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Agidew MM, Mulu AT, Teklemariam AB, Mengstie MA, Melake A, Zewde EA, Muche ZT, Dagnew SB, Baye ND, Adane B, Walle M, Derso G. Impact of aging on alanine aminotransferase levels and frailty in chronic kidney disease patients: laboratory-based cross-sectional study in Northwest Ethiopia. Front Med (Lausanne) 2025; 12:1524459. [PMID: 40357294 PMCID: PMC12066457 DOI: 10.3389/fmed.2025.1524459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 03/28/2025] [Indexed: 05/15/2025] Open
Abstract
Background Chronic kidney disease (CKD) is a non-communicable progressive condition that leads to a gradual decline in kidney functions, resulting in different complications. Serum alanine aminotransferase (ALT) is an important biomarker for diagnosing liver comorbidities. However, ALT levels in CKD patients could be affected by aging. Despite this challenge, there is a scarcity of data on the effect of aging on frailty and ALT levels in CKD patients in Ethiopia. Thus, this study aimed to assess the impact of aging on serum levels of ALT, the magnitude of frailty, and the associated factors among CKD patients in different age groups. Methods A hospital-based cross-sectional study involving 120 CKD patients was conducted in Bahir Dar, Ethiopia. Data were collected using structured questionnaire. Blood pressure, anthropometric parameters, ALT levels, and frailty were assessed according to standard procedures. Data were analyzed using SPSS version 25. Pearson's correlation analysis, multiple linear analysis, and logistic regression analysis were performed to identify predictors of ALT levels and frailty, with a statistical significance level of p < 0.05. Results The serum level of ALT was significantly lower in CKD patients aged ≥ 46 years compared to CKD patients aged 18-45 years. The magnitude of frailty in CKD patients aged 18-45 and ≥ 46 years was 8.5% (95% CI: 1.4-15.6) and 34.4% (95% CI: 22.5-46.4), respectively, and was significantly associated with ALT levels. Factors such as age category (AOR: 0.16, 95% CI: 0.04-0.60) and hypertension (HTN) (AOR: 10.16, 95% CI: 1.03-99.90) were significantly associated with frailty. Conclusion The serum level of ALT was significantly correlated with age and frailty in CKD patients. Thus, ALT levels can be used as a biomarker for aging and frailty. The age of CKD patients and HTN were factors significantly associated with frailty.
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Affiliation(s)
- Melaku Mekonnen Agidew
- Department of Biomedical Science, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Anemut Tilahun Mulu
- Department of Biomedical Science, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | | | - Misganaw Asmamaw Mengstie
- Department of Biomedical Science, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Addisu Melake
- Department of Biomedical Science, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Edgeit Abebe Zewde
- Department of Biomedical Science, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Zelalem Tilahun Muche
- Department of Biomedical Science, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Samuel Berihun Dagnew
- Department of Clinical Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Nega Dagnew Baye
- Department of Anatomy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Bezawit Adane
- Department of Epidemiology and Biostatistics, School of Public Health, College of Health Sciences, Injibara University, Injibara, Ethiopia
| | - Muluken Walle
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Girma Derso
- Amhara Regional State Health Bureau, Bahir Dar, Ethiopia
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Zhang Y, Li S, Fu K, Fang K, Zheng L, Lin Y, Zheng Y, Wu J. Development and evaluation of percentile curves of serum alanine aminotransferase in older adults: A multi-cohort study. Ann Hepatol 2025:101918. [PMID: 40288490 DOI: 10.1016/j.aohep.2025.101918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 02/25/2025] [Accepted: 03/01/2025] [Indexed: 04/29/2025]
Abstract
INTRODUCTION AND OBJECTIVES Age independently impacts alanine aminotransferase (ALT) levels. This study was conducted to develop age- and sex-specific ALT percentile curves among older adults and evaluate their diagnostic performance across two external cohorts. MATERIALS AND METHODS We developed ALT percentile curves using data from a reference population aged 50-90 years (n = 20,039). We evaluated diagnostic performance of various ALT thresholds (40 U/L, American College of Gastroenterology [ACG]'s 33 U/L [men] and 25 U/L [women], and the new percentile curves) for infections of hepatitis B virus and hepatitis C virus, metabolic dysfunction associated steatotic liver disease, and excessive alcohol consumption in two external cohorts. RESULTS ALT percentile curves declined with age. In men, the 95th percentile decreased from 31.4 U/L at 50 years to 21.7 U/L at 90 years; in women, from 26.1 U/L to 17.8 U/L. The 95th percentile curves achieved the highest Youden's index and area under the receiver operating characteristic (AUROC) across the three thresholds in two external validation cohorts, with the Youden's index and AUROC of 0.141 and 0.571 (95% CI: 0.555-0.586) in external cohort 1, and 0.435 and 0.717 (95% CI: 0.680-0.754) in external cohort 2, respectively. CONCLUSIONS The newly proposed ALT percentile curves may serve as a valuable reference for screening liver diseases in older adults.
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Affiliation(s)
- Yu Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
| | - Shuwen Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
| | - Kang Fu
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 258118, China
| | - Kailu Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
| | - Luyan Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
| | - Yushi Lin
- Department of Infectious Diseases, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yang Zheng
- Department of Allergic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
| | - Jie Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
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Youssef EM, Wu GY. Subnormal Serum Liver Enzyme Levels: A Review of Pathophysiology and Clinical Significance. J Clin Transl Hepatol 2024; 12:428-435. [PMID: 38638374 PMCID: PMC11022067 DOI: 10.14218/jcth.2023.00446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 02/09/2024] [Accepted: 02/18/2024] [Indexed: 04/20/2024] Open
Abstract
Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson's disease, deficiencies of divalent ions, or malnutrition. Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis, the use of certain medications, and in bone disease. Finally, subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia. The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.
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Affiliation(s)
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
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Shafrir A, Katz LH, Shauly-Aharonov M, Zinger A, Safadi R, Stokar J, Kalisky I. Low ALT Is Associated with IBD and Disease Activity: Results from a Nationwide Study. J Clin Med 2024; 13:1869. [PMID: 38610634 PMCID: PMC11012492 DOI: 10.3390/jcm13071869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 03/20/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
Background: Sarcopenia is underdiagnosed in patients with inflammatory bowel disease (IBD). Low alanine transaminase (ALT) is associated with sarcopenia. We evaluated the association between low ALT and the presence of IBD and disease activity. Methods: Data were collected from a national Israeli health insurer cohort comprising 976,615 patients. Patients with a diagnosis of IBD were compared to healthy controls. After exclusion of patients with liver disease, ALT > 40 IU/L and age < 18, a total of 233,451 patients were included in the analysis. Low ALT was defined as <10 IU/L. Results: Low ALT was more common amongst patients with IBD than in healthy controls (7.76% vs. 5.7% p < 0.001). Low ALT was found in 148 (7.9%) of the patients with CD and 69 (6.9%) of the patients with UC. For CD, low ALT was associated with increased fecal calprotectin (FC) and CRP (223.00 μg/mg [63.45-631.50] vs. 98.50 [31.98-324.00], p < 0.001, 9.10 mg/L [3.22-19.32] vs. 3.20 [1.30-8.30], p < 0.001) and decreased albumin and hemoglobin (3.90 g/dL [3.60-4.20] vs. 4.30 [4.00-4.50], p < 0.001,12.20 g/dL [11.47-13.00] vs. 13.60 [12.60-14.70], p < 0.001). For UC, low ALT was associated with higher FC and CRP (226.50 μg/mg [143.00-537.00] vs. 107.00 [40.85-499.50], p = 0.057, 4.50 mg/L [1.90-11.62] vs. 2.30 [1.00-6.20], p < 0.001) and with lower albumin and hemoglobin (4.00 g/dL [3.62-4.18] vs. 4.30 [4.10-4.40], p < 0.001, 12.40 g/dL [11.60-13.20] vs. 13.60 [12.60-14.60], p < 0.001). These findings remained consistent following multivariate regression and in a propensity score-matched cohort. Conclusions: Low ALT is more common in patients with IBD and is associated with biochemical disease activity indices.
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Affiliation(s)
- Asher Shafrir
- Meuhedet Health Medical Organization, Jerusalem District, Tel Aviv 6203854, Israel
- Institute of Gastroenterology and Hepatology, Hadassah Medical Center, Jerusalem 1200, Israel; (L.H.K.); (A.Z.); (I.K.)
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel; (R.S.); (J.S.)
| | - Lior H. Katz
- Institute of Gastroenterology and Hepatology, Hadassah Medical Center, Jerusalem 1200, Israel; (L.H.K.); (A.Z.); (I.K.)
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel; (R.S.); (J.S.)
| | - Michal Shauly-Aharonov
- Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel;
- The Jerusalem College of Technology, Jerusalem 9190401, Israel
| | - Adar Zinger
- Institute of Gastroenterology and Hepatology, Hadassah Medical Center, Jerusalem 1200, Israel; (L.H.K.); (A.Z.); (I.K.)
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel; (R.S.); (J.S.)
| | - Rifaat Safadi
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel; (R.S.); (J.S.)
- The Liver Institute, Hadassah Medical Organization, Jerusalem 91120, Israel
| | - Joshua Stokar
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel; (R.S.); (J.S.)
- Department of Endocrinology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel
| | - Itay Kalisky
- Institute of Gastroenterology and Hepatology, Hadassah Medical Center, Jerusalem 1200, Israel; (L.H.K.); (A.Z.); (I.K.)
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9190500, Israel; (R.S.); (J.S.)
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Wu C, Wang Q, Zhou CY, Sun HX, Lin YS, Jiao XF, Lu X, Xu JS, Shen ZK, Guo Y, Gao W. Association of AST/ALT (De Ritis) ratio with sarcopenia in a Chinese population of community-dwelling elderly. Heliyon 2023; 9:e20427. [PMID: 37822616 PMCID: PMC10562753 DOI: 10.1016/j.heliyon.2023.e20427] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 09/14/2023] [Accepted: 09/25/2023] [Indexed: 10/13/2023] Open
Abstract
Background The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, also known as De Ritis ratio, has been reportedly associated with malnutrition which plays a crucial role in sarcopenia. The aim of this study was to examine the relationship between AST/ALT ratio and sarcopenia in the Chinese community-dwelling elderly. Methods A cross-sectional study with 2751 participants (1343 men and 1408 women) aged ≥60 years was performed. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were measured to diagnose sarcopenia according to the latest Asian Working Group for Sarcopenia (AWGS) consensus. The association of AST/ALT ratio with sarcopenia was examined using logistic regression analysis. Results The prevalence of sarcopenia in the present study was 4.4%. AST/ALT ratio was higher in the sarcopenia group than in the non-sarcopenia group (1.30 ± 0.33 vs. 1.16 ± 0.62, P = 0.010). AST/ALT ratio was negatively correlated with the components of sarcopenia, including ASMI, grip strength, and gait speed. Logistic regression analysis indicated that high AST/ALT ratio (>1.20) was associated with increased risk of sarcopenia even after adjustment for potential confounders (adjusted OR = 2.33, 95%CI = 1.48-3.68, P < 0.001). Stratification analyses indicated that the association of high AST/ALT ratio with high risk of sarcopenia was more significant in males and the elderly with ≥70 years. Conclusions Our findings demonstrate that high AST/ALT ratio is associated with increased risk of sarcopenia in a Chinese population of community-dwelling elderly.
