1@AMSP 2010 Too Much Alcohol is Bad for Your Liver Alcohol and Your Liver Anna Lembke, MD Department...

1@AMSP 2010

Too Much Alcohol is Bad for Too Much Alcohol is Bad for Your LiverYour Liver

Alcohol and Your Liver

Anna Lembke, MDDepartment of Psychiatry and Behavioral Sciences

Stanford, University Medical CenterStanford, California

2@AMSP 2010

Your Healthy LiverYour Healthy Liver

3@AMSP 2010

Healthy Hepatic Portal Healthy Hepatic Portal TriadTriad

4@AMSP 2010

Your Liver on AlcoholYour Liver on Alcohol

5@AMSP 2010

Cirrhosis close-upCirrhosis close-up

6@AMSP 2010

This Lecture ReviewsThis Lecture Reviews

How a healthy liver metabolizes EtOHHow a healthy liver metabolizes EtOH

How too much EtOH damages the liverHow too much EtOH damages the liver

How much is too muchHow much is too much

How to helpHow to help

7@AMSP 2010






8@AMSP 2010

Alcohol MetabolismAlcohol Metabolism

ADHADH ALDHALDH

CH3CH2OH CH3CH2OH CH3CHO CH3CHO CH3COOHCH3COOH

Ethanol Ethanol AcetaldehydeAcetaldehyde Acetic AcidAcetic Acid

9@AMSP 2010

EtOH MetabolizedEtOH Metabolized

FasterFaster

MaleMale

High body mass High body mass

Heavy drinkerHeavy drinker

Fast metabolizerFast metabolizer

10@AMSP 2010

ALDH 2*2, 2*2 ALDH 2*2, 2*2 Homozygotes (ALDH 2*2, 2*2)Homozygotes (ALDH 2*2, 2*2)

Vomiting , diarrhea, etc.Vomiting , diarrhea, etc.

No alcoholicsNo alcoholics

Heterozygotes (ALDH2*2)Heterozygotes (ALDH2*2)

Alcohol reaction but not ill Alcohol reaction but not ill

Less alcoholismLess alcoholism

11@AMSP 2010

Alcohol Dehydrogenase Alcohol Dehydrogenase (ADH) Mutations(ADH) Mutations

Faster Faster ↓↓ EtOH EtOH

Faster Faster ↑↑ acetaldehyde acetaldehyde

Slightly Slightly ↓↓ alcoholic risk alcoholic risk

12@AMSP 2010






13@AMSP 2010

Alcoholic Liver Disease Alcoholic Liver Disease (ALD)(ALD)

Damage to liver by alcoholDamage to liver by alcohol

Typically occurs in progressionTypically occurs in progression

Fatty liver Fatty liver

Alcoholic hepatitis Alcoholic hepatitis

CirrhosisCirrhosis

14@AMSP 2010

Step 1: Fatty LiverStep 1: Fatty Liver

ADH metabolizes EtOHADH metabolizes EtOH

↑↑ Acetaldehyde and free radicals Acetaldehyde and free radicals

Acetaldehyde more toxic than alcohol Acetaldehyde more toxic than alcohol

Mild inflammationMild inflammation

Fat cell proliferationFat cell proliferation

15@AMSP 2010

Fatty LiverFatty Liver

Almost all heavy Almost all heavy drinkersdrinkers

Usually Usually asymptomaticasymptomatic

ReversibleReversible

16@AMSP 2010

Healthy Liver vs Fatty Healthy Liver vs Fatty LiverLiver

17@AMSP 2010

Step 2: HepatitisStep 2: Hepatitis

Alcohol Alcohol release of toxins from gut release of toxins from gut

Liver Kuppfer cells release cytokinesLiver Kuppfer cells release cytokines

Decrease inflammationDecrease inflammation

But also But also ↑↑ cell death cell death

18@AMSP 2010

Alcoholic HepatitisAlcoholic Hepatitis

Up to 35% of Up to 35% of hazardous hazardous drinkersdrinkers

Usually Usually reversiblereversible

19@AMSP 2010

Step 3: CirrhosisStep 3: Cirrhosis

Liver cell death Liver cell death ↑↑ Stellate cellsStellate cells

Specialized liver cellSpecialized liver cell Normal healingNormal healing

ScarringScarring

Disrupts architectureDisrupts architecture Impairs functionImpairs function

20@AMSP 2010

CirrhosisCirrhosis

~ 20% after 10 ~ 20% after 10 years years hazardous usehazardous use

12th leading 12th leading cause of death cause of death in adultsin adults

Damage Damage irreversibleirreversible

21@AMSP 2010

Other ALD Risk FactorsOther ALD Risk Factors GeneticGenetic

ALDH 2*2 protectsALDH 2*2 protects ADH 1C2 ADH 1C2 ↑↑ risk risk

Diet Diet ↑↑’s risk’s risk Drink without foodDrink without food ↑↑ Polyunsaturated fatsPolyunsaturated fats ObesityObesity ↑↑ IronIron ↑↑ Blood sugarBlood sugar

