Lower Alanine Aminotransferase Research Articles

Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT

Introduction and ObjectivesEarly diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care. Materials and MethodsAll patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31–41 U/L, 42–54 U/L and ≥55 U/L were compared. Results16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31–41 U/L, 31 (18 %) had ALT 42–54 U/L and 116 (69 %) had ALT ≥55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31–41 U/L, 28 (19 %) had ALT 42–54 U/L and 97 (67 %) had ALT ≥55 U/L. Conclusions33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31–54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care.

Diet Supplementation with Rosemary (Rosmarinus officinalis L.) Leaf Powder Exhibits an Antidiabetic Property in Streptozotocin-Induced Diabetic Male Wistar Rats

Diabetes mellitus is a metabolic disorder that has a high global health burden and causes high mortality and morbidity in humans. Medicinal herbs and plants offer a promising alternative to conventional therapies for the management of diabetes. Rosemary (Rosmarinus officinalis L.) is a traditional medicinal herb that has been used for the management of several diseases. Therefore, the present study investigates the antidiabetic properties of diets supplemented with R. officinalis leaf powder on streptozotocin-induced diabetic Wistar rats. First, the phytochemicals and 2,2-dephenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity of aqueous R. officinalis leaf extract were determined. Streptozotocin-induced diabetic male Wistar rats were fed a diet supplemented with R. officinalis leaf powder (ROP) at 3%, 6%, and 12%, respectively, for 6 weeks. Investigations of food intake, body weight, rat relative organ weights, blood glucose, lipid profiles, creatinine, bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were estimated according to standard procedures. The results show that ROP aqueous extract contains significant amounts of phenolics, flavonoids, and tannins, which exhibit in vitro DPPH free-radical scavenging activity. Based on an in vivo study, ROP reduced blood glucose levels in streptozotocin-induced diabetic animals (p &lt; 0.05). Dietary supplementation with ROP in diabetic rats significantly (p &lt; 0.05) lowered ALT, AST, bilirubin, creatinine, total triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels while increasing high-density lipoproteins (HDLs) when compared with the diabetic control group. Our findings demonstrate that a diet supplemented with R. officinalis leaf powder exhibits an antidiabetic potential with improved health outcomes, as demonstrated by the improved lipid and liver profile enzymes in our animal model.

Short-Term Efficacy of Tenofovir Alafenamide in Acute-On-Chronic Liver Failure: A Single Center Experience.

Patients with acute-on-chronic liver failure (ACLF) who take entecavir (ETV) and tenofovir disoproxil fumarate (TDF) experience a reduction in hepatic events and mortality. The effectiveness of tenofovir alafenamide (TAF) was not well investigated. This study was aim to compare the antiviral efficacy and mortality between TAF and ETV in patients with ACLF caused by the hepatitis B virus (HBV). One hundred and six patients with HBV-ACLF who received TAF (25 mg/day) and ETV (0.5 mg/day) for 12 weeks were analyzed. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Biochemical responses, virologic responses, mortality, drug safety, and side effects were evaluated. At 4 and 12 weeks of TAF treatment, patients showed significantly higher HBV-DNA reduction (P < .001), higher HBV-DNA undetectability rates (P < .001), and lower HBV DNA levels (P < .001) in serum. Lower Child-Turcotte-Pugh (CTP) scores (P = .003) were observed at 4 weeks in the TAF group, although the CTP scores showed no difference between TAF group and ETV group at 12 weeks (P = 1.143). Lower alanine aminotransferase (ALT) levels of patients in the TAF group at week 4 and 12 were observed (P = .023 and P < .0001, separately). The mortality of TAF group was lower after 4 weeks of treatment (P = .038); however, the 2 groups had similar mortality rates at week 8 and 12. Among the causes of death in HBV-ACLF patients, we found the same incidence of liver-related problems in both groups (P > .05). This study showed that ACLF patients with chronic HBV infection treated with TAF had a rapid decline in HBV DNA, a higher rate of ALT reduction and improved CTP scores compared to the ETV group, thereby improving patient survival.

Dexmedetomidine's Effects on the Livers and Kidneys of Rats with Pancreatic Ischemia-Reperfusion Injury.