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Affiliation(s)
- Cheng Wu
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Quan Wang
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
- Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chun-Ya Zhou
- Department of Rheumatology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Hui-Xian Sun
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Yu-Shuang Lin
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Xin-Feng Jiao
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Xiang Lu
- Department of Geriatrics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Jin-Shui Xu
- Jiangsu Province Center for Disease Control and Prevention, Nanjing, China
| | - Zheng-Kai Shen
- Jiangsu Province Center for Disease Control and Prevention, Nanjing, China
| | - Yan Guo
- Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Gao
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
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Zou J, Li H, Deng G, Wang X, Zheng X, Chen J, Meng Z, Zheng Y, Gao Y, Qian Z, Liu F, Lu X, Shi Y, Shang J, Huang Y, Chen R. A novel prognostic nomogram for older patients with acute-on-chronic liver diseases (AoCLD): a nationwide, multicentre, prospective cohort study. Age Ageing 2023; 52:afac313. [PMID: 36626326 PMCID: PMC9831261 DOI: 10.1093/ageing/afac313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 11/03/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND the incidence of acute-on-chronic liver disease (AoCLD) is increasing. OBJECTIVE to investigate the clinical features and risk factors of AoCLD and construct an effective prognostic nomogram model for older patients with AoCLD. METHODS data from 3,970 patients included in the CATCH-LIFE study were used, including 2,600 and 1,370 patients in the training and validation sets, respectively. Multivariate Cox regression analyses were performed to identify predictive risk factors in older individuals, and an easy-to-use nomogram was established. Performance was assessed using area under the curve, calibration plots and decision curve analysis (DCA). RESULTS of the 3,949 patients with AoCLD, 809 were older with a higher proportion of autoimmune-related abnormalities, hepatitis C viral infection and schistosomiasis. In the older patient group, the incidence of cirrhosis, hepatic encephalopathy (HE), infection, ascites and gastrointestinal bleeding; neutrophil-to-lymphocyte ratio (NLR), aspartate-to-alanine transaminase ratio (AST/ALT), creatinine and blood urea nitrogen levels were higher, whereas incidence of acute-on-chronic liver failure, white blood cell, platelet and haemoglobin levels; albumin, total bilirubin (TB), AST and ALT levels; international normalised ratio (INR), estimated glomerular filtration rate and blood potassium levels were lower than in the younger group. The final nomogram was developed based on the multivariate Cox analysis in training cohort using six risk factors: ascites, HE grades, NLR, TB, INR and AST/ALT. Liver transplantation-free mortality predictions were comparable between the training and validation sets. DCA showed higher net benefit for the nomograph than the treat-all or treat-none strategies, with wider threshold probabilities ranges. CONCLUSIONS our analysis will assist clinical predictions and prognoses in older patients with AoCLD.
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Affiliation(s)
- Ju Zou
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Hai Li
- Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
| | - Guohong Deng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xianbo Wang
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xin Zheng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, Institute of Infection and Immunology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Jinjun Chen
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhongji Meng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yubao Zheng
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanhang Gao
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Zhiping Qian
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Feng Liu
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Xiaobo Lu
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Yu Shi
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia Shang
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
- Department of Infectious Diseases, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Yan Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
- Chinese Chronic Liver Failure (CLIF) Consortium, Shanghai, China
| | - Ruochan Chen
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
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Liver Enzymes in a Cohort of Community-Dwelling Older Persons: Focus on Sex Contribution. Nutrients 2022; 14:nu14234973. [PMID: 36501002 PMCID: PMC9737251 DOI: 10.3390/nu14234973] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/16/2022] [Accepted: 11/21/2022] [Indexed: 11/25/2022] Open
Abstract
Dysfunctions in liver metabolic activities may increase the risk of cognitive impairment and dementia. In a cohort of community-dwelling older persons investigated for a suspected cognitive decline, we studied the association between liver status and dementia, considering sex and frailty contribution. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and the AST/ALT ratio were used to assess liver function in 419 older adults (248 persons with dementia and 171 age- and sex-matched subjects without cognitive decline). Although the serum concentrations of the liver enzymes were in the physiologic range, patients with dementia showed lower ALT concentrations (p = 0.005) and higher AST/ALT ratios (p = 0.003) compared to controls. The same differences were found when comparing men with and without dementia (ALT, p = 0.009; AST/ALT ratio, p = 0.003) but disappeared in women. Curiously, comparing women and men with the same diagnosis, the ALT concentrations were lower (p = 0.008), and the AST/ALT ratio was higher (p = 0.001) in control women than men, whereas no significant difference was found between persons with dementia. In conclusion, in our cohort of older people living in the community, the association between serum aminotransferases and dementia was remarked. Moreover, our results support attention to sex difference in liver function, suggesting a role in the pathogenesis of dementia.
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Dlamini SB, Wu MT, Dahms HU. Factors Associated with Antiretroviral Therapy Toxicity Out-Comes in Patients with and without Hypertension. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:11051. [PMID: 36078765 PMCID: PMC9518525 DOI: 10.3390/ijerph191711051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 08/28/2022] [Accepted: 08/30/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Negative effects of antiretroviral therapy (ART) drugs on HIV/AIDS patients are one of the major health issues in the therapeutic treatment of this communicable disease. This holds particularly for people living with HIV (PLHIV) who might have a non-communicable disease (like hypertension), which also requires a lifetime treatment. In this study, we investigated the association between hypertension and other possible factors on ART toxicity markers in patients with hypertension, compared to those without hypertension. METHODS This retrospective longitudinal study reviewed chronic patient files of 525 patients (of which 222 were hypertensive) who satisfied the inclusion criteria and were on ART at a hospital in central Eswatini. Specific levels of estimated glomerular filtration (eGFR), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used as drug toxicity markers. To analyze the longitudinal data between the exposure of interest and outcome variables, a Generalized Estimated Equation method was employed. RESULTS Participants with hypertension had decreased eGFR compared to those without hypertension (β = -2.22; p-value = 0.03). There was no significant association between ALT, AST and hypertension (p-value = 0.34 and 0.20, respectively). Factors that were found to have a significant association with ART toxicity markers included age, sex, ART duration, hypertension treatment and time of study. The eGFR was found to be significantly increasing over the study period (p-value < 0.001) for all participants. The significance was consistent in both hypertensive and non-hypertensive participants independently (p-value = 0.002 and <0.001, respectively). The overall trends of ALT and AST over time were also significant (p-value = 0.003 and <0.001, respectively). CONCLUSIONS Patients with hypertension had decreased eGFR, and there was a significant association of eGFR with time of the study. Special attention, therefore, to monitor calamities which are indicated by a decrease of eGFR (like renal impairment) should be given in PLHIV on ART with hypertension, especially more so if they were on ART for longer time.
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Affiliation(s)
- Sabelo Bonginkosi Dlamini
- Department of Public Health, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- PhD Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Tsang Wu
- Department of Public Health, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- PhD Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Hans-Uwe Dahms
- Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80708, Taiwan
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Wu Y, Liu F. Aspartate aminotransferase to alanine aminotransferase ratio and the risk of diabetic nephropathy progression in patients with type 2 diabetes mellitus: A biopsy-based study. J Diabetes Complications 2022; 36:108235. [PMID: 35853763 DOI: 10.1016/j.jdiacomp.2022.108235] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 05/17/2022] [Accepted: 06/19/2022] [Indexed: 10/17/2022]
Abstract
PURPOSE To study the relationship between baseline serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR) in both clinicopathological features and renal outcome among type 2 diabetes mellitus (T2DM) patients with biopsy-confirmed diabetic nephropathy (DN). METHODS As a retrospective cohort study, we included 253 patients with T2DM and biopsy-confirmed DN. For receiver operating characteristic (ROC) curve showed that the optimal cut-off for AAR to predict end stage renal disease (ESRD) was 1.22. So, patients were divided into two groups according to their AAR at the time of renal biopsy: high AAR Group (those with AAR > 1.22); low AAR Group (those with AAR ≤1.22). Association between AAR and clinicopathological features as well as renal outcome were analyzed. RESULTS Patients with higher AAR presented elder, more hypertensive, more insulin use, higher serum cholesterol, more proteinuria and lower estimated glomerular filtration rate (eGFR). Compared with low AAR group, patients with high AAR had more severe glomerular pathological lesions and interstitial fibrosis and tubular atrophy. For prognostic analysis, high AAR Group was associated with a higher risk of progression to ESRD in univariate analysis. No matter treated with continuous or categorical variate, higher AAR remained an independent predictor for ESRD after adjusted for various confounding factors: gender, age, the duration of diabetes, serum glucose level, hypertension, serum lipid level, smoking, insulin use, eGFR and proteinuria. CONCLUSION High AAR was associated with more severe renal pathologic lesions and worse renal function in patients with T2DM and DN, which might be a novel noninvasive predictor for ESRD. CLINICAL RELEVANCE To our knowledge, there was no biopsy-based cohort study. In our study, high AAR was associated with more severe renal pathologic lesions and worse renal function in patients with T2DM and DN, which might be a novel noninvasive predictor of ESRD for patients with DN.
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Affiliation(s)
- Yucheng Wu
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Fang Liu
- Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
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Huong NTC, Karimzadeh S, Thanh NT, Thuan TM, Sabbah GM, Ismaeil K, An DNT, Huong LT, Huy NT, Thi Le Hoa P. Updated upper limit of normal for serum alanine aminotransferase value in Vietnamese population. BMJ Open Gastroenterol 2022; 9:e000870. [PMID: 35613736 PMCID: PMC9134171 DOI: 10.1136/bmjgast-2022-000870] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 01/31/2022] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Alanine aminotransferase (ALT) is a marker of hepatic damage and its range can be affected by viral hepatitis, alcoholic hepatitis and non-alcoholic fatty liver diseases. We aimed to study the factors associated with higher ALT level and update the upper limit of normal (ULN) in the Vietnamese population. METHODS This cross-sectional study enrolled 8383 adults, aged 18 years and older who visited the Medical Center at Ho Chi Minh City for a health check-up. Following the exclusion criteria, 6677 subjects were included in the analysis. RESULTS Age ≤40 years, male gender, body mass index >23 kg/m2, diastolic blood pressure >85 mm Hg, cholesterol >5.2 mmol/L, triglyceride >1.7 mmol/L, positivity, anti-hepatitis C virus positivity and fatty liver (p<0.05) were associated with higher ALT level (>40 U/L). Without considering age and gender, healthy group is defined after exclusion of participants with one of the mentioned contributing factors. The median ALT level in the healthy group was 18 in men and 13 in women. The ULN at the 95th percentile of the healthy group was 40 U/L in men and 28 U/L in women. CONCLUSION The ULN for ALT in healthy women was lower than in healthy men. Updated ULN for ALT level can promote the identification of unhealthy subjects. More studies that involve ethnicity and lifestyle factors are needed to confirm the new ULN in the Vietnamese population.
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Affiliation(s)
- Nguyen Thi Cam Huong
- Department of Infectious diseases, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Sedighe Karimzadeh
- School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Nguyen Thi Thanh
- University of Medicine and Pharmacy at Ho Chi Minh city, Ho Chi Minh City, Viet Nam
| | - Tieu Minh Thuan
- McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
| | | | | | - Dang Nguyen Trung An
- Imaging Diagnostic Department, University of Medicine and Pharmacy at Ho Chi Minh city, Ho Chi Minh City, Viet Nam
| | - Lai To Huong
- Health Screening Department, University Medical Center, Ho Chi Minh City, Viet Nam
| | - Nguyen Tien Huy
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
| | - Pham Thi Le Hoa
- Department of Infectious Disease, University of Medicine and Pharmacy at Ho Chi Minh city, Ho Chi Minh City, Viet Nam
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11
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Petroff D, Bätz O, Jedrysiak K, Kramer J, Berg T, Wiegand J. Age Dependence of Liver Enzymes: An Analysis of Over 1,300,000 Consecutive Blood Samples. Clin Gastroenterol Hepatol 2022; 20:641-650. [PMID: 33524594 DOI: 10.1016/j.cgh.2021.01.039] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 01/13/2021] [Accepted: 01/24/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Upper levels of normal for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) generally take sex into account, but not age. This simplification may lead to misclassification and burden the patient and health system unnecessarily. METHODS Consecutive blood samples were analyzed from a German laboratory. Subcohorts included samples from a prescribed routine check-up and a healthy cohort, defined as patients without increased GGT, triglyceride, cholesterol, glycated hemoglobin, or glucose levels, and without known hepatitis B. RESULTS A total of 1,369,180 blood samples were analyzed from 601,779 participants (50.8% female; mean age, 58.5 y; SD, 18.0 y). There is an extreme age dependence in ALT values for men: increased values were seen in 20.0% (95% CI, 19.5%-20.4%) of patients in the age group of 25 to 34 years, but only 6.7% (95% CI, 6.4%-7.0%) for the ages of 65 to 74 years. The 95th percentile reaches values greater than 80 U/L instead of 50 U/L at the age of 35, and decrease to less than 50 U/L by the age of 75. Similar qualitative results were found in the healthy and prescribed routine check-up subcohorts. The age dependence is much weaker for ALT in women. The proportion of women with an increased AST level increases from approximately 6% to 12% at approximately age 50. The 95th percentile for GGT increases up to the age of 60 in men, and throughout life in women. CONCLUSIONS Current guidelines and reference values for ALT imply that subsequent diagnostics are needed for a large proportion of young men. Our data strongly suggest that age adaptation should be considered.
