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.

Effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease:Clinical implications

In this editorial,we comment on the article by Chen et al recently published in 2024.We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase(ALT)would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease(MAFLD).This is important given the increasing prevalence of MAFLD and obesity globally.Currently,a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT.The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered,particularly as their study found that 83.12%of their study population with a diagnosis of MAFLD had a normal ALT.The main advantages of screening would be to identify patients and provide intervention early,the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis.However,there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered.Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity,although studies have not yet shown a significant improvement in fibrosis regression.It would also require a huge amount of resource if a reduced ALT level alone was used as criteria;it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk.Currently,there is not a good argument to recommend wide-spread screening with a reduced ALT level as this is unlikely to be cost-effective.This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories.Although studies previously have suggested a more pragmatic approach in screening those over the age of 60,this is likely to change with the increasing incidence of obesity within the younger age groups.The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase(ALT)serum levels increase because of hepatocellular damage.Metabolic dysfunction-associated fatty liver disease(MAFLD),which identifies steatotic liver disease(SLD)associated with≥2 metabolic abnormalities,has prominent sexual differences.The Metabolic Syndrome defines a cluster comprising abdominal obesity,altered glucose metabolism,dyslipidemia,and hypertension.Male sex,body mass index,glucose,lipids,ferritin,hypertension,and age independently predict ALT levels among blood donors.Over the last few decades,the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges.With this backset,Chen et al have recently published a study which has two main findings.First,>80%of indi-viduals with MAFLD had normal ALT levels.Second,there was a linear increa-sing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD.This study has biologically credible findings.However,it inaccurately considered sex differences in the MAFLD arena.Therefore,future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Metabolic dysfunction-associated steatotic liver disease:The question of long-term high-normal alanine aminotransferase as a screening test

The growing prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)is being driven by the obesity epidemic.The quest for solutions continues particularly with regard to early detection.This editorial comments on the utility of long-term high-normal alanine aminotransferase(ALT)in screening for MASLD.Chen et al found that new onset MASLD can be detected by repetitively high normal ALT.Implicit in this concept is the question of what should be the accepted upper limit of normal(ULN)for ALT.It was previously set at 40 IU/L based on studies that included people with subclinical liver disease but the new consensus is 30/19 U/L in healthy males/females.Thus,when Chen et al defines the ULN as 40 U/L,others may view it as excessively high.It is important to recognize the variables affecting ULN e.g.instrumentation,diurnal variations,exercise and ageing.These variables matter when the distinctions are subtle e.g.normal vs high-normal.In this regard,the utility of long-term high normal ALT as a disease marker could be enhanced by combining it with other biomarkers,imaging and MASLD genetics to create machine learning classifiers.All in all,Chen et al’s work on long-term high normal ALT as a marker of new-onset MASLD deserves merit.

Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease

In this editorial,we comment on the article by Chen et al.Metabolic dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and obesity.Given its detri-mental health impact,early identification of at-risk individuals is crucial.MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic dysregulation.However,in large-scale epidemiological studies,liver biopsies are not feasible.The application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized software.Blood biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical.Analysis of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods.Accordingly,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.

Predictive value of serum alanine aminotransferase for fatty liver associated with metabolic dysfunction

In this editorial,we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology(2024;30:1346-1357).The study highlights a noteworthy association between persistently elevated,yet highnormal levels of alanine transaminase(ALT)and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease(MAFLD).MAFLD has emerged as a globally prevalent chronic liver condition,whose incidence is steadily rising in parallel with improvements in living standards.Left unchecked,MAFLD can progress from hepatic steatosis to liver fibrosis,cirrhosis,and even hepatocellular carcinoma,underscoring the importance of early screening and diagnosis.ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage.While ALT levels demonstrate a significant correlation with the severity of fatty liver disease,they lack specificity.The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels.Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD,emphasizing the need for closer monitoring and potential intervention in such cases.

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.

Longitudinal Changes in Liver Aminotransferases Predict Metabolic Syndrome in Chinese Patients with Nonviral Hepatitis

Objective This study explored the correlation of longitudinal changes in serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels with the incidence of metabolic syndrome （Mets） based on a dynamic health examination cohort. Methods A Mets-free dynamic cohort involving 4541 participants who underwent at least three health examinations from 2006 to 2011 was included in the study. Mets was defined according to the Chinese Medical Association Diabetes Branch definition that included hypertension, obesity, hyperlipidemia, and hyperglycemia. Generalized estimating equation （GEE） model was used to analyze multivariate relative risk （RR） of repeated observations of ALT and AST in quartiles for Mets or its components according to gender. Results In all, 826 Mets cases were reported. Adjustment of relevant parameters indicated that time-varying changes in ALT and AST levels were positively associated with the incidence of Mets in a dose-response manner. Positive association between high ALT levels and fatty liver was much stronger than that between high AST levels and fatty liver, particularly in male participants. These associations were consistently observed in the following subgroups： participants with ALT and AST levels of 〈40 U/L, participants with of 〈25 kg/m2, and participants with non-fatty liver. Furthermore, participants with 2 Mets components at baseline showed lower multivariate adjusted RRs of ALT and AST for Mets than participants with 0-1 Mets component. Conclusion These results suggested that elevated serum ALT and AST levels were early biomarkers of Mets or its components.

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.

