Evaluation of alcohol use pattern among OST patients using alcohol biomarkers: Report from community clinics in India.

Background: Opioid-dependent patients undergoing opioid substitution therapy (OST) consume alcohol in a hazardous pattern which adversely affects their treatment outcome. This study aims to measure alcohol biomarkers to screen for secondary alcohol use in OST patients.
Methods: A pilot study was planned to measure alcohol biomarkers (AST, ALT, GGT, and CDT) to assess alcohol use in OST patients from three community clinics. The biomarkers were categorized based on the reported frequency of alcohol use. The association of the biomarkers with the frequency of alcohol consumption was determined using the post hoc (Mann-Whitney) test.
Results: Forty-five patients with a mean (SD) age of 37.04 (10.7) years were included in the study. Alcohol intake was reported in daily, weekly, and monthly patterns by 22, 63, and 16% of the patients, respectively. High levels of ALT, GGT, and CDT were measured in patients with daily use of alcohol. Serum CDT levels significantly differentiate daily and weekly use from monthly consumption of alcohol. Conclusions: Alcohol biomarkers significantly predict the pattern of alcohol use among OST patients. These results can be prudent in low-resource community clinics to improve the overall outcomes of OST in India. Copyright:

INTRODUCTION

Opioids are a major class of problem drugs causing significant disease burden and drug-related deaths worldwide.[1] In India, the use of opioids was reported in 2.1% of the general population which includes 0.7% of opioid-dependents.[2] Long-term treatment with agonists like methadone and buprenorphine, known as opioid substitution therapy (OST), is regarded as a standard treatment option for opioid dependence.[3] OST has been shown to reduce illicit opioid usage, HIV risk behaviors, death from overdose and criminal activity, and stress on drug users and their families.[4]

The available reports suggest that 28–79% of OST recipients consume alcohol in a hazardous or dependent pattern (secondary alcohol use), thereby, impacting their treatment outcomes.[56] Routinely, a self-reported standardized questionnaire is used to establish the extent and pattern of alcohol consumption. Objective tools in the form of biomarkers can also aid clinicians to ascertain alcohol use. Frequent use of alcohol may lead to increased levels of biomarkers like aspartate and alanine aminotransferase (AST, ALT), gamma-glutamyl transferase (GGT), and carbohydrate-deficient transferrin (CDT).[7] However, the utility of these biomarkers has been rarely studied for assessing secondary alcohol use. Since these markers can easily be tested in community settings in an under-resourced country like India, we explored their association with the frequency of alcohol consumption among OST patients. This knowledge can subsequently be used to evaluate secondary alcohol use among OST patients from low-resource community clinics, and thereby, improve OST outcomes by early identification and treatment of secondary alcohol use and related complications.

METHODS

Study design

This report was part of a pilot study done to analyze the biomarkers for alcohol as an add-on tool to screen for harmful alcohol use from community OST clinics.

Participants

The study was carried out at a national level drug treatment center in North India. The samples were collected from community clinics run by the center in three different localities. The participants were males aged 18– 60 years with a history of self-reported secondary alcohol use. The participants were a part of OST program for at least 3 months from the clinic. Those with diagnosed alcohol dependence and already on treatment for the same were excluded.

Data & analysis

Data on socio-demographic variables and clinical parameters like compliance, craving, and history of use of other substances like cannabis were collected by the clinicians through a semi-structured proforma. After obtaining informed consent, patients were interviewed and a blood sample (2 mL) was drawn from each subject in gel-based vacutainers. The blood samples were transported to the central laboratory of the treatment center for analysis. All the biomarkers were measured by a chemistry analyzer (Au480, Beckman Coulter) as per our earlier report.[8]

Ethics clearance

The institute research ethics committee approved the study protocol. The study data were kept confidential and non-participation bore no consequence on the ongoing treatment.

Statistical analysis

Mean, standard deviation, and percentages were used to present the descriptive profile. Nonparametric tests (Kruskal–Wallis mean rank and Mann–Whitney) were used to compare groups, considering small sample size. SPSS version 21 (IBM, New York, USA) was used to perform all the analyses.

RESULTS

A total of forty-five (45) OST patients primarily maintained on buprenorphine were included in the study. The mean (SD) age of the patients was 37.04 (10.7) years. Out of the 45 patients, alcohol intake was reported in a daily pattern by 10 (22%), weekly by 28 (63%), and monthly by 7 (16%). All patients reported continued tobacco use, while less than half (20, 45%) had a history of daily cannabis consumption. About 76% of patients were “very regular” with their primary treatment (OST); defined in our clinic as taking buprenorphine for more than 24 days in a month. Only three patients reported craving for illicit opioids and four had minor side effects related to buprenorphine.