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Affiliation(s)
- David Petroff
- Clinical Trial Centre, University of Leipzig, Leipzig, Germany
| | - Olaf Bätz
- LADR Laboratory Group Dr. Kramer & Colleagues, Geesthacht, Germany
| | - Katrin Jedrysiak
- LADR Laboratory Group Dr. Kramer & Colleagues, Geesthacht, Germany
| | - Jan Kramer
- LADR Laboratory Group Dr. Kramer & Colleagues, Geesthacht, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Johannes Wiegand
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
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12
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Gallo P, De Vincentis A, Bandinelli S, Ferrucci L, Picardi A, Antonelli Incalzi R, Vespasiani-Gentilucci U. Combined evaluation of aminotransferases improves risk stratification for overall and cause-specific mortality in older patients. Aging Clin Exp Res 2021; 33:3321-3331. [PMID: 34506007 PMCID: PMC12159779 DOI: 10.1007/s40520-021-01979-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 09/01/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Recent studies identified low levels of alanine aminotransferase (ALT) as strong predictors of mortality in older people. AIMS Here we verified if the combined evaluation of aminotransferases may improve risk stratification for adverse outcomes in older patients. METHODS Data are from 761 participants aged more than 65 years from a prospective population-based database (InCHIANTI study), without known baseline chronic liver disease or malignancies. Associations between aminotransferase levels and the risk of all-cause, cardiovascular- and cancer-death were assessed by Cox-models with time-dependent covariates. RESULTS The association of ALT and aspartate aminotransferase (AST) with mortality was non-linear, mirroring a J- and a U-shaped curve, respectively. Based on quintiles of transaminase activities and on their association with overall mortality, low, intermediate (reference group) and high levels were defined. Having at least one transaminase in the low range [aHR 1.76 (1.31-2.36), p < 0.001], mainly if both [(aHR 2.39 (1.81-3.15), p < 0.001], increased the risk of overall mortality, as well as having both enzymes in the high range [aHR 2.14 (1.46-3.15), p < 0.001]. While similar trends were confirmed with respect to cardiovascular mortality, subjects with the highest risk of cancer mortality were those with both enzymes in the high range [aHR 3.48 (1.43-8.44), p = 0.006]. Low levels of transaminases were associated with frailty, sarcopenia and disability, while high levels did not capture any known proxy of adverse outcome. Conclusions and discussion The prognostic information is maximized by the combination of the 2 liver enzymes. While both aminotransferases in low range are characteristically found in the most fragile phenotype, both enzymes in high range are more likely to identify new-onset vascular/infiltrative diseases with adverse outcome.
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Affiliation(s)
- Paolo Gallo
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Rome, Italy
| | - Antonio De Vincentis
- Internal Medicine Unit, Campus Bio-Medico University, Via Alvaro del Portillo 200 , Rome, Italy.
| | | | - Luigi Ferrucci
- National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
| | - Antonio Picardi
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Rome, Italy
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13
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Valenti L, Pelusi S, Bianco C, Ceriotti F, Berzuini A, Iogna Prat L, Trotti R, Malvestiti F, D’Ambrosio R, Lampertico P, Colli A, Colombo M, Tsochatzis EA, Fraquelli M, Prati D. Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update. Hepatol Commun 2021; 5:1824-1832. [PMID: 34520121 PMCID: PMC8557310 DOI: 10.1002/hep4.1794] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/22/2021] [Accepted: 07/02/2021] [Indexed: 12/12/2022] Open
Abstract
The changing epidemiology of liver disease, and modifications in the recommended analytical methodology call for a re-evaluation of the upper reference limits (URLs) of alanine aminotransferase (ALT) levels. Using the same approach consolidated 20 years ago to define the healthy population, we defined the URL for the newly recommended International Federation of Clinical Chemistry (IFCC) standardized test. In a cross-sectional study, we examined 21,296 apparently healthy blood donors (age 18-65 years) and calculated the sex-specific URL by the 95th percentile in individuals without risk factors for liver disease. These were tested for the ability to predict liver damage in a subset of 745 participants with dysmetabolism, in an independent cohort of 977 unselected donors, and in 899 patients with chronic liver disease. ALT levels were measured by the IFCC test. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and younger age were independent ALT predictors (P < 0.001). Updated URLs were identified at 42/30 U/L in males/females, approximately 30% lower than those currently recommended by the IFCC. Due to improved sensitivity, they conferred the ability to detect steatosis and significant fibrosis in individuals with dysmetabolism (odds ratio [OR] = 2.31, range 1.40-3.80, P = 0.001; and OR = 3.35, range 1.19-9.42, P = 0.021; respectively), although with a limited accuracy, and significant fibrosis in unselected donors (OR = 2.32, 1.02-5.31, P = 0.045). Updated URLs had a moderate to high accuracy to discriminate liver conditions (area under the receiver operating characteristic curve = 0.81, range 0.78-0.91). Conclusion: Updated URLs by the IFCC method were lower than those calculated in initial studies, but higher than those in use with the recommended old, nonstandardized method, and were able to better predict liver disease. The limited awareness that different techniques are still in use should be regarded as a possible source of medical errors.
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Affiliation(s)
- Luca Valenti
- Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Serena Pelusi
- Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Cristiana Bianco
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
- Department of MedicineUdine HospitalUdineItaly
| | - Ferruccio Ceriotti
- Clinical LaboratoryFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico MilanMilanItaly
| | - Alessandra Berzuini
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Laura Iogna Prat
- UCL Institute for Liver and Digestive HealthRoyal Free Hospital and UCLLondonUnited Kingdom
| | - Roberta Trotti
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Francesco Malvestiti
- Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Roberta D’Ambrosio
- Division of Gastroenterology and HepatologyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico MilanMilanItaly
| | - Pietro Lampertico
- Division of Gastroenterology and HepatologyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico MilanMilanItaly
- CRC “A. M. and A. Migliavacca” Center for Liver DiseaseDepartment of Pathophysiology and TransplantationUniversity of MilanMilanItaly
| | - Agostino Colli
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | | | - Emmanuel A. Tsochatzis
- UCL Institute for Liver and Digestive HealthRoyal Free Hospital and UCLLondonUnited Kingdom
| | - Mirella Fraquelli
- Department of Gastroenterology and EndoscopyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico MilanMilanItaly
| | - Daniele Prati
- Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
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Ahmadinia AR, Pakkhesal M, Vakili MA. Evaluation of serum alanine aminotransferase and aspartate aminotransferase enzyme levels in women patients with chronic periodontitis. Health Care Women Int 2021; 43:367-375. [PMID: 34432616 DOI: 10.1080/07399332.2021.1961775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The authors' aim in this study was to investigate the relationship between chronic periodontitis and liver status using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in women patients. The researchers conducted a case-control study on women patients referred to Dental School. The researchers collected 5 ml of peripheral venous blood from women for the laboratory process after performing periodontal examination. Participants were 124 women aged 25-50 years (62 cases and 62 control). The difference in serum levels of ALT and the difference in serum levels of AST between the two groups were not statistically significant. However, there was a significant correlation between liver enzymes and periodontitis parameters.
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Affiliation(s)
- Amir Reza Ahmadinia
- Dental Research Center, Periodontics Department, School of Dentistry, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mina Pakkhesal
- Dental Research Center, Community Oral Health Department, School of Dentistry, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohammad Ali Vakili
- Department of Biostatistics and Epidemiology, Faculty of Health, Golestan University of Medical Sciences, Gorgan, Iran
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15
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Bekkelund SI. Serum alanine aminotransferase activity and risk factors for cardiovascular disease in a Caucasian population: the Tromsø study. BMC Cardiovasc Disord 2021; 21:29. [PMID: 33435884 PMCID: PMC7805181 DOI: 10.1186/s12872-020-01826-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 12/14/2020] [Indexed: 12/18/2022] Open
Abstract
Background High and low levels of serum alanine aminotransferase (ALT) are both associated with cardiovascular diseases (CVD) risks especially in elderly, but the mechanisms are less known. This study investigated associations between ALT and CVD risk factors including effects of sex and age in a Caucasian population. Methods Cross-sectional data were analysed sex-stratified in 2555 men (mean age 60.4 years) and 2858 women (mean age 60.0 years) from the population study Tromsø 6. Associations were assessed by variance analysis and multivariable logistic regression of odds to have abnormal ALT. Risk factors included body mass index (BMI), waist-to-hip-ratio, blood pressure, lipids, glucose, glycated haemoglobin and high-sensitive C-reactive protein (CRP). Results Abnormal elevated ALT was detected in 113 men (4.4%) and 188 women (6.6%). Most CVD risk factors associated positively with ALT in both sexes except systolic blood pressure and CRP (women only), while ALT was positively associated with age in men when adjusted for CVD risk factors, P < 0.001. BMI predicted ALT in men (OR 0.94; 95% CI 0.88–1.00, P = 0.047) and women (OR 0.90; 95% CI 0.86–0.95, P < 0.001). A linear inversed association between age and ALT in men and a non-linear inversed U-trend in women with maximum level between 60 and 64 years were found. Conclusion This study confirms a positive relationship between ALT and CVD risk factors, particularly BMI. Age is not a major confounder in the ALT-CVD relationship, but separate sex-analyses is recommended in such studies.
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Affiliation(s)
- Svein Ivar Bekkelund
- Department of Clinical Medicine, UiT - The Arctic University of Norway, 9037, Tromsø, Norway. .,Department of Neurology, University Hospital of North Norway, 9038, Tromsø, Norway.
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Claus M, Antoni C, Hofmann B. Factors associated with elevated alanine aminotransferase in employees of a German chemical company: results of a large cross-sectional study. BMC Gastroenterol 2021; 21:25. [PMID: 33422007 PMCID: PMC7797104 DOI: 10.1186/s12876-021-01601-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 01/04/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We aimed to determine the prevalence of elevated alanine aminotransferase (eALT) in employees of a German chemical company, and analyze its association with sociodemographic, work- and lifestyle-related factors. METHODS The cross-sectional study is based on data surveyed from occupational health check-ups between 2013 and 2018 at the site clinic of a chemical company based in Ludwigshafen, Germany. We used logistic regression analyses to assess the association between sociodemographic, work- and lifestyle-related characteristics and eALT. Quantile regression technique was applied to investigate if associations vary across different quantiles of the ALT distribution. RESULTS Participants (n = 15,348) were predominantly male (78.3%) with a mean age of 42.2 years (SD 10.7). The prevalence of eALT was 18.5% (21.6% in men/7.2% in women) with a geometric mean of 28.9 U/L (32.8 U/L in men/18.5 U/L in women). In the multivariable logistic regression model, odds of eALT were significantly higher for males (OR 2.61; 95%-CI 2.24-3.05), manual workers (OR 1.23; 95%-CI 1.06-1.43), overweight (OR 2.66; 95%-CI 2.36-3.00) or obese respondents (e.g. OR 7.88; 95%-CI 5.75-10.80 for obesity class III), employees who consume any number of alcoholic drinks/week (e.g. OR 1.32; 95%-CI 1.16-1.49 for ≥ 3 drinks per week) and diabetics (OR 1.47; 95%-CI 1.22-1.78). Additionally, season of participation was significantly associated with eALT, with odds being higher for participation in spring, fall or winter, as compared to summer. A significant interaction between age and gender (pInteraction < 0.001) was found, showing approximately a u-shaped age/ALT relationship in women and an inversely u-shaped relationship in men. Quantile regression showed an increasing positive effect of male gender, overweight/obesity, and for diabetics on ALT level when moving from the lowest (q0.1) to the highest (q0.9) considered quantile. Additionally, from the lowest to the highest quantile an increasing negative effect on ALT for older age was observed. CONCLUSIONS Prevalence of eALT in our sample of employees can be considered as high, with almost one in five participants affected. Identification of risk groups allows the implementation of targeted preventive measures in order to avoid transition to severe morbidity.
