Date post: | 19-Dec-2015 |
Category: |
Documents |
Upload: | jack-doyle |
View: | 215 times |
Download: | 0 times |
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
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
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
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
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
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
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
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
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