Gender: Gender: ↑ Risk in women (2x mortality)↑ Risk in women (2x mortality)

22@AMSP 2010






23@AMSP 2010

ALD Dose DependentALD Dose Dependent More EtOH x more time More EtOH x more time ↑↑ risk ALD risk ALD

>2 drinks/daily>2 drinks/daily ↑ risk ALD ↑ risk ALD

AUDIT-C AUDIT-C >> 5 5 ↑ risk ALD ↑ risk ALD

Standard drink = Standard drink = 12 oz. beer12 oz. beer 4 oz. wine4 oz. wine 1.5 oz. whiskey1.5 oz. whiskey

24@AMSP 2010

Screening Tests for Screening Tests for ConsumptionConsumption

Time-Line-Follow-Back (TLFB) MethodTime-Line-Follow-Back (TLFB) Method Counting backwards from todayCounting backwards from today

Standard drinks per dayStandard drinks per day

Total standard drinks per weekTotal standard drinks per week

Alcohol Use Disorders Identification Alcohol Use Disorders Identification Test for Consumption (AUDIT-C)Test for Consumption (AUDIT-C)

25@AMSP 2010

AUDIT-CAUDIT-C

3 Questions3 Questions How often do you have an EtOH drink?How often do you have an EtOH drink? How many drinks per drinking day?How many drinks per drinking day? How often How often >> 6 per occasion? 6 per occasion?

AUDIT-C Scores (0-12)AUDIT-C Scores (0-12) 0 = non-drinker0 = non-drinker 1-4 = low level drinker1-4 = low level drinker 5-8 moderate EtOH misuse5-8 moderate EtOH misuse 9-12 severe EtOH misuse9-12 severe EtOH misuse

26@AMSP 2010

Hazardous Alcohol Use Hazardous Alcohol Use

↑↑ Risk ALD Risk ALD Men Men

> 14 drinks/week or> 14 drinks/week or > 4 drinks on any occasion> 4 drinks on any occasion

WomenWomen > 7 drinks/week or> 7 drinks/week or > 3 drinks on any occasion> 3 drinks on any occasion

AUDIT-C score AUDIT-C score >> 5 5 1-2 drinks most days or 1-2 drinks most days or >> 6 per occasion some days 6 per occasion some days

27@AMSP 2010

EtOH in Moderation EtOH in Moderation Healthy?Healthy?

Moderate drinkers vs. non-drinkersModerate drinkers vs. non-drinkers

↓↓MortalityMortality ↓↓G.I. illnessesG.I. illnesses ↓↓Gastritis, gallstonesGastritis, gallstones ↓↓Cardiovascular diseaseCardiovascular disease ↓↓Dementia (vascular and Alzheimer’s)Dementia (vascular and Alzheimer’s)

Results may be misleadingResults may be misleading

28@AMSP 2010

Abuse vs. DependenceAbuse vs. Dependence

Abuse ( ≥1)Abuse ( ≥1) Role failureRole failure

Risk of harmRisk of harm

Run-ins with lawRun-ins with law

Relationship Relationship

troubletrouble

Dependence (≥3)Dependence (≥3) ToleranceTolerance WithdrawalWithdrawal Not sticking to limitsNot sticking to limits Not able to cut downNot able to cut down Spending time EtOH Spending time EtOH Less time elsewhereLess time elsewhere Despite problemsDespite problems

29@AMSP 2010






30@AMSP 2010

EtOH Misuse is PrevalentEtOH Misuse is Prevalent

77% Low-risk or abstention77% Low-risk or abstention

16% Hazardous or at-risk use16% Hazardous or at-risk use

7% Abuse or dependence7% Abuse or dependence

Almost Almost 1 out of 41 out of 4 is misusing EtOH is misusing EtOH

31@AMSP 2010

Screen for EtOH Screen for EtOH ConsumptionConsumption

Time Line Follow-Back (TLFB) MethodTime Line Follow-Back (TLFB) Method

Alcohol Use Disorders Identification Alcohol Use Disorders Identification Test for Consumption (AUDIT-C)Test for Consumption (AUDIT-C)

Single Question Screen: ”How many Single Question Screen: ”How many times in the past year have you times in the past year have you had…?”had…?” >4 drinks/day men>4 drinks/day men >3 drinks/day women>3 drinks/day women

32@AMSP 2010

Gamma-Glutamyl Gamma-Glutamyl Transferase (GGT)Transferase (GGT)

↑↑ Before damage to liver; GGT > 35 Before damage to liver; GGT > 35 IU/LIU/L

If GGT >51, may signal liver damageIf GGT >51, may signal liver damage

↑↑ in 75% of chronic heavy drinkersin 75% of chronic heavy drinkers

Not specific to ALD (70% specificity)Not specific to ALD (70% specificity)