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Affiliation(s)
- Matthias Claus
- Corporate Health Management, ESG/CS - H308, BASF SE, 67056, Ludwigshafen am Rhein, Germany.
| | - Christoph Antoni
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany
| | - Bernd Hofmann
- Corporate Health Management, ESG/CS - H308, BASF SE, 67056, Ludwigshafen am Rhein, Germany
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Pitchumoni CS. Gastrointestinal Physiology and Aging. GERIATRIC GASTROENTEROLOGY 2021:155-200. [DOI: 10.1007/978-3-030-30192-7_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Visaria A, Pai S, Fayngersh A, Kothari N. Association between alanine aminotransferase within the normal range and all-cause and cause-specific mortality: A nationwide cohort study. PLoS One 2020; 15:e0242431. [PMID: 33216778 PMCID: PMC7678955 DOI: 10.1371/journal.pone.0242431] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 10/23/2020] [Indexed: 01/04/2023] Open
Abstract
Background and aim We sought to determine the association between alanine aminotransferase (ALT) in the normal range and mortality in the absence of liver dysfunction to better understand ALT’s clinical significance beyond liver injury and inflammation. Methods A cohort of 2,708 male and 3,461 female adults aged 20–75 years without liver dysfunction (ALT<30 in males & <19 in females, negative viral serologies, negative ultrasound-based steatosis, no excess alcohol consumption) from the National Health and Nutrition Examination Survey (NHANES)-III (1988–1994) were linked to the National Death Index through December 31, 2015. Serum ALT levels were categorized into sex-specific quartiles (Females: <9, 9–11, 11–14, ≥14 IU/L, Male: <12, 12–15, 15–20, ≥20 U/L). The primary outcome was all-cause mortality. Hazard ratios (HRs) were estimated, adjusting for covariates and accounting for the complex survey design. Results Relative to males in the lowest quartile (Q1), males in the highest quartile (Q4) had 44% decreased risk of all-cause mortality (aHR [95% CI]: 0.56 [0.42, 0.74]). Females in Q4 had 45% decreased risk of all-cause mortality (aHR [95% CI]: 0.55 [0.40, 0.77]). Males with BMI <25 kg/m2 in Q4 had significantly lower risk of all-cause mortality than Q1; however, this association did not exist in males with BMI ≥25 (BMI<25: 0.36 [0.20, 0.64], BMI≥25: 0.77 [0.49, 1.22]). Risk of all-cause mortality was lower in males ≥50 years than in males<50 (age≥50: 0.55 [0.39, 0.77], age<50: 0.81 [0.39, 1.69]). These age- and BMI-related differences were not seen in females. Conclusion ALT within the normal range was inversely associated with all-cause mortality in U.S. adults.
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Affiliation(s)
- Aayush Visaria
- Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America
- * E-mail:
| | - Suraj Pai
- Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America
| | - Alla Fayngersh
- Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America
| | - Neil Kothari
- Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America
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The Impact of Hypoxic Hepatitis on Clinical Outcomes after Extracorporeal Cardiopulmonary Resuscitation. J Clin Med 2020; 9:jcm9092994. [PMID: 32948044 PMCID: PMC7565649 DOI: 10.3390/jcm9092994] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/10/2020] [Accepted: 09/14/2020] [Indexed: 12/18/2022] Open
Abstract
Although there have been several reports regarding the association between hypoxic hepatic injury and clinical outcomes in patients who underwent conventional cardiopulmonary resuscitation (CPR), limited data are available in the setting of extracorporeal CPR (ECPR). Patients who received ECPR due to either in- or out-of-hospital cardiac arrest from May 2004 through December 2018 were eligible. Hypoxic hepatitis (HH) was defined as an increased aspartate aminotransferase or alanine aminotransferase level to more than 20 times the upper normal range. The primary outcome was in-hospital mortality. In addition, we assessed poor neurological outcome defined as a Cerebral Performance Categories score of 3 to 5 at discharge and the predictors of HH occurrence. Among 365 ECPR patients, 90 (24.7%) were identified as having HH. The in-hospital mortality and poor neurologic outcomes in the HH group were significantly higher than those of the non-HH group (72.2% vs. 54.9%, p = 0.004 and 77.8% vs. 63.6%, p = 0.013, respectively). As indicators of hepatic dysfunction, patients with hypoalbuminemia (albumin < 3 g/dL) or coagulopathy (international normalized ratio > 1.5) had significantly higher mortalities than those of their counterparts (p = 0.005 and p < 0.001, respectively). In multivariable logistic regression, age and acute kidney injury requiring continuous renal replacement therapy were predictors for development of HH (p = 0.046 and p < 0.001 respectively). Furthermore age, arrest due to ischemic heart disease, initial shockable rhythm, out-of-hospital cardiac arrest, lowflow time, continuous renal replacement therapy, and HH were significant predictors for in-hospital mortality. HH was a frequent complication and associated with poor clinical outcomes in ECPR patients.
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Prevalence of Elevated Alanine Aminotransferase by Diagnostic Criterion, Age, and Gender among Adolescents. Gastroenterol Res Pract 2020; 2020:4240380. [PMID: 32411198 PMCID: PMC7204184 DOI: 10.1155/2020/4240380] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 12/28/2019] [Indexed: 12/18/2022] Open
Abstract
Background Serum alanine aminotransferase (ALT) activity was measured not only to detect liver disease, but also to monitor overall health. The purpose of this study was to obtain the prevalence of elevated ALT levels among adolescents. Methods In a school-based cross-sectional study, a representative sample was analyzed from 9 middle and high schools in Shenzhen, China, during 2017 to 2018. Elevated ALT was defined as diagnostic criterion I (>30 U/L for boys and >19 U/L for girls) and diagnostic criterion II (>40 U/L). Results From the adolescent population, a total of 7281 students (boys, 4014, and girls, 3267) aged from 10 to 17 years were collected. The prevalence of elevated ALT was 7.11% (6.88% for boys and 7.41% for girls) by criterion I and 2.72% (3.96% for boys and 1.19% for girls) by criterion II. Based on the Shenzhen census and Chinese national census population, the adjusted prevalence of elevated ALT was 7.65% (boys 7.19% and girls 8.21%) and 6.79% (boys 6.07% and girls 7.56%) by criterion I and 2.85% (boys 4.20% and girls 1.16%) and 2.43% (boys 3.49% and girls 1.29%) by criterion II. For age, the overall trends were increasing progressively, regardless of the use of diagnostic criteria for an elevated ALT activity. Conclusions This study supplements the gap that the prevalence of elevated ALT levels differed in gender, age, and criteria among adolescents of Shenzhen. We should take the prevalence as a predictor and continue to play a warning and preventive role in preparation for further intervention.
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21
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Lim AKH. Abnormal liver function tests associated with severe rhabdomyolysis. World J Gastroenterol 2020; 26:1020-1028. [PMID: 32205993 PMCID: PMC7081005 DOI: 10.3748/wjg.v26.i10.1020] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 01/06/2020] [Accepted: 03/09/2020] [Indexed: 02/06/2023] Open
Abstract
Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium, phosphate, urate and intracellular proteins such as myoglobin into the circulation, which may cause complications including acute kidney injury, electrolyte disturbance and cardiac instability. Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis. Typically, there is an increase in serum aminotransferases, namely aspartate aminotransferase and alanine aminotransferase. This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy. However, muscle can also be a source of the increased aminotransferase activity. This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association. It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases, and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury. Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury. This review also explores potential approaches to improve the accuracy of our diagnostic tools, so that excessive or unnecessary liver investigations can be avoided.
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Affiliation(s)
- Andy KH Lim
- Department of General Medicine, Monash Health, Clayton VIC 3168, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton VIC 3168, Australia
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Lim AKH, Arumugananthan C, Lau Hing Yim C, Jellie LJ, Wong EWW, Junckerstorff RK. A Cross-Sectional Study of the Relationship between Serum Creatine Kinase and Liver Biochemistry in Patients with Rhabdomyolysis. J Clin Med 2019; 9:jcm9010081. [PMID: 31905634 PMCID: PMC7019809 DOI: 10.3390/jcm9010081] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 12/20/2019] [Accepted: 12/22/2019] [Indexed: 12/20/2022] Open
Abstract
Abnormal liver function tests are commonly observed with rhabdomyolysis, but the nature of this association is not fully defined. This study aims to determine the functional relationship between serum creatine kinase, as a marker of rhabdomyolysis severity, and liver biochemistry. We used linear regression to model the relationship between liver biochemistry and peak serum creatine kinase. A total of 528 patients with a median age of 74 years were included. The distribution of creatine kinase, bilirubin, alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transferase were significantly skewed, and these variables were log-transformed prior to regression. There was a positive linear correlation between log-alanine aminotransferase and log-creatine kinase. In the multiple regression analysis, log-creatine kinase, age, acute kidney injury stage, and chronic liver disease were independently associated with log-alanine aminotransferase. This model explained 46% of the variance of log-alanine aminotransferase. We found no correlation between the log-creatine kinase and the log-bilirubin, log-alkaline phosphatase, or log-γ-glutamyl transferase. Serum alanine aminotransferase was not associated with inpatient mortality but a higher creatine kinase-alanine aminotransferase ratio was associated with lower odds of mortality. In conclusion, an isolated elevation in alanine aminotransferase can occur in rhabdomyolysis, and it may be possible to anticipate the level of increase based on the peak creatine kinase.
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Affiliation(s)
- Andy K. H. Lim
- General Medicine, Monash Health, Clayton, Victoria 3168, Australia; (C.A.); (C.L.H.Y.); (L.J.J.); (E.W.W.W.); (R.K.J.)
- Department of Medicine, Monash University, Clayton, Victoria 3168, Australia
- Correspondence:
| | - Chitherangee Arumugananthan
- General Medicine, Monash Health, Clayton, Victoria 3168, Australia; (C.A.); (C.L.H.Y.); (L.J.J.); (E.W.W.W.); (R.K.J.)
| | - Corinne Lau Hing Yim
- General Medicine, Monash Health, Clayton, Victoria 3168, Australia; (C.A.); (C.L.H.Y.); (L.J.J.); (E.W.W.W.); (R.K.J.)
| | - Lucy J. Jellie
- General Medicine, Monash Health, Clayton, Victoria 3168, Australia; (C.A.); (C.L.H.Y.); (L.J.J.); (E.W.W.W.); (R.K.J.)
| | - Elena W. W. Wong
- General Medicine, Monash Health, Clayton, Victoria 3168, Australia; (C.A.); (C.L.H.Y.); (L.J.J.); (E.W.W.W.); (R.K.J.)
| | - Ralph K. Junckerstorff
- General Medicine, Monash Health, Clayton, Victoria 3168, Australia; (C.A.); (C.L.H.Y.); (L.J.J.); (E.W.W.W.); (R.K.J.)
- Department of Medicine, Monash University, Clayton, Victoria 3168, Australia
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Nho K, Kueider-Paisley A, Ahmad S, MahmoudianDehkordi S, Arnold M, Risacher SL, Louie G, Blach C, Baillie R, Han X, Kastenmüller G, Trojanowski JQ, Shaw LM, Weiner MW, Doraiswamy PM, van Duijn C, Saykin AJ, Kaddurah-Daouk R. Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers. JAMA Netw Open 2019; 2:e197978. [PMID: 31365104 PMCID: PMC6669786 DOI: 10.1001/jamanetworkopen.2019.7978] [Citation(s) in RCA: 157] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
IMPORTANCE Increasing evidence suggests an important role of liver function in the pathophysiology of Alzheimer disease (AD). The liver is a major metabolic hub; therefore, investigating the association of liver function with AD, cognition, neuroimaging, and CSF biomarkers would improve the understanding of the role of metabolic dysfunction in AD. OBJECTIVE To examine whether liver function markers are associated with cognitive dysfunction and the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, serum-based liver function markers were measured from September 1, 2005, to August 31, 2013, in 1581 AD Neuroimaging Initiative participants along with cognitive measures, cerebrospinal fluid (CSF) biomarkers, brain atrophy, brain glucose metabolism, and amyloid-β accumulation. Associations of liver function markers with AD-associated clinical and A/T/N biomarkers were assessed using generalized linear models adjusted for confounding variables and multiple comparisons. Statistical analysis was performed from November 1, 2017, to February 28, 2019. EXPOSURES Five serum-based liver function markers (total bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) from AD Neuroimaging Initiative participants were used as exposure variables. MAIN OUTCOMES AND MEASURES Primary outcomes included diagnosis of AD, composite scores for executive functioning and memory, CSF biomarkers, atrophy measured by magnetic resonance imaging, brain glucose metabolism measured by fludeoxyglucose F 18 (18F) positron emission tomography, and amyloid-β accumulation measured by [18F]florbetapir positron emission tomography. RESULTS Participants in the AD Neuroimaging Initiative (n = 1581; 697 women and 884 men; mean [SD] age, 73.4 [7.2] years) included 407 cognitively normal older adults, 20 with significant memory concern, 298 with early mild cognitive impairment, 544 with late mild cognitive impairment, and 312 with AD. An elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and lower levels of ALT were associated with AD diagnosis (AST to ALT ratio: odds ratio, 7.932 [95% CI, 1.673-37.617]; P = .03; ALT: odds ratio, 0.133 [95% CI, 0.042-0.422]; P = .004) and poor cognitive performance (AST to ALT ratio: β [SE], -0.465 [0.180]; P = .02 for memory composite score; β [SE], -0.679 [0.215]; P = .006 for executive function composite score; ALT: β [SE], 0.397 [0.128]; P = .006 for memory composite score; β [SE], 0.637 [0.152]; P < .001 for executive function composite score). Increased AST to ALT ratio values were associated with lower CSF amyloid-β 1-42 levels (β [SE], -0.170 [0.061]; P = .04) and increased amyloid-β deposition (amyloid biomarkers), higher CSF phosphorylated tau181 (β [SE], 0.175 [0.055]; P = .02) (tau biomarkers) and higher CSF total tau levels (β [SE], 0.160 [0.049]; P = .02) and reduced brain glucose metabolism (β [SE], -0.123 [0.042]; P = .03) (neurodegeneration biomarkers). Lower levels of ALT were associated with increased amyloid-β deposition (amyloid biomarkers), and reduced brain glucose metabolism (β [SE], 0.096 [0.030]; P = .02) and greater atrophy (neurodegeneration biomarkers). CONCLUSIONS AND RELEVANCE Consistent associations of serum-based liver function markers with cognitive performance and A/T/N biomarkers for AD highlight the involvement of metabolic disturbances in the pathophysiology of AD. Further studies are needed to determine if these associations represent a causative or secondary role. Liver enzyme involvement in AD opens avenues for novel diagnostics and therapeutics.
