Alanine Aminotransferase In Group Research Articles

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.

Role of alanine aminotransferase in the effects of urinary caffeine concentration and its primary metabolite concentration on cognitive function in older adults: Bayesian Kernel Machine regression analysis and mediation analysis.

This study aimed to explore the role of alanine aminotransferase (ALT) in the effects of urinary caffeine and its primary metabolites on cognitive function in elderly people. In this investigation, we meticulously curated a cohort from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) database. Animal fluency emerged as the pivotal metric for assessing cognitive function within our study population. In order to navigate the intricacies of mixture analysis and circumvent potential complexities, we harnessed the power of Bayesian kernel machine regression (BKMR) models. This method allowed us to dissect the nuanced impacts of caffeine and its primary urinary metabolites on cognitive function. While accounting for caffeine and its metabolites, we analyzed the relationship between ALT and cognitive function through non-linear dynamics. Lastly, employing structural equation modeling, we probed the intriguing question of whether ALT mediates the influence of 3,7-dimethylxanthine on cognitive function. This comprehensive approach has unveiled a deeper understanding of the multifaceted interplay among these variables, offering invaluable insights into the determinants of cognitive function within our cohort. After meticulous adjustment for various covariates, our linear regression analysis unveiled a noteworthy finding: 3,7-dimethylxanthine demonstrated a significant positive correlation with cognitive function (p < 0.05). Importantly, within the BKMR model employed, 3,7-dimethylxanthine emerged as the most influential factor within the compound, with posterior inclusion probabilities of 0.995 and 0.939. Furthermore, our single-exposure effect model confirmed its presence at the 25th, 50th, and 75th percentile concentrations of other components within the compound. Interestingly, bivariate concentration curves indicated no interaction within the compound, underscoring the prominent impact of 3,7-dimethylxanthine on cognitive function. Subsequently, through a test of Restricted Cubic Splines (RCS), we revealed a non-linear relationship between ALT and cognitive function at the 10th, 50th, and 90th percentiles (p < 0.05), indicating a heightened risk of diminished cognitive function in the low ALT group. Employing structural equation modeling, we meticulously examined the mediating role of ALT in relation to 3,7-dimethylxanthine and cognitive function. However, our study results did not yield significant evidence of a mediating effect. This comprehensive analysis elucidates the intricate interplay between these variables, unveiling the subtle mechanisms governing cognitive function. In this study, a noteworthy positive correlation was observed between 3,7-dimethylxanthine and cognitive function. Additionally, a non-linear relationship was identified between ALT and cognitive function, with lower levels of ALT associated with a decline in cognitive function. The RCS trend suggested that higher levels of ALT may similarly lead to diminished cognitive performance. However, in our pursuit to ascertain potential mediation, we regrettably found no significant evidence supporting mediation among these factors involving ALT. This underscores the need for more comprehensive investigations and expanded clinical explorations into the intricate associations among these three pivotal elements.

Low Alanine Aminotransferase as a Marker for Sarcopenia and Frailty, Is Associated with Decreased Survival of Bladder Cancer Patients and Survivors-A Retrospective Data Analysis of 3075 Patients.

Sarcopenia is characterized by the loss of muscle mass and function and is associated with frailty, a syndrome linked to an increased likelihood of falls, fractures, and physical disability. Both frailty and sarcopenia are recognized as markers for shortened survival in a number of medical conditions and in cancer patient populations. Low alanine aminotransferase (ALT) values, representing low muscle mass (sarcopenia), may be associated with increased frailty and subsequently shortened survival in cancer patients. In the current study, we aimed to assess the potential relationship between low ALT and shorter survival in bladder cancer patients and survivors. This was a retrospective analysis of bladder cancer patients and survivors, both in and outpatients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. A total of 5769 bladder cancer patients' records were identified. After the exclusion of patients with no available ALT values or ALT levels above the upper normal limit, the final study cohort included 3075 patients (mean age 73.2 ± 12 years), of whom 80% were men and 1362 (53% had ALT ≤ 17 IU/L. The mean ALT value of patients within the low ALT group was 11.44 IU/L, while the mean value in the higher ALT level group was 24.32 IU/L (p < 0.001). Patients in the lower ALT group were older (74.7 vs. 71.4 years; p < 0.001), had lower BMI (25.8 vs. 27; p < 0.001), and their hemoglobin values were lower (11.7 vs. 12.6 g/dL; p < 0.001). In a univariate analysis, low ALT levels were associated with a 45% increase in mortality (95% CI 1.31-1.60, p < 0.001). In a multivariate model controlling for age, kidney function, and hemoglobin, low ALT levels were still associated with 22% increased mortality. Low ALT values, indicative of sarcopenia and frailty, are associated with decreased survival of bladder cancer patients and survivors and could potentially be applied for optimizing individual treatment decisions.