Pancreatic surgeries inherently cause ischemia-reperfusion (IR) injury, affecting not only the pancreas but also distant organs. This study was conducted to explore the potential use of dexmedetomidine, a sedative with antiapoptotic, anti-inflammatory, and antioxidant properties, in mitigating the impacts of pancreatic IR on kidney and liver tissues. A total of 24 rats were randomly divided into four groups: control (C), dexmedetomidine (D), ischemia reperfusion (IR), and dexmedetomidine ischemia reperfusion (D-IR). Pancreatic ischemia was induced in the IR and D-IR groups. Dexmedetomidine was administered intraperitoneally to the D and D-IR groups. Liver and kidney tissue samples were subjected to microscopic examinations after hematoxylin and eosin staining. The levels of thiobarbituric acid reactive substances (TBARS), aryllesterase (AES), catalase (CAT), and glutathione S-transferase (GST) enzyme activity were assessed in liver and kidney tissues. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine were measured. A comparison of the groups revealed that the IR group exhibited significantly elevated TBARS (p<0.0001), AES (p=0.004), and CAT enzyme activity (p<0.0001) levels in the liver and kidney compared to groups C and D. Group D-IR demonstrated notably reduced histopathological damage (p<0.05) and low TBARS (p<0.0001), AES (p=0.004), and CAT enzyme activity (p<0.0001) in the liver and kidney as well as low AST and ALT activity levels (p<0.0001) in the serum compared to the IR group. The preemptive administration of dexmedetomidine before pancreatic IR provides significant protection to kidney and liver tissues, as evidenced by the histopathological and biochemical parameters in this study. The findings underscored the potential therapeutic role of dexmedetomidine in mitigating the multiorgan damage associated with pancreatic surgeries.

Phytochemical components analysis and hypolipidemic effect on hyperlipidemia mice of the aerial parts from Allium sativum.

The bulbs of Allium sativum are widely used as food or seasoning (garlic), while they have also been utilized as a famous traditional medicine since ancient eras for the treatment of scabies, tuberculosis, pertussis, diarrhea and dysentery, etc. However, very few studies focus on their abundant aerial parts, which are normally discarded during the harvest season. The hyperlipidemic mice model has been used to study the lipid-lowering effect of the aerial parts in this article. 180 mice were randomly divided into 18 groups, including blank control (BC), model (Mod), positive control (PC), and low-, medium-, and high-dose groups of the crude extract, petroleum ether, ethyl acetate, n-butanol, and residual water extracts (corresponding to CE, PEE, EAE, NBE, WE), with 10 mice in each group. The preventive effects of the extracts on hyperlipidemic mice lasted for four weeks. Ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) were used to analyze the chemical components of NBE and PEE respectively. The results of the mice experiment showed that n-butanol extract (NBE) and petroleum ether extract (PEE) from the aerial parts could significantly reduce the contents of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) in serum of hyperlipidemic mice, and increase the contents of high density lipoprotein cholesterol (HDL-C). They could enhance the activity of superoxide dismutase (SOD) in liver and reduce the level of malondialdehyde (MDA). At the same time, they could improve steatosis and inflammation of liver cells. The results of phytochemical components analysis showed that NBE was rich in organic acids, flavonoids and nitrogen-containing constituents, while PEE contained organic sulfur compounds, aliphatic acids and derivatives, alkaloids, phytosterols, etc. These results support that the aerial parts of A. sativum are an interesting source of bioactive ingredients that may be useful in the prevention and treatment of hyperlipidemia.

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.

Association of Serum Liver Enzymes with Brain Amyloidopathy and Cognitive Performance.

Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and periphery, particularly the liver, in regulating Aβ homeostasis. This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance in patients with complaints of cognitive decline. A total of 1,036 patients (mean age 74 years, 66.2% female) with subjective cognitive decline, mild cognitive impairment, AD dementia, and other neurodegenerative diseases were included using the Smart Clinical Data Warehouse. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, and albumin, were assessed. After propensity score matching, logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid PET positivity. Lower ALT levels and higher AST-to-ALT ratios were significantly associated with amyloid PET positivity and AD diagnosis. The AST-to-ALT ratio was also significantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (AUC = 0.642) for age, sex, and apolipoprotein E ɛ4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio. These findings highlight the potential association of liver function on AD and its potential as a diagnostic and therapeutic implications.

Liver integrity and the risk of Alzheimer's disease and related dementias.

