By Husham Syed-Mohammed

Richard Grucza, Andrew Plunk, Laura Bierut, Pamela Hipp

Liver Enzymes- Biomarkers ofAlcohol Intake

Liver Enzymes

• GGT is a glycoprotein enzyme involved in counteracting oxidative stress

• Increase in serum levels with repeated excessive alcohol consumption

• Asparate and Alanine Aminotransferase are liver enzymes involved in amino acid metabolism.

• Used clinically as indicators of liver cell injury• Commonly tested in clinical settings in liver panel

tests

GGT Morbidity and Mortality

• Studies have linked high GGT levels in risk prediction of type 2 diabetes, cardiovascular events, chronic kidney disease, and cancer

• Numerous studies have associated GGT with all-cause mortality independent of alcohol use

Significance

EtOH ?MortalityGGT

GGTEtOH

GGT Mortality

Research

• Is GGT a more sensitive indicator of alcohol drinking patterns than ALT or AST?

• Do drinking patterns impact GGT levels over and above total alcohol intake?

• How are alcohol drinking behaviors associated with all-cause mortality?

• How does GGT influence mortality at different levels of drinking?

NHANES

• National Health and Nutritional Examination Survey

• Designed to assess the health and nutritional status of adults and children in the United States

• Began in early 1960’s and data is still being currently collected

• Combines interviews, physical examinations, and lab tests

Demographics

• N=16,811• Data from five administrations of NHANES

(1999-2008)• All past-year drinkers 21 years and older • Drinkers were described as those having at

least 12 drinks in the past year• Whites, Hispanics, and Blacks

GGT, AST, ALT Association with Drinking Behaviors

• Compared the association of binge-drinking and non binge-drinking behaviors with GGT, AST, and ALT serum levels

• Binge-drinking was described as having five or more drinks per drinking episode

• “Moderate-drinking” was described as having four or less drinks per drinking episode

Male Female Male Female Male Female 0.0000

0.5000

1.0000

1.5000

2.0000

2.5000

GGT is More Sensitive to Binge-Drinking and Moderate-Drinking Patterns

Binge Drinking Days Per Week

Moderate Drinking Days per Week

Liver Enzyme (Enzyme levels analyzed as T-Scores)

Regr

essi

on C

oeffi

cien

t

FIGURE 1. Analysis were controlled for age, smoking behaviors, race, and weight to height ratio.

GGT AST ALT

Association of GGT with Binge-Drinking Behaviors

• Compared association of serum GGT levels with different drinking patterns in different categories of total alcohol consumption

• This was to test our hypothesis if drinking patterns impact GGT levels over and above total alcohol intake?

Zero Light Med. Heavy50

51

52

53

54

55

56

57

58

59Total Alcohol Consumption and Binge Drinking Increase GGT Levels

0-2 drinks per week2-6 drinks per week6-14 drinks per week14-192 drinks per week

Binge-Drinking Behavior

Seru

m G

GT

Leve

ls (T

-Sco

re)

Average Weekly Consumption of Alcohol

FIGURE 2. Zero=zero days in year binge drinking, light=1-12 days in year binge drinking, med=13-52 days in year binge-drinking, heavy=53 or more days in year binge drinking.

Mortality Study

• N=6,834• Used the same inclusion criteria as previous

study • Survival Analysis: Mortality predicted from

alcohol drinking patterns• Survival Analysis: Mortality predicted from

GGT serum levels in different binge-drinking categories

Moderate Drinks Per Week Binge Drinks Per Week0.700000000000001

0.800000000000001

0.900000000000001

1

1.1

1.2

1.3

Effects of Drinking Patterns on Mortality

Male Hazard Ratios

Female Hazard Ratios

Categories

Haza

rd R

atio

Figure 3. Controls for this analysis included age, race, smoking behavior, poverty index, and waist to hip ratio.

0 Days in Year Binge Drinking 1-12 Days in Year Binge Drinking 13-52 Days in Year Binge Drinking1

1.1

1.2

1.3

1.4

1.5

1.6GGT is More Predictive of Mortality in Heavy Binge-Drinkers

Male Hazard RatiosFemale Hazard Ratios

Binge Drinking Category

Haza

rd R

atio

Figure 4 The analysis was controlled for age, race, smoking behavior, poverty index, and waist to hip ratio.

Conclusions

• GGT serum levels are the most sensitive liver enzyme associated with alcohol consumption

• Both the amount of drinking and the pattern of drinking effects GGT levels

• Binge-drinking behaviors strongly predict mortality, while moderate-drinking behaviors do not seem to have an effect

• The association between GGT and mortality may be stronger in heavier drinkers

Thank You

• Thank you everyone who helped with the research this summer:– ARTSS Internship program– Richard Grucza– Pamela Hipp– Andrew Plunk– Laura Bierut