The data were analyzed for levels of alcohol biomarkers and their association with the frequency of alcohol consumption through the Kruskal–Wallis test (by mean rank). The blood parameters were categorized into three groups based on the reported frequency of alcohol use: daily (A), weekly (B), and monthly (C), for comparison of mean ranks. Table 1 indicates that the number of patients with elevated ALT, GGT, and CDT was higher daily as compared to weekly and monthly consumers of alcohol. However, the mean rank difference was only significant for levels of CDT (H = 6.42; P = 0.04). Similarly on post hoc Mann–Whitney analysis, intergroup differences were significant for daily versus monthly (A vs. C; P = 0.04) and weekly versus monthly (B vs. C; P = 0.01) for CDT levels only. The differences in the groups concerning other biomarkers levels could not reach statistical significance.

Table 1

Alcohol biomarkers and alcohol-use pattern among OST patients (n=45)

Biomarker Mean (SD)	Self-reported pattern of alcohol use (past 90 days)			Kruskal–Wallis test by mean rank post hoc (Mann-Whitney) X (p)	P
	Group A Daily (n=10)	Group B Weekly (n=28)	Group C Monthly (n=7)
AST (U/L) % elevated	45.6 (22.5) 20%	58.14 (70.58) 28.6%	44.2 (24.39) 14.0%	0.633 (0.729)	A vs B: 0.40 B vs C: 1.00 A vs C: 0.74
ALT (U/L) % elevated	39.9 (28.5) 20%	52.53 (97.7) 17.8%	55.0 (69.15) 14.0%	0.974 (0.614)	A vs B: 0.35 B vs C: 0.60 A vs C: 1.00
GGT (U/L) % elevated	49.9 (37.8) 30%	58.32 (74.19) 28.6%	29.0 (14.4) 0.0%	0.748 (0.688)	A vs B: 0.59 B vs C: 0.65 A vs C: 0.36
CDT (ng/ml) % elevated	510.48 (372.15) 60%	636.05 (584.52) 57.2%	245.5 (116.9) 14.0%	6.42 (0.040)	A vs B: 0.66 B vs C: 0.015* A vs C: 0.040*

*P statistically significant

DISCUSSION

Early screening for alcohol use patterns can be utilized as an indicator of problematic alcohol use in community settings among OST patients.[9] It is useful in identifying and dealing with alcohol-related problems as well as in improving OST-related outcomes.[10] A prospective Indian study among ODS patients on buprenorphine maintenance treatment reported one-fourth of the patients consume alcohol in a harmful hazardous manner.[11] This pilot study used a clinic-based sample already undergoing treatment for drug dependence, for which very limited data were available from India.[8] Early identification of problematic alcohol use through routine blood testing can be potentially useful in improving OST outcomes in community settings. A few studies tried to use blood biomarkers in the evaluation of secondary alcohol use in OST patients.[1213]

This study observed that CDT levels were associated with the frequency of alcohol consumption among OST patients. Recently, a Chinese study reported serum CDT levels as a marker for alcohol consumption (P = 0.16) and to be promoted for identification of problematic alcohol use.[14] A similar finding has not yet been demonstrated in patients stabilized on OST. Since this was a pilot study on relatively small sample size, larger multi-centric studies should be able to improve the accuracy and validity of this association. Another notable finding was that these patients were relatively stable on their respective OST dosage; as apparent from the fact that around 80% were very compliant and less than 5% had any side effects related to buprenorphine. Despite that being stable on OST, they continued to consume alcohol. Moreover, almost half of the patients consume cannabis daily which is similar to other reports from community clinics in India.[15]

The limitations of the study include a pre-fixed limited sample size (considering the pilot nature of the study, due to feasibility); a sample limited to those reporting alcohol use (sampling bias), and a lack of a control arm for blood sample measurements. Additionally, we did not look for secondary liver disease. Despite these limitations, findings from this pilot study can be used to build larger multi-center trials in the community setting to use blood biomarkers as add-on tools to identify secondary alcohol use in OST patients. Since India is working on the scale-up of OST across the country, it will be prudent to evaluate secondary alcohol use more comprehensively.

CONCLUSION

Serum CDT can be used as a reliable tool for identifying frequent alcohol consumption in stabilized OST patients, especially in resource-constrained settings. For other basic biomarkers, more work needs to be done to establish their association with alcohol consumption in this population. Larger studies with robust methodologies should be conducted to further explore this area.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.