We examined midlife (1990-1992, mean age 57) and late-life (2011-2013, mean age 75) nonalcoholic fatty liver disease (NAFLD) and aminotransferase with incident dementia risk through 2019 in the Atherosclerosis Risk in Communities (ARIC) Study. We characterized NAFLD using the fatty liver index and fibrosis-4, and we categorized aminotransferase using the optimal equal-hazard ratio (HR) approach. We estimated HRs for incident dementia ascertained from multiple data sources. Adjusted for demographics, alcohol consumption, and kidney function, individuals with low, intermediate, and high liver fibrosis in midlife (HRs: 1.45, 1.40, and 2.25, respectively), but not at older age, had higher dementia risks than individuals without fatty liver. A U-shaped association was observed for alanine aminotransferase with dementia risk, which was more pronounced in late-life assessment. Our findings highlight dementia burden in high-prevalent NAFLD and the important feature of late-life aminotransaminase as a surrogate biomarker linking liver hypometabolism to dementia. Highlights Although evidence of liver involvement in dementia development has been documented in animal studies, the evidence in humans is limited. Midlife NAFLD raised dementia risk proportionate to severity. Late-life NAFLD was not associated with a high risk of dementia. Low alanine aminotransferase was associated with an elevated dementia risk, especially when measured in late life.

Effects of nano zinc oxide supplementation on metabolic parameters during the transition period in Lacaune ewes

ABSTRACT This study was conducted to determine the influence of nano zinc oxide (N-ZnO) on metabolic parameters in transition periods of the Lacaune ewes. The animals were allocated into two equal groups: the control group (n = 10) and the experimental group (n = 10) supplemented with 20 mg/kg of N-ZnO. Blood samples were collected from all ewes on days −30, −15, 0 (parturition), + 15 and +30. A time effect was observed on aspartate aminotransferase which decreased in both groups from day −30 to day 0 (P ≤ 0.05). All ewes on day 0 had lower alanine aminotransferase than on day −30 (P ≤ 0.001) and day −15 (P ≤ 0.05). In both groups, albumin and total protein levels on day −30, blood urea nitrogen level on day +30 (P ≤ 0.001), β-hydroxybutyric acid and non-esterified fatty acid levels on day +15 (P ≤ 0.05) were higher. Triglycerides on day +30, glucose on days −15, 0, + 30 were lower (P ≤ 0.001). Blood calcium was lower (P ≤ 0.05) and zinc was higher on day +30 (P ≤ 0.001). In conclusion, there was no significant effect of N-ZnO/kg supplementation during the transition period, but changes in metabolic parameters due to a time effect were observed.

Evaluation of the Protective and Regenerative Properties of Commercially Available Artichoke Leaf Powder Extract on Plasma and Liver Oxidative Stress Parameters.

Hepatocellular damage by the harmful effects of xenobiotics, which increase the production of free radicals, is a widespread phenomenon. The extract from the leaves of Cynara scolymus L. available as an artichoke preparation (natural source) of antioxidants may serve as a potential hepatoprotective factor. This study aimed to evaluate the impact of the protective and regenerative properties of artichoke preparation on the liver in three extract doses: 0.5; 1.0; and 1.5 g/kg bw/day. The evaluation was conducted by measuring the levels of oxidative stress parameters, including glutathione (GSH), glutathione S-transferases (GST), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), Trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx), paraoxonase 1 (PON1), SH- group, nitrosylated protein (RSNO), as well as such liver enzymes as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in the plasma and liver homogenate of rats with liver damage induced by CCl4 (1 mL/kg bw). Measurements were taken in plasma and liver homogenate. The results have demonstrated that the artichoke preparation, owing to its high antioxidative potential, exhibits protective and regenerative effects on the liver. This is supported by the observation of higher GSH levels in the plasma of rats treated with artichoke extract for two weeks before CCl4 exposure. Furthermore, the artichoke extract has shown regenerative properties, as evidenced by lower ALT, AST, and SOD activity in the group treated with artichoke extract after CCl4 exposure. These findings suggest that the in vivo administration of artichoke preparation may be beneficial for the protection and regeneration of the liver.

