Submit manuscript...
Journal of
eISSN: 2471-1381

Liver Research, Disorders & Therapy

Research Article Volume 3 Issue 5

What are the factors affecting GGT elevation in patients with severe alcohol use disorders in Albanian population?

Sonila Bitri Tivari,1 Esmeralda Thoma,2 Entela Puca,3 Eugjen Sotiri,4 Edmond Puca5

1Department of Clinical Toxicology and Addiction, American Hospital, Albania
2University of Medicine of Tirana, Albania
3Department of Endocrinology, American Hospital, Albania
4Department of Psychiatry, University Hospital Center Mother Theresa, Albania
5Department of Infection Diseases, University Hospital Center Mother Theresa, Albania

Correspondence: Sonila Bitri Tivari, Clinical toxicologist, Department of Clinical Toxicology and Addiction Medicine, American Hospital 2, Rruga e Dibres, Tirana, Albania, Tel 00 3556 8902 5828

Received: October 05, 2017 | Published: November 10, 2017

Citation: Tivari SB, Thoma E, Puca E, et al. What are the factors affecting GGT elevation in patients with severe alcohol use disorders in Albanian population?. J Liver Res Disord Ther. 2017;3(5):123-126. DOI: 10.15406/jlrdt.2017.03.00069

Download PDF

Abstract

Objective: A specific and sensitive marker of alcohol abuse is serum γ-glutamyl transferase (GGT). A wide range of changes is met even between heavy drinkers. Through this work we wanted to see the variation of GGT according to age and alcohol consumption in patients with severe Alcohol Use disorders (AUD). We wanted also to evaluate the lower amount of alcohol, causing GGT elevation.

Method: This is a retrospective study performed in American Hospital, Tirana, Albania during the period 2013-2015. Serum GGT values were measured in 157 patients diagnosed with severe AUD according to Diagnostic and Statistical Manual of Mental Disorders 5 edition (DSM-5). They were all males with mean age 42±4.9years old, who presented voluntary in the hospital for alcohol detoxification. They were divided in subgroups according to age and alcohol amount consumption. Values are expressed as mean ±SD. Comparisons were made by logistic correlation. A P-value <0.05 was considered statistically significant.

Results: We found a statistically significant correlation between GGT and ethanol intake (P<0.0001), (r=0.7) and a positive correlation between GGT and age. Normal mean values of GGT are found in the group of patients who consumed less than 10drinks/day. 5-10 drinks/day was the limit to induce GGT elevation in our sample.

Conclusion: Our findings show that GGT activities respond to ethanol intake and are age-dependent in patients with severe AUD. Early detection is associated to less complication and can lead to a better outcome.

Keywords: alcohol use disorders, γ-glutamyl transferase, age, drink/day, cardiomyopathies

Abbreviations

GGT, γ-glutamyl transferase; AUD, alcohol use disorders; DSM, diagnostic and statistical manual; AASLD, american association for study of liver disease

Introduction

Alcohol Use Disorders (DSM-5) and the related complications have a high prevalence throughout the world.1 People can go from one disorder to another, without even noticing any changes, except of the higher dosages of alcohol. When alcohol consumption is part of tradition, as in our country Albania,2 first drink can be met in very young people, especially males. Sometimes it is encouraged even from the familiars. Besides this, many patients consider heavy alcohol use as social drinking, leading to a late clinical diagnosis and more complications.3,4 American Association for the Study of Liver Disease (AASLD) guidelines define as significant alcohol consumption, amounts of more than 21 drinks per week for males and 14 drinks per week for females.5,6 In severe AUD the amount of alcohol largely exceeds these limits, causing important changes in laboratory findings and biomarkers.

A specific and sensitive marker of alcohol abuse is serum γ-glutamyl transferase (GGT).7 It is a very sensitive marker not only to diagnose the alcohol misuse but also to follow the changes during the treatment.8,9 Levels of GGT generally rise after heavy alcohol intake for several weeks, and decrease after 2-6weeks of abstinence and treatment. GGT seems to be more specific marker for continuous than episodic heavy drinking.10 But it can elevate even in obesity, dyslipidemia, hypertension or diabetes.11 Even if several studies report a positive correlation between ethanol intake and serum GGT in abstainer, moderate or heavy drinkers, notable variation in GGT values are seen even between heavy drinkers.12,13 Many studies highlight the possible age-related or amount related effects on serum GGT activities in heavy drinkers.14,15

Aim

Through this work we wanted to have an overview of the age related and amount related variation of GGT in heavy drinkers in Albania. We wanted also to evaluate the lower amount of alcohol, causing GGT elevation.

