Age- and sex-specific reference intervals for ALT with 95% CIs among sub-Saharan adults

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Elevated serum Alanine Aminotransferase (ALT) levels are the most specific biomarker of hepatocyte necrosis. However, reference intervals (RIs) for ALT remain undetermined in Cameroon. This study aimed to establish 95% CI reference intervals for serum ALT among Cameroonian adults. Methods From November 2019 to June 2020, we conducted a cross-sectional study of 274 healthy volunteers aged 18-65 years. The assays were performed on a Cobas 6000®. We used the percentile method with 95% CI to assess the RI and examined the influence of age, sex, place of residence, food cultural habits, and education level on ALT levels owing multivariate analysis via Stata 15. The Results Among the 274 participants, the mean age was 31.68 years, and the sex ratio was 0.68. The median ALT levels was 13.5 [IQR, 9.9-18.7] IU/L. These levels were influenced by age ( P = 0.003) and sex ( P < 0.0001). The reference intervals were 6.4 [95% CI, 4.9-7.4] to 39.1 (33.8-58.2) IU/L overall, 7.4 [95% CI, 5.6-8.3] to 39.1 [95% CI, 34.1-46.1] IU/L for men, and 5.9 [95% CI, 1.2-7.3] to 28.9 [95% CI, 27.4-36.1] IU/L for women. In terms of age group, the reference intervals were 5.9 [95% CI, 2.7-7.3] to 33.8 [95% CI, 29.8-42.8] IU/L for those under 35 years and 6.9 [95% CI, 6.1-8.6] to 36.2 [95% CI, 32.4-39.0] IU/L for those 35 years and older. Conclusion This study pioneered the establishment of ALT reference intervals with 95% CIs in Africa and the exploration of RIs based on age group among 18-65 years people. reference interval precision ALT Africa Highlights The ALT reference intervals were 6.4 [95% CI, 4.9-7.4] to 39.1 (33.8-58.2) IU/L overall, 7.4 [95% CI, 5.6-8.3] to 39.1 [95% CI, 34.1-46.1] IU/L for men, and 5.9 [95% CI, 1.2-7.3] to 28.9 [95% CI, 27.4-36.1] IU/L for women. Overall reference intervals were strongly in concordance with data from the French Society of Clinical Biology. In terms of sex, there was no significant agreement with the data from the American College of Gastroenterology. 1. Introduction The liver is an organ of the upper right abdominal wall that plays important biochemical roles in basic metabolism, digestion, detoxification, and excretion of many substances and drugs [ 1 ]. Most plasma proteins are synthesized exclusively or primarily in the liver [ 2 ]. It is also involved in the synthesis of several hormones, lipid metabolism and the regulation of blood glucose concentrations [ 3 ]. The diagnosis or management of acute or chronic liver diseases requires the measurement of transaminases [ 4 ]. Alanine aminotransferase (ALT) is an enzyme predominantly found in the cytosol of hepatocytes [ 5 ]. It catalyzes the equilibrium transfer reaction of the NH2 radical from L-alanine to 2-oxoglutarate to produce L-glutamate and pyruvate [ 6 ]. Hepatocyte necrosis and liver inflammation are strongly correlated with elevated serum ALT levels [ 7 ]. Over 254 and 50 million people suffer from chronic viral hepatitis B and C, respectively [ 8 ]. Of these, 68% lived in Africa or the Western Pacific. In addition, viral hepatitis B will cause 1.3 million deaths with 3,500 deaths per day in 2022 [ 9 ]. Cameroon is an endemic country for viral hepatitis with a global prevalence of 9.5% for hepatitis B and 3.5% for hepatitis C [ 10 , 11 ]. Furthermore, access to primary health care services is still difficult and expensive for most Cameroonians [ 12 ]. According to the World Health Organization strategies, early detection of liver fibrosis should be performed to improve outcomes [ 13 , 14 ]. In fact, several noninvasive liver fibrosis scores have been proposed and most of them use ALT levels in their formulas [ 15 – 17 ]. Strong studies have shown a very good positive correlation between ALT levels and hepatocyte necrosis activity and a negative correlation with the efficacy of treatment for liver disease [ 18 ]. Despite its necessity, no study is yet available on the reference intervals of ALT in the Cameroonian population. A biomarker, regardless of its sensitivity and specificity, cannot be useful in practice if its reference intervals are not yet known in the relevant population; the establishment of a local reference range is essential to ensure the quality of a clinical laboratory [ 19 ]. In particular, knowledge of the upper limit of normal (ULN) for serum ALT is crucial for establishing an algorithm for the differential diagnosis of acute or chronic liver diseases; moreover, the ULN for serum ALT helps in choosing drug therapy and following the efficacy of treatment [ 20 ]. In addition, the determination of the ULN for serum ALT is essential for clinical interpretation and therapeutic decisions in cases of liver damage [ 20 ]. The reference intervals can be established via three statistical methods: the nonparametric percentile method, the normal distribution method, and the robust method [ 19 – 21 ]. The International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI) currently recommend the percentile method, also known as Reed’s method [ 21 ]. As described by Reed et al., the percentile method consists of determining the 2.5th and 97.5th percentiles as the lower and upper limits of normal, respectively. A 90% confidence interval was calculated for both limits of normal according to CLSI guidelines C28-A3; however, the authors of these guidelines acknowledge that a 90% confidence interval can sometimes be large and does not always provide sufficient statistical precision to define the exact pathologic threshold for a biomarker in clinical practice [ 21 – 24 ]. Studies on reference intervals for serum ALT are very rare compared with those on other biomarkers, especially in sub-Saharan Africa. In addition, laboratories in Cameroon commonly use normal values provided by manufacturers; although these values are most often used, the results of studies conducted in the West [ 26 ]. There may also be genotypic differences in reference ranges for ALT between sub-Saharan and Caucasian individuals, as is the case for reference ranges for serum haptoglobin [ 26 ]. Therefore, the aim of this study was to assess the upper and lower limits of normal for ALT among Cameroonian adults with a 95% confidence interval and effects of sociodemographic characteristics on ALT levels. 2. Methods Study design and population We conducted a cross-sectional study of Cameroonian adults, volunteers, living in Yaoundé and aged 18–65 years. The study period was from November 2019 to August 2020. After exclusion on the basis of clinical and biological criteria, 274 healthy volunteers were included. Sampling First, we informed the people of Yaoundé about the study through social media, television, and radio. Volunteers invited people to participate in a screening campaign. At the screening campaign site, we explained the details and stages of this study. We then obtained informed consent from 640 volunteers. After that, we screened and examined past medical history, comorbidities, clinical features, current medications, and diseases that could affect the serum ALT level. At the end of each interview, we excluded people who had at least one comorbidity that could affect the serum ALT level (Table 1 ). Table 1 Clinical exclusion criteria Abdominal pain or bloating Jaundice Diabetes Ascites Heart failure Fever or infectious syndrome Pregnancy High blood pressure Cancer Body mass index ≥ 25 kg/m 2 Chronic renal failure Recent physical trauma Known HIV infection Muscle pain Autoimmunes diseases Abdominal mass or nodule at ultrasonography biliary disorders, pancreatitis (acute or chronic) Alcohol consumption prior or current Recent limb trauma Tobacco intake Cardiovascular illnesses Systolic blood pressure >140 mmHg Acute or chronic kidney disease Diastolic blood pressure >90 mmHg Thyroid conditions Genetic deficiencies or abnormalities Treatment with nonsteroidal anti-inflammatory drugs, thiazide diuretics or urate-lowering drugs, colchicine Acute or chronic liver diseases Habitual or recent consumption of sulfonamides, corticosteroids, hypolipidemic agents, diuretics, antidepressants, levodopa, dobesilate, vitamin C, N-acetyl-cysteine, metamizole sodium Cocaine or others illegal drugs Use of combined oral contraceptives any symptom or physical sign of apparent illness kg/m 2 : Kilogram per square meter After this step, 400 volunteers remained and these underwent several biological examinations to search for insidious diseases that could interact with the ALT measurement or ALT level. Among these 400 subjects, 126 were excluded on the basis of at least one biological exclusion criterion (Table 2 ). Finally, we retained 274 healthy volunteers for our reference population. Sample collection and biological assays Beforehand, we informed through