SAT660 Predictors Of Achieving Body Weight Reduction ≥20% With Tirzepatide In People With Overweight Or Obesity In SURMOUNT-1

Abstract Disclosure: R. Srinath: Grant Recipient; Self; Dexcom. S. Pedersen: Other; Self; AstraZeneca, Bausch, Eli Lilly &amp; Company, Novo Nordisk, Jansen Pharmaceuticals, Boehringer Ingelheim, Sanofi, Merck, Abbott Laboratories, HLS, Bayer, Inc., Pfizer, Inc., Dexcom. L. Neff: Employee; Self; Eli Lilly &amp; Company. D. Cao: Employee; Self; Eli Lilly &amp; Company. C.Y. Kao: Employee; Self; Eli Lilly &amp; Company. A. Stefanski: Employee; Self; Eli Lilly &amp; Company. N. Ahmad: Employee; Self; Eli Lilly &amp; Company. C.J. Lee: Employee; Self; Eli Lilly &amp; Company. Background: Obesity is a chronic progressive disease affecting a growing number of adults and associated with many related complications. Next-generation anti-obesity medications (AOM) help achieve substantial body weight (BW) reduction needed to delay or prevent obesity-related complications. BW reduction of 20% or greater, once considered possible only with bariatric surgery, is now an achievable goal with next-generation AOMs. Tirzepatide, a GIP/GLP-1 receptor agonist approved for T2D and in development for chronic weight management, resulted in mean BW reduction of 15 - 21% in the Phase 3 SURMOUNT-1 double-blind, randomized, controlled trial. In this analysis we aimed to investigate predictors of achieving BW reduction ≥20 % with tirzepatide treatment in this trial. Methods: Adults with overweight or obesity who were randomized to receive once-weekly, subcutaneous (SC) tirzepatide (5 mg, 10 mg, or 15 mg) for 72 weeks and adherent to tirzepatide (≥75% doses received) were included in this analysis. Descriptive statistics were calculated for baseline values. Univariate logistic regression was performed on baseline demographics and laboratory values. Variables identified through a stepwise logistic regression were further analysed using a multivariate logistic regression model. Results: Among 1834 participants included in this analysis, 951 (52%) participants achieved 20% or greater BW reduction at week 72. Baseline factors associated with significantly higher odds of achieving BW reduction of ≥20% were female sex (OR [95% CI], p-value) (2.38 [1.90, 2.98], &amp;lt;0.001), lower baseline serum alanine aminotransferase (ALT) levels (1.17 [1.05, 1.30], 0.005), lower baseline HbA1c levels (1.62 [1.24, 2.10), &amp;lt;0.001), and no diagnosed hypertension (1.35 [1.09, 1.68], 0.005) based on multivariate analysis. Baseline factors not associated with higher odds of achieving BW reduction ≥20% were age, race, BW, years of education, fasting insulin, and systolic blood pressure. Conclusions: Approximately half of participants with obesity or overweight, without diabetes, treated with tirzepatide achieved BW reduction of 20% or greater in the SURMOUNT-1 study. Factors associated with a higher likelihood of achieving BW reduction of 20% or greater were female sex, lower ALT, lower HbA1c and no diagnosed hypertension at baseline. These findings may help guide obesity treatment goals and expectations with tirzepatide treatment, which is under investigation for chronic weight management. Presentation: Saturday, June 17, 2023

Patients with low ALT levels are at increased risk for severe COVID-19.

Frailty is a known risk factor for many diseases, including COVID-19. However, many frail patients are undiagnosed as the diagnosis can be cumbersome. Alanine transaminase (ALT) is found not only in the liver but also in the muscle tissue, and multiple studies show that frail sarcopenic patients have lower ALT. Frail patients are at increased risk for severe COVID-19. We evaluated the association between pre-infection low ALT and the risk for severe COVID-19. We collected data regarding all subjects tested for SARS-CoV-2 between 1 March 2020 and 31 December 2021 from a national state-mandatory HMO in Israel, serving more than 1.3 million patients. Clinical and laboratory data were collected, including ALT from the year prior to infection. Severe COVID-19 was defined either as death, ICU admission, or ≥10 hospitalization days. Patients with low ALT (ALT ≤ 10 IU/l) were compared with patients with normal ALT (11-40 IU/l). Patients younger than 18 years with a diagnosis of liver disease and with ALT > 40 IU/l were excluded. During the study period, 58,961 patients tested positive for SARS-CoV-2. The patients in the low ALT group were younger (40.53 vs. 42.73, p < 0.001), less likely to be males (12.3 vs. 38.7%, p < 0.001), and had lower BMI (25.97 vs. 27.15, p < 0.001). The patients in the low ALT group had higher mortality (2.36 vs. 0.57%, p < 0.001), more ICU hospitalizations (0.49 vs. 0.41%, p = 0.47), and more prolonged hospitalizations [2.63% (95% CI 2-3.2%) vs. 0.98% (95% CI 0.86-1.1%) p < 0.001]. In multivariate logistic regression analyses, low ALT was associated with an increased risk of severe COVID-19, with increased mortality (OR 1.88, 95% CI 1.37-2.56) and prolonged hospitalization (OR 1.78, 95% CI 1.33-2.35). Low ALT level prior to infection is a significant risk factor for morbidity and mortality from COVID-19 infection. Further studies are warranted to address treatment options for this population.

