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.

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.

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.

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.

血清甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT检测对早期原发性肝癌的诊断价值

目的 研究血清甲胎蛋白、异常凝血酶原(PIVKA-Ⅱ)、γ-谷氨酰转移酶(GGT)、GGT/丙氨酸氨基转移酶(GGT/ALT)在早期原发性肝癌诊断中的临床价值。方法 研究方法为前瞻性分析,观察对象为2020年1月至2023年1月攀枝花市中西医结合医院的80例疑似早期原发性肝癌患者,将细胞学、病理学活检诊断结果作为本次研究的金标准划分两组,分别命名为恶性组(n=53)与良性组(n=27)。分别采集血液样本检测血清甲胎蛋白、PIVKA-Ⅱ、GGT、ALT水平,并计算GGT/ALT比值;比较两组患者血清甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT表达水平。比较两组患者血清甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT阳性情况。所有患者均进行细胞学、病理学活检,分析血清甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT单一指标、联合指标诊断原发性肝癌与病理学诊断结果的一致性。采用受试者工作特征(ROC)曲线评估血清甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT 4项指标单一与联合对原发性肝癌的诊断效能。结果 恶性组患者的血清甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT表达水平分别为(1 118.82±67.85) ng/mL、(582.43±197.17) mAU/mL、(102.06±9.47) U/L、3.19±1.71,均明显高于良性组[(9.30±4.76) ng/mL、(31.18±7.34) mAU/mL、(71.64±21.98) U/L、1.61±0.64],差异均有统计学意义(P<0.05)。恶性组患者血清甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT单一及联合指标阳性率分别为73.58%、88.68%、100.00%、54.72%、100.00%,均明显高于良性组(40.74%、14.81%、70.37%、18.52%、33.33%),差异均有统计学意义(P<0.05)。血清甲胎蛋白与组织病理学诊断之间的一致性系数Kappa=0.320(P=0.004),血清PIVKA-Ⅱ与组织病理学诊断之间的一致性系数Kappa=0.725(P<0.001),血清GGT与组织病理学诊断之间的一致性系数Kappa=0.358(P<0.001),血清GGT/ALT与组织病理学诊断之间的一致性系数Kappa=0.309(P=0.002),联合诊断与组织病理学诊断之间的一致性系数Kappa=0.385(P=0.001)。ROC曲线显示,甲胎蛋白、PIVKA-Ⅱ、GGT、GGT/ALT诊断早期原发性肝癌的曲线下面积(AUC)分别为0.842、0.943、0.908、0.899、0.997。结论 在早期原发性肝癌诊断中,血清PIVKA-Ⅱ水平检测的诊断价值优于甲胎蛋白、GGT、GGT/ALT,AFP、PIVKA-Ⅱ、GGT、GGT/ALT 4项指标联合检测的价值优于单一指标检测。

无偿献血者ALT检测不合格的影响因素分析

目的 探讨183例无偿献血者丙氨酸氨基转移酶(ALT)不合格影响因素,制订针对性护理干预策略,降低血液报废率。方法 选取2021年1月—2021年12月我市中心血站无偿献血者58677例作为研究对象,并收集献血者信息和采血信息。采用单因素和多因素Logistic回归分析筛选ALT的危险因素。结果 58677例无偿献血者中,出现ALT检测不合格者有183例0.31%。单因素比较显示献血者性别、年龄、文化程度、生活习惯、采集后是否应用全程血液冷链管理、阿森斯失眠量表(AIS)评分相比,差异有统计学意义(均P <0.05)。多因素Logistic回归分析显示男(OR=2.526)、46~55岁(OR=0.554)、生活习惯差(OR=4.585)采集后未应用血液冷链管理(OR=6.189)、AIS评分≥6分(OR=3.235)是无偿献血者ALT检测不合格的影响因素(均P <0.05)。结论 无偿献血者ALT检测不合格与献血者性别、年龄、生活习惯、AIS评分及是否应用全程血液冷链管理等多种因素相关,建议医护人员应严格规范采前初筛工作,并监管血液运输过程,以减少血液报废。

CT引导下射频消融术治疗肝细胞癌患者的效果及对AST、ALT水平的影响

目的探讨CT引导下射频消融术治疗肝细胞癌患者的效果及对天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平的影响。方法选择2019年8月至2022年8月本院收治的40例肝细胞癌患者为研究对象,根据随机数字表法将其分为对照组(20例,肝动脉栓塞化疗)和观察组(20例,CT引导下射频消融术+肝动脉栓塞化疗)。比较两组的治疗效果。结果治疗后,观察组的AST、ALT、总胆红素(TBIL)及甲胎蛋白(AFP)水平低于对照组(P<0.05)。治疗后,观察组的CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)高于对照组,CD8^(+)低于对照组(P<0.05)。观察组的近期治疗总有效率、并发症总发生率优于对照组(P<0.05)。结论CT引导下射频消融术可明显提高肝细胞癌患者的肝功能、免疫功能,调节AFP水平,且并发症发生率低,安全性更高。