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Affiliation(s)
- Kwangsik Nho
- Center for Computational Biology and Bioinformatics, Indiana Alzheimer Disease Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis
| | | | - Shahzad Ahmad
- Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | | | - Matthias Arnold
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina
- Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Shannon L. Risacher
- Center for Computational Biology and Bioinformatics, Indiana Alzheimer Disease Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis
| | - Gregory Louie
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina
| | - Colette Blach
- Duke Molecular Physiology Institute, Duke University, Durham, North Carolina
| | | | - Xianlin Han
- University of Texas Health Science Center at San Antonio, San Antonio
| | - Gabi Kastenmüller
- Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - John Q. Trojanowski
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia
| | - Leslie M. Shaw
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia
| | - Michael W. Weiner
- Center for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco Veterans Affairs Medical Center and University of California, San Francisco
| | - P. Murali Doraiswamy
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina
- Duke Institute of Brain Sciences, Duke University, Durham, North Carolina
- Department of Medicine, Duke University, Durham, North Carolina
| | - Cornelia van Duijn
- Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
- Nuffield Department of Population Health, Oxford University, Oxford, United Kingdom
| | - Andrew J. Saykin
- Center for Computational Biology and Bioinformatics, Indiana Alzheimer Disease Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis
| | - Rima Kaddurah-Daouk
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina
- Duke Institute of Brain Sciences, Duke University, Durham, North Carolina
- Department of Medicine, Duke University, Durham, North Carolina
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Xu L, Lin K, Li SL. Factors associated with reverse change of serum ALT activity in patients with chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2018; 26:1996-2001. [DOI: 10.11569/wcjd.v26.i34.1996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the factors associated with the reverse change of serum alanine aminotransferase (ALT) activity in patients with chronic hepatitis B.
METHODS The clinical information of 516 patients with chronic hepatitis B treated from September 2010 to September 2015 was collected. The patients with serum ALT activity ≤ 40 IU/L were divided into a study group, while those with serum ALT activity > 40 IU/L was assigned to a control group.
RESULTS The reverse change rate of ALT activity was 25.78% (133/516) in chronic hepatitis B patients. The reverse change rate of ALT activity was 51.18% (65/127) in the population with combined cirrhosis, significantly higher than that of patients without cirrhosis (17.48%, P < 0.05). Compared to the control group, serum albumin, direct bilirubin, indirect bilirubin, total bile acids, potassium, sodium, calcium, and triglycerides in the study group were significantly lower, while serum globulin and uric acid were significantly higher (P < 0.05). Multivariate unconditional logistic regression analysis showed that cirrhosis and serum uric acid were positively associated with the reverse change of ALT activity (P < 0.05), while serum albumin, total bile acids, potassium, calcium, and chloride were negatively correlated with the reverse change of ALT activity (P < 0.05).
CONCLUSION Combined liver cirrhosis, increased serum globulin and uric acid, and declined serum albumin, direct bilirubin, indirect bilirubin, total bile acid, potassium, calcium, triglyceride, and chloride may be factors influencing the reverse change of serum ALT activity. When serum ALT activity is not consistent with clinical symptoms of chronic hepatitis B, attention should be paid to these factors as well.
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Affiliation(s)
- Lei Xu
- Department of Gastroenterology, the Hospital Affiliated to Guilin Medical College, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Kai Lin
- Department of Gastroenterology, the Hospital Affiliated to Guilin Medical College, Guilin 541001, Guangxi Zhuang Autonomous Region, China
| | - Sheng-Lian Li
- Department of Health Toxicology, School of Public Health, Guilin Medical College, Guilin 541001, Guangxi Zhuang Autonomous Region, China
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25
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Risk of mortality and level of serum alanine aminotransferase among community-dwelling elderly in Israel. Eur J Gastroenterol Hepatol 2018; 30:1428-1433. [PMID: 30048334 DOI: 10.1097/meg.0000000000001225] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Serum alanine aminotransferase (ALT) levels below and above the reference range have been found to serve as a marker of liver injury and to predict all-cause mortality. The need to adjust the reference range by age, sex, or other parameters remains unclear. The current reference range of serum ALT in Israel is 0-34 IU/l for women and 0-45 IU/l for men. We aimed to test the applicability of the current reference range values of ALT in specific people - the elderly population. METHODS A retrospective design was used. The study population consisted of community-dwelling individuals aged at least 65 years who were tested for serum ALT in 2002 at a large health management organization and followed until the end of December 2012. Data were collected on demographics, laboratory tests, comorbidities, and mortality. RESULTS A total of 49 634 participants (59% women, mean age 83.2±6.3 years) were included. ALT levels between 16 and 25 IU/l were associated with the lowest mortality (hazard ratio=1), and values of less than 16 IU/l and more than 25 IU/l (unadjusted) were associated with higher mortality risk, yielding a U-shaped pattern.Highest mortality rates were also revealed at serum ALT levels more than 56 IU/l and less than 10 IU/l. A significant association of higher mortality risk was noted with lower mean values of hemoglobin, albumin, and total cholesterol, both for patients with lower serum ALT levels (<10 IU/l) and patients with higher serum levels (>56 IU/l). CONCLUSION Very low and very high levels of serum ALT within the current reference range are associated with an increased risk of death in community-dwelling individuals of at least 65 years old.
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26
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Vespasiani-Gentilucci U, De Vincentis A, Ferrucci L, Bandinelli S, Antonelli Incalzi R, Picardi A. Low Alanine Aminotransferase Levels in the Elderly Population: Frailty, Disability, Sarcopenia, and Reduced Survival. J Gerontol A Biol Sci Med Sci 2018; 73:925-930. [PMID: 28633440 PMCID: PMC6001897 DOI: 10.1093/gerona/glx126] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Accepted: 06/17/2017] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Although low alanine aminotransferase (ALT) levels have been associated with poor outcomes in the elderly population, the determinants subtending this association have been poorly explored. To gain insight into this topic, we analyzed data from a prospective population-based database (InCHIANTI study) in which frailty, disability, sarcopenia, and pyridoxine levels were systematically assessed. METHODS Data are from 765 participants aged more than 65 years (mean age 75.3 years, women 61.8%), without chronic liver disease, malignancies, or alcohol abuse. Frailty was defined according to Fried criteria, sarcopenia through peripheral Quantitative-Computed-Tomography (lowest gender-specific tertile of the residuals of a linear regression of muscle mass from height and fat mass), and disability as self-reported need for help in at least one basic daily living activity. Associations of ALT with overall and cardiovascular mortality were assessed by Cox-models with time-dependent covariates. RESULTS ALT activity was inversely associated with frailty, sarcopenia, disability, and pyridoxine deficiency; however, higher ALT was confirmed to be protective with respect of overall and cardiovascular mortality even in multiple-adjusted models including all these covariates (overall: hazard ratio [HR] 0.98 [0.96-1], p = .02; cardiovascular: 0.94 [0.9-0.98], p < .01). The association between ALT activity and mortality was nonlinear (J-shaped), and subjects in the lower quintiles of ALT levels showed a sharply increased overall and cardiovascular mortality. CONCLUSIONS These results suggest that reduced ALT levels in older individuals can be considered as a marker of frailty, disability, and sarcopenia, and as an independent predictor of adverse outcomes. The possible relationship between reduced ALT and impaired hepatic metabolic functions should be explored.
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Affiliation(s)
| | - Antonio De Vincentis
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
| | - Luigi Ferrucci
- National Institute on Aging, National Institutes of Health, Baltimore, Maryland
| | | | | | - Antonio Picardi
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
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27
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Cheng SQ. Influence of non-pathological factors on ALT measurements. Shijie Huaren Xiaohua Zazhi 2017; 25:3005-3020. [DOI: 10.11569/wcjd.v25.i34.3005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Alanine transaminase (ALT) is still the most sensitive marker for evaluating the damage of liver cells. ALT measurements may be affected by common non-pathological factors such as gender, age, pregnancy, different physiological conditions, circadian rhythm, diet, drinking, smoking, strenuous exercise, metabolic factors, drugs, blood collection methods, and specimen collection, transmission, and preservation. It is important to emphasize the definition of limits of normal ALT and the influence of the above-mentioned non-pathological factors on its test results.
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Affiliation(s)
- Shu-Quan Cheng
- Department of Hepatology, the Third People's Hospital of Guilin, Guilin 541002, Guangxi Zhuang Autonomous Region, China
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28
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Ming K, Chen Y, Shi J, Yang J, Yao F, Du H, Zhang W, Bai J, Liu J, Wang D, Hu Y, Wu Y. Effects of Chrysanthemum indicum polysaccharide and its phosphate on anti-duck hepatitis a virus and alleviating hepatic injury. Int J Biol Macromol 2017; 102:813-821. [DOI: 10.1016/j.ijbiomac.2017.04.093] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 02/28/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023]
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29
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Harada PHN, Cook NR, Cohen DE, Paynter NP, Rose L, Ridker PM. Relation of Alanine Aminotransferase Levels to Cardiovascular Events and Statin Efficacy. Am J Cardiol 2016; 118:49-55. [PMID: 27317931 DOI: 10.1016/j.amjcard.2016.04.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Revised: 04/08/2016] [Accepted: 04/08/2016] [Indexed: 12/23/2022]
Abstract
The relation between hepatic serum markers within the normal range and cardiovascular risk is uncertain. We sought to address this issue within a prospective randomized trial of statin therapy. Men and women (n = 17,515) free of cardiovascular disease participating in a randomized placebo controlled trial of rosuvastatin 20 mg/day had baseline levels of alanine aminotransferase (ALT) below <40 IU/l and were followed prospectively for the first-ever cardiovascular events. Cox proportional hazards models were used to calculate the relative risks of these events according to increasing tertiles and each SD increase in baseline ALT levels. ALT levels at study entry, all within the normal range, were inversely associated with age, smoking status, and inflammation and were positively associated with male gender, alcohol use, and triglycerides. Incident cardiovascular event rates were highest in those in the lowest tertile of baseline ALT; specifically, incidence rates were 1.43, 0.98, and 0.85 per 100 person-years of exposure for those in the lowest, middle, and highest tertile of baseline ALT within the normal range, respectively (p <0.001). These inverse effects remained statistically significant after multivariate adjustment for a wide range of vascular risk factors risk markers such that each higher SD unit of ALT was associated with an 18% lower event rate (relative risk 0.82, 95% confidence interval 0.72 to 0.93, p = 0.002). The efficacy of statin therapy was not modified by baseline ALT level. In conclusion, increasing ALT levels within the normal range are inversely associated with future cardiovascular risk but had limited clinical utility and also did not modify the efficacy of statin therapy.
