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.     

Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese

AIM:To determine the upper cut-off values of serumalanine aminotransferase(ALT)and aspartate aminotransferase(AST)in a Northern Chinese population.METHODS:A total of 3769 subjects in Jilin Province Northeast China were stratified to determine the potential factors affecting serum ALT and AST levels.The upper cut-off values of serum ALT and AST in these subjects were determined using receiver operating characteristic analysis and their sensitivity and specificity were evaluated.RESULTS:Stratification analysis revealed that serum ALT and AST levels were associated with gender,alcohol consumption,serum cholesterol and triglyceride levels,and body mass index.The upper cut-off values of serum ALT and AST were 22.15 U/L and 25.35 U/L for healthy men and 22.40 U/L and 24.25 U/L for healthy women,respectively.The new cut-off values had a higher sensitivity,but a slightly lower specificity than the current standards.CONCLUSION:Our results indicate that the new upper cut-off values of serum ALT and AST are markedly lower than current standards and may be valuable for the evaluation of liver function.     

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.     

Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity

BACKGROUND & AIMS: Studies that evaluate the risk of hepatotoxicity from statins in hyperlipidemic subjects with elevated baseline serum transaminases are lacking. We conducted a study to test the hypothesis that patients with elevated baseline liver enzymes have higher risk of statin hepatotoxicity. METHODS: Our study consisted of the following 3 cohorts of patients seen between January 1, 1998 and June 31, 2002: Cohort 1: 342 hyperlipidemic patients with elevated baseline enzymes (AST >40 IU/L or ALT >35 IU/L) who were prescribed a statin; cohort 2: 1437 hyperlipidemic patients with normal transaminases who were prescribed a statin; and cohort 3: 2245 patients with elevated liver enzymes but who were not prescribed a statin. The effect of statins on liver biochemistries was assessed over a 6-month period after statins were prescribed. Elevations in liver biochemistries during follow-up were categorized into mild-moderate or severe based on predefined criteria. RESULTS: The incidence of mild-moderate elevations and severe elevations in liver biochemistries in cohort 1 were 4.7% and 0.6%, respectively. Compared with cohort 1, individuals in cohort 2 had lower incidence of mild-moderate elevations (1.9%, P = 0.002) but not severe elevations (0.2%, P = 0.2). However, between cohorts 1 and 3, there were no differences in the incidence of mild-moderate elevations (4.7% vs. 6.4%, respectively, P = 0.2) or severe elevations (0.6% vs. 0.4%, respectively, P = 0.6). Statin discontinuation during the follow-up was similar between cohorts 1 and 2 (11.1% vs. 10.7%, respectively, P = 0.8). CONCLUSIONS: These data suggest that individuals with elevated baseline liver enzymes do not have higher risk for hepatotoxicity from statins.     

Non-Viral Related Liver Enzymes Elevation After Kidney Transplantation

Background:

Liver enzymes elevations (LEE) can be observed after kidney transplantation due to multifactorial causes.

Objectives:

We performed a retrospective study on 1589 kidney transplants, 971 male and 618 female, who were hepatitis B surface antigen (HBsAg) and hepatitis C virus-antibody (HCV Ab) negative, and had no other liver diseases, to detect the prevalence of LEE and its risk factors in these patients between May 2008 and May 2010.

Patients and methods:

Liver enzymes and other biochemical parameters were measured in all recipients. Patients were divided into three groups, according to laboratory test time since transplantation: Group I, less than 3 months, Group II, 4 - 12 months after transplantation, and Group III, more than one year post-transplantation.

Results:

The highest LEE was more frequent in older patients (P < 0.001) and male individuals (P < 0.001). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in patients who received kidneys from deceased donors (10.4% and 23.8%, respectively) as compared to living donor transplants (5.6% and 14.8%, respectively) (P < 0.001). The elevation of ALT was the liver enzyme abnormality after kidney transplantation with the highest prevalence (34.3%). The levels of ALT and AST were significantly elevated within the first 3 months after transplantation, followed by the 4-12 months period (P < 0.001). There was a reverse correlation between liver enzyme levels and renal allograft function in both univariate and linear regression analyses. This correlation increased over time. There was also a significant relation between cyclosporine blood levels and liver enzyme values in the univariate analysis. However, this relationship was attenuated over time. Elevated liver enzymes also correlated with anemia.

Conclusions:

The LEE is a common finding among kidney transplant recipients. Serial monitoring of aminotransferases, particularly ALT, should be performed in all patients after kidney transplantation.     

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.     

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.     

