Serum alanine aminotransferase levels and all-cause mortality

Karaphillis, Erica; Goldstein, Ryan; Murphy, Sharif; Qayyum, Rehan

doi:10.1097/meg.0000000000000778

Cited by 16 publications

(17 citation statements)

References 22 publications

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“…As also shown in previous studies [1][2][3][4][5][6]9,11,12], we found that people with low serum ALT activity are at a higher risk of mortality. However, the ranges of serum ALT activity that made positive and negative contributions to mortality overlapped (Figure 1 and Figure 3), which may have reduced the overall contribution calculated for serum ALT activity in the present study.…”

Section: Discussionsupporting

confidence: 90%

“…It can be difficult to identify older members of the community who are at a high risk of mortality, particularly using the conventional biochemical parameters measured in clinical practice. During the past two decades, many studies have shown that low serum alanine aminotransferase (ALT) activity and high aspartate transaminase (AST)/ALT ratio are associated with high mortality in older people [1][2][3][4][5][6][7][8][9][10][11][12][13]. However, the mechanisms involved remain to be conclusively established [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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High Aspartate Aminotransferase/Alanine Aminotransferase Ratio is the Conventional Biochemical Biomarker that is Most Closely Associated with All-Cause Mortality in Older People

Nakajima¹,

Yuno²,

Tanaka³

et al. 2022

Preprint

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Low serum alanine aminotransferase activity and high aspartate aminotransferase (AST)/ALT ratio may be associated with high mortality in older people. We aimed to confirm this in an 8-year retrospective cohort study. Clinical data for 5,958 people aged 67–104 years were analyzed for their relationships with all-cause mortality using artificial intelligence (AI; Prediction One [Sony Network Communications Inc.]) and conventional statistical analysis (SAS Enterprise Guide [SAS Institute Inc.]). In total, 1,413 (23.7%) participants died during the study. Auto-AI analysis with five rounds of cross-validation showed that AST/ALT ratio was the third largest contributor to mortality, following age and sex. Serum albumin concentration and body mass index were the fourth and fifth largest contributors, and the individual serum ALT and AST activities were the seventh and tenth largest contributors. Conventional survival analysis showed that ALT, AST, and AST/ALT ratio as continuous variables were all associated with mortality (adjusted hazard ratios (95% confidence intervals): 0.98 (0.97–0.99), 1.02 (1.02–1.03), 1.46 (1.32–1.62), respectively; all p <0.0001). In conclusion, both AI and conventional analysis suggest that of the conventional biochemical markers, high AST/ALT ratio is most closely associated with all-cause mortality in older people.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

High Aspartate Aminotransferase/Alanine Aminotransferase Ratio is the Conventional Biochemical Biomarker that is Most Closely Associated with All-Cause Mortality in Older People

Nakajima¹,

Yuno²,

Tanaka³

et al. 2022

Preprint

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“…In contrast, patients in the lowest quartile of ALT randomized to placebo had minimal to unchanged mean ALT values that remained ≤ 15 U/L through 48 weeks of treatment. In the general population, serum concentrations of ALT < 17 U/L are associated with increased all‐cause mortality 47,48 . Therefore, increases in ALT induced by bardoxolone methyl, particularly in the subset of patients with the lowest serum ALT concentrations, may reflect restoration of Nrf2 and ALT activity to normal levels and are therefore associated with the improved metabolic and anti‐inflammatory effects of bardoxolone methyl treatment.…”

Section: Discussionmentioning

confidence: 99%

Effects of Bardoxolone Methyl on Hepatic Enzymes in Patients with Type 2 Diabetes Mellitus and Stage 4 CKD