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Affiliation(s)
- Paulo H N Harada
- Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Nancy R Cook
- Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - David E Cohen
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Nina P Paynter
- Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Lynda Rose
- Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Paul M Ridker
- Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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30
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Oh CM, Won YJ, Cho H, Lee JK, Park BY, Jun JK, Koh DH, Ki M, Jung KW, Oh IH. Alanine aminotransferase and gamma-glutamyl transferase have different dose-response relationships with risk of mortality by age. Liver Int 2016; 36:126-35. [PMID: 26036985 DOI: 10.1111/liv.12879] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 05/28/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS It remains unclear whether the respective dose-response relationships between serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels and risk of mortality are consistent by age. METHODS We used sampled cohort data from the National Health Insurance Corporation to conduct a retrospective cohort study. A total of 313 252 participants who received medical health check-ups from 2002 to 2008 were assessed for risk of death according to serum ALT and GGT levels over an average of 6 years. The hazard ratios (HRs) for mortality were analysed with Cox proportional hazard model. RESULTS The crude mortality rate increased linearly with increasing serum ALT and GGT levels in adults aged <60 years. However, the all-cause mortality rate showed a J-shaped relationship with increasing serum ALT levels whereas all-cause mortality rate showed a linear relationship with increasing serum GGT levels in adults aged ≥60 years. The HR of death showed U-shaped relationships with increasing serum ALT levels in adults aged ≥60 years. On the contrary, the HR of death from any cause had a linear association with increasing serum GGT levels among all age groups. CONCLUSIONS In this study, U-shaped relationship patterns were demonstrated between serum ALT levels and risk for all-cause mortality in adults aged ≥60 years while serum GGT levels showed a linear relationship with risk for all-cause death. Very low levels of serum ALT in elderly patients suggest that they are at high risk of mortality.
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Affiliation(s)
- Chang-Mo Oh
- Cancer Registration and Statistic Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Young-Joo Won
- Cancer Registration and Statistic Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea.,Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Hyunsoon Cho
- Cancer Registration and Statistic Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea.,Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Jong-Keun Lee
- Cancer Registration and Statistic Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Bo Young Park
- Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.,Cancer Early Detection Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Jae Kwan Jun
- Cancer Information and Education Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Dong-Hee Koh
- Department of Occupational and Environmental Medicine, International St. Mary's Hospital, Catholic Kwandong University, Gangneung, Korea
| | - Moran Ki
- Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Kyu-Won Jung
- Cancer Registration and Statistic Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - In-Hwan Oh
- Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
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31
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Coppell KJ, Miller JC, Gray AR, Schultz M, Mann JI, Parnell WR. Obesity and the extent of liver damage among adult New Zealanders: findings from a national survey. Obes Sci Pract 2015; 1:67-77. [PMID: 27774250 PMCID: PMC5063157 DOI: 10.1002/osp4.13] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 09/04/2015] [Accepted: 09/15/2015] [Indexed: 12/18/2022] Open
Abstract
Objective Non‐alcoholic fatty liver disease (NAFLD), defined as excessive fat accumulation in hepatocytes when no other pathologic causes are present, is an increasingly common obesity‐related disorder. We sought to describe the prevalence of elevated liver enzymes, a marker of liver damage, among New Zealand adults, and high‐risk subgroups including those with an elevated body mass index and those with pre‐diabetes or diabetes, to gain a better understanding of the burden of liver disease. Methods A total of 4,721 New Zealanders aged 15+ years participated in a nationally representative nutrition survey. Liver enzymes, alanine transaminase (ALT) and gamma glutamyl transpeptidase (GGT) were measured in serum. Results were available for 3,035 participants, of whom 10.8% were Māori and 4.5% Pacific. Results Overall, the prevalence of elevated ALT and elevated GGT was 13.1% (95% confidence interval [CI]: 11.2 – 15.0) and 13.7% (95% CI: 12.0 – 15.4), respectively. Odds ratios for an elevated ALT or GGT markedly increased with increasing body mass index. Men with obesity had the highest elevated ALT prevalence (28.5%; 95% CI: 21.7–35.4), and women with diabetes had the highest elevated GGT prevalence (36.5%; 95% CI: 26.0–47.0). Adding alcohol consumption categories to each of the adjusted models did not meaningfully change any results, although for women, heavy alcohol consumption was associated with an elevated GGT (overall p = 0.03). Conclusions Obesity‐related liver disease is likely to increasingly burden the New Zealand health sector and contribute to health disparities unless effective obesity treatment and prevention measures are given high priority. © 2015 The Authors. Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society.
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Affiliation(s)
- K J Coppell
- Edgar Diabetes and Obesity Research, Department of Medicine University of Otago Dunedin New Zealand
| | - J C Miller
- Department of Human Nutrition University of Otago Dunedin New Zealand
| | - A R Gray
- Department of Preventive and Social Medicine University of Otago Dunedin New Zealand
| | - M Schultz
- Gastroenterology, Department of Medicine University of Otago Dunedin New Zealand
| | - J I Mann
- Edgar Diabetes and Obesity Research, Department of Medicine University of Otago Dunedin New Zealand; Department of Human Nutrition University of Otago Dunedin New Zealand
| | - W R Parnell
- Department of Human Nutrition University of Otago Dunedin New Zealand
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Kunutsor SK, Bakker SJ, Kootstra-Ros JE, Blokzijl H, Gansevoort RT, Dullaart RP. Inverse linear associations between liver aminotransferases and incident cardiovascular disease risk: The PREVEND study. Atherosclerosis 2015; 243:138-47. [DOI: 10.1016/j.atherosclerosis.2015.09.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 08/26/2015] [Accepted: 09/02/2015] [Indexed: 12/18/2022]
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Deetman PE, Alkhalaf A, Landman GWD, Groenier KH, Kootstra-Ros JE, Navis G, Bilo HJG, Kleefstra N, Bakker SJL. Alanine aminotransferase and mortality in patients with type 2 diabetes (ZODIAC-38). Eur J Clin Invest 2015; 45:807-14. [PMID: 26046667 DOI: 10.1111/eci.12474] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 06/01/2015] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Combined data suggest a bimodal association of alanine aminotransferase (ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes. DESIGN A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. Cox regression analyses were performed to determine the associations of log2 -transformed baseline ALT with all-cause, cardiovascular and noncardiovascular mortality. RESULTS In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8-16) U/L. During median follow-up for 11.1 (6.1-14.0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.72-0.92), independently of potential confounders. This was less attributable to cardiovascular mortality (HR 0.87; 95% CI 0.72-1.05), than to noncardiovascular mortality (HR 0.77; 95% CI 0.65-0.90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal (P = 0.003). DISCUSSION In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal.
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Affiliation(s)
- Petronella E Deetman
- Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Alaa Alkhalaf
- Department of Gastroenterology, Isala Clinics, Zwolle, the Netherlands
| | - Gijs W D Landman
- Department of Medicine, Gelre Hospital, Apeldoorn, the Netherlands.,Diabetes Centre, Isala Clinics, Zwolle, the Netherlands
| | - Klaas H Groenier
- Diabetes Centre, Isala Clinics, Zwolle, the Netherlands.,Department of General Practice, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jenny E Kootstra-Ros
- Department of Laboratory Medicine, University Medical Center Groningen, Groningen, the Netherlands
| | - Gerjan Navis
- Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Henk J G Bilo
- Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.,Diabetes Centre, Isala Clinics, Zwolle, the Netherlands
| | - Nanne Kleefstra
- Diabetes Centre, Isala Clinics, Zwolle, the Netherlands.,Langerhans Medical Research Group, Zwolle, the Netherlands
| | - Stephan J L Bakker
- Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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He KP, Zhao C, Qiang Y, Liu HR, Chen N, Tao XJ, Chen LL, Song H. Impact of elevated aspartate and alanine aminotransferase on metabolic syndrome and its components among adult people living in Ningxia, China. Chronic Dis Transl Med 2015; 1:124-132. [PMID: 29062997 PMCID: PMC5643566 DOI: 10.1016/j.cdtm.2015.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Metabolic syndrome (MS) is a combination of medical disorders that increase the risk for cardiovascular disease and diabetes mellitus. It suggests an association between an elevated serum aminotransferase level and MS. Little data show the relationship between the levels of serum aminotransferase and the incidence of MS in Ningxia, China. METHODS A total of 5415 subjects who received medical health checkups from 2007 to 2009 were enrolled in the study. The participants were interviewed by trained health workers under a structured questionnaire. MS was defined according to the modified ATPIII criteria for Asian Americans by the American Heart Association (AHA-ATP III). RESULTS The prevalence of elevated aspartate aminotransferase (AST) and ALT (>40 U/L) were 7.1% and 22.2% in males, and 2.1% and 4.8% in females respectively. The prevalence of MS was 32.1% in males and 15.4% in females. The components of MS were significantly more in the group with elevated aminotransferase levels than in the group with normal aminotransferase levels. The odds ratios (95% CI) for elevated AST were 1.90 (1.49, 2.42), 2.59 (2.01, 3.39), 1.68 (1.32, 2.15), and 1.81 (1.36, 2.42) in the adults with abdominal obesity, high serum triglycerides levels, high blood pressure, and high plasma glucose levels respectively. After adjustment for age, the odds ratios (95% CI) for elevated ALT were 3.08 (2.63, 3.61), 4.30 (3.64, 5.08), 1.26 (1.08, 1.48), 2.16 (1.93, 2.65) and 2.38 (1.96, 2.87) in adults with abdominal obesity, high serum triglycerides levels, low serum high-density lipoproteincholesterol (HDL-C), high blood pressure, and high plasma glucose levels respectively. The odds ratios (95% CI) for elevated AST were 1.67 (1.06, 2.63), 2.28 (1.46, 3.63), 2.59 (1.59, 4.21) and for elevated ALT 2.02 (1.50, 2.73), 2.68 (1.96, 3.65), 3.94 (2.86, 5.43) for the subjects with 1, 2, and ≥3 risk factors after adjustment for age, gender, and BMI. CONCLUSION The serum aminotransferase levels were higher in males compared to females, and serum ALT level was more closely associated with MS than the AST level in adults in Ningxia, China. With an increasing the number of components of MS, the aminotransferase levels and the risks for elevated aminotransferase increase, whereas the AST/ALT ratios decrease.
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Affiliation(s)
- Kun-Peng He
- School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Chuan Zhao
- School of Basic Medical, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450002, China
| | - Yan Qiang
- General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - He-Rong Liu
- School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Nan Chen
- School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Xiu-Juan Tao
- School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Li-Li Chen
- School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Hui Song
- School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China
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Mirghani S, Yousefi M. The effect of interval recovery periods during HIIT on liver enzymes and lipid profile in overweight women. Sci Sports 2015. [DOI: 10.1016/j.scispo.2014.09.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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McCallum L, Panniyammakal J, Hastie CE, Hewitt J, Patel R, Jones GC, Muir S, Walters M, Sattar N, Dominiczak AF, Padmanabhan S. Longitudinal Blood Pressure Control, Long-Term Mortality, and Predictive Utility of Serum Liver Enzymes and Bilirubin in Hypertensive Patients. Hypertension 2015; 66:37-43. [PMID: 25941342 PMCID: PMC4461392 DOI: 10.1161/hypertensionaha.114.04915] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Accepted: 04/12/2015] [Indexed: 01/04/2023]
Abstract
Supplemental Digital Content is available in the text. There is accruing evidence from general population studies that serum bilirubin and liver enzymes affect blood pressure (BP) and cardiovascular risk, but it is unclear whether these have an impact on hypertensive patients in terms of long-term survival or BP control. We analyzed 12 000 treated hypertensive individuals attending a tertiary care clinic followed up for 35 years for association between baseline liver function tests and cause-specific mortality after adjustment for conventional cardiovascular covariates. Generalized estimating equations were used to study the association of liver tests and follow-up BP. The total time at risk was 173 806 person years with median survival 32.3 years. Follow-up systolic BP over 5 years changed by −0.4 (alanine transaminase and bilirubin), +2.1(alkaline phosphatase), +0.9(γ-glutamyl transpeptidase) mm Hg for each standard deviation increase. Serum total bilirubin and alanine transaminase showed a significant negative association with all-cause and cardiovascular mortality, whereas alkaline phosphatase and γ-glutamyl transpeptidase showed a positive association and aspartate transaminase showed a U-shapedassociation. Serum bilirubin showed an incremental improvement of continuous net reclassification improvement by 8% to 26% for 25 year and 35 year cardiovascular mortality, whereas all liver markers together improved continuous net reclassification improvement by 19% to 47% compared with reference model. In hypertensive patients, serum liver enzymes and bilirubin within 4 standard deviations of the mean show independent effects on mortality and BP control. Our findings would support further studies to elucidate the mechanisms by which liver enzymes and bilirubin may exert an effect on BP and cardiovascular risk, but there is little support for using them in risk stratification.