Comparison of the effects of pea protein and whey protein on the metabolic profile of soccer athletes: a randomized, double-blind, crossover trial.

Pea protein (PP) concentrate is a plant-based alternative to animal protein sources, such as whey protein (WP). In addition to its valuable amino acid composition, PP has a low environmental impact, making it a sustainable, nutritious, and viable alternative for enhanced sports performance, such as in soccer. PP Therefore, this study aimed to evaluate the effects of PP and WP supplementation on biochemical and metabolic parameters in soccer players. Twelve male under-20 soccer players were included in this double-blind, randomized crossover intervention study. For 10 consecutive days, each participant received either 0.5 g/kg of the PP or WP supplementation after training, starting 7 days before the test game, and continuing until 2 days after. After a 4-day washout period, the athletes switched groups and the intervention was restarted. Blood samples were collected before and after the game, as well as 24 h, 48 h, and 72 h intervals thereafter. Creatine kinase (CK), aspartate transaminase, alanine transaminase (ALT), lactate (LA), urea, creatinine, and uric acid were analyzed using commercial kits. Exploratory metabolic profiling of the serum samples was performed using nuclear magnetic resonance spectroscopy. A comparison of biochemical markers showed that the PP group had lower CK in the post-game moment, 24 h, and 48 h. Lower LA in the post-game moment, and lower ALT in the post-game moment and at 24 h. Of the 48 metabolites analyzed, 22 showed significant differences between the time points, such as amino acids, ketone bodies, and glucose metabolism. Glutamate and lactate levels significantly increased between the pre- and post-game moments in the WP group. After the game, the WP group exhibited reduced levels of metabolites such as arginine and taurine, whereas no such change was observed in the PP group. There was no difference in metabolites 72 h after the game. Despite the slight advantage of the PP group in specific biochemical markers, these differences are not sufficient to justify the choice of a particular type of protein. However, the results highlight the viability of plant protein as a potential alternative to animal protein without compromising athletic performance or recovery.

Low Alanine-Aminotransferase Blood Activity Is Associated with Increased Mortality in Chronic Lymphocytic Leukemia Patients: A Retrospective Cohort Study of 716 Patients.

Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies, especially among elderlies. Several prognostic scores are available that utilize the characteristics of patients' blood counts and cytogenetic anomalies-all are features of the disease rather than of the patient. Addressing the route of personalized rather than precise medicine, we refer to the assessment of patients' status of sarcopenia and frailty. Low alanine aminotransferase (ALT) was already shown to function as a surrogate marker for sarcopenia and frailty. We decided to find a possible correlation between low ALT values and poor prognosis of CLL patients. This is a retrospective cohort study of CLL patients treated in a large, tertiary medical center, as outpatients or inpatients. Their frailty status was evaluated in a retrospective manner. We defined patients with ALT below 12 IU/L as frail and divided our cohort into two groups including a low ALT level group (ALT < 12) and a normal ALT level group (ALT ≥ 12). Overall, our final analysis included 716 CLL patients, of which 161 (22.5%) had ALT levels lower than 12 IU/L. There was no significant difference in patients' age between the two groups. Patients with the low ALT had a lower hemoglobin concentration (median 10.8 g/dL [IQR = 2.7] vs. 12.2 [IQR = 3.1]; p < 0.001) and a higher proportion of patients were classified as Binet C score [48.4% vs. 31.1%]; p < 0.001). Frail CLL patients' survival was significantly shorter when compared to non-frail patients, in both the univariate [HR = 1.6 [95% confidence interval, CI 1.23, 2.0]; p < 0.01] and multivariate analyses [HR = 1.3 [95% CI 1.0, 1.7]; p = 0.03]. Sarcopenia and frailty assessment, based on blood ALT measurements, could potentially point out differences in CLL patients' prognoses. Such assessment could serve the purpose of treatment personalization of CLL patients.

