ISSN 1757-8515
Sensitivity, Specificity and Diagnostic Efficiency of Serum Sialic Acid as a Biochemical Marker in Alcohol Abuse
Veerendra Kumar Arumalla, G Narender, R Kathaini and A Pullaiah
Cite this article as: BJMP 2012;5(2):a517
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Abstract Background: Many biochemical markers have been used for detection of alcohol abuse, but each of them has clinical limitations. Sialic acid (SA) has been suggested as a new potential marker of excessive alcohol consumption. |
INTRODUCTION:
The prevalence of current use of alcohol in India ranged from 7% in western states of Gujarat (officially under prohibition) to 75% in the North eastern state of Arunachal Pradesh 1.The prevalence of hazardous use of alcohol was 14.2% in rural south India2. Thus, alcohol abuse has a major public, family and health related problems withimpairment of social, legal, inter personal and occupational functioning in thoseindividuals who have been addicted to alcoholism.
A wide variety of biochemical and haematological parameters are affected by regular excessive alcohol consumption. The blood tests traditionally used most commonly as markers of recent drinking are the liver enzymes, gamma glutamyltranserase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and the mean volume of the red blood cells (mean corpuscular volume (MCV). But they were not sensitive or specific enough for use as single tests3.
Elevated Gamma glutamyltransferase levels are an early indicator of liver disease; chronic heavy drinkers, especially those who also take certain other drugs, often have increased GGT levels. However, GGT is not a very sensitive marker, showing up in only 30–50 percent of excessive drinkers in the general population. It is not a specific marker of chronic heavy alcohol use, because other digestive diseases, such as pancreatitis and prostate disease, also can raise GGT levels 4.
AST and ALTare enzymes that help metabolize amino acids, the building blocks of proteins. They are an even less sensitive measure of alcoholism than GGT; indeed, they are more useful as an indication of liver disease than as a direct link to alcohol consumption. Nevertheless, research finds that when otherwise healthy people drink large amounts of alcohol, AST and ALT levels in the blood increase. Of the two enzymes, ALT is the more specific measure of alcohol-induced liver injury because it is found predominantly in the liver, whereas AST is found in several organs, including the liver, heart, muscle, kidney, and brain. Very high levels of these enzymes (e.g., 500 units per liter) may indicate alcoholic liver disease. Clinicians often use a patient’s ratio of AST to ALT to confirm an impression of heavy alcohol consumption. However, because these markers are not as accurate in patients who are under age 30 or over age 70, they are less useful than some of the other more comprehensive markers5.
AST /ALT ratio of more than1.5 strongly suggests and ratio >2.0 is almost indicative of alcohol induced damaged to liver 6.It has been suggested that an AST/ ALT ratio greater than 2 is highly suggestive or indicative of alcoholic etiology of liver disease. But extreme elevations of this ratio, with AST level greater than five times the normal should suggest non-alcoholic cause of hepatocellular necrosis 7.
Sialic acid, which is a derivative of acetyl neuraminic acid, attached to non-reducing residues of carbohydrate chain of glycoproteins and glycolipids is found to be elevated in alcohol abuse 8.
In this study we compared sensitivity, specificity and diagnostic efficiency of serum Sialic acid with other traditional markers like AST (Aspartate amino transaminase), ALT (Alanine amino transaminase), GGT (Gamma Glutamyl Transferase), as a marker of alcohol abuse.
MATERIALS AND METHODS:
This was a case-control study which was conducted on 100 male subjects aged 20-60 years, 50 cases and 50 controls. Cases comprised of patients diagnosed to have Alcohol Dependant Syndrome (ADS) who were admitted in Psychiatry-ADS ward, at Mahathma Gandhi Memorial Hospital,Warangal. Study was approved by the Institutional ethical committee. Amount, duration and the type of alcohol in the form of Rum, Whisky, Brandy, Vodka, Gin, Arrack, etc consumed was enquired, those subjects who consumed more than half bottles of these spirits daily (or intermittently with abstinence of 2-3 days), for more than 5 years were chosen for this study. Dependence of their alcoholism was enquired in the form of CAGE questionnaire 9.
C : Cut down drinking,
A : Annoyed others by drinking,
G : Guilty feeling of drinking.
E : Eye-opener
Those who satisfied two or more questions were taken as cases 10 and their blood samples were collected for the study after their informed consent. Controls were selected from healthy subjects came for master health check up at MGMH health clinic, with no history ofalcoholism.
Exclusion criteria:
Patients with history of Diabetes mellitus, Cardiac disease, Viral/Bacterial Hepatitis, Alcoholic hepatitis, tumors, meningitis and history of current use of hepatotoxic and nephrotoxic drugs were excluded from the study.