Liver magnetic resonance elastography and fat fraction in pediatric patients withcystic fibrosis versus healthy children.

Liver involvement is an important cause of morbidity and mortality in patients withcystic fibrosis (CF). While liver biopsy is the gold standard for demonstrating involvement, its invasiveness prompts a search for noninvasive alternatives. To evaluate liver involvement in pediatric patients with CF(versus healthy controls) using magnetic resonance (MR) elastography/spectroscopy and to correlate the imaging findings with clinical/laboratory characteristics. This was a single-center, prospective cross-sectional study conducted between April 2020 and March 2022 in patients withCF versus healthy controls. Patients with CF were divided into two subgroups: those with CF-related liver disease and those without. MR images were acquired on a 1.5-tesla machine. Kilopascal (kPa) values were derived from processing MR elastography images. MR spectroscopy was used to measure liver fat fraction, as an indication of hepatosteatosis. Groups were compared using either the Student's t test or the Mann‒Whitney U test. The chi-square test or Fisher's exact test were used to compare qualitative variables. Fifty-one patients with CF (12 ± 3.3years, 32 boys) and 24 healthy volunteers (11.1 ± 2.4years, 15 boys) were included in the study. Median liver stiffness (P=0.003) and fat fraction (P=0.03) were higher in the CF patients than in the controls. Median liver stiffness values were higher in CF patients with CF-related liver disease than in those without CF-related liver disease (P=0.002). Liver stiffness values of CF patients with high alanine aminotransferase (ALT), high gamma-glutamyl transferase, and thrombocytopenia were found to be higher than those without (P=0.004, P<0.001, P<0.001, respectively). Only the high ALT group showed a high fat fraction (P=0.002). Patients withCF had higher liver stiffness than the control group, and patients withCF-related liver disease had higher liver stiffness than both the CF patients without CF-related liver disease and the control group. Patients withCF had a higher fat fraction than the control group. Noninvasive assessment of liver involvement using MR elastography/spectroscopy can support the diagnosis of CF-related liver disease and the follow-up of patients withCF.

Accurate resection of hilar cholangiocarcinoma using eOrganmap 3D reconstruction and full quantization technique.

For treatment of hilar cholangiocarcinoma (HCCA), the rate of radical resection is low and prognosis is poor, and preoperative evaluation is not sufficiently accurate. 3D visualization has the advantage of giving a stereoscopic view, which makes accurate resection of HCCA possible. To establish precise resection of HCCA based on eOrganmap 3D reconstruction and full quantification technology. We retrospectively analyzed the clinical data of 73 patients who underwent HCCA surgery. All patients were assigned to two groups. The traditional group received traditional 2D imaging planning before surgery (n = 35). The eOrganmap group underwent 3D reconstruction and full quantitative technical planning before surgery (n = 38). The preoperative evaluation, anatomical classification of hilar hepatic vessels, indicators associated with surgery, postoperative complications, liver function, and stress response indexes were compared between the groups. Compared with the traditional group, the amount of intraoperative blood loss in the eOrganmap group was lower, the operating time and postoperative intestinal ventilation time were shorter, and R0 resection rate and lymph node dissection number were higher (P < 0.05). The total complication rate in the eOrganmap group was 21.05% compared with 25.71% in the traditional group (P > 0.05). The levels of total bilirubin, Albumin (ALB) , aspartate transaminase, and alanine transaminase in the eOrganmap group were significantly different from those in the traditional group (intergroup effect: F = 450.400, 79.120, 95.730, and 13.240, respectively; all P < 0.001). Total bilirubin, aspartate transaminase, and alanine transaminase in both groups showed a decreasing trend with time (time effect: F = 30.270, 17.340, and 13.380, respectively; all P < 0.001). There was an interaction between patient group and time (interaction effect: F = 3.072, 2.965, and 2.703, respectively; P = 0.0282, 0.032, and 0.046, respectively); ALB levels in both groups tended to increase with time (time effect: F = 22.490, P < 0.001), and there was an interaction effect between groups and time (interaction effect: F = 4.607, P = 0.004). In the eOrganmap group, there was a high correlation between the actual volume of intraoperative liver specimen resection and the volume of preoperative virtual liver resection (t = 0.916, P < 0.001). The establishment of accurate laparoscopic resection of hilar cholangiocarcinoma based on preoperative eOrganmap 3D reconstruction and full quantization technology can make laparoscopic resection of hilar cholangiocarcinoma more accurate and safe.

