Evidence-Based Reviews

‘I’m sober, Doctor, really’: Best biomarkers for underreported alcohol use

Current Psychiatry. 2008 September;7(9):15-16,19-22,27

David R. Spiegel, MD

Neetu Dhadwal, MD

Frances Gill, MD

When and how to use highly specific combinations to assess withdrawal risk.

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References

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Hospitalized patients who are not truthful about their alcohol consumption may be at risk for an unplanned withdrawal. Self-reports of alcohol use—such as CAGE and the Alcohol Use Disorders Identification Test (AUDIT)—are valid, inexpensive, and noninvasive, but patients easily can feign results.¹ Biochemical measures are more objective, and combinations of markers are an effective tool to detect recent heavy drinking in the 10% to 25% of patients who underreport alcohol use.²

Biochemical measures can detect acute alcohol intoxication and recent prolonged drinking. Because marker levels return to normal after long-term abstinence, ongoing monitoring can help detect a relapse before a patient admits to it.³

This article presents 3 cases in which biochemical markers helped prevent alcohol withdrawal in patients who denied alcohol abuse. We discuss why we ordered biochemical tests and which combinations provided highly sensitive results.

CASE 1: Depression and substance abuse

Ms. C, age 39, presents with bleeding gums due to excessive warfarin, which she takes prophylactically for a history of deep vein thrombosis. She is seen by the psychiatric consultation service for depression—which she says she has experienced since “the day I was born”—and substance abuse that includes a history binge drinking. Ms. C says she has stopped drinking and remained abstinent for the past year because she is fearful of further damaging her kidneys. She also denies psychosis. She does not have a history or symptoms of hepatobiliary or hematologic disease.

Clinical Point

Because biomarker levels return to normal after abstinence, ongoing monitoring can help detect relapse

Challenge. Despite Ms. C’s self-reported 1 year of sobriety, her history of binge drinking and depression calls for evaluating her alcohol withdrawal risk. Laboratory markers of alcohol abuse are the only means to assess her recent drinking behavior.

Discussion. Lab results include serum albumin of 3.4 g/dL, total bilirubin of 0.3 mg/dL, total protein of 6.3 g/dL, aspartate aminotransferase (AST) of 13 U/L, alanine aminotransferase (ALT) of 19 U/L, alkaline phosphatase of 136 U/L, and blood ammonia level of 37 μg/dL. Gamma-glutamyl transferase (GGT) is elevated at 104 U/L (normal range for women: 0 to 45 U/L). Mean corpuscular volume (MCV) is elevated at 101 fL (normal range 80 to 100 fL).

The combination of elevated MCV and GGT has a 95% sensitivity for alcohol abuse.⁴ GGT levels become elevated after 24 hours to 2 weeks of heavy alcohol consumption and return to normal within 2 to 6 weeks of abstinence, which allows them to detect binge drinking. MCV takes 6 to 8 weeks of heavy drinking—we which we define as consuming ≥40 grams of alcohol/day⁵—to become elevated and returns to normal within 3 months of abstinence.

These data provide evidence that Ms. C recently consumed substantial amounts of alcohol. As a result, we start her on alcohol withdrawal precautions (AWP).

Markers of alcohol abuse

Biochemical markers commonly used to detect alcohol abuse (Table 1) include:

blood alcohol level (BAL)
MCV
liver function tests (LFTs) such as ALT, AST, and GGT
carbohydrate deficient transferrin (CDT).

Table 1

By the numbers: Biomarkers of excessive alcohol consumption

	Biomarker
	CDT	GGT	AST	ALT	MCV
Blood test normal range		Women: 0 to 45 U/L Men: 0 to 53 U/L	10 to 34 U/L	8 to 37 U/L	80 to 100 fL
Blood test abnormal range	>1.3% of total transferrin concentration	Women: >45 U/L Men: >53 U/L	Levels rarely exceed 500 U/L	Levels rarely exceed 300 U/L	>100 fL
Time to elevation	2 to 3 weeks	24 hours to 2 weeks	3 to 7 days	3 to 7 days	After 6 weeks
Time to descent to normal levels	2 to 4 weeks of abstinence	2 to 6 weeks of abstinence	Half-life 12 to 24 hours	Half-life 37 to 57 hours	3 months
Dose-response of alcohol	60 g/d	80 to 200 g/d	≥40 g/d	≥40 g/d	≥40 g/d
Sensitivity	55% to 90%^a-e	37% to 85%^{b, f, g}	AST:ALT ratio >2:1 has a 70% sensitivity and 92% to 100% specificity for alcoholic-induced liver disease^h-j		20% to 70%^b,k
Relapse sensitivity	55% to 76%^a,l,m	50%^a,e			20%^a,n
Specificity	92% to 97%^a,b	18% to 93%^a,b,e			64% to 66%^b,k,n
Positive predictive value	46% to 75%^c,g	41%^g			36%^g
Negative predictive value	72% to 98%^a,c,g	69% to 92%^a,e,g			67%^g
AST: aspartate aminotransferase; ALT: alanine aminotransferase; CDT: carbohydrate deficient transferrin; GGT: gamma-glutamyl transferase; MCV: mean corpuscular volume
Source: Reference Citations: click here

BAL can document acute alcohol intoxication, but its use is limited because alcohol has a 4-hour half-life and an elimination rate of 7 grams/hour—equivalent to 1 drink/hour.⁶ (A “drink” typically is defined as a 12-ounce bottle of beer or wine cooler, a 5-ounce glass of wine, or 1.5 ounces of 80-proof distilled spirits.) Therefore, BAL will identify as false negatives alcohol-dependent patients who abstain from alcohol within 24 hours of testing.

MCV is an index of the average volume of erythrocytes. Macrocytosis occurs when the volume exceeds 100 fL. Elevated MCV is the most typical morphologic abnormality associated with excessive alcohol consumption^7,8 and macrocytosis—sometimes without associated anemia—is often evident in persons with alcoholism. MCV elevates after 6 weeks of alcohol misuse and may remain elevated for up to 3 months after a person has stopped drinking.⁹