Lewis

Jadoul

Block

et al. 2020

Clinical Translational Sci

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In a multinational placebo‐controlled phase III clinical trial in 2,185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, treatment with the Nrf2 activator bardoxolone methyl increased estimated glomerular filtration rate, a measure of kidney function, but also resulted in increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase. These increases in liver enzyme level(s) were maximal after 4 weeks of treatment and reversible, trending back toward baseline through week 48. Total bilirubin concentrations did not increase, and no cases met Hy’s Law criteria, although two subjects had ALT concentrations that exceeded 10 × the upper limit of the population reference range leading to discontinuation of treatment. Animal and cell culture experiments suggested that the increases in ALT and AST induced by bardoxolone methyl may be related to its pharmacological activity. Bardoxolone methyl significantly induced the mRNA expression of ALT and AST isoforms in cultured cells. Expression of ALT and AST isoforms in liver and kidney also positively correlated with Nrf2 status in mice. Overall, these data suggest that the increases in ALT and AST observed clinically were, at least in part, related to the pharmacological induction of aminotransferases via Nrf2 activation, rather than to any intrinsic form of hepatotoxicity.

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“…GOT, also known as aspartate aminotransferase, is a mitochondrial and cytoplasmic enzyme, with an important role in cell energy production [ 56 ]. Alterations in GOT levels in blood are considered well-known markers of hepatic, myocardial and skeletal muscle cytolysis, while GPT also known as alanine aminotransferase, is mainly a hepatic cytoplasmic enzyme [ 57 , 58 , 59 ]. In our study, the lack of a significant association between PEF and GPT levels in blood suggests that the association between PEF and GOT levels is related to myocardial or skeletal muscle metabolism.…”

Section: Discussionmentioning

confidence: 99%

Respiratory Muscle Strengths and Their Association with Lean Mass and Handgrip Strengths in Older Institutionalized Individuals

Martínez-Arnau

Buigues

Fonfría-Vivas

et al. 2020

JCM

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The study of reduced respiratory muscle strengths in relation to the loss of muscular function associated with ageing is of great interest in the study of sarcopenia in older institutionalized individuals. The present study assesses the association between respiratory muscle parameters and skeletal mass content and strength, and analyzes associations with blood cell counts and biochemical parameters related to protein, lipid, glucose and ion profiles. A multicenter cross-sectional study was performed among patients institutionalized in nursing homes. The respiratory muscle function was evaluated by peak expiratory flow, maximal respiratory pressures and spirometry parameters, and skeletal mass function and lean mass content with handgrip strength, walking speed and bioimpedance, respectively. The prevalence of reduced respiratory muscle strength in the sample ranged from 37.9% to 80.7%. Peak expiratory flow significantly (p < 0.05) correlated to handgrip strength and gait speed, as well as maximal inspiratory pressure (p < 0.01). Maximal expiratory pressure significantly (p < 0.01) correlated to handgrip strength. No correlation was obtained with muscle mass in any of parameters related to reduced respiratory muscle strength. The most significant associations within the blood biochemical parameters were observed for some protein and lipid biomarkers e.g., glutamate-oxaloacetate transaminase (GOT), urea, triglycerides and cholesterol. Respiratory function muscle parameters, peak expiratory flow and maximal respiratory pressures were correlated with reduced strength and functional impairment but not with lean mass content. We identified for the first time a relationship between peak expiratory flow (PEF) values and GOT and urea concentrations in blood which deserves future investigations in order to manage these parameters as a possible biomarkers of reduced respiratory muscle strength.

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Serum alanine aminotransferase levels and all-cause mortality

Cited by 16 publications

References 22 publications

High Aspartate Aminotransferase/Alanine Aminotransferase Ratio is the Conventional Biochemical Biomarker that is Most Closely Associated with All-Cause Mortality in Older People

High Aspartate Aminotransferase/Alanine Aminotransferase Ratio is the Conventional Biochemical Biomarker that is Most Closely Associated with All-Cause Mortality in Older People

Effects of Bardoxolone Methyl on Hepatic Enzymes in Patients with Type 2 Diabetes Mellitus and Stage 4 CKD

Respiratory Muscle Strengths and Their Association with Lean Mass and Handgrip Strengths in Older Institutionalized Individuals

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