The impact of bariatric surgery on liver enzymes in people with obesity: A 5-year observational study

Background and purposeNon-alcoholic fatty liver disease (NAFLD) has increasing worldwide prevalence, fuelled by rising obesity rates, and weight reduction is the mainstay of its management. We sought to study the effect of bariatric surgery, the most effective long-term treatment for obesity and associated metabolic disorders, on liver function in people with obesity. MethodsWe performed a retrospective longitudinal cohort study of 511 patients who had undergone bariatric surgery (71 sleeve gastrectomy and 440 gastric bypass) over 60 months of follow-up. Patients were stratified into groups based on their baseline alanine aminotransferase (ALT) into Group A (ALT < 40 U/L) and Group B (ALT > 40 U/L). Postoperative follow-up weight loss, liver function tests, HbA1c, blood pressure and lipid profiles were collected. FindingsBariatric surgery resulted in nadir total weight loss of 33.1% by 24 months (p < 0.001) with no significant difference between groups. In people with raised baseline ALT (Group B), ALT and gamma glutamyl transferase (GGT) levels decreased significantly by 4 months postoperatively (p < 0.001) and sustained over 60 months of follow-up. There was also significant and sustained reduction in HbA1c, blood pressure, total cholesterol, and non-HDL cholesterol overall with no differences between groups. ConclusionsBariatric surgery results in significant weight loss, improves liver function tests and metabolic outcomes in people with obesity. Bariatric surgery could be a therapeutic consideration for patients with NAFLD associated with severe obesity who have otherwise been unresponsive to conservative management.

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications.

To explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset. This was a single-center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three-degree, five-level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate-to-severe OHSS were divided into two groups. A control group included 3427 (96.54%) non-OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores. There was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P< 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P< 0.05). In patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.

Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase.

The histologic status of the immune-tolerant (IT) phase of chronic hepatitis B relative to long-term outcomes is unclear. This study aimed to discover how the serological criteria currently in use correspond to histologic criteria in determining the IT phase and indication for liver biopsy. Patients in the serological IT phase determined by positive hepatitis B e antigen, hepatitis B virus (HBV) DNA ≥106 IU/mL, and normal or minimally elevated alanine aminotransferase (ALT) ≤60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of the histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of the serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation, and death, were also analyzed. Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to the histologic IT phase. Age over 35, high AST, and low albumin were useful for ruling out the histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of the histologic IT phase. A significant number of patients who belonged to the serological IT phase were not in the histologic IT phase. Patients over 35 years and those with high AST, low albumin, and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered.

Changes in Lp-PLA 2 are associated with elevated alanine aminotransferase levels: A nested case-control study in a three-year prospective cohort

