{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:43:16Z","timestamp":1790196196422,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T00:00:00Z","timestamp":1694822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018990","name":"Alfaisal University Internal Research Grant","doi-asserted-by":"publisher","award":["IRG23312"],"award-info":[{"award-number":["IRG23312"]}],"id":[{"id":"10.13039\/501100018990","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are important liver enzymes in clinical settings. Their levels are known to be elevated in individuals with underlying liver diseases and those consuming hepatotoxic drugs. Serum ALT and AST levels are crucial for diagnosing and assessing liver diseases. Serum ALT is considered the most reliable and specific candidate as a disease biomarker for liver diseases. ALT and AST levels are routinely analyzed in high-risk individuals for the bioanalysis of both liver function and complications associated with drug-induced liver injury. Typically, ALT and AST require blood sampling, serum separation, and testing. Traditional methods require expensive or sophisticated equipment and trained specialists, which is often time-consuming. Therefore, developing countries have limited or no access to these methods. To address the above issues, we hypothesize that low-cost biosensing methods (paper-based assays) can be applied to the analysis of ALT and AST levels in biological fluids. The paper-based biodetection technique can semi-quantitatively measure ALT and AST from capillary finger sticks, and it will pave the way for the development of an inexpensive and rapid alternative method for the early detection and diagnosis of liver diseases. This method is expected to significantly reduce the economic burden and aid routine clinical analysis in both developed and underdeveloped countries. The development of low-cost testing platforms and their diagnostic utility will be extremely beneficial in helping millions of patients with liver disorders.<\/jats:p>","DOI":"10.3390\/diagnostics13182967","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T23:25:26Z","timestamp":1694993126000},"page":"2967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Low-Cost Point-of-Care Monitoring of ALT and AST Is Promising for Faster Decision Making and Diagnosis of Acute Liver Injury"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2288-4287","authenticated-orcid":false,"given":"Raja","family":"Chinnappan","sequence":"first","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"},{"name":"Tissue\/Organ Bioengineering & BioMEMS Lab, Organ Transplant Centre of Excellence, Transplant Research & Innovation Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanveer Ahmad","family":"Mir","sequence":"additional","affiliation":[{"name":"Tissue\/Organ Bioengineering & BioMEMS Lab, Organ Transplant Centre of Excellence, Transplant Research & Innovation Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3807-1870","authenticated-orcid":false,"given":"Suliman","family":"Alsalameh","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4237-2016","authenticated-orcid":false,"given":"Tariq","family":"Makhzoum","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Alzhrani","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"},{"name":"Tissue\/Organ Bioengineering & BioMEMS Lab, Organ Transplant Centre of Excellence, Transplant Research & Innovation Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"},{"name":"Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1372-9883","authenticated-orcid":false,"given":"Khaled","family":"Al-Kattan","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-910X","authenticated-orcid":false,"given":"Ahmed","family":"Yaqinuddin","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.dsx.2008.10.001","article-title":"Significance of ALT\/AST Ratio for Specifying Subjects with Metabolic Syndrome in Its Silent Stage","volume":"3","author":"Ohgo","year":"2009","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"s74","DOI":"10.1210\/jc.2008-1399","article-title":"Obesity-Associated Liver Disease","volume":"93","author":"Marchesini","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e367","DOI":"10.1002\/edm2.367","article-title":"The Association between Obesity with Serum Levels of Liver Enzymes, Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase and Gamma-Glutamyl Transferase in Adult Women","volume":"5","author":"Jalili","year":"2022","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/hep.22109","article-title":"Serum Activity of Alanine Aminotransferase (ALT) as an Indicator of Health and Disease","volume":"47","author":"Kim","year":"2008","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/toxsci\/kft009","article-title":"Assessment of Emerging Biomarkers of Liver Injury in Human Subjects","volume":"132","author":"Schomaker","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.14218\/JCTH.2017.00027","article-title":"Elevated Liver Enzymes in Asymptomatic Patients\u2013What Should I Do?","volume":"5","author":"Malakouti","year":"2017","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2036.2011.04724.x","article-title":"Systematic Review: The Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis in Adults","volume":"34","author":"Vernon","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/dmrr.666","article-title":"Alanine Aminotransferase as a Marker of Non-alcoholic Fatty Liver Disease in Relation to Type 2 Diabetes Mellitus and Cardiovascular Disease","volume":"22","author":"Schindhelm","year":"2006","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2017-314924","article-title":"Guidelines on the Management of Abnormal Liver Blood Tests","volume":"67","author":"Newsome","year":"2018","journal-title":"Gut"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0009-8981(70)90069-0","article-title":"A New Colorimetric Ultramicromethod for Serum Glutamicoxalacetic and Glutamic-Pyruvic Transaminase Determination","volume":"28","author":"Lippi","year":"1970","journal-title":"Clin. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/clinchem\/20.1.43","article-title":"Sources of Error in Spectrophotometric Measurement of Aspartate Aminotransferase and Alanine Aminotransferase Activities in Serum","volume":"20","author":"Rodgerson","year":"1974","journal-title":"Clin. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1016\/S1452-3981(23)07795-7","article-title":"Bioelectrochemical Detection of Alanine Aminotransferase for Molecular Diagnostic of the Liver Disease","volume":"9","author":"Paula","year":"2014","journal-title":"Int. J. Electrochem. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0956-5663(03)00194-5","article-title":"Development of an Electrochemical Immunosensor for Alanine Aminotransferase","volume":"19","author":"Xuan","year":"2003","journal-title":"Biosens. Bioelectron."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43793","DOI":"10.1364\/OE.447202","article-title":"Taper-in-Taper Fiber Structure-Based LSPR Sensor for Alanine Aminotransferase Detection","volume":"29","author":"Wang","year":"2021","journal-title":"Opt. Express"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1021\/ac9013989","article-title":"Diagnostics for the Developing World: Microfluidic Paper-Based Analytical Devices","volume":"82","author":"Martinez","year":"2010","journal-title":"Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/am1002266","article-title":"Thread as a Matrix for Biomedical Assays","volume":"2","author":"Reches","year":"2010","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6565","DOI":"10.1021\/jf100377n","article-title":"Magnetic Levitation in the Analysis of Foods and Water","volume":"58","author":"Mirica","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chinnappan, R., Mir, T.A., Alsalameh, S., Makhzoum, T., Alzhrani, A., Alnajrani, M.K., Adeeb, S., Al Eman, N., Ahmed, Z., and Shakir, I. (2023). Emerging Biosensing Methods to Monitor Lung Cancer Biomarkers in Biological Samples: A Comprehensive Review. Cancers, 15.","DOI":"10.3390\/cancers15133414"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1002\/ange.201001005","article-title":"Paper-based ELISA","volume":"122","author":"Cheng","year":"2010","journal-title":"Angew. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Baek, S.H., Park, C., Jeon, J., and Park, S. (2020). Three-Dimensional Paper-Based Microfluidic Analysis Device for Simultaneous Detection of Multiple Biomarkers with a Smartphone. Biosensors, 10.","DOI":"10.20944\/preprints202010.0506.v1"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, H.-L., Chu, C.-H., Tsai, S.-J., and Yang, R.-J. (2016). Aspartate Aminotransferase and Alanine Aminotransferase Detection on Paper-Based Analytical Devices with Inkjet Printer-Sprayed Reagents. Micromachines, 7.","DOI":"10.3390\/mi7010009"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"756","DOI":"10.3390\/s6070756","article-title":"Aspartate Aminotransferase (AST\/GOT) and Alanine Aminotransferase (ALT\/GPT) Detection Techniques","volume":"6","author":"Huang","year":"2006","journal-title":"Sensors"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121818","DOI":"10.1016\/j.talanta.2020.121818","article-title":"Aptamer Selection and Aptasensor Construction for Bone Density Biomarkers","volume":"224","author":"Chinnappan","year":"2021","journal-title":"Talanta"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Alomran, N., Chinnappan, R., Alsolaiss, J., Casewell, N.R., and Zourob, M. (2022). Exploring the Utility of SsDNA Aptamers Directed against Snake Venom Toxins as New Therapeutics for Snakebite Envenoming. Toxins, 14.","DOI":"10.1101\/2022.05.22.492967"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8272","DOI":"10.1021\/acs.chemrev.7b00063","article-title":"Metal Sensing by DNA","volume":"117","author":"Zhou","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114856","DOI":"10.1016\/j.bios.2022.114856","article-title":"An Integrated Lab-on-a-Chip Platform for Pre-Concentration and Detection of Colorectal Cancer Exosomes Using Anti-CD63 Aptamer as a Recognition Element","volume":"220","author":"Chinnappan","year":"2023","journal-title":"Biosens. Bioelectron."