Methods

This is a retrospective study performed in American Hospital, Tirana, Albania during the period 2013-2015. Serum GGT values were measured in 157 heavy drinkers (more than 20 drinks/week, usual number of drinks per occasion ≥ five), all males, Albanian nationality, mean age 42±4.9years, range 25-66years old, who had been admitted in our hospital for alcohol detoxification and relapse prevention treatment. They presented voluntary in the hospital to begin the treatment procedures. The diagnosis of severe Alcohol Use Disorders was made using AUDIT, CAGE questionnaires and DSM-5 criteria. The patients who were blood donors 3months prior to hospitalization, or had used any prescription drugs during the preceding 2weeks, were not included in the study. Moderate or binge drinkers, patients with other known diseases as, cardiomyopathies, nephropathies, cancer, diabetes or other metabolic syndromes, obese patients (Body Mass Index BMI≥29.9) were excluded from the study. Any female was presented to our department for AUD treatment.

All patients had a history of chronic ethanol consumption in average amounts of 11.6±5.6 drinks/day (range 3-50 drinks/day). One drink equal to 8gms of pure alcohol. The patients sample was divided according to age as follows: less than 35years: 33%; 36-45years: 27%; 46-55years: 20%; more than 56years: 20%. While according to alcohol consumption the subgroups were up to 10 drinks/day-58%; 11-20 drinks/day-22%; 21-30 drinks/day-12%; more than 30 drinks/day-8%. All patients had used alcohol 24hours prior to sampling. Normal range of GGT was considered 8-61UI/L.

Statistical methods

Values are expressed as mean±SD. Comparisons were made by logistic correlation. The correlation coefficient ‘r’ was measured and P-value <0.05 was considered statistically significant.

Results

We found a statistically significant correlation between GGT and ethanol intake (P<0.0001, r= 0.72). Same conclusions were found also when the patients were divided in subgroups according to age (Table 1) with ‘p’ value respectively P<0.005 in less than 35 years old (r=0.6) and 46-55 years old group (r=0.7); P<0.0001 in 36-45 years old (r=0.8) and P<0.05 in more than 56 years old patients (r=0.7). When we measured the mean GGT in different age groups, we observed a progressive elevation of this value with aging from 106.1 UI/L in the youngest age group, to 342 UI/L to the oldest age group (Figure 1), proving a positive correlation between GGT and age, even if not statistically significant.

Age (years)

Less than 35

36-45

46-55

More than 56

GGT mean±SD UI/L

106.1

177

286

342

Alcohol drinks

7.7

10

15

17

Table 1 GGT and alcohol consumption in different age groups.

Figure 1 GGT values (mean±SD) UI/L in different age groups.

An interesting finding was the variation of GGT in the group of patients younger than 35 years old. All the normal GGT values were found in patients younger than 30 years. Only 11% of the latter one had elevated GGT values (Figure 2). On the other hand, we found that the mean alcohol consumption increased progressively with aging, going from 7.7 drinks to17 drinks/day (Figure 3). When we sub grouped our patients according to amount consumption, to study the correlation between GGT and age, we observed that the average GGT activity increased with increasing alcohol amount (Table 2). A More notable difference was observed with dose increasing from 0-10 drinks/day group to 11-20 drinks/day groups. With higher alcohol amounts, the difference was not so pronounced (Figure 4). Normal mean± SD GGT values were found in patients who consumed 0-10 drinks/day. The mean ± SD number of drinks in the latter group was 5 drinks, and 70% of patients took ≤ drinks/day (Figure 5).

Figure 2 Variation of GGT in patients younger than 30 years old.

Figure 3 Alcohol consumption (drinks/day) in different age groups.

Alcohol drinks

0-10

20-Nov

21-30

More than 30

GGT mean ±SD in UI/L

59

317

545

783

Table 2 GGT values (mean ±SD) in groups classified according to alcohol consumption.