Background/Aim: Elevation in liver enzymes and hepatic fat may indicate a higher susceptibility to cardiovascular disease (CVD). This research sought to find anthropometric/biochemical variables significantly related to the alanine aminotransferase (ALT) increase in healthy populations. Methods: Nine hundred healthy subjects were included in a 3-year prospective cohort study. The initial screening revealed that 538 were found to be nondiabetic (fasting glucose &lt; 126 mg/dL) and had normal ALT levels. Among them, 79 individuals with slightly elevated ALT levels after three years were assigned to the elevated ALT group. Of the remaining 459 participants, 241 subjects matched to the increased ALT group were the control group. Results: After three years of follow-up, individuals with elevated ALT showed notably higher aspartate aminotransferase (AST), ALT, gamma-glutamyl-transferase (g-GT), high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2 ) activity, oxidised low-density lipoprotein (ox-LDL), urinary 8-epi-prostaglandin F2a (8-epi-PGF2a) levels and brachial-ankle pulse wave velocity (ba-PWV) in comparison to the control group. Changes (D) in ALT showed a positive correlation with D AST, D gammaGT, D hs-CRP, D Lp-PLA2 activity, D ox-LDL, D urinary 8-epi-PGF2a and D ba-PWV. Furthermore, a direct positive link was observed between the D Lp-PLA2 activity and D AST, D ox-LDL and D ba-PWV. Conclusion: Increased Lp-PLA2 activity and other CVD risk indicators were observed to have a pronounced association with elevated ALT levels. This mild ALT elevation could potentially contribute to chronic low-grade inflammation.

Effectiveness of antiviral treatment in HBeAg-negative chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase: a retrospective study

BackgroundThere are inadequate data and no histological evidence regarding the effects of antiviral treatment for hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). This study investigated the effects of antiviral treatment on these patients.MethodsWe retrospectively analysed the outcomes of antiviral treatment for HBeAg-negative CHB patients with normal or mildly elevated ALT who were treated with nucleoside/nucleotide analogues (NAs) for up to 96 weeks.ResultsA total of 128 patients were enrolled; 74 patients had normal ALT and 54 patients had mildly elevated ALT. The total cumulative rates of viral suppression were 64.06%, 81.97%, and 96.39%, at weeks 24, 48, and 96, respectively. The cumulative rates of viral suppression for the normal and mildly elevated ALT groups were 67.85% and 58.97%, 86.39% and 76.31%, and 93.13% and 97.04% at weeks 24, 48, and 96, respectively. The serum HBV DNA levels at week 12 and hepatitis B surface antigen (HBsAg) levels at week 24 were significant predictors of the 96-week virological response. Of the 128 patients, 54 with normal ALT and 33 with mildly elevated ALT underwent FibroScan at baseline. Significant fibrosis (F ≥ 2) was found in 44.4% (n = 24) and 51.5% (n = 17) of the patients in the normal ALT group and mildly elevated ALT group, respectively. Compared with the values at baseline, liver stiffness values significantly decreased at week 48 (8.12 kPa vs. 6.57 kPa; p < 0.001) and week 96 (8.87 kPa vs. 6.43 kPa; p < 0.001), respectively.ConclusionsHBeAg-negative CHB patients with normal ALT could benefit from antiviral therapy with NAs, similar to patients with mildly elevated ALT. Antiviral treatment is strongly recommended for HBeAg-negative CHB patients with normal ALT. Additionally, significant liver fibrosis is not rare in HBeAg-negative CHB patients with ALT less than two-times the upper limit of normal, and FibroScan should be performed regularly for these patients.

Investigation of a relationship between serum concentrations of microRNA-122 and alanine aminotransferase activity in hospitalised cats.

ObjectivesCurrent blood tests to diagnose feline liver diseases are suboptimal. Serum concentrations of microRNA (miR)-122 have been shown in humans, dogs and rodents to be a sensitive and specific biomarker for liver injury. To explore the potential diagnostic utility of measuring serum concentrations of miR-122 in cats, miR-122 was measured in a cohort of ill, hospitalised cats with known serum alanine aminotransferase (ALT) activity.MethodsIn this retrospective study, cats were grouped into those with an ALT activity within the reference interval (0–83 U/l; n = 38) and those with an abnormal ALT activity (>84 U/l; n = 25). Serum concentrations of miR-122 were measured by real-time quantitative PCR and the relationship between miR-122 and ALT was examined.ResultsmiR-122 was significantly higher in the group with high ALT activity than the ALT group, within normal reference limits (P <0.0004). There was also a moderately positive correlation between serum ALT activity and miR-122 concentrations (P <0.001; r = 0.52).Conclusions and relevanceConcentrations of miR-122 were reliably quantified in feline serum and were higher in a cohort of cats with increased ALT activity than in cats with normal ALT activity. This work highlights the potential diagnostic utility of miR-122 as a biomarker of liver damage in cats and encourages further investigation to determine the sensitivity and specificity of miR-122 as a biomarker of hepatocellular injury in this species.

