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LETTER TO THE EDITOR

Effect of Age and Alcohol Consumption in Patients with Severe Alcohol Use

Disorders. What is the Lowest Amount of Alcohol That Might Be Causing

Serum γ-glutamyltransferase Elevation?

Dear Editor,

I am writing this letter to discuss the topic of variation of GGT (γ-glutamyltransferase) in heavy drinkers in Albania, and to talk about the lowest amount of alcohol that might be causing GGT changes in the current population.

Alcohol Use Disorders (AUD) DSM-5-(Diagnostic and Statistical Manual of Mental Disorders-5) and the related com- plications have a high prevalence throughout the world (Connor et al., 2016)where alcohol is cheap, readily available, and heavily promoted. Common, mild disorders often remit in young adult- hood, but more severe disorders can become chronic and need long-term medical and psychological management. Doctors are uniquely placed to opportunistically assess and manage alcohol use disorders, but in practice diagnosis and treatment are often delayed. Brief behavioural intervention is effective in primary care for hazardous drinkers and individuals with mild disorders. Brief interventions could also encourage early entry to treatment for people with more-severe illness who are underdiagnosed and undertreated. Sustained abstinence is the optimum outcome for severe disorder. The stigma that discourages treatment seek- ing needs to be reduced, and pragmatic approaches adopted for patients who initially reject abstinence as a goal. To engage peo- ple in one or more psychological and pharmacological treatments of equivalent effectiveness is more important than to advocate a specific treatment. A key research priority is to improve the diag- nosis and treatment of most affected people who have comorbid mental and other drug use disorders.”,”DOI”:”10.1016/S0140- 6736(15. In several countries where alcohol consumption is part

8 LETTER TO THE EDITOR: ALCOHOL USE DISORDERS

of their tradition, as for instance our country Albania (EMCDDA National_Report_Albania_2013), the first drink can be intro- duced in at a very young age, especially with males. Every so often, it is encouraged even from their family members. In addi- tion, many patients consider heavy alcohol use as social drinking. This perception is actually leading the patients to a late clinical diagnosis followed by more complications (Tynjälä et al., 2012) recent studies have also implicated it as a predictor of morbidity due to extrahepatic causes. Therefore, further information on the associations between ethanol intake and GGT activities in appar- ently healthy individuals appears warranted.\nMETHODS: Data on alcohol consumption and serum GGT activities were collected from 18,899 individuals (8807 men, 10,092 women. As a result, early intervention can prevent the severe tissue toxicity.

GGT is a very sensitive marker for continuous heavy drink- ing, (van Beek et al., 2014)there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemiological association between alcohol intake and GGT at the population level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits. However, it can also be elevated in obesity, dyslipidemia, hyper- tension or diabetes (Elshorbagy et al., 2009).

Even though several studies highlight the possible age-related or amount related effects on serum GGT activities, notable vari- ation in GGT values are seen even between heavy drinkers (van Beek et al., 2014)there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemi- ological association between alcohol intake and GGT at the pop- ulation level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits. Some studies report racial and ethnic variation of GGT due to alcohol abuse (Stewart, 2002).

We performed a retrospective study in the American Hospital, Tirana, Albania during the period (2013-2014) to give a repre- sentation of these correlations in the Albanian population and to propose a limit of alcohol amount that causes GGT changes.

9LETTER TO THE EDITOR: ALCOHOL USE DISORDERS

Serum GGT values were measured in 73 heavy drinkers (more than 20 drinks/week: usual number of drinks per occasion ≥ five); all males; Albanian nationality; mean age 42 ± 4.9 years a range of 25-66 years old. All patients had been admitted to our hospital for alcohol detoxification and relapse prevention treatment. We want to emphasize the fact that no female patients came into hos- pital for AUD treatment. This is the reason why all the data we collected is from male patients.

The diagnosis of severe AUD was performed using AUDIT (Alcohol Use Disorders Identification Test), CAGE question- naires and DSM-5 criteria.