Figure 4 Correlation between GGT and Alcohol drinks consumption.

Figure 5 Alcohol consumption in 0-10 drinks/day group. 70% of patient takes less than 5 drinks/day.

Discussion

In our study 60%of the patients were less than 45years old. Larger study made in Albania in16 for similar topics; state that service users for narcotics and alcohol are mainly young persons.2 Similar findings had Liberto, Karlamangla et al.17 In their studies they show that with age, there are a decrease in alcohol consumption and alcohol-related problems among heavy drinkers.17,18 Lower income, higher risk for complication and comorbidities, can influence in this reduction rate. In our country stigma may be another important factor.2 Even if more exposed to risky lifestyle and multi substance abuse,19 younger ages are more informed about hazardous drinking. They are more open minded and can easier address to a healthcare facility. The present work shows that GGT values are influenced significantly from ethanol intake. The differences are more pronounced with dose increasing, especially in amounts more than 10drinks/day.

What we found interesting in our study was the normal mean average values of GGT in the group who consumed less than 10U alcohol/day. About 70% of these patients consumed less than 5drinks/day and the mean ± SD alcohol consumption was 5drinks/day. This may be considered as a threshold to cause more sensitive liver induction in our sample. These findings lead us to the conclusion that 5-10 drinks/day was enough to raise the GGT levels in regular drinkers with a long drinking history. So, it is important detecting patients at this level of abuse. Similar conclusions are seen in other countries and in larger population. When John P Allen et al.20 studies the liver tests variation in heavy drinking,20 he found that GGT raise after several week consumption of 10 drink/day. Sillanauke et al.21 had same findings in another large work.21 Age is another important factor in drug misuse.14 Younger males may be more resistant to the harmful effects of alcohol showing lower GGT activities than expected. Conigrave et al.22 states that markers are more likely to be elevated in those aged more than 30years. On the other hand, some other studies highlight the low specify of GGT in adults younger than 30years old,22 even when they meet the criteria for alcohol dependence.23

Similar findings had our study. We found lower alcohol abuse and normal GGT mean values in patients younger than 30years old. With aging we observed increasing alcohol abuse, related also to tolerance development. With higher amounts and accumulative toxicity, we found more liver damages and progressive elevation of GGT. Some studies18,22have found lower alcohol abuse in ages higher than 65-70 and as a consequence lower GGT activities. We couldn’t investigate for similar findings as the patients included in the study were up to 65years old. Sex differences4,7,24 are observed in a lot of studies. Females seemed to be more vulnerable to alcohol toxicity explained from the metabolism of ethanol and glutathione. We couldn’t share any experience as till now, stigma is an important factor impeaching woman seeking medical help for alcohol abuse. In our study we didn’t find important changes in BMI, another important factor affecting liver function.11,25,26

Conclusion

Our study helped us to have some highlights of GGT activity in heavy alcohol abusers in Albania. Our findings showed that GGT activities respond to ethanol intake and are age-dependent in patients with severe AUD. Larger studies need to be done to strengthen our findings.

Acknowledgements

None.

Conflict of interest

All authors have no conflict of interest.

Funding

Authors state that this study was financed with internal funds. No sponsor played a role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