A cohort study on the correlation between alanine aminotransferase trajectories and new-onset metabolic fatty liver disease

Objective: To explore the correlation between alanine aminotransferase (ALT) trajectories and new-onset metabolic fatty liver disease (MAFLD) to provide a scientific basis for the prevention and treatment of MAFLD. Methods: The study cohort was composed of 3 553 subjects who met the inclusion criteria in the cohort study of the Henan physical examination population. According to the ALT levels of the subjects' physical examination from 2017-2019, three different ALT trajectory groups were determined by R LCTMtools, namely low-stable group, medium-stable group, and high-stable group. The incidence of MAFLD during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product-limit method, and Cox proportional hazards regression model analyzed the correlation between different ALT trajectories and new-onset MAFLD. Results: The incidence rate of MAFLD parallelly increased with the increase of ALT locus, which was 6.93%, 15.42%, and 19.05%, respectively, and the difference was statistically significant (P<0.001). After adjusting for multiple confounding factors, such as gender, waist circumference, blood pressure, BMI, fasting blood sugar, and blood lipid by Cox proportional hazards regression model, the risks of MAFLD in ALT medium-stable and the high-stable group were still 1.422 times (95%CI:1.115-1.813) and 1.483 times (95%CI:1.040-2.114) of low-stable ALT group (P<0.05). Conclusions: The risk of MAFLD parallelly increases with the increase of ALT level in the normal long-term range. it is necessary to carry out the intervention for MAFLD with long-term average high value to avoid the progress of MAFLD disease to achieve the early prevention on MAFLD.

Serum levels of IL-12, IL-18, and IL-21 are indicators of viral load in patients chronically infected with HBV.

This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.

Liver enzymes and risk of ocular motor cranial nerve palsy: a nationwide population-based study.

This study aimed to assess the associations between liver enzymes including γ-glutamyl transferase (GGT) and the development of ocular motor cranial nerve palsy (CNP) using the National Sample Cohort database from Korea's National Health Insurance Service. We analyzed data from 4,233,273 medical screening examinees aged 20years or more in 2009. Study participants were followed up until December 31, 2018. A Cox proportional hazard regression analysis was performed for quartiles of liver enzymes to determine the linkage between each value and ocular motor CNP using quartile 1 as a reference after adjusting for potential confounders. A total of 5,807 (0.14%) patients developed ocular motor CNP during the follow-up period of 8.22 ± 0.94years. The incidence of ocular motor CNP gradually increased as the GGT levels increased. The highest quartile of the GGT group had hazard ratio (HR) of 1.245 (95% confidence interval [CI], 1.136-1.365). Regarding alanine aminotransferase (ALT), the highest quartile of the ALT group had HR of 1.141 (95% CI, 1.049-1.241). However, the incidence of ocular motor CNP did not gradually increase as the ALT levels increased. The coexistence of the increased level of GGT, metabolic syndrome, and obesity showed a stronger association with ocular motor CNP development (HR, 1.331; 95% CI, 1.173, 1.511) compared to having a single factor or two factors. In conclusion, our population-based cohort study demonstrated a significant association between serum GGT level and the incidence of ocular motor CNP, suggesting that GGT could be a new clinical marker for predicting the occurrence of ocular motor CNP.

Low ALT levels are associated with poor outcomes in acute coronary syndrome patients in the intensive cardiac care unit

BackgroundFrailty is an underrecognized and important entity that bears worse prognosis. Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients. MethodsA retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU)between 1/5/2011 and 1/12/2020 at a single tertiary medical center. ResultsThe study included 3956 patients after excluding patients with ALT >40 IU/L, cirrhosis, and missing data, followed for a medianduration of 47 months (IQR 20-77).Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT >10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 years vs. 65 years, p<0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, p< 0.001), had higher rates of comorbiditiesat baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (p< 0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, p = 0.99), long-termmortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, p< 0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46-3). ConclusionsLower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU.