33@AMSP 2010

Carbohydrate Deficient Carbohydrate Deficient Transferrin (CDT)Transferrin (CDT)

Plasma protein carries iron to bonePlasma protein carries iron to bone

>> 2.6% suggestive of 5+ drinks/day 2.6% suggestive of 5+ drinks/day

Sensitivity/specificity slightly > GGTSensitivity/specificity slightly > GGT

34@AMSP 2010

Liver function tests Liver function tests (ALT/AST)(ALT/AST)

Alanine transaminase (ALT) Alanine transaminase (ALT) (9-60 IU/L normal range)(9-60 IU/L normal range)

Aspartate transaminase (AST) Aspartate transaminase (AST) (10-40 IU/L normal range)(10-40 IU/L normal range)

AST/ALT ratio > 2/1 AST/ALT ratio > 2/1 suggestive of ALDsuggestive of ALD

35@AMSP 2010

Intervene at Level of Intervene at Level of NeedNeed

Drinking typeDrinking type

Abuse/Dependence Abuse/Dependence

Hazardous Use Hazardous Use

Low risk/abstention Low risk/abstention

Intervention typeIntervention type

TreatmentTreatment

Brief interventionBrief intervention

No interventionNo intervention

36@AMSP 2010

If Hazardous Use…If Hazardous Use…

Try “SBIRT” Try “SBIRT”

Screening, brief intervention, referral to Screening, brief intervention, referral to tx.tx.

SBIRT can ↓ avg. # drinks/week by ~25% SBIRT can ↓ avg. # drinks/week by ~25%

Assess, Advise, Agree, Assist, ArrangeAssess, Advise, Agree, Assist, Arrange

37@AMSP 2010

If Abuse or If Abuse or Dependence…Dependence…

Refer to 12-step mutual help groups Refer to 12-step mutual help groups Alcoholics AnonymousAlcoholics Anonymous Double Trouble in RecoveryDouble Trouble in Recovery Narcotics AnonymousNarcotics Anonymous

Refer to higher level of AUD careRefer to higher level of AUD care Day treatmentDay treatment ResidentialResidential Clean and sober living environmentClean and sober living environment Consider medicationsConsider medications

38@AMSP 2010

Medications for EtOH; Medications for EtOH; Use with Care in ALD Use with Care in ALD

Naltrexone: 50-150 mg/dailyNaltrexone: 50-150 mg/daily

Acamprosate: ~ 2 g/dailyAcamprosate: ~ 2 g/daily

Disulfiram: 250 mg/daily Disulfiram: 250 mg/daily

39@AMSP 2010

Treating ALDTreating ALD

Stop drinkingStop drinking

Limit medicationsLimit medications

Low sodium diet Low sodium diet

40@AMSP 2010

Reduce AscitesReduce Ascites Diuretic Diuretic

ParacentesisParacentesis

AntibioticsAntibiotics

Transjugular Transjugular intrahepatic intrahepatic portosystemic portosystemic shunt shunt (TIPS)(TIPS)

41@AMSP 2010

Control Variceal Control Variceal BleedingBleeding

Vasoconstrictor Vasoconstrictor medicationsmedications

Shunts: redirect Shunts: redirect blood flowblood flow

Endoscopic Endoscopic variceal bandingvariceal banding

42@AMSP 2010

Minimize Minimize EncephalopathyEncephalopathy

Lactulose Lactulose Powerful laxativePowerful laxative Prevents build-up of gut ammoniaPrevents build-up of gut ammonia Dose = up to 60 mL/dayDose = up to 60 mL/day

Low protein dietLow protein diet

Avoid SedativesAvoid Sedatives

43@AMSP 2010

Summary: How to HelpSummary: How to Help

ScreenScreen TLFB/AUDIT-CTLFB/AUDIT-C One questionOne question Abuse or DependenceAbuse or Dependence

InterveneIntervene Hazardous use Hazardous use SBIRT, MM SBIRT, MM Dependence Dependence AA, day treatment, residential AA, day treatment, residential

Treat ALDTreat ALD Control ascites, varices, encephalopathyControl ascites, varices, encephalopathy Liver transplantLiver transplant

44@AMSP 2010

Take-Home MessageTake-Home Message

Too much alcohol is bad for your Too much alcohol is bad for your liverliver

Too much =Too much = Men > 14 drinks/wk, > 4 drinks/occ.Men > 14 drinks/wk, > 4 drinks/occ. Women > 7 drinks/wk, > 3 Women > 7 drinks/wk, > 3

drinks/occ.drinks/occ. AUDIT-C AUDIT-C >> 55

1@AMSP 2010 Too Much Alcohol is Bad for Your Liver Alcohol and Your Liver Anna Lembke, MD Department...

Documents

Transcript of 1@AMSP 2010 Too Much Alcohol is Bad for Your Liver Alcohol and Your Liver Anna Lembke, MD Department...