Effect of saffron supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials

Background and aimsPossible protective effects of saffron (Crocus sativus L) have been reported in several randomized clinical trials (RCTs). Current systematic review was performed to summarize the efficacy of saffron intake on liver enzymes.MethodsAn electronic database search was conducted on PubMed/Medline, Scopus, Web of Science, and Cochrane for RCTs comparing effect of saffron and placebo on liver enzymes from inception to July 2021. There was no restriction in language of included studies and we calculated the standardized mean difference (SMD) and 95% Confidence Intervals (CI) for each variable. Random-effect model was used to calculate effect size.ResultsEight studies (n = 463 participants) were included in the systematic review. The saffron intake was associated with a statistically significant decrease in aspartate aminotransferase (AST) (SMD: −0.18; 95% CI: −0.34, −0.02; I² = 0%) in comparison to placebo intake. Our results also indicated that saffron consumption did not have a significant effect on alanine aminotransferase (ALT) (SMD: −0.14; 95% CI: −0.36, 0.09; I² = 47.0%) and alkaline phosphatase (ALP) levels (SMD: 0.14; 95% CI: −0.18, 0.46; I² = 42.9%) compared to placebo.ConclusionsSaffron intake showed beneficial impacts on circulating AST levels. However, larger well-designed RCTs are still needed to clarify the effect of saffron intake on these and other liver enzymes.     

Liver overload in Brazilian triathletes after half-ironman competition is related muscle fatigue

Triathlon competition is dependent on the athletes’ ability to perform each discipline at optimal time, without excessive fatigue influencing the next one. Objectives: Determine the effects of a long distance triathlon on biochemistry parameters related to liver function. Design and methods: Blood samples from six athletes were collected before (T = 0) and immediately after the triathlon competition (T = 1). AST, ALT and alkaline phosphatase (ALP) values were assessed. Results: Significant changes after triathlon competition were found for AST and ALP and no significant changes were found for ALT over time.Conclusions: A series of metabolically alterations, mainly related to energy production and also to muscle and skeletal adaptations occurs during and after strenuous exercise. The altered status of those metabolical changes cannot directly reflect the intensity of any possible muscular or hepatic damage or overload and elevated AST/ALT ratio is better associated to skeletal muscle lesion during competition.     

Can the single-breath helium dilution method predict lung volumes as measured by whole-body plethysmography?

OBJECTIVE:

To compare TLC and RV values obtained by the single-breath helium dilution (SBHD) method with those obtained by whole-body plethysmography (WBP) in patients with normal lung function, patients with obstructive lung disease (OLD), and patients with restrictive lung disease (RLD), varying in severity, and to devise equations to estimate the SBHD results.

METHODS:

This was a retrospective cross-sectional study involving 169 individuals, of whom 93 and 49 presented with OLD and RLD, respectively, the remaining 27 having normal lung function. All patients underwent spirometry and lung volume measurement by both methods.

RESULTS:

TLC and RV were higher by WBP than by SBHD. The discrepancy between the methods was more pronounced in the OLD group, correlating with the severity of airflow obstruction. In the OLD group, the correlation coefficient of the comparison between the two methods was 0.57 and 0.56 for TLC and RV, respectively (p < 0.001 for both). We used regression equations, adjusted for the groups studied, in order to predict the WBP values of TLC and RV, using the corresponding SBHD values. It was possible to create regression equations to predict differences in TLC and RV between the two methods only for the OLD group. The TLC and RV equations were, respectively, ∆TLC_WBP-SBHD in L = 5.264 − 0.060 × FEV₁/FVC (r² = 0.33; adjusted r² = 0.32) and ∆RV_WBP-SBHD in L = 4.862 − 0.055 × FEV₁/FVC (r² = 0.31; adjusted r² = 0.30).

CONCLUSIONS:

The correction of TLC and RV results obtained by SBHD can improve the accuracy of this method for assessing lung volumes in patients with OLD. However, additional studies are needed in order to validate these equations.     

Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients

PURPOSE: Obesity has been associated with obstructive sleep apnea and hepatic steatosis. We investigated the effects of obstructive sleep apnea and treatment with nasal continuous positive airway pressure (CPAP) on serum aminotransferase levels in obese patients. METHODS: We studied 40 obese men with obstructive sleep apnea syndrome. None had hepatitis B antigen or C antibody, autoimmune disease, or an excessive intake of alcohol. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, glucose, insulin, and leptin were determined in the afternoon and in the morning immediately after sleep, before and after nasal CPAP treatment. RESULTS: Aminotransferase levels were abnormal in 35% (n = 14) of patients. Before treatment, mean (+/- SD) aspartate aminotransferase levels were higher in the morning than in the previous afternoon (presleep, 34 +/- 20 IU/L; postsleep, 39 +/- 28 IU/L; P = 0.006). The overnight mean increases in aminotransferase levels were less marked after the first night of nasal CPAP treatment (aspartate aminotransferase: from 6 +/- 11 IU/L to 2 +/- 6 IU/L, P = 0.0003; alanine aminotransferase: from 5 +/- 9 IU/L to 2 +/- 6 IU/L, P = 0.006). Leptin levels (n = 23) decreased significantly after treatment (P = 0.0002), whereas insulin resistance (calculated by the homeostasis model assessment method) and triglyceride levels were unchanged. Improvements in aspartate and alanine aminotransferase levels were maintained after 1 and 6 months of nasal CPAP treatment. CONCLUSION: Nasal CPAP therapy may have beneficial effects on serum aminotransferase abnormalities in obese patients who have obstructive sleep apnea.     