Low ALT levels are associated with poor outcomes in acute coronary syndrome patients admitted to the intensive cardiac care unit

Abstract Background Frailty is an under recognized and important entity that bears worse prognosis. Purpose Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients. Methods A retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU) between 1/5/2011 and 1/12/2020 at a single tertiary medical center. Results The study included 3956 patients after excluding patients with ALT &amp;gt;40 IU/L, cirrhosis and missing data, followed for a median duration of 47 months (IQR 20–77). Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT &amp;gt;10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 vs. 65, P&amp;lt;0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, P&amp;lt;0.001), had higher rates of comorbidities at baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (P&amp;lt;0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, P=0.99), long-term mortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, P&amp;lt;0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46–3). Conclusion Lower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU. Funding Acknowledgement Type of funding sources: None. 5-year survival according to baseline ALForest plot of variables associated with

Prevalence of increased transaminases and its association with sex, age, and metabolic parameters in children and adolescents with obesity \u2013 a nationwide cross-sectional cohort study

BackgroundChildhood obesity increases the risk of non-alcoholic fatty liver disease marked by elevated alanine aminotransferase (ALT). This study investigated the prevalence of increased ALT in children and adolescents with obesity, and its associations with sex, age, degree of obesity, and metabolic parameters.MethodsIndividuals between 5 and 17.99 years of age enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) before March 2020 were included. Mildly increased ALT was defined by ALT 27–51 U/L (males) and 23–43 U/L (females), while markedly increased ALT by levels above. Multiple logistic regression models were used for statistical analysis.ResultsAmong 11,776 individuals (age 11.0 ± 3.3 years, 53.5% males), the prevalence of mildly and markedly increased ALT were 37.9 and 10.6%, respectively. A sex-age interaction was found, where increasing age strengthened the odds of markedly increased ALT in males (OR, 99% CI: 1.34, 1.29–1.4 for each year) while the corresponding pattern in females with was minuscule (1.09, 1.02–1.10). Compared to class I obesity, class II and III obesity had greater odds ratios for mildly increased ALT (class II obesity OR, 99% CI: 1.51, 1.35–1.70; class III obesity OR, 99% CI: 2.17, 1.66–2.61) and for markedly increased ALT (class II obesity OR, 99% CI: 1.82, 1.51–2.20; class III obesity OR, 99% CI 3.38, 2.71–4.23). Dyslipidemia was associated with both mildly and markedly increased ALT, all p < 0.001. Prevalence of impaired fasting glucose was 19.1% in normal ALT group, 20.4% in mildly increased ALT group, and 29.0% in markedly increased ALT group.ConclusionsThe risk of markedly increased ALT increased exponentially with age among boys, but not among girls. Higher degree of obesity was observed in individuals with mildly and markedly increased ALT. Further, metabolic derangements were more prevalent among individuals with mildly and markedly increased ALT.

Can Baseline Characteristics be Used to Predict Liver Disease Outcomes in Pediatric Nonalcoholic Fatty Liver Disease?

Longitudinal studies on childhood predictors of nonalcoholic fatty liver disease (NAFLD) progression are lacking. The objective of this study was to determine whether baseline clinical or laboratory measures predict liver disease outcomes in a pediatric NAFLD cohort. A retrospective study of patients with presumed NAFLD was conducted using baseline and follow-up clinical and laboratory measures. Disease outcomes were defined using the mean serum alanine aminotransferase (ALT) levels from 24 to 36 months after the first visit. Logistic regression assessed the relationship between ALT progression/regression and predictor variables. Multivariable regression determined the best model for predicting the ALT outcome. Markov process modeling explored the likelihood for a patient to transition between ALT states. Of a total of 816 patients identified, 144 had sufficient data. Regression was seen in 26%, whereas 30% progressed. No baseline clinical or laboratory measurements had a significant effect on disease outcomes. Markov modeling demonstrated that subjects were more likely to either remain in their baseline ALT group or worsen rather than improve. Routinely obtained baseline clinical or laboratory measures cannot help risk-stratify youth with presumed NAFLD in terms of long-term outcomes. Close clinical, radiographic, and histologic evaluation of patients is warranted to determine those at risk of progression.

Low ALT values amongst hospitalized patients are associated with increased risk of hypoglycemia and overall mortality: a retrospective, big-data analysis of 51 831 patients.