4ml of blood was collected from each subject from median cubital vein by venipuncture, serum was separated and the different parameters were analyzed. Estimation of serum Sialic acid was done by modified thiobarbturic acid assay of warren11 (Lorentz and Krass) by colorimetric method. Estimations of Aspartate transaminase 12, 13, 14 Alanine transaminase 13, 15, 16 Gamma glutamyl transferase 17, 18 were done by IFCC recommended methods on Dimension Clinical chemistry system (auto analyzer).
Statistical analysis: Student t test (two tailed, independent) has been used to find the significance of study parameters between controls and cases. Receiving Operating Characteristics (ROC) tool (SPSS 17 version) has been used to find the diagnostic performance of study parameters.
RESULTS:
It was observed that all the study parameters were significantly increased (p value < 0.001) in subjects with alcohol abuse when compared to the controls as shown in the Table 1. The ROC analyses of the different parameters were shown in Fig 1 and Table 2. GGT was having highest Diagnostic efficacy followed by AST and SA as a marker of alcohol abuse.
Figure 1: ROC Curve analysis of different parameters
Table1: Comparison of study parameters between controls and cases
| Parameters | controls | cases | P value |
| AST(U/L) | 24.83±7.57 | 87.9 ±53.72 | <0.001 |
| ALT(U/L) | 47.63 ±18.77 | 88.83± 46.53 | <0.001 |
| AST/ALT | 0.58 ± 0.23 | 0.982 ± 0.29 | <0.001 |
| GGT(U/L) | 39.36 ±v 20.23 | 264.13± 298.74 | <0.001 |
| SA(m mol/L) | 1.81 ± 0.42 | 2.92±0.706 | <0.001 |
Table 2: ROC Analysis of different study parameters
| Parameters | Best-Cutoff value | Sensitivity | Specificity | Diagnostic efficacy | AUC |
| AST(U/L) | 37.50 | 86.66 % | 93.33% | 90% | 0.946 |
| ALT(U/L) | 71.00 | 63.33% | 93.33% | 78.33% | 0.811 |
| AST/ALT | 0.732 | 83.33% | 76.66% | 80% | 0.869 |
| GGT(U/L) | 55.50 | 96.66% | 86.66% | 91.66% | 0.929 |
| SA(m mol/L) | 2.3 | 80% | 93.33% | 86.66% | 0.939 |
DISSCUSSION:
Alcoholism is a serious health issue with major socio-economic consequences. Significant morbidity is related to chronic heavy alcohol use and alcoholics seek advice only when a complication of drinking sets in. The diagnosis is often based on patients self-reporting of alcohol consumption, which is unreliable and requires high degree of clinical suspicion.
Clinical histories and questionnaires are the commonest initial means of detection of alcohol abuse. They are cheap, easily administered but are subjective. If the history remains uncertain and there is suspicion of alcohol abuse, biological markers provide objectivity. A combination of markers remains essential in detection. Liver is the prime target organ for alcohol-induced disease. Liver enzymes are also important indicators of liver dysfunction, possibly as markers of alcohol dependence. Commonly used markers are GGT, AST and ALT. Laboratory markers help clinicians to raise the issue of excessive drinking as the possible cause of health problem, unfortunately because of lack of sensitive and specific methods, the detection of problem dinking in clinical settings has remained difficult. Therefore, findings of increased serum SA concentrations in alcoholics have raised the possibility of developing new tools for such purpose.
In the present study on analyzing the results it was found that an increased concentration of Serum Sialic acid and other traditional biochemical markers GGT, AST, ALT was observed in cases compared to that of controls. Over all GGT had a good sensitivity and specificity. The other traditional markers used in alcohol abuse varied considerably in their specificities and sensitivities. The increase in serum Sialic acid concentration in alcohol abusers in our present study is in accordance with the studies conducted by other investigators 8, 19, 20, 21.The diagnostic accuracy of SA was in accordance with the study by Antilla P et al 19 .The increase in serum GGT, ALT and AST concentration in alcohol abusers were in accordance with the studies conducted by other investigators 19, 22.
CONCLUSION:
In our study, Sialic Acid proved to be a good test with sensitivity of 80% and specificity of 93.33% with a diagnostic accuracy of 86.66% showing that SA can be used as a biochemical marker in alcohol abuse where secondary effects of liver disease hamper the use of traditional markers.
Limitations of the study are as follows: This study was done in small group of people only; a larger study consisting of alcohol abusers with and without specific liver disease should be conducted to confirm the role of SA as a new marker for alcohol abuse where the traditional markers will be altered by the different liver diseases.