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Affiliation(s)
- Linsay McCallum
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Jeemon Panniyammakal
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Claire E Hastie
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Jonathan Hewitt
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Rajan Patel
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Gregory C Jones
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Scott Muir
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Matthew Walters
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Anna F Dominiczak
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Sandosh Padmanabhan
- From the BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
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Hepatic Enzyme's Reference Intervals and Their Modulating Factors in Western Indian Population. Indian J Clin Biochem 2015; 31:108-16. [PMID: 26855497 DOI: 10.1007/s12291-015-0508-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2015] [Accepted: 04/20/2015] [Indexed: 01/03/2023]
Abstract
The reference intervals (RIs) of serum aminotransferases and Gamma-glutamyl transferase (GGT) have been established many years ago. Recent RIs are not available. The prospective study was conducted to re-evaluate the RIs of liver enzymes and the effect of demographic and anthropometric variables on them in western Indian population. A total of 1059 blood donors comprised the study population. Anthropometry and serum liver enzymes levels were measured. Subjects were categorized into normal weight and overweight by using body mass index (BMI) and waist circumference (WC). For RI determination, non-parametric methodology recommended by IFCC/CLSI was adopted. Mann-Whitney test and Spearman's rank correlation were used for statistical analysis. Upper limit of normal reference value of liver enzymes were lower in female compared to male. (ALT-23.55 F vs 36.00 M, GGT-34.58 F vs 36.20 M) When RI of liver enzymes were calculated according to body mass index, the upper limit of normal of ALT and GGT were higher in overweight group compared to normal weight group. (ALT-38.00 vs 27.00 IU/L and GGT-37.59 vs 35.26 IU/L). In both male and female, liver enzymes correlated significantly with age. WC and BMI were positively correlated with AST, ALT and GGT in both subgroups and the correlation was stronger in male. Demographic factors should be considered for making liver enzyme tests more clinically relevant. Gender based partitioning should be adopted for serum alanine aminotransferase (ALT) and GGT reference values for Western Indian population.
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Chen Y, Song M, Wang Y, Xiong W, Zeng L, Zhang S, Xu M, Du H, Liu J, Wang D, Wu Y, Hu Y. The anti-DHAV activities of Astragalus polysaccharide and its sulfate compared with those of BSRPS and its sulfate. Carbohydr Polym 2015; 117:339-345. [DOI: 10.1016/j.carbpol.2014.09.071] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 09/03/2014] [Accepted: 09/21/2014] [Indexed: 12/18/2022]
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Kallwitz ER, Daviglus ML, Allison MA, Emory KT, Zhao L, Kuniholm MH, Chen J, Gouskova N, Pirzada A, Talavera GA, Youngblood ME, Cotler SJ. Prevalence of suspected nonalcoholic fatty liver disease in Hispanic/Latino individuals differs by heritage. Clin Gastroenterol Hepatol 2015; 13:569-76. [PMID: 25218670 PMCID: PMC4333050 DOI: 10.1016/j.cgh.2014.08.037] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 08/20/2014] [Accepted: 08/28/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) was shown to disproportionally affect Hispanic persons. We examined the prevalence of suspected NAFLD in Hispanic/Latino persons with diverse backgrounds. METHODS We studied the prevalence of suspected NAFLD among 12,133 persons included in the Hispanic Community Health Study/Study of Latinos. We collected data on levels of aminotransferase, metabolic syndrome (defined by National Cholesterol Education Program-Adult Treatment Panel III guidelines), demographics, and health behaviors. Suspected NAFLD was defined on the basis of increased level of aminotransferase in the absence of serologic evidence for common causes of liver disease or excessive alcohol consumption. In multivariate analyses, data were adjusted for metabolic syndrome, age, acculturation, diet, physical activity, sleep, and levels of education and income. RESULTS In multivariate analysis, compared with persons of Mexican heritage, persons of Cuban (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.57-0.85), Puerto Rican (OR, 0.67; 95% CI, 0.52-0.87), and Dominican backgrounds (OR, 0.71; 95% CI, 0.54-0.93) had lower rates of suspected NAFLD. Persons of Central American and South American heritage had a similar prevalence of suspected NAFLD compared with persons of Mexican heritage. NAFLD was less common in women than in men (OR, 0.49; 95% CI, 0.40-0.60). Suspected NAFLD associated with metabolic syndrome and all 5 of its components. CONCLUSIONS On the basis of an analysis of a large database of health in Latino populations, we found the prevalence of suspected NAFLD among Hispanic/Latino individuals to vary by region of heritage.
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Affiliation(s)
- Eric R Kallwitz
- Department of Medicine, Loyola University Medical Center, Maywood, Illinois.
| | - Martha L Daviglus
- Department of Preventive Medicine, University of Illinois, Chicago, Illinois
| | - Matthew A Allison
- Department of Family and Preventive Medicine, University of California, San Diego, California
| | - Kristen T Emory
- Department of Family and Preventive Medicine, University of California, San Diego, California
| | - Lihui Zhao
- Department of Preventive Medicine, University of Illinois, Chicago, Illinois
| | - Mark H Kuniholm
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
| | - Jinsong Chen
- Department of Preventive Medicine, University of Illinois, Chicago, Illinois
| | - Natalia Gouskova
- Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, North Carolina
| | - Amber Pirzada
- Department of Preventive Medicine, University of Illinois, Chicago, Illinois
| | - Gregory A Talavera
- School of Public Health, San Diego State University, San Diego, California
| | - Marston E Youngblood
- Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, North Carolina
| | - Scott J Cotler
- Department of Medicine, Loyola University Medical Center, Maywood, Illinois
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Fisher L, Srikusalanukul W, Fisher A, Smith P. Liver function parameters in hip fracture patients: relations to age, adipokines, comorbidities and outcomes. Int J Med Sci 2015; 12:100-15. [PMID: 25589886 PMCID: PMC4293175 DOI: 10.7150/ijms.10696] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Accepted: 04/11/2014] [Indexed: 02/07/2023] Open
Abstract
AIM To asses liver markers in older patients with hip fracture (HF) in relation to age, comorbidities, metabolic characteristics and short-term outcomes. METHODS In 294 patients with HF (mean age 82.0±7.9 years, 72.1% women) serum alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate, magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I were measured. RESULTS Elevated ALT, GGT, ALP or bilirubin levels on admission were observed in 1.7%-9.9% of patients. With age GGT, ALT and leptin decrease, while PTH and adiponectin concentrations increase. Higher GGT (>30 U/L, median level) was associated with coronary artery disease (CAD), diabetes mellitus (DM), and alcohol overuse; lower ALT (≤20 U/L, median level) with dementia; total bilirubin>20 μmol/L with CAD and alcohol overuse; and albumin>33 g/L with CAD. Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol overuse and DM as independent and significant determinants of GGT (as continuous or categorical variable); GGT for each other liver marker; and PTH for adiponectin. The risk of prolonged hospital stay (>20 days) was about two times higher in patients with GGT>30 U/L or adiponectin>17.14 ng/L (median level) and 4.7 times higher if both conditions coexisted. The risk of in-hospital death was 3 times higher if albumin was <33 g/L. CONCLUSIONS In older HF patients liver markers even within the normal range are associated with age-related disorders and outcomes. Adiponectin (but not 25(OH)vitaminD, PTH, leptin or resistin) is an independent contributor to higher GGT. Serum GGT and albumin predict prolonged hospital stay and in-hospital death, respectively. A unifying hypothesis of the findings presented.
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Affiliation(s)
- Leon Fisher
- 1. Department of Gastroenterology, The Canberra Hospital, Canberra, ACT, Australia
| | - Wichat Srikusalanukul
- 2. Department of Geriatric Medicine, The Canberra Hospital, Canberra, ACT, Australia
| | - Alexander Fisher
- 2. Department of Geriatric Medicine, The Canberra Hospital, Canberra, ACT, Australia ; 4. Australian National University Medical School, Canberra, ACT, Australia
| | - Paul Smith
- 3. Department of Orthopaedic Surgery, The Canberra Hospital, Canberra, ACT, Australia ; 4. Australian National University Medical School, Canberra, ACT, Australia
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Vespasiani-Gentilucci U, Gallo P, Piccinocchi G, Piccinocchi R, Schena E, Galati G, De Vincentis A, Dell'Unto C, Picardi A. Determinants of alanine aminotransferase levels in a large population from Southern Italy: relationship between alanine aminotransferase and age. Dig Liver Dis 2014; 46:909-915. [PMID: 24953204 DOI: 10.1016/j.dld.2014.05.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 05/19/2014] [Accepted: 05/25/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Determinants of alanine aminotransferase levels have never been investigated in real-life settings. The relationship between alanine aminotransferase and age remains controversial. We evaluated epidemiological, anthropometric, and metabolic factors associated with alanine aminotransferase, focusing on the relationship between alanine aminotransferase and age. METHODS A 5-year retrospective analysis was performed on data recorded by 120 general practitioners from Naples (Italy), caring for 170,000 subjects. Exclusion criteria were age <18 years, diagnosis of chronic liver disease, positive markers for viral hepatitis, alcohol abuse, and alanine aminotransferase >100UI/L. RESULTS 44,232 subjects were enrolled (42.7% males, mean age 56±18 years). Alanine aminotransferase showed independent direct associations with body mass index, glycaemia, cholesterol, and triglycerides (p<0.001), and inverse associations with high-density lipoprotein cholesterol (p<0.001) and creatinine (p<0.01). The relationship between alanine aminotransferase and age was better expressed by polynomial regression (r=0.18, p<0.001), creating an inverted parabola. Mean alanine aminotransferase increased until the third decade in males and the fifth in females, with a subsequent progressive decrease in both genders. The inverse association between alanine aminotransferase and age in older subjects was independent from metabolic factors. CONCLUSIONS This real-life setting study, supports the concept that dysmetabolism is a strong determinant of liver injury. Based on our data, a reduction of the standard upper limit of normal alanine aminotransferase should be considered for older subjects.
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Affiliation(s)
| | - Paolo Gallo
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico of Rome, Italy
| | | | | | - Emiliano Schena
- Unit of Measurement and Biomedical Instrumentation, University Campus Bio-Medico of Rome, Italy
| | - Giovanni Galati
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico of Rome, Italy
| | - Antonio De Vincentis
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico of Rome, Italy
| | - Chiara Dell'Unto
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico of Rome, Italy
| | - Antonio Picardi
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico of Rome, Italy
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Kim HY, Kim CW, Lee CD, Choi JY, Park CH, Bae SH, Yoon SK, Han K, Park YM. Can "healthy" normal alanine aminotransferase levels identify the metabolically obese phenotype? Findings from the Korea national health and nutrition examination survey 2008-2010. Dig Dis Sci 2014; 59:1330-7. [PMID: 24705695 DOI: 10.1007/s10620-013-2995-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Accepted: 12/10/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND There is no established parameter with which to screen metabolically obese phenotypes. AIM The aim of the study was to revise the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) and to investigate the predictive value of updated ALT levels for metabolic obese phenotype stratified according to body mass index (BMI). METHODS We analyzed a nationally representative data from the Fourth Korea National Health and Nutrition Examination Survey. This cross-sectional study included 2,416 healthy people aged 33.9 ± 0.3 years. The ULN of healthy ALT level was set at the 95th percentile of the healthy population. A metabolic obese phenotype was defined as having insulin resistance or metabolic syndrome. A logistic regression analysis was performed to assess the odds ratio for a metabolic obese phenotype according to the healthy ALT level. RESULTS The revised ULN of serum ALT level in healthy participants were 30 IU/L and 22 IU/L for males and females, respectively. Serum ALT level was higher in individuals with metabolic obesity compared with those without metabolic obesity in both genders, stratified according to BMI. After adjusting for age, BMI, smoking, alcohol drinking, and regular physical activity, unhealthy normal ALT levels (males 30-40 IU/L, females 22-40 IU/L) were significantly associated with metabolic obesity, especially in both obese and non-obese women. CONCLUSIONS A newly revised threshold for ALT is proposed as a simple clinical metabolic parameter that can identify a metabolic obese phenotype. We suggest that people with unhealthy normal ALT levels may need further investigation for the presence of metabolic obesity.