Isolated elevated aspartate aminotransferase in an asymptomatic woman due to macro-aspartate aminotransferase: A case report

BACKGROUND Macro-aspartate aminotransferase(AST), a macroenzyme, is a high-molecular mass complex formed by self-polymerization or association with other serum components that are difficult for the kidney to clear, leading to the isolated elevation of serum AST activity. Cases of macro-AST formation are rare, with only 3 published in the English language literature up to September 2019 in China. In this paper, we present a case in which an asymptomatic woman with persistent isolated elevated AST was confirmed as having macro-AST by the polyethylene glycol precipitation method.CASE SUMMARY A 34-year-old woman was referred to our clinic for elevated AST levels with normal levels of other liver-associated enzymes on November 12, 2018. Her AST level of liver function test had been abnormal for 7 mo before she came to the clinic. The patient was asymptomatic with a normal physical examination. There was no relevant family history and no alcohol consumption or smoking. She had a several-month history of traditional Chinese medical taking and had stopped it 1 year prior. The laboratory tests in our clinic showed only the elevation of AST(89.5 U/L) with no other significant abnormalities. We performed the precipitation technique with polyethylene glycol to confirm the presence of macro-AST. Then for almost a year, her AST level still fluctuated in the abnormal range.CONCLUSION This case highlights that clinical physicians should be familiar with this rare condition of persistent isolated AST elevation due to the presence of macro-AST to avoid unnecessary investigation and patient anxiety.

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

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 x 10(9)/ml) 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.

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 lipoprotein 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 multiple stepwise regression analysis, SBP lost its significance, and had no correlation with HDL-c in women. Moreover, in the 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 relationship between ALT levels and MS in NAFLD and revealed that the cluster of MS components might be the predictor for ALT elevations.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM： To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B （CHB）. METHODS： A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase （ALT） level. The sensitivity, specificity, positive predictive value （PPV）, negative predictive value （NPV）, the likelihood ratio （LR） of aminotransferase/platelet ratio index （APRI） ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid （HA） cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis （fibrosis stages 2 and 4） and no to mild fibrosis/cirrhosis （fibrosis stages 0 and 1）. RESULTS： The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis （stages 2-4） in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION： The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.

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 no- tably elevated alanine aminotransferase （ALT）. METHODS： All the inpatients with ALT levels above 10 times upper limit of normal range （ULN） were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS： A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury （n = 46, 35.7%）, DILl （n = 25, 19.4%） and malignancy （n = 21, 16.3%） were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury （14.5 5.6 ULN vs 32.5 ：I： 30.7 ULN, P = 0.001）. Among DILI patients, one （4%） case was classified as definite, 19 （76%） cases were clas- sified as probable and 5 （20%） as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 （92%） cases and mixed in 2 （8%）. The extent of severity of liver injury was mild in 21 （84%） patients and moderate in 4 （16%）. Before discharge, 10 （40%） patients were recovered and the other 15 （60%） were improved. The improved patients tended to have a higher peak ALT （808 ＋ 348 U/L vs 623 ＋ 118 U/L, P = 0.016） and shorter treatment duration before discharge （8 ＋ 6 d vs 28 ~ 12 d, P = 0.008） compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 （32%） cases, followed by glucocorticoids in 6 （24%） cases. Twenty-four （96%） cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs （e.g., glycyr- rhizinate）, antioxidants （e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin）, polyene phospha- tidyl choline and herbal extracts （e.g., protoporphyrin disodium and silymarin）. Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio （OR） 32.7, 95%CI （2.8-374.1）,CONCLUSION： DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.

Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia

Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia pathological Metavir fibrosis score of the liver wedgespecimens of 91 BA infants. The prognostic value ofpreoperative APRI for jaundice persistence, liver injury,and occurrence of cholangitis within 6 mo after KP wasstudied based on the follow-up data of 48 BA infants.RESULTS： APRI was significantly correlated withMetavir scores （rs = 0.433; P 〈 0.05）. The mean APRIvalue was 0.76 in no/mild fibrosis group （Metavir scoreF0-F1）, 1.29 in significant fibrosis group （F2-F3）, and2.51 in cirrhosis group （F4） （P 〈 0.001）. The areaunder the ROC curve （AUC） of APRI for diagnosingsignificant fibrosis and cirrhosis was 0.75 （P 〈 0.001）and 0.81 （P = 0.001）, respectively. The APRI cut-offof 0.95 was 60.6% sensitive and 76.0% specific forsignificant fibrosis diagnosis, and a threshold of 1.66was 70.6% sensitive and 82.7% specific for cirrhosis.The preoperative APRI in infants who maintainedjaundice around 6 mo after KP was higher than thatin those who did not （1.86 ± 2.13 vs 0.87 ± 0.48, P 〈0.05）. The AUC of APRI for prediction of postoperativejaundice occurrence was 0.67. A cut-off value of0.60 showed a sensitivity of 66.7% and a specificityof 83.3% for the prediction of jaundice persistence.Preoperative APRI had no significant association withlater liver injury or occurrence of cholangitis.CONCLUSION： Our study demonstrated that APRIcould diagnose significant liver fibrosis, especiallycirrhosis in BA infants, and the elevated preoperativeAPRI predicts jaundice persistence after KP.

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse(ARFI), aspartate aminotransferase to platelet ratio index(APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B(CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage(all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI(P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage(Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI(Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

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.