press releases that the volunteers would observe a 12-hour fast beginning the evening before the day of the screening campaign. After all volunteers without clinical exclusion criteria had fasted for at least 12 hours and a maximum of 16 hours, we collected samples from a superficial vein in the elbow crease after a 15-minute rest in a seated position with rigorous asepsis. Each sample which contained 15 ml of whole blood, was transported to the PRIMA SARL laboratory of Yaoundé. Plasma was obtained from 5 ml of whole blood collected in an EDTA tube and used for serological tests. The serum was obtained after centrifugation at 3000 rpm for 10 minutes and placed in tubes with a serum separator gel for biochemical analyses. Serological tests included HIV-1 and HIV-2, hepatitis B and C, and Plasmodium falciparum malaria; pregnancy status was determined via rapid urine test kits. The Combi-14 dipstick was used to detect hematuria, glycosuria, biliburinuria, and proteinuria (Table 2 ). Table 2 Biological exclusion criteria Biological exclusion criteria Dosage methods Blood sugar > 110 mg/dL Enzymatic Serum creatinine > 1.30 mg/dL Colorimetric Kinetic (Jaffe’s Method). GFR 4 mIU/L or 2.5 g/L Enzymatic, colorimetric End point (CHOD-PAP 2th Generation) Triglyceridemia > 1.5 g/L Enzymatic, colorimetric End point (GPO-PAP 4th Generation) LDL- cholesterol > 1 g/L Colorimetric enzymatic, Direct selective detergent HDL- cholesterol 0.6 mg/dL Spectrophotometry/immunoturbidimetry Serum uric acid : male >70 mg/L and female >60 mg/L Colorimetric enzymatic Positive AgHbs Rapid test by Determine® Positive AcHCV Rapid test by Determine® TSH: thyroid-stimulating hormone; GFR: glomerular filtration rate; CHOD-PAP: cholesterol oxidase-peroxidase; GPO-PAP: glycerol phosphatase-peroxidase; LDL: low-density lipoprotein; HDL: high-density lipoprotein; hs-CRP: high-sensitivity C-reactive lipoprotein; AgHbs: surface antigen of hepatitis B virus; AcHCV: antibody against hepatitis C virus. All tests were carried out in accordance with the manufacturers' instructions. Biochemical testing for exclusion biomarkers was performed within 3 hours of sample collection. Dosage method for ALT The serum ALT level was determined via enzymatic colorimetry via the detection of pyridoxal phosphate via a Cobas® 6000 autoanalyzer (Roche Diagnostics, France, 2020). This analyzer is a random-access, software-controlled system for immunoassay and photometric analyses intended for qualitative and quantitative in vitro determinations via a wide variety of tests. The Cobas 6000 analyzer series is optimized for workloads via a combination of photometric and ion-selective electrode (ISE) determinations (c501 module) and electrochemiluminescence (ECL) signals in the immunoassay analysis module (e601 module). The International Federation of Clinical Chemistry (IFCC) recognized this standard method especially for routine practice [ 24 ]. Quality management and safety This study was carried out in a laboratory accredited by ASQUALAB. All aspects of the sample processing procedure were performed according to the ISO 15189 standard. All abnormally low or high biological test results were repeated twice. The means of the three results were retained. Variables and Statistical Analysis The database was edited via Excel 2016 and analyzed via the Statistical Package for Social Sciences (SPSS) version 26 and STATA version 15. We collected data on age, sex, educational level, lifestyle, body mass index (BMI) and alanine transaminase (ALT) levels. We studied the dietary habits associated with the two main lifestyles in urban or rural and main food cultural habits in Cameroon, as specific questionnaires do not exist in this context. As defined by the United Nations, the urban lifestyle refers to the way of life in densely populated human settlements and the quality of life in cities; it includes taxis, buses, supermarkets and fast food. In addition, rural lifestyles are related to the activities and characteristics of people living in the countryside. It emphasizes agriculture and natural foods [ 27 ]. ALT levels were summarized using the median and interquartile range. Boxplots and the Grubbs test were employed to identify and exclude outliers. Age, sex, education level, ethnicity, and place of residence were reported in numbers and frequencies. Differences in ALT medians across categorical variables were assessed via either the Mann‒Whitney test or the Kruskal‒Wallis test, depending on the number of classes. Reference intervals were set at the 2.5th percentile (lower limit of normal) and 97.5th percentile (upper limit of normal with 95% CI), and then, we calculated the 95% confidence interval for both limits on the basis of factors significantly influencing ALT levels. Logistic regression was used to examine the influence of age, sex, ethnicity, education level, and place of residence on ALT values. Multivariate analysis via a logistic regression model was performed to identify factors influencing ALT levels. Finally, we compared them with the American College of Gastroenterology (ACG) and Société Française de Biologie Clinique (SFBC) reference ranges via the Mac Nemar test. The level of agreement was evaluated via the kappa coefficient (k). For all hypothesis tests, a P value < 0.05 was considered significant. 3. Results Among the 274 individuals included, 106 were males and 168 females, resulting in a sex ratio of 0.63 M/F. The mean age was 31.68 years [IQR, 30.41–32.94] with a range of 19–65 years. There was no significant difference between the mean ages of women and men ( P = 0.741). The age group from 18–35 years was the most represented (n = 188; 68.6%). The participants most often resided in urban areas (n = 272; 99%) and had a university level of education (n = 184; 67.2%). The median serum ALT level was 13.5 [9.9–18.7] IU/L with a range of 4.8 IU/L to 39.9 IU/L. There was a significant difference in median ALT levels according to sex ( P < 0.0001) and age groups < 35 and ≥ 35 years ( P = 0.003). On the other hand, these values were not influenced by BMI ( P = 0.413), level of education ( P = 0.705), place of residence ( P = 0.903) or food cultural habits ( P = 0.145) as described below (Table 3 ). Table 3 Relationship between ALT levels and sociodemographic characteristics Variables N % Median (IIQ)* ALT in IU/L P value Sex Female 168 61.3 11.5 (8.95-16.0) < 0.0001 Male 106 38.7 16.5 (12.2–25.0) Level of education None 4 1.5 9.25 (10.8–34.2) 0.705 Primary 15 5.5 15 (12.55–18.1) Secondary 71 25.8 13.85 (10.8–18.1) University 184 67.2 13.4 59.5-18.85) Residence Urban 272 99.3 13.4 (9.5-18.85) 0.903 Rural 2 0.7 14.05 (13.1–15) Age groups (in years) < 35 188 68.6 12.95 (9.15–18.3) 0.003 ≥ 35 86 31.4 15.5 (11.1–21.4) Food cultural habits Bantou 112 40,9 12.50 (10,78 − 16,99) 0.145 Semi-bantou 132 48,2 13,72 (11,25 − 17,12) Soudanese 30 10,9 15,75 (11,6–19,3) *=Interquartile range The 95% CI for the serum ALT reference interval was 6.4–39.1 UI/L for the overall reference population. After logistic regression, age and sex significantly influenced the 95% CI ALT reference values. The reference intervals were 5.9 to 33.8 UI/L for volunteers under 35 years of age and 6.9 to 36.2 for those in the 35 + age group. We did not find learned societies that already presented reference intervals for ALT levels on the basis of age group. With respect to sex, the 95% CI reference intervals were 5.9 to 28.9 UI/L for women and 7.4 to 39.1 UI/L for men. There was good and very significant ( P < 0.0001) concordance between the overall reference interval and the data from the French Society of Clinical Biology (SFBC), with a Cohen’s kappa coefficient equal to 69%. There was no significant agreement between our results and those of the American College of Gastroenterology regarding reference intervals in women ( P = 0.065) or men ( P = 0.389) as described below (Table 4 ). Table 4 Age- and sex-specific reference intervals for ALT after logistic regression and level of agreement with learned societies Variables ALT lower limit of normal (95% CI) in IU/L ALT upper limit of normal (95% CI) in IU/L ALT median (95% CI) in IU/L RG from SFBC* in IU/L RI from ACG** in IU/L Overall 6.4 (4.9–7.4) 39.1 (33.8–58.2) 13.5 (12.5–14.5) RI = 4–40 - n / A P < 0.0001 k = 69% Sex Female 5.9 (1.2–7.3) 28.9 (27.4–36.1) 11.5 (10.8–13.1) - n / A RI = 19–25 P = 0.065 k = 2.5% Male 7.4 (5.6–8.3) 39.1 (34.1–46.1) 16.5 (14.5–18.9) - n / A RI = 29–33 P = 0.389 k = 0.6% Age groups (in years) < 35 5.9 (2.7–7.3) 33.8 (29.8–42.8) 12.9 (11.5–13.8) - n / A - n / A ≥ 35 6.9 (6.1–8.6) 36.2 (32.4–39.0) 15.4 (13.2–16.4) RG = Reference ranges; *=French Society of Clinical Biology; **=American College of Gastroenterology Guidelines; n/a =Not available; k = Cohen's kappa coefficient 4. Discussion The median serum level of ALT in this study was 13.5 (9.9–18.7) IU/L, with extremes of 4.8 IU/L and 39.9 IU/L. This aligns with findings from a study on young adults in Nigeria, where the median ALT level was reported to be 16.0 IU/L, ranging from 3.5 IU/L to 63.2 IU/L [ 28 ]. A statistically significant difference was observed in the median serum ALT level when sex ( P < 0.0001) and age ( P = 0.003) were considered. Males presented a median value of of 16.5 IU/L, whereas females presented a median value of 11.5 IU/L. Similarly, Bawaua et al., among Ghanaian adults, reported that the median serum ALT was twice as high in males compared with females (21 vs 13 IU/L) [ 29 ]. The physiological differences between males and females can significantly influence the production and clearance of serum enzymes such as ALT. Factors such as muscle mass, metabolism, and hormonal differences play important roles. Males generally have greater muscle mass than females do. Since ALT is found at high concentrations in the liver and skeletal muscle, higher muscle mass in males could contribute to higher ALT levels [ 30 ]. Similarly, metabolic rates can vary between males and females due to differences in body composition and hormone levels. Males typically have a relatively high basal metabolic rate, which could influence the production and clearance of enzymes [ 31 ]. Hormones, particularly steroid hormones, also play crucial roles in regulating various physiological processes, including enzyme production and clearance. For example, estrogen, the predominant sex hormone in women, has been found to have an impact on fat and muscle composition. Similarly, it could also influence the regulation of enzymes such as ALT. The 95% CI reference intervals for ALT were found to be 6.4–39.1 IU/L in overall. These values are in significant agreement with the data from the Société Française de Biologie Clinique (SFBC), as indicated by a Cohen’s kappa coefficient of 69%. Concerning males and females, 95% CI reference intervals were 7.4 to 39.1 U/L and 5.9 to 28.9 U/L, respectively. These sex-specific RIs were no significant in concordance with the data provided by the American College of Gastroenterology (ACG) [ 32 ]. First, this could be explained by the absence of sex-specific reference intervals (RIs) for Black Americans in the ACG’s study. Second, our selection criteria excluded volunteers with abnormal TSH and creatinine levels. Moreover, according to guidelines of International Federation of Clinical Chemistry (IFCC), we collected blood samples in a location with a temperature of 37°C in a tube with a gel separator to reduce hemolysis [ 34 ]. The samples were collected after 12 hours of fasting to decrease the effect of the last meal and analyzed less than two hours after collection. The timing of the blood draw, the type of collection tube used, and how the sample is handled and processed can improve the measurement of ALAT levels. The analytical procedure used to measure serum ALAT levels could also influence the results [ 35 ]. However, we did not find details on the preanalytical and analytical procedures in the ACG guidelines. Furthermore, individuals younger than 35 years had serum ALAT levels twice as high as individuals older than 35 years. These results imply that age is an important factor to consider when evaluating reference intervals (RIs) among Sub-Saharan African adults. This could be due to various factors, such as lifestyle differences, overall health, and physiological changes associated with aging [ 36 ]. Aging is also associated with decreased hepatocyte synthesis activity and a lower basal metabolic rate (BMR). This could lead to decreased production of amino acid enzymes, such as ALAT. Conversely, younger adults may have different lifestyle factors, such as dietary habits and levels of physical activity that could increase ALAT levels. 5. Conclusions The ALT reference intervals can vary depending on patient characteristics, environmental context, and laboratory methods. Overall, 95% confidence intervals (CIs) were aligned with data from the French Society of Clinical Biochemistry. This study also showed that the 95% confidence interval (CI) reference intervals for serum alanine aminotransferase (ALT) were influenced by age and sex in Cameroon. However, the sex-specific reference intervals were inconsistent with the American College of Gastroenterology's data. This study was the first to assess the 95% confidence interval reference intervals (RIs) for alanine transaminase (ALT) in Africa and demonstrate the differences between younger and older adults in the 18–65 year old reference population. However, this study has a few limitations. First, alcohol consumption status was reported using a questionnaire based on the participants' medical history rather than ethanol measurements. It is possible that some alcohol consumers did not disclose their true alcohol consumption habits. However, serum ethanol measurement does not represent the selection criteria described by learned societies. Finally, due to the lack of a diet-specific questionnaire for Cameroonian adults, we could not examine the influence of individual lifestyle on reference intervals for serum ALT. We suggest that the African scientific community conduct more studies on the subject to reach a consensus on the age- and sex-dependent upper limits of normal ALT. Declarations Competing interests All the authors declare that they have no competing interests for this research. Ethical Approval This study was approved by the Public Health Regional Center at N°CE/2112/CRERSHC/2020 and the Research Ethics Committee of the Faculty of Medicine and Biomedical Sciences at the University of Yaoundé I at N°276/UYI/FMSB/VDRC/DASSR/CDS, according to the Helsinki and Nuremberg declarations. All volunteers provided written informed consent to participate in the study before their inclusion and sampling. Consent for Publication In accordance with the guidelines of ISO 15189, all data were collected in biomedical laboratories, except those containing personal information of patients, which could be used for scientific research. Availability of Data All datasets from the current study are available via a request to the corresponding author. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions: Conception: SFMM, DCT, LMK, VJA-M. Design: AWNN, BEEE, NNA, JDMN, MEO, DCT, VJA-M. Data collection: JMT, MEO, SZ, DCT. Laboratory analysis: BEEE, MEO, SZ, DCT, VJA-M. Statistical analysis: SFMM, NNA, AWNN, JDMN, AMEO. Data interpretation: SFMM, AMEO, NNA, AWNN, DCT, VJA-M. Supervision: AWNN, BEEE, SZ, DCT, LMK, VJA-M Validation: SFMM, BEEE, AMEO, DCT, VJA-M Manuscript drafting: SFMM, AWNN, NNA, JDMN, SZ, DCT, BEEE. Manuscript review: SFMM, AWNN, AMEO, JDMN, BEEE, SZ, JMT, DCT, LMK, VJA-M. Accepted the final version of the manuscript All authors have approved and validated the final version of the manuscript submitted. Acknowledgments We would like to thank all the volunteers, lab technicians, and supervisors who gave their consent to take part in this study. References Sakagishi Y. Alanine aminotransferase (ALT). Nihon Rinsho . 1995, 53 (5):1146-50. Sherman KE. Alanine aminotransferase in clinical practice. A review . Arch Intern Med. 1991, 151(2):260-5. Liu Z, Que S, Xu J, Peng T. 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(eds) Sustainable Cities and Communities (2020). Encyclopedia of the UN Sustainable Development Goals. Springer, Cham. https://doi.org/10.1007/978-3-319-95717-3_54 Ayemoba O, Okeji N, Hussain N, Umar T, Ajemba-Life A, Kene T, et al. Reference intervals of common clinical biochemistry analytes in young Nigerian adults. PLOS ONE [Internet]. 2021 Mar 1 [cited 2023 Nov 22];16(3):e0247672. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247672 Bawua SA, Ichihara K, Keatley R, Arko-Mensah J, Ayeh-Kumi PF, Erasmus R, Fobil J. Derivation of sex and age-specific reference intervals for clinical chemistry analytes in healthy Ghanaian adults. Clin Chem Lab Med. 2022; 60(9):1426-39. doi: 10.1515/cclm-2022-0293. https://www.degruyter.com/document/doi/10.1515/cclm-2022-0293 Schorr M, Dichtel LE, Gerweck AV, Valera RD, Torriani M, Miller KK et al. Sex differences in body composition and association with cardiometabolic risk Biology of Sex Differences. 2018; 9:28. https://doi.org/10.1186/s13293-018-0189-3 Pethusamy K, Gupta A, Yadav R. Basal Metabolic Rate (BMR). In: Vonk J, Shackelford T, editors. Encyclopedia of Animal Cognition and Behavior [Internet]. Cham: Springer International Publishing; 2019 [cited 2023 Nov 22]. p. 1–3. https://doi.org/10.1007/978-3-319-47829-6_1429-1 Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol 2017; 112:18–35; https://doi:10.1038/ajg.2016.517 Katayev A, Balciza C, Seccombe DW. Establishing Reference Intervals for Clinical Laboratory Test Results. Am J Clin Pathology. 