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"126133","DOI":"10.1016\/j.foodchem.2019.126133","article-title":"Aptameric Biosensor for the Sensitive Detection of Major Shrimp Allergen, Tropomyosin","volume":"314","author":"Chinnappan","year":"2020","journal-title":"Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chinnappan, R., Mir, T.A., Alsalameh, S., Makhzoum, T., Adeeb, S., Al-Kattan, K., and Yaqinuddin, A. (2023). Aptasensors Are Conjectured as Promising ALT and AST Diagnostic Tools for the Early Diagnosis of Acute Liver Injury. Life, 13.","DOI":"10.3390\/life13061273"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"122887","DOI":"10.1016\/j.talanta.2021.122887","article-title":"Highly Sensitive and Selective Lateral Flow Aptasensor for Anti-Coagulant Dabigatran Etexilate Determination in Blood","volume":"236","author":"Alnajrani","year":"2022","journal-title":"Talanta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0956-5663(98)00115-8","article-title":"Chemiluminometric Flow Injection Analysis Procedures for the Enzymatic Determination of L-Alanine, \u03b1-Ketoglutarate and L-Glutamate","volume":"14","author":"Janasek","year":"1999","journal-title":"Biosens. Bioelectron."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/0003-2697(81)90282-7","article-title":"A Sensitive Determination of \u03b1-Keto Acids by Gas-Liquid Chromatography and Its Application to the Assay of l-Glutamate Dehydrogenase and Aminotransferases","volume":"112","author":"Ohmori","year":"1981","journal-title":"Anal. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0003-2670(01)95170-0","article-title":"Fluorimetric Assay of Serum Glutamate Oxaloacetate Transaminase, Glutamate Pyruvate Transaminase and \u03b1-Hydroxybutyrate Dehydrogen\u00e0se by Solution An","volume":"77","author":"Rietz","year":"1975","journal-title":"Anal. Chim. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0003-2670(00)81882-6","article-title":"Pyruvate Oxidase and Oxaloacetate Decarboxylase Enzyme Electrodes: Simultaneous Determination of Transaminases with a Two-Electrode-Based Analyzer","volume":"222","author":"Peguin","year":"1989","journal-title":"Anal. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00604-021-05056-w","article-title":"Optical Assay Using B-Doped Core\u2013Shell Fe@ BC Nanozyme for Determination of Alanine Aminotransferase","volume":"189","author":"Tian","year":"2022","journal-title":"Microchim. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.snb.2019.02.116","article-title":"Double-Layered Microfluidic Paper-Based Device with Multiple Colorimetric Indicators for Multiplexed Detection of Biomolecules","volume":"288","author":"Li","year":"2019","journal-title":"Sens. Actuators B Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8447","DOI":"10.1021\/ac901307q","article-title":"Quantifying Colorimetric Assays in Paper-Based Microfluidic Devices by Measuring the Transmission of Light through Paper","volume":"81","author":"Ellerbee","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11835","DOI":"10.1021\/acs.chemrev.0c01335","article-title":"Microfluidic Paper-Based Analytical Devices: From Design to Applications","volume":"121","author":"Noviana","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1021\/ac800112r","article-title":"Simple Telemedicine for Developing Regions: Camera Phones and Paper-Based Microfluidic Devices for Real-Time, off-Site Diagnosis","volume":"80","author":"Martinez","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1002\/ange.200603817","article-title":"Patterned Paper as a Platform for Inexpensive, Low-volume, Portable Bioassays","volume":"119","author":"Martinez","year":"2007","journal-title":"Angew. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1021\/ac203434x","article-title":"Measuring Markers of Liver Function Using a Micropatterned Paper Device Designed for Blood from a Fingerstick","volume":"84","author":"Vella","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"152ra129","DOI":"10.1126\/scitranslmed.3003981","article-title":"A Paper-Based Multiplexed Transaminase Test for Low-Cost, Point-of-Care Liver Function Testing","volume":"4","author":"Pollock","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_42","unstructured":"(2023, June 05). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV (Department of Health and Human Services, Washington, DC 2021), Available online: https:\/\/Clinicalinfo.Hiv.Gov\/Sites\/Default\/Files\/Guidelines\/Archive\/AdultandAdolescentGL_2021_08_16.Pdf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.aca.2010.06.019","article-title":"Use of Multiple Colorimetric Indicators for Paper-Based Microfluidic Devices","volume":"674","author":"Dungchai","year":"2010","journal-title":"Anal. Chim. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6985","DOI":"10.1021\/acsami.1c21578","article-title":"Hydrogel-Involved Colorimetric Platforms Based on Layered Double Oxide Nanozymes for Point-of-Care Detection of Liver-Related Biomarkers","volume":"14","author":"Liu","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"339158","DOI":"10.1016\/j.aca.2021.339158","article-title":"Development of a Paper-Based Analytical Device for the Colourimetric Detection of Alanine Transaminase and the Application of Deep Learning for Image Analysis","volume":"1188","author":"Resmi","year":"2021","journal-title":"Anal. Chim. Acta"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/18\/2967\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:52:09Z","timestamp":1760129529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/18\/2967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,16]]},"references-count":45,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["diagnostics13182967"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13182967","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,16]]}}}