Sarcopenia and frailty influence clinical patients' outcomes. Low alanine aminotransferase (ALT) serum activity is a surrogate marker for sarcopenia and frailty. In-hospital hypoglycemia is associated, also with worse clinical outcomes. We evaluated the association between low ALT, risk of in-hospital hypoglycemia and subsequent mortality. This was a retrospective cohort analysis. We included patients hospitalized in a tertiary hospital between 2007 and 2019. Patients' data were retrieved from their electronic medical records. The cohort included 51 831 patients (average age 70.88). The rate of hypoglycemia was 10.8% (amongst diabetics 19.4% whereas in non-diabetics 8.3%). The rate of hypoglycemia was higher amongst patients with ALT < 10 IU/l in the whole cohort (14.3% vs. 10.4%, P < 0.001) as well as amongst diabetics (24.6% vs. 18.8%, P < 0.001). Both the overall and in-hospital mortality were higher in the low ALT group (57.7% vs. 39.1% P < 0.001 and 4.3% vs. 3.2%, P < 0.001). A propensity score matching, after which a regression model was performed, showed that patients with ALT levels < 10 IU/l had higher risk of overall mortality (HR = 1.21, CI 1.13-1.29, P < 0.001). Low ALT values amongst hospitalized patients are associated with increased risk of in-hospital hypoglycemia and overall mortality.

Hepatic Adaptation to Therapeutic Doses of Acetaminophen: An Exploratory Study in Healthy Individuals

PurposeAcetaminophen (APAP) has hepatotoxic potential when overdosed. Recent studies have reported serum alanine aminotransferase (ALT) elevations that resolve spontaneously with continued use of the drug, referred to as adaptation, in several individuals receiving therapeutic doses of APAP. However, the clinical significance of these ALT elevations remains unclear. This study was performed to investigate the incidence and characteristics of hepatic adaptation to therapeutic doses of APAP in healthy individuals. MethodsIn a randomized, single-blind, placebo-controlled study, 242 healthy Japanese individuals were enrolled. Each person received 3 g/d of APAP (n = 202) or placebo (n = 40) for 28 days. All study participants underwent analysis of genetic polymorphisms of CYP2E1 and UGT1A1; measurements of plasma APAP concentration and urine metabolites (glucuronide, sulfate, cysteine, and mercapturate); liver function monitoring, including ALT, microRNA-122, and high-mobility group box 1. Individuals with ALT levels remaining below the upper limit of normal (ULN; 40 U/L) during the study period were defined as tolerant and those with ALT elevations above the ULN as susceptible. Susceptible individuals who developed ALT elevations exceeding 2 × ULN discontinued use of the study drug for tolerability consideration. Susceptible individuals who had ALT elevations that decreased toward the ULN spontaneously with continued use of the study drug were classified as adaptation. FindingsIn the APAP group, 129 individuals (66%) were classified as tolerant and 65 (34%) as susceptible. Among 65 susceptible individuals, 12 (18%) discontinued use of APAP because of ALT elevations (>2 × ULN), whereas 53 (82%) completed 28-day APAP dosing. Thirty of 65 susceptible individuals (46%) had adaptation within 28 days. In the placebo group, no individuals was withdrawn from the study because of elevated ALT levels, 33 individuals (89%) were classified as tolerant, and 4 (11%) were classified as susceptible. None had clinical signs of liver injury. ALT level correlated significantly with microRNA-122 but not with high-mobility group box 1. No association was found between plasma APAP concentrations and ALT levels. Urinary excretion of APAP mercapturate was higher in susceptible than in tolerant individuals (P = 0.018, Wilcoxon or Kruskal-Wallis test). The frequency of homozygotes and compound heterozygotes for UGT1A1∗28 and UGT1A1∗6 (∗28/∗28, ∗6/∗6, and ∗6/∗28) was higher in susceptible than in tolerant individuals (13.9% vs 3.9%; P = 0.011, χ2 test). ImplicationsThese findings indicate that in healthy individuals, APAP at a therapeutic dose can cause transient and self-limiting ALT elevation, reflecting subclinical hepatocellular damage, and these ALT elevations may be associated with the disposition of APAP metabolites and genetic factors. UMIN-CTR identifier: UMIN000019607.