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Affiliation(s)
- Hee Yeon Kim
- Division of Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu-si, Gyeonggi-do, Korea,
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Bush Sophora Root polysaccharide and its sulfate can scavenge free radicals resulted from duck virus hepatitis. Int J Biol Macromol 2014; 66:186-93. [DOI: 10.1016/j.ijbiomac.2014.02.038] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 02/13/2014] [Accepted: 02/17/2014] [Indexed: 12/18/2022]
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Mohammadi F, Qorbani M, Kelishadi R, Baygi F, Ardalan G, Taslimi M, Mahmoudarabi M, Motlagh ME, Asayesh H, Larijani B, Heshmat R. Association of cardiometabolic risk factors and hepatic enzymes in a national sample of Iranian children and adolescents: the CASPIAN-III study. J Pediatr Gastroenterol Nutr 2014; 58:463-8. [PMID: 24253369 DOI: 10.1097/mpg.0000000000000246] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Elevated liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may be associated with metabolic syndrome (MetS) and cardiovascular disease. We investigated the association of cardiometabolic risk factors and liver enzymes in a nationally representative sample of Iranian children and adolescents. METHODS The national study was conducted in the framework of the third survey of Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable Disease study. Subjects were 3948 students (1942 girls, 67.55% urban, mean age 14.7 ± 2.4 years) who were recruited by multistage random cluster sampling from 27 provincial counties in Iran. Physical examination and laboratory tests were conducted under standard protocols. RESULTS Participants with elevated serum ALT had higher levels of almost all cardiometabolic risk factors than other participants; this difference was not significant for fasting blood glucose, total cholesterol, and diastolic blood pressure in both sexes, as well as low-density lipoprotein cholesterol in girls. Participants with generalized and abdominal obesity, MetS, elevated blood pressure, triglycerides, and total cholesterol had increased risk for elevated ALT; this risk remained significant after adjusting for sex and age. Low high-density lipoprotein cholesterol was found as a predictor for both elevated ALT (odds ratio 2.182, 95% confidence interval 1.533-3.105) and AST (odds ratio 2.022, 95% confidence interval 1.438-2.844) even after adjusting for all potential confounders. General (B 0.158, SE 0.030) and abdominal obesity (B 0.058, SE 0.029), MetS (B 0.231, SE 0.048), and triglycerides (B 0.094, SE 0.030) were associated with ALT:AST ratio after adjusting for all potential confounders (P < 0.001). CONCLUSIONS We documented strong relations of elevated ALT, AST levels, and ALT:AST ratio with most cardiometabolic risk factors. This relation was independent of anthropometric indexes. Liver enzymes can be considered as a cardiometabolic risk factor from childhood, and as an additional component of the MetS.
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Affiliation(s)
- Fatemeh Mohammadi
- *Department of Food and Nutrition Policy and Planning Research, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran †Department of Public Health, Alborz University of Medical Sciences, Karaj ‡Pediatrics Department, Child Growth and Development Research Center, and Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan §Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran ¶Department of Pediatrics, Ahvaz Jundishapur University of Medical Sciences, Ahvaz #Department of Medical Emergencies, Qom University of Medical Sciences, Qom **Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Liu Z, Ning H, Que S, Wang L, Qin X, Peng T. Complex association between alanine aminotransferase activity and mortality in general population: a systematic review and meta-analysis of prospective studies. PLoS One 2014; 9:e91410. [PMID: 24633141 PMCID: PMC3954728 DOI: 10.1371/journal.pone.0091410] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 01/30/2014] [Indexed: 02/06/2023] Open
Abstract
Objective Controversy exists in using alanine aminotransferase (ALT) activity for predicting long-term survival. Therefore, this research study investigated the association between ALT activity and mortality through a systematic review and meta-analysis of previous prospective studies. Methods Electronic literature databases, including PubMed, Embase, and the Institute for Scientific Information (ISI), were searched for relevant prospective observational studies (published before Dec 30, 2013) on the association between baseline ALT activity and ensuing all-cause/disease-specific mortality. Information on nationality, sample size, participant characteristics, follow-up duration, comparison, outcome assessment, hazard ratios (HRs) and adjusted covariates was extracted. Pooled HRs and corresponding 95% confidence intervals (CIs) were separately calculated for categorical risk estimates (highest vs. lowest ALT categories) and continuous risk estimates (per 5 U/l of ALT increment) in subgroups separated by age (<70/≥70 years). Results A total of twelve prospective cohort studies, totaling 206,678 participants and 16,249 deaths, were identified and analyzed. In the younger age group, the pooled HR for mortality related to liver-disease was about 1.24 (95% CI: 1.23–1.25) per 5 U/l of ALT increment. The dose-response HRs of all-cause mortality, cardiovascular (CV) disease-related mortality, and cancer-related mortality were 0.91 (0.88–0.94), 0.91 (0.85–0.96), 0.92 (0.86–0.98) respectively per 5 U/l of ALT elevation, with insignificant heterogeneity in the older population. There was an approximate decrease of 4‰ observed on HRs of all-cause, CV-related, and cancer-related mortality followed with one year's increment through meta-regression (all P<0.05). Conclusions The ALT-mortality association was inconsistent and seems particularly susceptible to age after synthesizing the previous prospective studies. In terms of the age, ALT activity was more valuable in predicting mortality in the older population; extremely low ALT levels indicated a higher all-cause, CV-related, and cancer-related mortality. ALT activity may therefore be a useful biomarker when predicting the long-term survival of elderly patients.
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Affiliation(s)
- Zhengtao Liu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University, Nanning, China
| | - Huaijun Ning
- Department of Pediatrics, Women and children's hospital of Guangxi, Nanning, China
| | - Shuping Que
- Department of Pediatrics, Women and children's hospital of Guangxi, Nanning, China
- Department of Pediatrics, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Linlin Wang
- Department of Pediatrics, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xue Qin
- Clinical Laboratory Center, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning, China
- * E-mail:
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Koehler EM, Sanna D, Hansen BE, van Rooij FJ, Heeringa J, Hofman A, Tiemeier H, Stricker BH, Schouten JNL, Janssen HLA. Serum liver enzymes are associated with all-cause mortality in an elderly population. Liver Int 2014; 34:296-304. [PMID: 24219360 DOI: 10.1111/liv.12311] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 08/29/2013] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Little is known about the association of serum liver enzymes with long-term outcome in the elderly. We sought to clarify the association of serum gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with all-cause and cause-specific mortality in an elderly population. METHODS This study was embedded in the Rotterdam Study, a large population-based cohort of persons aged 55 years or older. Cox-regression analyses were performed to examine the association of baseline serum GGT, ALP, and aminotransferase levels with mortality, adjusted for age, sex, education, smoking status, alcohol intake, hypertension, diabetes mellitus, body mass index and total cholesterol levels. Liver enzyme levels were categorized according to sample percentiles; levels <25th percentile were taken as a reference. RESULTS During a follow-up of up to 19.5 years, 2997 of 5186(57.8%) participants died: 672 participants died of causes related to cardiovascular diseases (CVD) and 703 participants died of cancer. All serum liver enzymes were associated with all-cause mortality (all P < 0.001). Moreover, GGT was associated with increased CVD mortality (P < 0.001), and ALP and AST with increased cancer-related mortality (P = 0.03 and P = 0.005 respectively). Participants with GGT and ALP in the top 5% had the highest risk for all-cause mortality (HR1.55; 95%CI 1.30-1.85 and HR1.49; 95%CI 1.25-1.78 respectively). AST and ALT <25th percentile were also associated with a higher risk of all-cause mortality. CONCLUSIONS All serum liver enzymes were positively associated with long-term mortality in this elderly population. Why participants with low ALT and AST levels have higher risk of mortality remains to be elucidated.
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Affiliation(s)
- Edith M Koehler
- Department of Gastroenterology and Hepatology, Erasmus MC University Hospital, Rotterdam, the Netherlands
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Liu Z, Que S, Xu J, Peng T. Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci 2014; 11:925-35. [PMID: 25013373 PMCID: PMC4081315 DOI: 10.7150/ijms.8951] [Citation(s) in RCA: 173] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Accepted: 06/12/2014] [Indexed: 02/06/2023] Open
Abstract
Measurement of serum alanine aminotransferase (ALT) is a common, readily available, and inexpensive laboratory assay in clinical practice. ALT activity is not only measured to detect liver disease, but also to monitor overall health. ALT activity is influenced by various factors, including viral hepatitis, alcohol consumption, and medication. Recently, the impact of metabolic abnormalities on ALT variation has raised concern due to the worldwide obesity epidemic. The normal ranges for ALT have been updated and validated considering the metabolic covariates in the various ethnic districts. The interaction between metabolic and demographic factors on ALT variation has also been discussed in previous studies. In addition, an extremely low ALT value might reflect the process of aging, and frailty in older adults has been raised as another clinically significant feature of this enzyme, to be followed with additional epidemiologic investigation. Timely updated, comprehensive, and systematic introduction of ALT activity is necessary to aid clinicians make better use of this enzyme.
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Affiliation(s)
- Zhengtao Liu
- 1. Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Shuping Que
- 2. Department of Pediatrics, Women and children's hospital of Guangxi, Nanning, 530005, Guangxi province, China
| | - Jing Xu
- 1. Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Tao Peng
- 1. Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
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Kabir A, Pourshams A, Khoshnia M, Malekzadeh F. Normal limit for serum alanine aminotransferase level and distribution of metabolic factors in old population of kalaleh, iran. HEPATITIS MONTHLY 2013; 13:e10640. [PMID: 24348633 PMCID: PMC3842514 DOI: 10.5812/hepatmon.10640] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/09/2013] [Accepted: 04/15/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUNDS Normal or elevated values of serum alanine aminotransferase level (ALT) vary in different studies mostly related to characteristics of reference population including age, gender, body mass index, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome prevalence. OBJECTIVES To measure upper normal limit (UNL) for serum ALT in an apparently healthy Iranian old population (which we had not sufficient data before this study), and its modulating factors. PATIENTS AND METHODS All inhabitants (> 50 years old) of Kalaleh, Golestan, Iran (N = 1986) were invited to the study. ALT measurements were performed for all subjects using the same laboratory method. Upper limit of normal (ULN) ALT was calculated based on its 95th percentile in normal weight subjects. Modulating factors of ALT were determined by multivariate analysis. RESULTS A total of 1309 subjects, with the mean age of 61.5 ± 7.5 years were included. UNL of ALT was 18.8 U/L and 21.4 U/L in women and men, respectively. Based on univariate analysis, waist circumference (r = 0.124, P = 0.01), body mass index (r = 0.118, P = 0.01), triglyceride (r = 0.143, P = 0.01), and having metabolic syndrome (OR = 2.04) modulate ALT levels in men. Also triglyceride (r = 0.119, P = 0.01) modulates ALT levels in women. CONCLUSIONS The calculated level for UNL of ALT is considerably far lower than previous accepted value. Age, gender, ethnicity, and metabolic factors should be accounted in future studies to determine normal ALT level.
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Affiliation(s)
- Ali Kabir
- Department of Epidemiology, Faculty of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
- Center for Educational Research in Medical Sciences, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Akram Pourshams
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Masoud Khoshnia
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, IR Iran
| | - Fatemeh Malekzadeh
- Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran
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Rowland R, O'Hara GA, Hamill M, Poulton ID, Donaldson H, Dinsmore L, James T, Barnes E, Klenerman P, Gilbert SC, Hill AVS, Shine B, McShane H. Determining the validity of hospital laboratory reference intervals for healthy young adults participating in early clinical trials of candidate vaccines. Hum Vaccin Immunother 2013; 9:1741-51. [PMID: 23733037 PMCID: PMC3906276 DOI: 10.4161/hv.24998] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
This was a retrospective study to determine the validity of institutional reference intervals for interpreting biochemistry and hematology results in healthy adults in the context of clinical trials of preventive vaccines. An example population of 974 healthy adults participating in clinical trials at the Jenner Institute, Oxford, UK, between 1999 and 2009 was studied. Methods for calculating the central 95% ranges and determining the coefficients of within person variation were demonstrated. Recommendations have been made as to how these data can be usefully applied to the interpretation of blood results in healthy adult subjects for the purposes of clinical trial inclusion decisions and post-vaccination safety monitoring.
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Drug-Induced Liver Injury Throughout the Drug Development Life Cycle: Where We Have Been, Where We are Now, and Where We are Headed. Perspectives of a Clinical Hepatologist. Pharmaceut Med 2013. [DOI: 10.1007/s40290-013-0015-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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