The patients who were blood donors 3 months prior to hospi- talization, or had used any prescription drugs during the preced- ing 2 weeks, were not included in the study. Moderate or binge drinkers, patients with other known diseases such as, cardiomy- opathies, nephropathies, cancer, diabetes or other metabolic syn- dromes and obese patients (Body Mass Index BMI≥ 29.9) were excluded from the study.

All patients included in the study had a history of chronic eth- anol consumption and in the last year the average amount of alco- hol consumed was 11.6+-5.6 drinks/day (range 3-50 drinks/day).

The patients were divided according to age as follows: less than 35 years: 33%; 36-45 years: 27%; 46-55 years: 20%; more than 56 years: 20%. According to alcohol consumption, the sub- groups drank up to 10 drinks/day: 58%; 11-20 drinks/day: 22 %; 21-30drinks/day:12%; more than 30 drinks/day 8%.

All patients had used alcohol 24 hours prior to sampling. Normal range of GGT was considered 8-61 UI/L.

In our study, 60% of the patients were less than 45 years old. There was a larger study performed in Albania in 2013 (EMCDDA National_Report_Albania_2013) for similar topics, which showed that service users for narcotics and alcohol were mainly young people. Karlamangla also had similar findings. In his study, he shows that with age, there is a decrease in alcohol consumption and alcohol-related problems among heavy drinkers (Karlamangla et al., 2006)period, cohort and other demographic influences on heavy alcohol consumption and trajectories of

10 LETTER TO THE EDITOR: ALCOHOL USE DISORDERS

heavy drinking in American adults. Design Prospective cohort of 14 127 participants, aged 25–74 years at baseline. Generalized estimating equations to model longitudinal change in the prob- ability of heavy drinking and its association with demographic factors. Setting National, population-based sample of non-insti- tutionalized civilians. Measurements Heavy alcohol consump- tion (usual number of drinks per occasion ≥ five for men; ≥ four for women. Lower income and higher risk for complication and comorbidities can contribute to the alcohol consumption reduc- tion rate.

In our country, stigma may be an another important factor (EMCDDA National_Report_Albania_2013). Younger individ- uals are more informed about hazardous drinking, even though they are more exposed to risky lifestyles and multi substance abuse (Hingson et al.,2006). They are more open minded and can more easily go to a healthcare facility.

We found a statistically significant and positive correlation between GGT and ethanol intake (P<0.0001), (r = 0.72) in the total sample, and also when divided in subgroups according to age.

What we found interesting in our study was the normal mean average values of GGT in the group which consumed less than 10 U alcohol/day. About 70% of these patients consumed less than 5 drinks/day and the mean ± SD alcohol consumption in this group, was 5 drinks/day. This may be considered as a threshold to cause more sensitive liver induction in our patients. These findings lead us to the conclusion that 5-10 drinks/day were enough to raise the GGT levels in regular alcohol abusers with a long drinking history. So, it is important to detect patients at this level of abuse.

Similar conclusions are seen in other countries with larger populations. When John. P. Allen studied the liver tests varia- tion in heavy drinking (John Allen et al., NIAA publ), he found that the GGT was higher after several weeks of consuming of 10 drinks/day.

When we measured the mean GGT in different age groups, we observed a progressive elevation of this value with aging.

11LETTER TO THE EDITOR: ALCOHOL USE DISORDERS

An interesting finding was the variation of GGT in the group of patients younger than 35 years of age. 89% of them had normal GGT values and these were the only normal values found in the total sample. Conigrave states that markers are more likely to be elevated in individuals greater than 30 years of age. On the other hand, some other studies highlighted the low specify of GGT in adults younger than 30 years of age (Conigrave et al., 2002), even when they met the criteria for alcohol dependence.

Sex differences (Tynjälä et al., 2012) are observed in a lot of studies. Females seemed to be more vulnerable to alcohol toxic- ity explained by the metabolism of ethanol and glutathione. We couldn’t share any experiences because, stigma is still an import- ant factor impeding women from seeking medical help for alco- hol abuse.