mAST/ALT对严重发热伴血小板减少综合征患者预后的预测价值

目的探讨线粒体天门冬氨酸氨基转移酶(mAST)/丙氨酸转氨酶(ALT)与严重发热伴血小板减少综合征(SFTS)患者生存的相关性,并探讨其在诊断SFTS患者预后中的应用价值。方法选取2021年1月~2023年1月在我院确诊的317例SFTS患者,将全部SFTS患者和入住重症监护室(ICU)患者入院1周内的临床特征进行对比,使用Logistic多元回归分析影响全部SFTS患者和入住ICU患者死亡的独立危险因素,分析mAST/ALT在SFTS患者预后评估中的应用价值。结果死亡组的年龄、碱性磷酸酶(ALP)、ALT、AST、AST/ALT、胞质AST(cAST)、cAST/ALT、mAST、mAST/ALT、肌酸激酶同工酶(CK-MB)、肌酸激酶(CK)、γ-谷氨酰基转移酶(GGT)、α-羟基丁酸脱氢酶(α-HBDH)水平均高于生存组(P<0.05);入住ICU死亡者的年龄、AST、cAST、mAST、AST/ALT、cAST/ALT、mAST/ALT、CK及α-HBDH水平均明显高于幸存者(P<0.05);Logistic多元回归分析显示,年龄、α-HBDH、AST/ALT、cAST/ALT及mAST/ALT是所有SFTS患者死亡的独立危险因素(P<0.05),而AST/ALT、cAST/ALT及mAST/ALT是入住ICU患者死亡的独立危险因(P<0.05),且mAST/ALT的OR值最高;绘制受试者工作特征(ROC)曲线,上述参数的AUC值均大于0.7,有一定预测价值,且mAST/ALT的特异性和灵敏度最高,预后预测价值最好。结论AST/ALT、cAST/ALT及mAST/ALT水平和SFTS患者预后有关,其中mAST/ALT水平对重症SFTS患者预后价值最好。

血清AST、ALT、ESR及IL-21预测系统性红斑狼疮肝损伤的价值

目的探究血清天门冬氨酸基转移酶(AST)、丙氨酸氨基转移酶(ALT)、红细胞沉降率(ESR)及白介素-21(IL-21)预测系统性红斑狼疮肝损伤的价值。方法选取2020年3月-2022年3月我院收治的80例系统性红斑狼疮患者作为研究对象,根据是否发生肝损伤分为肝损伤组和未损伤组,获取患者临床资料,分析脂血清AST、ALT、ESR及IL-21的预测价值。结果经logistic回归分析显示,AST、ALT、ESR、IL-21是系统性红斑狼疮肝损伤独立影响因素(P<0.05)。经ROC曲线分析显示:当AST、ALT、ESR、IL-21截断值分别为(194.64)、(0.794)、(17.64)、(119.56)时可获得最佳预测效能,此时AUC为0.899(95%CI:0.866~0.932),敏感度为(92.26),特异度为(80.64)、约登指数为(0.618)。结论血清AST、ALT、ESR及IL-21是系统性红斑狼疮肝损伤影响因素,4项联合检测可提高对肝损伤预测价值。

妊娠期糖尿病孕妇血WBC、FBG、Cr、ALT变化及早期筛查和风险评估价值

目的:探讨妊娠期糖尿病(GDM)患者白细胞计数(WBC)、空腹血糖(FBG)、血肌酐(Cr)与丙氨酸氨基转移酶(ALT)水平及早期筛查和风险评估价值。方法:回顾性分析2020年5月—2021年12月在本院产前检查的孕妇542例临床资料,分为GDM组(n=60)与对照组(n=482),对比两组WBC、FBG、Cr、ALT差异,采用Spearman相关系数分析以上指标与GDM发病关系;绘制受试者工作特征(ROC)曲线分析WBC、FBG、Cr、ALT早期筛查GDM效能;多因素回归分析GDM发病相关风险因子。结果:GDM组Cr、WBC、FBG、ALT表达均高于对照组,且均与GDM发病正相关(均P<0.05);ROC分析,WBC、FBG、Cr、ALT联合检测的曲线下面积最高(0.851),敏感度90.1%、特异度为87.6%;WBC≥6.41×10~9/L、FBG≥5.16mmol/L、ALT≥14.98U/L、体质指数≥22.32kg/m~2、Cr≥50.62μmol/L、吸烟是GDM发生的风险因子,而孕妇本科及以上学历为保护因素。结论:GDM妇女血WBC、FBG、ALT、Cr异常高表达,联合检测对早期筛查GDM有一定效能,控制BMI、降低吸烟频率并提高孕产妇知识储备对降低GDM发生有一定作用。

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.

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.

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.

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.

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.

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

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 of the 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.

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.