     

Healthy ranges of serum alanine aminotransferase levels in Tranian blood donors

AIM:The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors.METHODS: A total of 1 939 blood donors were included.ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels.RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L,and for non-overweight men was 40 U/L.CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Serum markers for necroinflammatory activity in patients with chronic viral hepatitis and normal or mildly elevated aminotransferase levels

Background: Reports on the usefulness of serum markers for predicting liver necroinflammation are limited. The aim of this study was to determine the serum markers that predict significant inflammation in patients with chronic hepatitis B (CHB) and C (CHC) and normal or mildly elevated serum aminotransferase levels. Methods: Two hundred twenty‐seven patients with CHB or CHC with normal or mildly elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (≤60 IU/L) were enrolled in this study. Significant inflammation was defined as inflammatory grade ≥3 activities using the Batt–Ludwig scoring system. The correlation between liver histology and serum markers of liver inflammation was analysed. Results: Forty‐eight (21.1%) and eight patients (3.5%) had grade 3 and 4 inflammation respectively. Univariate analysis revealed that age, platelet coun, and AST, ALT, γ‐glutamyl transpeptidase, alkaline phosphatase, hyaluronic acid, haptoglobin, apolipoprotein A1 and procollagen III N‐terminal peptide levels were significantly different between the patients with and without significant inflammation. There were no significant differences in the cytokeratin‐18 fragment levels between the two groups. On the basis of multivariate analysis, the AST and apolipoprotein A1 levels and stage of fibrosis were highly predictive of significant inflammation. Using AST and apolipoprotein cut‐off values ≥44 IU/L and ≤100 ng/ml, respectively, the presence of significant inflammation was predicted with high specificity (96.5%) and with a negative predictive value of 76.3%. Conclusion: The AST and apolipoprotein A1 levels were shown to be independent predictors of significant inflammatory activities in patients with CHB and CHC and normal or mildly elevated aminotransferase levels.     

Healthy ranges of serum alanine aminotransferase levels in Iranian blood donors

AIM: The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors. METHODS: A total of 1,939 blood donors were included. ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels. RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L, and for non-overweight men was 40 U/L. CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Subjects with sonographical hepatic steatosis should be excluded from studies to establish upper reference levels of serum transaminases

Background and aims: Correct upper reference limits (URL) of serum liver enzyme activities are used to select individuals in whom further diagnostic procedures for suspected liver disorders are warranted and to compare the prevalence and incidence of increased serum liver enzyme levels within and among populations. We sought to establish URL in a general adult population by not only generating a disease‐free population but also further excluding subjects with ultrasonographical diagnosis of hepatic steatosis. Methods: We used data from 4242 subjects (2154 women) aged 20–79 years recruited for the population‐based Study of Health in Pomerania. A reference population was selected comprising 1953 subjects (1129 women). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ‐glutamyltransferase (GGT) were measured photometrically. Results: The exclusion of 630 subjects with hepatic steatosis and 20 subjects with equivocal data on liver ultrasound from the reference population predominantly affected the URL for serum ALT and GGT levels in younger age groups. URL for serum ALT, AST and GGT levels were 1.00 μmol/L/s (60 U/L), 0.55 μmol/L/s (33 U/L) and 1.11 μmol/L/s (67 U/L), respectively, in men as well as 0.57 μmol/L/s (34 U/L), μmol/L/s (25 U/L) and μmol/L/s (39 U/L), respectively, in women. Conclusions: URL for serum liver enzyme activities are higher than recommended previously. Creating a reference population for establishing URL for serum liver enzyme activities should include liver ultrasound in order to exclude subjects with subclinical hepatic steatosis.     

Correlation between serum alanine aminotransferase activity and age: an inverted U curve pattern

BACKGROUND: Alanine aminotransferase (ALT) activity is the most widely used laboratory test for the recognition of liver disease. Normality limits for values of serum ALT activity have been questioned lately. One reason for this recent uncertainty may be an unrecognized decline in aminotransferase levels in the aging population. AIMS: Cross-sectional evaluation of the association between age and ALT activity. METHODS: Laboratory data of residents in single home for the aged and of adult subjects in three general practice clinics in Jerusalem, Israel were reviewed, excluding subjects with known liver disease. A single laboratory performed all the tests. We examined the associations of serum aminotransferase levels with age, sex, body-mass-index (BMI), and estimated glomerular filtration rate (GFR). Polynomial regression and analysis of variance (ANOVA) with corrections for multiple comparisons were utilized for the statistical analyses. RESULTS: One hundred and twenty-eight individuals from the home for the aged and 207 individuals from three family practices were included. ALT activity linearly regressed with age (r = 0.22, p < 0.0001). However, polynomial regression revealed a better fit (r = 0.33, p < 0.0001), creating an inverted U curve with a peak at 40-55 yr. According to age groups, serum ALT level was 19 +/- 13 U/L in those under 40 yr, 25 +/- 19 U/L in 40-55 yr olds, 22 +/- 10 U/L in 56-72 yr olds, 17 +/- 9 U/L in 73-83 yr olds, and 13 +/- 5 U/L in 83-100 yr olds (p < 0.0001). GFR (r = 0.1, p < 0.05) and BMI (r = 0.14, p < 0.01) weakly correlated with ALT. Gender also associated with ALT; 22 +/- 15 U/L in men, and 17 +/- 11 U/L in women (p < 0.005). Multiple regression analysis including age, gender, GFR, and BMI revealed that age (p= 0.01) and gender (p= 0.04) retained association with ALT activity. No such associations were noted for aspartate aminotransferase (AST) activity. CONCLUSIONS: Our data suggest a significant association between age and serum ALT activity. This association is not a simple linear correlation, but rather an inverted-U-like relation. Thus, when interpreting the laboratory results of a subject suspected of liver disease, age should probably be taken into account. Larger-scale studies are needed to better characterize this issue.     