Effects of Anticoccidial Vaccination and Taraxacum officinale Extract on the Growth Performance, Biochemical Parameters, Immunity, and Intestinal Morphology of Eimeria-Challenged Chickens.

A total of 160 Ross 308 male chickens were used in a 2 × 2 factorial design to examine the effects of anticoccidial vaccination (ACV; lack or 1× dose recommended by the manufacturer) and dietary supplementation with Taraxacum officinale (dandelion) extract (DE; with or without) on growth performance, immunity, biochemical parameters, and intestinal morphology in broiler chickens challenged with Eimeria spp. At 20 days of age, all birds were challenged with a 25× dose of ACV, including Eimeria acervulina, E. maxima, E. mitis, and E. tenella. No interaction between ACV and DE was observed in terms of growth performance. Vaccinated birds showed increased feed intake (FI) and feed conversion ratio (FCR) during the 11-20 day period. Meanwhile, DE supplementation led to decreased FI and body weight gain (BWG) during the 1-10 day period. ACV effectively induced immunity against Eimeria, as evidenced by reduced oocyst shedding and less intestinal lesions, decreased levels of pro-inflammatory interleukin-6, and improved BWG during both the post infection (PI) period (21-35 days) and the entire growth period. DE supplementation lowered FCR and increased BWG during the 35-42 day period, increased the concentration of butyric acid in the cecal digesta, and lowered oocyst shedding PI. In vaccinated birds, DE elevated levels of plasma total protein and immunoglobulin M, and influenced tight junction proteins zonula occludens-1 and claudin-3, indicating a more robust epithelial barrier. DE also lowered alanine aminotransferase activity in unvaccinated birds. Both ACV and DE independently improved intestinal morphology in the jejunum, decreasing crypt depth and increasing the villus height-to-crypt ratio. These findings suggest that both ACV and DE could be effective strategies for managing coccidiosis in broiler chickens.

Hepatitis C Screening in Post–Baby Boomer Generation Americans: One Size Does Not Fit All

ObjectivesTo analyze the impact of access to routine health care, as estimated by health insurance coverage, on hepatitis C virus (HCV) infection prevalence in US adults born after 1965 (post–baby boomer birth cohort [post-BBBC]) and to use the data to formulate strategies to optimize population screening for HCV. Patients and MethodsAdult examinees in the National Health and Nutrition Examination Survey with available anti-HCV data were divided into era 1 (1999-2008) and era 2 (2009-2016). The prevalence of HCV infection, as defined by detectable serum HCV RNA, was determined in post-BBBC adults. In low prevalence groups, prescreening modalities were considered to increase the pretest probability. ResultsOf 16,966 eligible post-BBBC examinees, 0.5% had HCV infection. In both eras, more than 50% had no insurance. In era 2, HCV prevalence was 0.26% and 0.83% in those with and without insurance, respectively (P<.01). As a prescreening test, low alanine aminotransferase level (<23 U/L in women and 32 U/L in men) would identify 54% of post-BBBC adults with an extremely low (0.02%) HCV prevalence. Based on these data, a tiered approach that tests all uninsured directly for HCV and prescreens the insured with alanine aminotransferase would reduce the number to test by 56.5 million while missing less than 1% infections. ConclusionFor HCV elimination, passive “universal” screening in routine health care settings is insufficient, although the efficiency of screening may be improved with alanine aminotransferase prescreening. Importantly, for individuals with limited access to health care, proactive outreach programs for HCV screening are still needed.

Low Alanine Aminotransferase, as a Marker of Sarcopenia and Frailty, Is Associated with Shorter Survival Among Prostate Cancer Patients and Survivors. A Retrospective Cohort Analysis of 4064 Patients