References

  1. Connor JP, Haber PS, Hall WD. Alcohol use disorders. Lancet. 2016;387(10022):988‒998.
  2. EMCDDA. Albania country overview-a summary of the national drug situation. 2016.
  3. Rehm J, Gmel G, Shield KD. Lifetime-risk of alcohol-attributable mortality based on different levels of alcohol consumption in seven European countries : Implications for low-risk drinking guidelines. Centre for Addiction and Mental Health. 2015.
  4. Tynjälä J, Kangastupa P, Laatikainen T, et al. Effect of age and gender on the relationship between alcohol consumption and serum GGT: time to recalibrate goals for normal ranges. Alcohol Alcohol. 2012;47(5):558‒562.
  5. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005‒2023.
  6. Niemelä O. Biomarker-Based Approaches for Assessing Alcohol Use Disorders. Int J Environ Res Public Health. 2016;13(2):166.
  7. Anton RF, Lieber C, Tabakoff B. Carbohydrate-deficient transferrin and gamma-glutamyltransferase for the detection and monitoring of alcohol use: results from a multisite study. Alcohol Clin Exp Res. 2002;26(8):1215‒1222.
  8. Conigrave KM, Davies P, Haber P, et al. Traditional markers of excessive alcohol use. Addiction. 2003;98(Suppl 2):31‒43.
  9. Alatalo P, Koivisto H, Puukka K, et al. Biomarkers of liver status in heavy drinkers, moderate drinkers and abstainers. Alcohol Alcohol. 2009;44(2):199‒203.
  10. Sohail U, Satapathy SK. Diagnosis and management of alcoholic hepatitis. Clin Liver Dis. 2012;16(4):717‒736.
  11. Elshorbagy AK, Refsum H, Smith AD, et al. The Association of Plasma Cysteine and γ-Glutamyltransferase With BMI and Obesity. Obesity (Silver Spring). 2009;17(7):1435‒1440.
  12. Sharpe PC. Biochemical detection and monitoring of alcohol abuse and abstinence. Ann Clin Biochem. 2001;38(Pt 6):652‒664.
  13. Van Beek JHDA, De Moor MHM, Geels LM, et al. The association of alcohol intake with γ-glutamyl transferase (GGT) levels: evidence for correlated genetic effects. Drug Alcohol Depend. 2014;134:99‒105.
  14. Puukka K, Hietala J, Koivisto H, et al. Age-Related Changes on Serum Ggt Activity and the Assessment of Ethanol Intake. Alcohol Alcohol. 2006;41(5):522‒527.
  15. Liangpunsakul S, Qi R, Crabb DW, et al. Relationship Between Alcohol Drinking and Aspartate Aminotransferase:alanine Aminotransferase (AST:ALT) Ratio, Mean Corpuscular Volume (MCV), Gamma-Glutamyl Transpeptidase (GGT), and Apolipoprotein A1 and B in the U.S. Population. J Stud Alcohol Drugs. 2010;71(2):249‒252.
  16. http://www.emcdda.europa.eu/system/files/publications/806/National_Report_Albania_2013_EN_483828.pdf
  17. Liberto JG, Oslin DW, Ruskin PE. Alcoholism in Older Persons: A Review of the Literature. Hosp Community Psychiatry. 1992;43(10):975‒984.
  18. Karlamangla A, Zhou K, Reuben D, et al. Longitudinal trajectories of heavy drinking in adults in the United States of America. Addiction. 2006;101(1):91‒99.
  19. Hingson RW, Heeren T, Winter MR. Age of alcohol-dependence onset: associations with severity of dependence and seeking treatment. Pediatrics. 2006;118(3):e755‒e763.
  20. http://pubs.niaaa.nih.gov/publications/AssessingAlcohol/biomarkers.htm
  21. Sillanaukee P, Massot N, Jousilahti P, et al. Dose Response of Laboratory Markers to Alcohol Consumption in a General Population. Am J Epidemiol. 2000;152(8):747‒751.
  22. Conigrave KM, Degenhardt LJ, Whitfield JB, et al. CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project. Alcohol Clin Exp Res. 2002;26(3):332‒339.
  23. Bisson JI, Milford-Ward A. A Comparison of Carbohydrate Deficient Transferrin with Other Markers of Alcohol Misuse in Male Soldiers Under the Age of Thirty. Alcohol and Alcoholism. 1994;29(3):315‒321.
  24. Niemelä O, Parkkila S, Pasanen M, et al. Induction of cytochrome P450 enzymes and generation of protein-aldehyde adducts are associated with sex-dependent sensitivity to alcohol-induced liver disease in micropigs. Hepatology. 1999;30(4):1011‒1017.
  25. Daeppen JB, Smith TL, Schuckit MA. Influence of age and body mass index on gamma-glutamyltransferase activity: a 15-year follow-up evaluation in a community sample. Alcohol Clin Exp Res. 1998;22(4):941‒944.
  26. Lee DH, Ha MH, Christiani DC. Body weight, alcohol consumption and liver enzyme activity--a 4-year follow-up study. Int J Epidemiol. 2001;30(4):766‒770.
Creative Commons Attribution License

©2017 Tivari, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.