2010; 133(2):180-6, https://doi.org/10.1309/AJCPN5BMTSF1CDYP Bergmeyer HU, Hørder M, Rej R. International Federation of Clinical Chemistry (IFCC) Scientific Committee, Analytical Section: approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC method for alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2). J Clin Chem Clin Biochem. 1986 Jul;24(7):481-95. Kennedy AD, Ford L, Wittmann B, Conner J, Wulff J, Mitchell M et al. Global biochemical analysis of plasma, serum and whole blood collected using various anticoagulant additives. PLoS One. 2021; 16(4): e0249797. Doi:10.1371/journal.pone.0249797 Badtrick T, El-Khoury JM, Theodorsson E. Laboratory reference intervals - history and modern approaches for improved utility. Scand J Clin and Lab Investigation. 2025; 82(4):229-41. https://doi.org/10.1080/00365513.2025.2512995 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 27 Oct, 2025 Reviews received at journal 26 Oct, 2025 Reviewers agreed at journal 24 Oct, 2025 Reviews received at journal 24 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers agreed at journal 08 Oct, 2025 Reviewers invited by journal 08 Oct, 2025 Editor invited by journal 16 Sep, 2025 Editor assigned by journal 11 Aug, 2025 Submission checks completed at journal 11 Aug, 2025 First submitted to journal 07 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7320761","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":531671699,"identity":"98a38fe1-a134-4671-ad90-db2886749970","order_by":0,"name":"Stéphane Fargeon MBOUNA-MASSIN","email":"data:image/png;base64,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","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":true,"prefix":"","firstName":"Stéphane","middleName":"Fargeon","lastName":"MBOUNA-MASSIN","suffix":""},{"id":531671700,"identity":"247b08f6-722f-462e-8db5-9fe2b02742fc","order_by":1,"name":"Antonin Wilson NDJITOYAP-NDAM","email":"","orcid":"","institution":"General Hospital of Yaoundé, University of Yaoundé I","correspondingAuthor":false,"prefix":"","firstName":"Antonin","middleName":"Wilson","lastName":"NDJITOYAP-NDAM","suffix":""},{"id":531671701,"identity":"5e17ef14-6311-4eee-bbb9-9a8c43cd0951","order_by":2,"name":"Ngolé Néri ATABE","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Ngolé","middleName":"Néri","lastName":"ATABE","suffix":""},{"id":531671705,"identity":"1e23d336-c4ec-49d2-910b-f0808d3e09b8","order_by":3,"name":"Manuela Audrey EKO ONDOUA","email":"","orcid":"","institution":"University Teaching Hospital of Yaoundé","correspondingAuthor":false,"prefix":"","firstName":"Manuela","middleName":"Audrey EKO","lastName":"ONDOUA","suffix":""},{"id":531671707,"identity":"c1e8f6c6-b74c-45bc-afd8-c06f146471a2","order_by":4,"name":"Jessica Dilane MELELE-NDELE","email":"","orcid":"","institution":"Higher Institute of Medical Technology","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"Dilane","lastName":"MELELE-NDELE","suffix":""},{"id":531671708,"identity":"ae88a539-adf8-468f-8562-78a15a983568","order_by":5,"name":"Bertille Elodie EDINGA","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Bertille","middleName":"Elodie","lastName":"EDINGA","suffix":""},{"id":531671710,"identity":"82c79de8-b068-4cca-a312-f1462e3689bb","order_by":6,"name":"Stéphanie ZIBI","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Stéphanie","middleName":"","lastName":"ZIBI","suffix":""},{"id":531671713,"identity":"c3b9d3de-a8be-4b3c-9daa-1f0aadac4c62","order_by":7,"name":"Jean Maximilien TANG","email":"","orcid":"","institution":"PRIMA SARL 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10:18:20","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":100886,"visible":true,"origin":"","legend":"","description":"","filename":"36ce0612ed0a4236be6d096bac1342841structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7320761/v1/3b36e6063c246f39d88e3820.xml"},{"id":94011578,"identity":"74317d6c-1f67-4d1e-adf5-f0228ff21488","added_by":"auto","created_at":"2025-10-21 10:18:14","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":115283,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7320761/v1/3ac86d00a2f36af9cd242d11.html"},{"id":94012148,"identity":"60b0a707-cf8a-49f5-b2d2-4cf3db519b5d","added_by":"auto","created_at":"2025-10-21 10:20:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":782038,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7320761/v1/5b860259-09bf-4517-81be-313db3b116a1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eAge- and sex-specific reference intervals for ALT with 95% CIs among sub-Saharan adults\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Highlights","content":"\u003cul\u003e\n \u003cli\u003eThe ALT reference intervals were 6.4 [95% CI, 4.9-7.4] to 39.1 (33.8-58.2) IU/L overall, 7.4 [95% CI, 5.6-8.3] to 39.1 [95% CI, 34.1-46.1] IU/L for men, and 5.9 [95% CI, 1.2-7.3] to 28.9 [95% CI, 27.4-36.1] IU/L for women.\u003c/li\u003e\n \u003cli\u003eOverall reference intervals were strongly in concordance with data from the French Society of Clinical Biology.\u003c/li\u003e\n \u003cli\u003eIn terms of sex, there was no significant agreement with the data from the American College of Gastroenterology.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eThe liver is an organ of the upper right abdominal wall that plays important biochemical roles in basic metabolism, digestion, detoxification, and excretion of many substances and drugs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Most plasma proteins are synthesized exclusively or primarily in the liver [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is also involved in the synthesis of several hormones, lipid metabolism and the regulation of blood glucose concentrations [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The diagnosis or management of acute or chronic liver diseases requires the measurement of transaminases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Alanine aminotransferase (ALT) is an enzyme predominantly found in the cytosol of hepatocytes [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It catalyzes the equilibrium transfer reaction of the NH2 radical from L-alanine to 2-oxoglutarate to produce L-glutamate and pyruvate [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Hepatocyte necrosis and liver inflammation are strongly correlated with elevated serum ALT levels [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOver 254 and 50\u0026nbsp;million people suffer from chronic viral hepatitis B and C, respectively [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Of these, 68% lived in Africa or the Western Pacific. In addition, viral hepatitis B will cause 1.3\u0026nbsp;million deaths with 3,500 deaths per day in 2022 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Cameroon is an endemic country for viral hepatitis with a global prevalence of 9.5% for hepatitis B and 3.5% for hepatitis C [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, access to primary health care services is still difficult and expensive for most Cameroonians [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. According to the World Health Organization strategies, early detection of liver fibrosis should be performed to improve outcomes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In fact, several noninvasive liver fibrosis scores have been proposed and most of them use ALT levels in their formulas [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Strong studies have shown a very good positive correlation between ALT levels and hepatocyte necrosis activity and a negative correlation with the efficacy of treatment for liver disease [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Despite its necessity, no study is yet available on the reference intervals of ALT in the Cameroonian population.