BackgroundSarcopenia is characterized by loss of muscle mass and function and is associated with frailty, a syndrome with higher likelihood of falls, fractures, physical disability, and mortality. Both frailty and sarcopenia are known markers of shorter survival in various cancer patient populations. Low alanine aminotransferase (ALT), reflecting loss of muscle mass (sarcopenia), may be associated with greater frailty and shorter survival in multiple cancers. ObjectiveTo assess the potential association between low ALT and shorter survival among prostate cancer (PCa) patients and survivors. Design, setting, and participantsThis was a retrospective analysis of a historical cohort of PCa patients and survivors. Patients were defined as those still actively receiving PCa treatment, while those no longer receiving such treatment were classified as PCa survivors. Outcome measurements and statistical analysisALT data were obtained from results for basic biochemical blood testing carried out for patients on their first hospital admission. Patients were divided into two groups: those with ALT ≥17 IU/l and those with ALT <17 IU/l. Univariate and multivariable analyses were conducted for between-group survival comparisons. Results and limitationsWe identified 9489 PCa records. The final study cohort with ALT data available included 4064 patients with ALT <40 IU/l. Of this cohort, 536 patients were actively receiving medical anticancer therapy for PCa. The mean age for the entire cohort was 74.6 yr (standard deviation 9.6) and the median ALT level was 19.28 IU/l; 1676 patients (41%) had low ALT (<17 IU/l). On univariate analysis, low ALT was associated with a 78% increase in mortality risk (95% confidence interval [CI] 1.62–1.97; p < 0.001). A sensitivity analysis of the 536 patients actively receiving medical anticancer treatment revealed that low ALT was associated with a 48% increase in mortality risk (95% CI 1.19–1.85; p = 0.001). In a multivariable model controlled for age, kidney disease, history of cerebrovascular event/transient ischemic attack, and baseline prostate-specific antigen, low ALT was still associated with a 35% increase in mortality risk (95% CI 1.12–1.63; p = 0.001). Limitations include the single-center, retrospective design. ConclusionsLow ALT, which is indicative of sarcopenia and frailty, is associated with shorter survival among PCa patients and survivors and could potentially be used for treatment personalization. Patient summaryWe compared survival for prostate cancer patients and survivors according to their blood level of the protein alanine aminotransferase (ALT). Low ALT levels in the general population are associated with loss of muscle mass. We found that in our group of prostate cancer patients and survivors, the risk of death from any cause was higher for those with low ALT levels.

Liver Enzymes and the Risk of Stroke among the General Japanese Population: A Prospective Cohort Study

Introduction: Stroke is a major cause of morbidity and mortality. Liver enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), are markers of liver diseases with potential cardiovascular implications. This study aimed to investigate the prospective association between liver enzymes and stroke risk. Methods: We analyzed data from 3,379 men and 4,007 women without cardiovascular disease and registered in the Suita Study, a Japanese population-based prospective cohort study. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of stroke risk were estimated per quintiles of ALT, AST, and GGT in men and women. Results: Within a median follow-up period of 16.7 years, 438 incident stroke events were diagnosed. In men, compared to the second quintiles, the fifth (highest) quintiles of liver enzymes showed increased stroke risks: HRs (95% CIs) = 2.07 (1.35, 3.18) in ALT, 1.66 (1.10, 2.53) in AST, and 1.76 (1.11, 2.81) in GGT. The associations did not change with cerebral infarction risk: HRs (95% CIs) = 2.09 (1.24, 3.50) in ALT, 1.84 (1.11, 3.06) in AST, and 1.74 (1.00, 3.04) in GGT. The lowest ALT, AST, and GGT quintiles tended to show increased stroke and cerebral infarction risks, yet these associations were statistically insignificant. No such associations were shown in women. Conclusion: Elevated ALT, AST, and GGT levels were associated with increased stroke and cerebral infarction risks among Japanese men.

Low alanine aminotransferase activity gene variant in a Siberian Husky with copper-associated hepatopathy

BackgroundAlanine aminotransferase (ALT) is commonly used as a marker of hepatocellular injury. Increased serum ALT activity due to hepatocyte injury occurs in copper-associated hepatopathy (CuCH) and other necroinflammatory liver conditions. Blood ALT concentrations are frequently used to monitor therapy in cases of CuCH. Low serum ALT activities have been associated with an allele at a CFA13 locus.Case presentationA 9-year-old female spayed Siberian Husky was diagnosed with CuCH (hepatic copper dry weight 2680 µg/g [normal, 120–400 µg/g; toxic, > 1500 µg/g]) and a normal ALT (78 U/L; reference range, 10–125 U/L). Mild hepatocellular necrosis was evident histologically. Genetic testing (Embark) revealed that the dog was heterozygous for the low ALT activity gene allele.ConclusionsThis case report illustrates the clinical implications for diagnosing and managing necroinflammatory liver disease such as CuCH in dogs with a low ALT activity genotype.