In the Albanian population, GGT activities respond to etha- nol intake and are age-dependent in patients with severe AUD. 5-10 drinks/day can be the limit which creates the elevation of GGT values. Further and larger research is needed to be done to strengthen our findings.

Sonila Tivari Bitri, MD Department of Clinical Toxicology and Addiction Medicine American Hospital Tirana, Albania

Esmeralda Thoma, PhD University of Medicine of Tirana Tirana, Albania

Entela Puca, PhD Department of Endocrinology American Hospital Tirana, Albania

Edmond Puca, PhD Department of Infection Diseases University Hospital Center “Mother Theresa” Tirana, Albania

12 LETTER TO THE EDITOR: ALCOHOL USE DISORDERS

Correspondence concerning this article should be addressed to: Sonila Tivari Bitri, Clinical Toxicologist, American Hospital 2, Rr e Dibres, Tirana, Albania, Telephone: 00355689025828, E-mail: [email protected].

REFERENCES

Biomarkers of Heavy Drinking. (n.d.). Retrieved July 27, 2016, from http://pubs.niaaa.nih.gov/publications/AssessingAlcohol/biomark- ers.htm

Conigrave, K. M., Degenhardt, L. J., Whitfield, J. B., Saunders, J. B., Helander, A., Tabakoff, B., & WHO/ISBRA Study Group. (2002). CDT, GGT and AST as markers of alcohol use: the WHO/ISBRA collaborative project. Alcoholism, Clinical and Experimental Research, 26(3), 332-339.

Connor, J. P., Haber, P. S., & Hall, W. D. (2016). Alcohol use disor- ders. Lancet (London, England), 387(10022), 988-998. https://doi. org/10.1016/S0140-6736(15)00122-1

Hingson, R. W., Heeren, T., & Winter, M. R. (2006). Age of alco- hol-dependence onset: associations with severity of dependence and seeking treatment. Pediatrics, 118(3), e755-763. https://doi. org/10.1542/peds.2006-0223

Karlamangla, A., Zhou, K., Reuben, D., Greendale, G., & Moore, A. (2006). Longitudinal trajectories of heavy drinking in adults in the United States of America. Addiction, 101(1), 91-99. https:// doi.org/10.1111/j.1360-0443.2005.01299.x https://doi.org/10.1176/ ps.43.10.975

National_Report_Albania_2013_EN_483828.pdf. (n.d.). Retrieved from http://www.emcdda.europa.eu/system/files/publications/806/ National_Report_Albania_2013_EN_483828.pdf

Rehm, J., Gmel, G., & Shield, K. D. (2015). Lifetime-risk of alco- hol-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; Terveyden ja hyvinvoinnin laitos THL. Retrieved from http:// www.julkari.fi/handle/10024/125502

13LETTER TO THE EDITOR: ALCOHOL USE DISORDERS

Stewart, S. H. (2002). Racial and Ethnic Differences in Alcohol- Associated Aspartate Aminotransferase and γ-Glutamyltransfer- ase Elevation. Archives of Internal Medicine, 162(19), 2236-2239. https://doi.org/10.1001/archinte.162.19.2236

Tynjälä, J., Kangastupa, P., Laatikainen, T., Aalto, M., & Niemelä, O. (2012). Effect of age and gender on the relationship between alco- hol consumption and serum GGT: time to recalibrate goals for nor- mal ranges. Alcohol and Alcoholism (Oxford, Oxfordshire), 47(5), 558-562. https://doi.org/10.1093/alcalc/ags072

Van Beek, J. H. D. A., de Moor, M. H. M., Geels, L. M., Sinke, M. R. T., de Geus, E. J. C., Lubke, G. H., Boomsma, D. I. (2014). The association of alcohol intake with γ-glutamyl transfer- ase (GGT) levels: evidence for correlated genetic effects. Drug and Alcohol Dependence, 134, 99-105. https://doi.org/10.1016/j. drugalcdep.2013.09.016

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