\u003c/p\u003e\u003cp\u003eA biomarker, regardless of its sensitivity and specificity, cannot be useful in practice if its reference intervals are not yet known in the relevant population; the establishment of a local reference range is essential to ensure the quality of a clinical laboratory [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In particular, knowledge of the upper limit of normal (ULN) for serum ALT is crucial for establishing an algorithm for the differential diagnosis of acute or chronic liver diseases; moreover, the ULN for serum ALT helps in choosing drug therapy and following the efficacy of treatment [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In addition, the determination of the ULN for serum ALT is essential for clinical interpretation and therapeutic decisions in cases of liver damage [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe reference intervals can be established via three statistical methods: the nonparametric percentile method, the normal distribution method, and the robust method [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI) currently recommend the percentile method, also known as Reed\u0026rsquo;s method [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. As described by Reed et al., the percentile method consists of determining the 2.5th and 97.5th percentiles as the lower and upper limits of normal, respectively. A 90% confidence interval was calculated for both limits of normal according to CLSI guidelines C28-A3; however, the authors of these guidelines acknowledge that a 90% confidence interval can sometimes be large and does not always provide sufficient statistical precision to define the exact pathologic threshold for a biomarker in clinical practice [\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eStudies on reference intervals for serum ALT are very rare compared with those on other biomarkers, especially in sub-Saharan Africa. In addition, laboratories in Cameroon commonly use normal values provided by manufacturers; although these values are most often used, the results of studies conducted in the West [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. There may also be genotypic differences in reference ranges for ALT between sub-Saharan and Caucasian individuals, as is the case for reference ranges for serum haptoglobin [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTherefore, the aim of this study was to assess the upper and lower limits of normal for ALT among Cameroonian adults with a 95% confidence interval and effects of sociodemographic characteristics on ALT levels.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cb\u003eStudy design and population\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe conducted a cross-sectional study of Cameroonian adults, volunteers, living in Yaound\u0026eacute; and aged 18\u0026ndash;65 years. The study period was from November 2019 to August 2020. After exclusion on the basis of clinical and biological criteria, 274 healthy volunteers were included.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSampling\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFirst, we informed the people of Yaound\u0026eacute; about the study through social media, television, and radio. Volunteers invited people to participate in a screening campaign. At the screening campaign site, we explained the details and stages of this study. We then obtained informed consent from 640 volunteers. After that, we screened and examined past medical history, comorbidities, clinical features, current medications, and diseases that could affect the serum ALT level. At the end of each interview, we excluded people who had at least one comorbidity that could affect the serum ALT level (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical exclusion criteria\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal pain or bloating\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eJaundice\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAscites\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFever or infectious syndrome\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePregnancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHigh blood pressure\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBody mass index\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic renal failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRecent physical trauma\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnown HIV infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMuscle pain\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutoimmunes diseases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbdominal mass or nodule at ultrasonography\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ebiliary disorders, pancreatitis (acute or chronic)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAlcohol consumption prior or current\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecent limb trauma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTobacco intake\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular illnesses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSystolic blood pressure \u0026gt;140 mmHg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute or chronic kidney disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiastolic blood pressure \u0026gt;90 mmHg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThyroid conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGenetic deficiencies or abnormalities\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment with nonsteroidal anti-inflammatory drugs, thiazide diuretics or urate-lowering drugs, colchicine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute or chronic liver diseases\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHabitual or recent consumption of sulfonamides, corticosteroids, hypolipidemic agents, diuretics, antidepressants, levodopa, dobesilate, vitamin C,\u003c/p\u003e\u003cp\u003eN-acetyl-cysteine, metamizole sodium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCocaine or others illegal drugs\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUse of combined oral contraceptives\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eany symptom or physical sign of apparent illness\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003ekg/m\u003csup\u003e2\u003c/sup\u003e: Kilogram per square meter\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAfter this step, 400 volunteers remained and these underwent several biological examinations to search for insidious diseases that could interact with the ALT measurement or ALT level. Among these 400 subjects, 126 were excluded on the basis of at least one biological exclusion criterion (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Finally, we retained 274 healthy volunteers for our reference population.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSample collection and biological assays\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBeforehand, we informed through press releases that the volunteers would observe a 12-hour fast beginning the evening before the day of the screening campaign. After all volunteers without clinical exclusion criteria had fasted for at least 12 hours and a maximum of 16 hours, we collected samples from a superficial vein in the elbow crease after a 15-minute rest in a seated position with rigorous asepsis. Each sample which contained 15 ml of whole blood, was transported to the PRIMA SARL laboratory of Yaound\u0026eacute;. Plasma was obtained from 5 ml of whole blood collected in an EDTA tube and used for serological tests. The serum was obtained after centrifugation at 3000 rpm for 10 minutes and placed in tubes with a serum separator gel for biochemical analyses. Serological tests included HIV-1 and HIV-2, hepatitis B and C, and Plasmodium falciparum malaria; pregnancy status was determined via rapid urine test kits. The Combi-14 dipstick was used to detect hematuria, glycosuria, biliburinuria, and proteinuria (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBiological exclusion criteria\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiological exclusion criteria\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDosage methods\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood sugar\u0026thinsp;\u0026gt;\u0026thinsp;110 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEnzymatic\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum creatinine\u0026thinsp;\u0026gt;\u0026thinsp;1.30 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric Kinetic (Jaffe\u0026rsquo;s Method).\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEstimated from CKD-EPI formula\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTSH\u0026thinsp;\u0026gt;\u0026thinsp;4 mIU/L or \u0026lt;\u0026thinsp;0.4 mIU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eImmunoturbidimetry\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal cholesterol in serum\u0026thinsp;\u0026gt;\u0026thinsp;2.5 g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEnzymatic, colorimetric End point (CHOD-PAP 2th Generation)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTriglyceridemia\u0026thinsp;\u0026gt;\u0026thinsp;1.5 g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEnzymatic, colorimetric End point (GPO-PAP 4th Generation)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDL- cholesterol\u0026thinsp;\u0026gt;\u0026thinsp;1 g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric enzymatic, Direct selective detergent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHDL- cholesterol\u0026thinsp;\u0026lt;\u0026thinsp;0.4 g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric enzymatic, Direct selective detergent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehs-CRP\u0026thinsp;\u0026gt;\u0026thinsp;0.6 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSpectrophotometry/immunoturbidimetry\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum uric acid :\u003c/p\u003e\u003cp\u003emale \u0026gt;70 mg/L and female \u0026gt;60 mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric enzymatic\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePositive AgHbs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRapid test by Determine\u0026reg;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePositive AcHCV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRapid test by Determine\u0026reg;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTSH: thyroid-stimulating hormone; GFR: glomerular filtration rate; CHOD-PAP: cholesterol oxidase-peroxidase; GPO-PAP: glycerol phosphatase-peroxidase; LDL: low-density lipoprotein; HDL: high-density lipoprotein; hs-CRP: high-sensitivity C-reactive lipoprotein; AgHbs: surface antigen of hepatitis B virus; AcHCV: antibody against hepatitis C virus.