2型糖尿病患者丙氨酸氨基转移酶、天冬氨酸氨基转移酶水平与代谢紊乱、胰岛素抵抗之间的关系

目的探讨2型糖尿病患者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)与胰岛素抵抗和代谢紊乱之间的关系。方法分析了806例2型糖尿病住院患者和103例健康体检者ALT、AST、体脂参数、血压、血脂、血糖、外周白细胞计数(WBC)水平,采用稳态模式(HOMA)评价胰岛素抵抗。根据ALT四分间距,分为ALT1组(<10 U/L)、ALT2组(10~14.9 U/L)、ALT3组(15~21.9 U/L)和ALT4组(≥22 U/L)。结果随着ALT水平升高,空腹胰岛素(FINS)和HOMA-IR呈升高趋势(P<0.05)。随着代谢紊乱数目增多,Log ALT和Log AST呈升高趋势(P<0.05)。校正性别和年龄后LogALT与LogFINS和LogHOMA-IR仍呈正相关(P<0.05),LogAST与LogHOMA-IR仍呈正相关(P<0.05)。多元逐步回归分析显示,Log ALT与代谢紊乱数目和LogHOMA-IR呈独立正相关(P<0.05)。结论2型糖尿病患者ALT、AST水平升高与胰岛素抵抗、代谢紊乱密切相关。     

AST/ALT比值在慢性肝病患者中的特点和判断预后价值

目的 分析不同病因、不同病情的慢性肝病患者天冬氨酸氨基转移酶和丙氨酸氨基转移酶比值(AST/ALT)的特点,评价AST/ALT比值判断慢性肝病患者预后方面的价值.方法 对534例不同病因的肝硬化、原发性肝癌患者的住院资料进行分析,比较各类患者AST/ALT比值的特点.运用接受者运行曲线(ROC)及曲线下面积,比较AST/ALT比值与终末期肝病模型(MELD)、Child-Turcotte-Pugh(CTP)分级(CC)和评分(CS)在判断慢性肝病患者中短期预后方面的准确性;运用非参数相关分析,计算Spearman相关系数,分析三者之间的相关性.结果 在原发性肝癌患者,AST/ALT比值明显高于肝硬化患者(P＜0.05);病毒性肝病患者和非病毒性肝病患者的AST/ALT比值无明显差异(P=0.852).死亡患者的AST/ALT比值明显高于生存患者的平均值(P=0.000);随着CTP分级的升高,AST/ALT比值也逐渐升高,A、B、C三级之间的AST/ALT比值具有显著差异(P＜0.05).AST/ALT比值和MELD、CS及CC在判断慢性肝病患者生存3个月的ROC曲线下面积分别是0.88、0.92、0.69和0.59,判断生存1年时间的ROC曲线下面积分别为0.64、0.77、0.65和0.63;AST/ALT比值与MELD、CS和CC三者之间的相关系数分别是0.185、0.291和0.297(P=0.000).结论 AST/ALT比值随着肝脏病变的加重而逐渐升高.AST/ALT比值和MELD在判断慢性肝病患者短期预后方面是较好的指标.AST/ALT比值和MELD、CS、CC三者之间具有显著相关性.     

The association between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension

Previous studies had shown that an increased aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) was associated with cardiovascular disease. This study aimed to assess the relationship between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension.By March 31, 2020, a cohort of 14,220 Chinese hypertensive patients was followed up. The end point was all-cause and cardiovascular death. Hazard ratios (HRs) and 95% CIs were calculated for mortality associated with AST/ALT ratio, using Cox proportional hazards models and competing risk model.In an average of 1.7 years of follow-up, 1.39% (n = 198) of patients died, 55.5% (n = 110) of whom from cardiovascular disease. AST/ALT ratio was associated with increased risk of all-cause death (HR:1.37, 95% CI:1.15–1.63) and cardiovascular death (HR:1.32, 95% CI:1.03–1.68) after adjustment for other potential confounders. Compared with low AST/ALT ratio (Tertile 1), high AST/ALT ratio was associated with high cause mortality (Tertile 2: HR:1.35, 95% CI:0.86–2.10; Tertile 3: HR:2.10, 95% CI:1.37–3.21; P for trend <.001). Compared with low AST/ALT ratio (Tertile 1), a statistically significant increased risk of cardiovascular mortality was also observed (Tertile 2: HR:1.27, 95% CI:0.70–2.29; Tertile 3: HR:1.92, 95% CI:1.09–3.37; P for trend <.001). High AST/ALT ratio was also associated with high cardiovascular mortality (Tertile 2: HR:1.27, 95% CI:0.70–2.29; Tertile 3: HR:1.92, 95% CI:1.09–3.37; P for trend <.001).Present study indicated that increased AST/ALT ratio levels were predictive of all-cause and cardiovascular mortality among Chinese hypertensive patients.Trial registration: CHICTR, CHiCTR1800017274. Registered 20 July 2018.     

Celiac disease screening in patients with cryptogenic cirrhosis

We write a letter to the editor commenting the article “Who to screen and how to screen for celiac disease”. We discuss the present literature on cirrhosis and celiac disease (CD) and recommend screening and treating CD in individuals with cryptogenic cirrhosis.