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Competing Interests None declared Author Details VEERENDRA KUMAR ARUMALLA, MD, Assistant professor, Department of Biochemistry, Shri Sathya Sai Medical College and Research Institute, Ammapettai, Tamil Nadu, India. G NARENDER, MD, Assistant professor, Department of Biochemistry, Kakatiya Medical College, Warangal, Andhra Pradesh, India. R KATHAINI, MD, Assistant professor, Department of Biochemistry, Kakatiya Medical College, Warangal, Andhra Pradesh, India. A PULLAIAH, MD, Assistant professor, Department of Biochemistry, Kakatiya Medical College, Warangal, Andhra Pradesh, India. CORRESPONDENCE: VEERENDRA KUMAR ARUMALLA, MD, Assistant professor, Department of Biochemistry, Shri Sathya Sai Medical College and Research Institute, Ammapettai, 603108, Kancheepuram(Dt), Tamil Nadu, India Email: drveerendraarumalla@gmail.com |
References
1. Vivek benegal India: alcohol and public health Addiction Aug 2005, Volume 100, Issue 8, pages 1051–1056.
2. A. John, A. Barman, D. Bal, G. Chandy, Hazardous alcohol use in rural southern India: Nature, prevalence and risk factors. Natl Med J India 2009; 22: 123–5.
3. Katherine M. Conigrave Peter Davies,Paul Haber & John B. Whitfield.Traditional markers of excessive alcohol use. Addiction, 98(Suppl. 2), 31–43.
4. Conigrave, K.M.; Davies, P.; Haber, P.; AND Whitfield, J.B. Traditional markers of excessive alcohol use. Addiction 98(Suppl. 2):31–43, 2003.
5. HalvorsoN, M.R.; Campbell, J.L.; Sprague, G; et al. Comparative evaluation of the clinical utility of three markers of ethanol intake: The effect of gender. Alcoholism: Clinical and Experimental Research 17(2):225–229, 1993.
6. Peter C. Sharpe. Biochemical detection and monitoring of alcohol abuse and abstinence. Ann Clin Biochem 2001; 38: 652-664.
7. Himmelstein DU, Woolhandler SJ, Adler R.D. Elevated SGOT/SGPT ratio in alcoholic patients with acetaminophen toxicity. Am J Gastroenterol 1984; 79 (9): 718-720.
8. Romppanen Jarrko, Punnonen Kari, Antilla Petra, Jakabosson, Tuula, Blake, Joan, Niemela Onni. Serum Sialic acid as a marker of alcohol consumption; effect of liver disease and heavy drinking (Diagnosis and treatment). Alcohol Clin Exp Res 2002; 26(8): 1234-1238.
9. Ewing JA. Detecting alcoholism. The CAGE questionnaire. Am J Psych, 1984; 252: 1905-1907.
10. Peter C. Sharpe. Biochemical detection and monitoring of alcohol abuse and abstinence. Ann Clin Biochem 2001; 38: 652-664.
11.Lorentz KT, Weib, Krass. Sialic acid in Humans serum and cerebrospinal fluid. J Clin Chem Biochem 1986; 24: 189-198.
12. Bergmeyer HU, Bowers GN, Horder M, Moss DW. IFCC method for aspartate aminotransferase. Clin Chim Acta 1976; 70 (2): 31-40.
13. Bergmeyer HU, Scheibie P, Wahlefeld AS. Optimization of methods for Aspartate transaminases and alanine aminotranferase. Clin Chem 1978; 24: 58-73.
14. Saris NE. Revised IFCC method of aspartate aminotranferase. Clin Chem 1978; 24: 720-721.
15. Bergmeyer HU. Horder M. IFCC method for measurement of catalytic concentration of enzymes part 3 IFCC method for Alanine aminotransferase. J Clin Chem Clin Biochem 1980; 18 (8): 521-534.
16. Gruber W, Bergmeyer HU. Normal range for serum transaminases Br Med J 1971; 4 (789): 749-750.
17. Shaw IM, Stromme JH, London JL, Theodorsen L. IFCC methods for determination of enzymes part 4. IFCC method for gamma glutamyl transferase (Gammaglutamyl peptide): Amino acid gamma glutamyl transferase. Clinica Chemica Acta 1983; 15F-338F.
18. Rosalki SB, Rau D. Serum gamma glutamyl transpeptidase activity in alcoholism Clin Chem 1972; 39: 41.
19. Antilla P, Jarvi K, Latvala J, RomPgannen J, Punnonen K, Niemela O. Biochemical markers of alcohol consumption in patients classified according to the degree of liver disease severity. Scand J Clin Lab Invest.2005; 65(2): 141-151.
20. Lech Chrostek, Bogdan Cylwik, Maciej Szmiitkowski and Walenty Korcz. The diagnostic accuracy of Carbohydrate Deficient Transferrin, Sialic acid and commonly used markers of alcohol abuse during abstinence. Clin Chem Acta 2006; 364 (1-2): 167-171.
21. Sillanaukee P, Ponnio M, Seppa K. Sialic acid: New potential marker of alcohol abuse, Alcohol Clin Exp Res 1999; 23(6): 1039-43.
22. Vaswani M, Rao Ravindra V. Biochemical measures of alcohol dependence using discriminate analysis. Indian J Med Sci 2005; 59 (10): 423-430.
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