\u003c/p\u003e\u003cp\u003eAll tests were carried out in accordance with the manufacturers' instructions. Biochemical testing for exclusion biomarkers was performed within 3 hours of sample collection.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDosage method for ALT\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe serum ALT level was determined via enzymatic colorimetry via the detection of pyridoxal phosphate via a Cobas\u0026reg; 6000 autoanalyzer (Roche Diagnostics, France, 2020). This analyzer is a random-access, software-controlled system for immunoassay and photometric analyses intended for qualitative and quantitative in vitro determinations via a wide variety of tests. The Cobas 6000 analyzer series is optimized for workloads via a combination of photometric and ion-selective electrode (ISE) determinations (c501 module) and electrochemiluminescence (ECL) signals in the immunoassay analysis module (e601 module). The International Federation of Clinical Chemistry (IFCC) recognized this standard method especially for routine practice [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eQuality management and safety\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study was carried out in a laboratory accredited by ASQUALAB. All aspects of the sample processing procedure were performed according to the ISO 15189 standard. All abnormally low or high biological test results were repeated twice. The means of the three results were retained.\u003c/p\u003e\u003cp\u003e\u003cb\u003eVariables and Statistical Analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe database was edited via Excel 2016 and analyzed via the Statistical Package for Social Sciences (SPSS) version 26 and STATA version 15. We collected data on age, sex, educational level, lifestyle, body mass index (BMI) and alanine transaminase (ALT) levels. We studied the dietary habits associated with the two main lifestyles in urban or rural and main food cultural habits in Cameroon, as specific questionnaires do not exist in this context. As defined by the United Nations, the urban lifestyle refers to the way of life in densely populated human settlements and the quality of life in cities; it includes taxis, buses, supermarkets and fast food. In addition, rural lifestyles are related to the activities and characteristics of people living in the countryside. It emphasizes agriculture and natural foods [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. ALT levels were summarized using the median and interquartile range. Boxplots and the Grubbs test were employed to identify and exclude outliers. Age, sex, education level, ethnicity, and place of residence were reported in numbers and frequencies. Differences in ALT medians across categorical variables were assessed via either the Mann‒Whitney test or the Kruskal‒Wallis test, depending on the number of classes. Reference intervals were set at the 2.5th percentile (lower limit of normal) and 97.5th percentile (upper limit of normal with 95% CI), and then, we calculated the 95% confidence interval for both limits on the basis of factors significantly influencing ALT levels. Logistic regression was used to examine the influence of age, sex, ethnicity, education level, and place of residence on ALT values. Multivariate analysis via a logistic regression model was performed to identify factors influencing ALT levels. Finally, we compared them with the American College of Gastroenterology (ACG) and Soci\u0026eacute;t\u0026eacute; Fran\u0026ccedil;aise de Biologie Clinique (SFBC) reference ranges via the Mac Nemar test. The level of agreement was evaluated via the kappa coefficient (k). For all hypothesis tests, a \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eAmong the 274 individuals included, 106 were males and 168 females, resulting in a sex ratio of 0.63 M/F. The mean age was 31.68 years [IQR, 30.41\u0026ndash;32.94] with a range of 19\u0026ndash;65 years. There was no significant difference between the mean ages of women and men (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.741). The age group from 18\u0026ndash;35 years was the most represented (n\u0026thinsp;=\u0026thinsp;188; 68.6%). The participants most often resided in urban areas (n\u0026thinsp;=\u0026thinsp;272; 99%) and had a university level of education (n\u0026thinsp;=\u0026thinsp;184; 67.2%).\u003c/p\u003e\u003cp\u003eThe median serum ALT level was 13.5 [9.9\u0026ndash;18.7] IU/L with a range of 4.8 IU/L to 39.9 IU/L. There was a significant difference in median ALT levels according to sex (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and age groups\u0026thinsp;\u0026lt;\u0026thinsp;35 and \u0026ge;\u0026thinsp;35 years (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). On the other hand, these values were not influenced by BMI (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.413), level of education (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.705), place of residence (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.903) or food cultural habits (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.145) as described below (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRelationship between ALT levels and sociodemographic characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMedian (IIQ)*\u003c/p\u003e\u003cp\u003eALT in IU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e168\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.5 (8.95-16.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e106\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.5 (12.2\u0026ndash;25.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eLevel of education\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.25 (10.8\u0026ndash;34.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.705\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (12.55\u0026ndash;18.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSecondary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.85 (10.8\u0026ndash;18.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUniversity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e184\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.4 59.5-18.85)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eResidence\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrban\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e272\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.4 (9.5-18.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.903\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRural\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.05 (13.1\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eAge groups (in years)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt; 35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e188\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.95 (9.15\u0026ndash;18.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge; 35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.5 (11.1\u0026ndash;21.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFood cultural habits\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBantou\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e112\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40,9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.50 (10,78\u0026thinsp;\u0026minus;\u0026thinsp;16,99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.145\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSemi-bantou\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e132\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48,2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13,72 (11,25\u0026thinsp;\u0026minus;\u0026thinsp;17,12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSoudanese\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10,9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15,75 (11,6\u0026ndash;19,3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*=Interquartile range\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe 95% CI for the serum ALT reference interval was 6.4\u0026ndash;39.1 UI/L for the overall reference population. After logistic regression, age and sex significantly influenced the 95% CI ALT reference values. The reference intervals were 5.9 to 33.8 UI/L for volunteers under 35 years of age and 6.9 to 36.2 for those in the 35\u0026thinsp;+\u0026thinsp;age group. We did not find learned societies that already presented reference intervals for ALT levels on the basis of age group.