人体血尿酸水平对血清谷丙转氨酶和谷草转氨酶水平的影响

目的探讨人体不同浓度的血尿酸对血清谷丙转氨酶（ALT）和谷草转氨酶（AST）的影响。方法检测入选者血液尿酸（UA）、ALT、AST、血糖、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）以及身高、体质量等指标,对计数资料采用2χ检验,计量资料行Logistic回归分析,观察尿酸与ALT及AST的关系。结果高尿酸血症组ALT、AST、TG、TC、HDL、LDL等检测指标异常发生率明显高于尿酸正常组（P〈0.05或〈0.01）;随血尿酸水平升高,AST与ALT水平均明显升高,尿酸与AST、ALT间存在线性相关。结论高尿酸血症与AST、ALT水平升高有关,血尿酸水平升高是肝脏转氨酶水平升高的独立危险因素。     

Effects of sodium-glucose co-transporter-2 inhibitors on serum alanine aminotransferase levels in people with type 2 diabetes: A multi-institutional cohort study

Clinical trials have indicated that sodium-glucose co-transporter-2 (SGLT2) inhibitors have a favourable effect on serum alanine aminotransferase (ALT) levels in people with type 2 diabetes (T2D), but supporting evidence from real-world studies is lacking. We identified patients with T2D who initiated SGLT2 inhibitors during the period 2016 to 2017 from Chang Gung Research Database, which covers 1.3 million individuals from seven hospitals (6% of the Taiwan population). We classified patients by baseline ALT level and evaluated changes in ALT values from baseline to 1 year after initiation of SGLT2 inhibitors. We identified 11 690 new users of SGLT2 inhibitors with a mean (SD) age of 59.3 (11.8) years. The mean (SD) glycated haemoglobin and ALT levels were 8.9 (1.7)% and 34.7 (28.9) U/L at baseline, respectively. The mean change in ALT levels was −5.0 U/L (95% confidence interval [CI] –6.4, −3.5) 1 year after initiation of SGLT2 inhibitors. In patients with ALT levels ≤1× the upper limit of normal (ULN), the change in ALT levels was 1.6 U/L (95% CI –0.1, 3.4), while in those with ALT levels >1× ULN, the change in ALT levels was −26.5 U/L (95% CI –28.6, −24.3). The higher the baseline ALT level, the greater the decline after SGLT2 inhibitor treatment. Our findings suggest the initiation of SGLT2 inhibitors for T2D management could improve serum ALT levels in clinical practice, particularly in patients with especially high ALT levels.     

肝细胞脂肪变导致HBV DNA载量慢性乙型肝炎患者转氨酶增高

目的 分析HBV DNA低载量HBsAg阳性患者转氨酶异常的原因.方法 研究对象为血清HBsAg阳性时间持续1年以上、HBV DNA(PCR法)<103拷贝/ml和ALT>1.25×ULN超过6个月的患者,剔除合并HCV和HIV等病毒感染及其他慢性肝病.患者均进行肝活组织检查并结合临床资料分析转氨酶增高的原因. 结果有119例患者纳入研究,男性102例,HBeAg阴性88例(73.9%);平均年龄(33.9±9.7)岁,体重指数(23.4±3.7)kg/m2,ALT(150.0±166.6)U/L,AST(102.4±193.2)U/L.肝活组织检杏有32例(26.9%)为肝细胞脂肪变,64例(53.8%)为慢性肝炎,7例(5.9%)为两者并存,15例(12.6%)为非特异性改变,1例为止常肝组织.30例接受核苷类似物抗病毒治疗的患者,17例有肝脂肪变,占56.7%;89例未进行抗病毒治疗的患者,有22例有肝脂肪变,占24.7%,两组比较x2=10.394,P<0.01,差异有统计学意义.单因素分析显示,肝脂肪变组(n=39)体重指数、甘油三酯、总胆固醇、载脂蛋白B以及尿酸水平显著高十尢肝脂肪变组(n=64);而ALT、AST和载脂蛋白-A水半则显著低于无肝脂肪变组,t值分别为5.369、4.276、3.216、4.223、2.438以及-2.234、-3.877和-2.956,P值均<0.05.肝脂肪变组男性的比例.超重和肥胖,高尿酸血症和高脂血症的患病率亦显著高于无肝脂肪变组;而肝组织炎症和纤维化程度却显著降低,x2分别为3.829、7.659、13.389、0.549和20.978、17.550,P值均<0.05.与肝脏非特异性改变患者相比较,慢性肝炎患者ALT、AST、GGT水平显著升高,P值均<0.05;但其他相关指标无统计学差异. 结论代谢紊乱及其相关肝细胞脂肪变为HBV DNA低载量HBsAg阳性患者转氨酶升高的原因之一.