\u003c/p\u003e\u003cp\u003eWith respect to sex, the 95% CI reference intervals were 5.9 to 28.9 UI/L for women and 7.4 to 39.1 UI/L for men. There was good and very significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) concordance between the overall reference interval and the data from the French Society of Clinical Biology (SFBC), with a Cohen\u0026rsquo;s kappa coefficient equal to 69%. There was no significant agreement between our results and those of the American College of Gastroenterology regarding reference intervals in women (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.065) or men (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.389) as described below (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAge- and sex-specific reference intervals for ALT after logistic regression and level of agreement with learned societies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eALT lower limit of normal\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003cp\u003ein IU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eALT upper limit of normal\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003cp\u003ein IU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eALT median\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003cp\u003ein IU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRG from SFBC*\u003c/p\u003e\u003cp\u003ein IU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRI from ACG**\u003c/p\u003e\u003cp\u003ein IU/L\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e6.4 (4.9\u0026ndash;7.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e39.1 (33.8\u0026ndash;58.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e13.5 (12.5\u0026ndash;14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRI\u0026thinsp;=\u0026thinsp;4\u0026ndash;40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e- \u003csup\u003en / A\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ek\u0026thinsp;=\u0026thinsp;69%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e5.9 (1.2\u0026ndash;7.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e28.9 (27.4\u0026ndash;36.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e11.5 (10.8\u0026ndash;13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e- \u003csup\u003en / A\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRI\u0026thinsp;=\u0026thinsp;19\u0026ndash;25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.065\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ek\u0026thinsp;=\u0026thinsp;2.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e7.4 (5.6\u0026ndash;8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e39.1 (34.1\u0026ndash;46.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e16.5 (14.5\u0026ndash;18.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e- \u003csup\u003en / A\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRI\u0026thinsp;=\u0026thinsp;29\u0026ndash;33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.389\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ek\u0026thinsp;=\u0026thinsp;0.6%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eAge groups (in years)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.9 (2.7\u0026ndash;7.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.8 (29.8\u0026ndash;42.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.9 (11.5\u0026ndash;13.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e- \u003csup\u003en / A\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e- \u003csup\u003en / A\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.9 (6.1\u0026ndash;8.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.2 (32.4\u0026ndash;39.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.4 (13.2\u0026ndash;16.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eRG\u0026thinsp;=\u0026thinsp;Reference ranges; *=French Society of Clinical Biology; **=American College of Gastroenterology Guidelines; \u003csup\u003en/a\u003c/sup\u003e =Not available; k\u0026thinsp;=\u0026thinsp;Cohen's kappa coefficient\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe median serum level of ALT in this study was 13.5 (9.9\u0026ndash;18.7) IU/L, with extremes of 4.8 IU/L and 39.9 IU/L. This aligns with findings from a study on young adults in Nigeria, where the median ALT level was reported to be 16.0 IU/L, ranging from 3.5 IU/L to 63.2 IU/L [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA statistically significant difference was observed in the median serum ALT level when sex (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and age (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) were considered. Males presented a median value of of 16.5 IU/L, whereas females presented a median value of 11.5 IU/L. Similarly, \u003cem\u003eBawaua\u003c/em\u003e et al., among Ghanaian adults, reported that the median serum ALT was twice as high in males compared with females (21 vs 13 IU/L) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The physiological differences between males and females can significantly influence the production and clearance of serum enzymes such as ALT. Factors such as muscle mass, metabolism, and hormonal differences play important roles. Males generally have greater muscle mass than females do. Since ALT is found at high concentrations in the liver and skeletal muscle, higher muscle mass in males could contribute to higher ALT levels [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Similarly, metabolic rates can vary between males and females due to differences in body composition and hormone levels. Males typically have a relatively high basal metabolic rate, which could influence the production and clearance of enzymes [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Hormones, particularly steroid hormones, also play crucial roles in regulating various physiological processes, including enzyme production and clearance. For example, estrogen, the predominant sex hormone in women, has been found to have an impact on fat and muscle composition. Similarly, it could also influence the regulation of enzymes such as ALT.\u003c/p\u003e\u003cp\u003eThe 95% CI reference intervals for ALT were found to be 6.4\u0026ndash;39.1 IU/L in overall. These values are in significant agreement with the data from the Soci\u0026eacute;t\u0026eacute; Fran\u0026ccedil;aise de Biologie Clinique (SFBC), as indicated by a Cohen\u0026rsquo;s kappa coefficient of 69%. Concerning males and females, 95% CI reference intervals were 7.4 to 39.1 U/L and 5.9 to 28.9 U/L, respectively. These sex-specific RIs were no significant in concordance with the data provided by the American College of Gastroenterology (ACG) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. First, this could be explained by the absence of sex-specific reference intervals (RIs) for Black Americans in the ACG\u0026rsquo;s study. Second, our selection criteria excluded volunteers with abnormal TSH and creatinine levels. Moreover, according to guidelines of International Federation of Clinical Chemistry (IFCC), we collected blood samples in a location with a temperature of 37\u0026deg;C in a tube with a gel separator to reduce hemolysis [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The samples were collected after 12 hours of fasting to decrease the effect of the last meal and analyzed less than two hours after collection. The timing of the blood draw, the type of collection tube used, and how the sample is handled and processed can improve the measurement of ALAT levels. The analytical procedure used to measure serum ALAT levels could also influence the results [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. However, we did not find details on the preanalytical and analytical procedures in the ACG guidelines.\u003c/p\u003e\u003cp\u003eFurthermore, individuals younger than 35 years had serum ALAT levels twice as high as individuals older than 35 years. These results imply that age is an important factor to consider when evaluating reference intervals (RIs) among Sub-Saharan African adults. This could be due to various factors, such as lifestyle differences, overall health, and physiological changes associated with aging [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Aging is also associated with decreased hepatocyte synthesis activity and a lower basal metabolic rate (BMR). This could lead to decreased production of amino acid enzymes, such as ALAT. Conversely, younger adults may have different lifestyle factors, such as dietary habits and levels of physical activity that could increase ALAT levels.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThe ALT reference intervals can vary depending on patient characteristics, environmental context, and laboratory methods. Overall, 95% confidence intervals (CIs) were aligned with data from the French Society of Clinical Biochemistry. This study also showed that the 95% confidence interval (CI) reference intervals for serum alanine aminotransferase (ALT) were influenced by age and sex in Cameroon. However, the sex-specific reference intervals were inconsistent with the American College of Gastroenterology's data.\u003c/p\u003e\u003cp\u003eThis study was the first to assess the 95% confidence interval reference intervals (RIs) for alanine transaminase (ALT) in Africa and demonstrate the differences between younger and older adults in the 18\u0026ndash;65 year old reference population. However, this study has a few limitations. First, alcohol consumption status was reported using a questionnaire based on the participants' medical history rather than ethanol measurements. It is possible that some alcohol consumers did not disclose their true alcohol consumption habits. However, serum ethanol measurement does not represent the selection criteria described by learned societies. Finally, due to the lack of a diet-specific questionnaire for Cameroonian adults, we could not examine the influence of individual lifestyle on reference intervals for serum ALT.\u003c/p\u003e\u003cp\u003eWe suggest that the African scientific community conduct more studies on the subject to reach a consensus on the age- and sex-dependent upper limits of normal ALT.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors declare that they have no competing interests for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Public Health Regional Center at N°CE/2112/CRERSHC/2020 and the Research Ethics Committee of the Faculty of Medicine and Biomedical Sciences at the University of Yaoundé I at N°276/UYI/FMSB/VDRC/DASSR/CDS, according to the Helsinki and Nuremberg declarations. All volunteers provided written informed consent to participate in the study before their inclusion and sampling.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with the guidelines of ISO 15189, all data were collected in biomedical laboratories, except those containing personal information of patients, which could be used for scientific research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll datasets from the current study are available via a request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception: SFMM, DCT, LMK, VJA-M.\u003c/p\u003e\n\u003cp\u003eDesign:\u0026nbsp;AWNN, BEEE, NNA, JDMN, MEO, DCT, VJA-M.\u003c/p\u003e\n\u003cp\u003eData collection: JMT, MEO, SZ, DCT.\u003c/p\u003e\n\u003cp\u003eLaboratory analysis: BEEE, MEO, SZ, DCT, VJA-M.\u003c/p\u003e\n\u003cp\u003eStatistical analysis: SFMM, NNA,\u0026nbsp;AWNN, JDMN, AMEO.\u003c/p\u003e\n\u003cp\u003eData interpretation: SFMM, AMEO, NNA,\u0026nbsp;AWNN, DCT, VJA-M.\u003c/p\u003e\n\u003cp\u003eSupervision:\u0026nbsp;AWNN, BEEE, SZ, DCT, LMK, VJA-M\u003c/p\u003e\n\u003cp\u003eValidation: SFMM, BEEE, AMEO, DCT, VJA-M\u003c/p\u003e\n\u003cp\u003eManuscript drafting: SFMM,\u0026nbsp;AWNN, NNA, JDMN, SZ, DCT, BEEE.\u003c/p\u003e\n\u003cp\u003eManuscript review: SFMM,\u0026nbsp;AWNN, AMEO, JDMN, BEEE, SZ, JMT, DCT, LMK, VJA-M.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAccepted the final version of the manuscript\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have approved and validated the final version of the manuscript submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank all the volunteers, lab technicians, and supervisors who gave their consent to take part in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSakagishi Y. 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Establishing Reference Intervals for Clinical Laboratory Test Results. Am J Clin Pathology. 2010; 133(2):180-6, https://doi.org/10.1309/AJCPN5BMTSF1CDYP \u003c/li\u003e\n\u003cli\u003eBergmeyer HU, H\u0026oslash;rder M, Rej R. International Federation of Clinical Chemistry (IFCC) Scientific Committee, Analytical Section: approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC method for alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2). J Clin Chem Clin Biochem. 1986 Jul;24(7):481-95.\u003c/li\u003e\n\u003cli\u003eKennedy AD, Ford L, Wittmann B, Conner J, Wulff J, Mitchell M et al. Global biochemical analysis of plasma, serum and whole blood collected using various anticoagulant additives. PLoS One. 2021; 16(4): e0249797. Doi:10.1371/journal.pone.0249797\u003c/li\u003e\n\u003cli\u003eBadtrick T, El-Khoury JM, Theodorsson E. Laboratory reference intervals - history and modern approaches for improved utility. Scand J Clin and Lab Investigation. 2025; 82(4):229-41. https://doi.org/10.1080/00365513.2025.2512995\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"reference interval, precision, ALT, Africa","lastPublishedDoi":"10.21203/rs.3.rs-7320761/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7320761/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLiver diseases, especially chronic hepatitis B and C, are common and are associated with a high mortality rate in Africa. Elevated serum Alanine Aminotransferase (ALT) levels are the most specific biomarker of hepatocyte necrosis. However, reference intervals (RIs) for ALT remain undetermined in Cameroon. This study aimed to establish 95% CI reference intervals for serum ALT among Cameroonian adults.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom November 2019 to June 2020, we conducted a cross-sectional study of 274 healthy volunteers aged 18-65 years. The assays were performed on a Cobas 6000®. We used the percentile method with 95% CI to assess the RI and examined the influence of age, sex, place of residence, food cultural habits, and education level on ALT levels owing multivariate analysis via Stata 15. The\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 274 participants, the mean age was 31.68 years, and the sex ratio was 0.68. The median ALT levels was 13.5 [IQR, 9.9-18.7] IU/L. These levels were influenced by age (\u003cem\u003eP\u003c/em\u003e = 0.003) and sex (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.0001). The reference intervals were 6.4 [95% CI, 4.9-7.4] to 39.1 (33.8-58.2) IU/L overall, 7.4 [95% CI, 5.6-8.3] to 39.1 [95% CI, 34.1-46.1] IU/L for men, and 5.9 [95% CI, 1.2-7.3] to 28.9 [95% CI, 27.4-36.1] IU/L for women. In terms of age group, the reference intervals were 5.9 [95% CI, 2.7-7.3] to 33.8 [95% CI, 29.8-42.8] IU/L for those under 35 years and 6.9 [95% CI, 6.1-8.6] to 36.2 [95% CI, 32.4-39.0] IU/L for those 35 years and older.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study pioneered the establishment of ALT reference intervals with 95% CIs in Africa and the exploration of RIs based on age group among 18-65 years people.\u003c/p\u003e","manuscriptTitle":"Age- and sex-specific reference intervals for ALT with 95% CIs among sub-Saharan adults","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-21 10:13:31","doi":"10.21203/rs.3.rs-7320761/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-27T08:20:19+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-26T04:42:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"93614482985160636091174650758756021639","date":"2025-10-24T10:50:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-24T08:37:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261359392107047106284866010077265776161","date":"2025-10-13T08:28:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221445277614721331718677077270280844909","date":"2025-10-09T03:52:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-08T15:58:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-16T10:00:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-11T04:51:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-11T04:49:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-08-07T16:32:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"358853bf-3d88-4195-b6dc-cff0ce89ae13","owner":[],"postedDate":"October 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-21T17:08:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-21 10:13:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7320761","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7320761","identity":"rs-7320761","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}