Alcoholic/Nonalcoholic/Inherited Liver Disease Flashcards Preview

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Flashcards in Alcoholic/Nonalcoholic/Inherited Liver Disease Deck (65)
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1

Alcoholic Liver Disease: Epidemiology

-up to 41% of liver disease in Native Americans
-as high as 65% of all deaths from chronic liver disease in Native Americans
-24% of chronic liver disease (40% deaths from cirrhosis)
-hospitalizations costs b/w $600 million and $1.8 billion/year

2

Ethanol Use in US

63% >18 drink
top 20% drink 80% of ethanol
top 2.5% drink 27% of ethanol
alcohol dependence/abuse 7.4% (11% men, 4% women)

3

Alcoholic Liver Disease

-steatosis
-alcoholic hepatitis
-alcoholic cirrhosis (hepatocellular carcinoma, cholangiocarcinoma)

4

Alcohol in Alcoholic Liver Disease

Ethanol >40-80gm/day
>5 year
(12gm is 12oz beer, 4oz wine, 1oz liquor)

5

Risk of Cirrhosis

3 drinks/day in women
differences in volume of distribution
dec. gastric alcohol dehydrogenase activity, particularly in younger adults
-differences in first pass metabolism

6

Men >6 or >10 drinks per day

only 9% ALD 6.4% cirrhosis
only 11.8% 8% cirrhosis

7

Alcoholic Hepatitis

-40-60 years old
->80 gm/d > 5 years
-often >5 years
-rapid onset of jaundice
-fever, muscle wasting, ascites
-hepatomegaly with tenderness
-AST, ALT rarely over 300
-AST > 2x ALT
-frequent leukocytosis
-elevated INR
-prevalence unknown
-approximately 20% of 1604 alcoholic patients undergo liver biopsy

8

Alcoholic Hepatitis: Pathogenesis

-many proposed mechanisms of ethanol induced injury
-few animal models
-no one theory accepted

9

Alcoholic Hepatitis: Genetics

-concordance rate for alcoholic cirrhosis 3x higher in monozygotic twins than dizygotic twins
-in East Asians, functional polymorphisms of ADH2*1 gene were associated with increased susceptability to ALD
-in caucasians, the only replicated association is the TNF-alpha 238 polymorphism and ALD

10

Risk of Alcoholic Cirrhosis

1% >30-60gm/d
5.7% >120gm/d

11

Alcoholic Cirrhosis: Mechanisms

-ethanol, acetylaldehyde cause intestinal injury and increased permeability resulting in endotoxemia
-endotoxemia results in an inflammatory response by Kupffer cels

12

Two Hit Theory: Alcoholic Cirrhosis

1st Hit: Fatty Liver
-oxidative stress, inc. NADH/NAD ration, obesity and DM (genetics/diet), fat sensitizes liver to 2nd hit
2nd Hit: inflammation & necrosis, oxidative stress/hypoxia/immunological reaction

13

Alcoholic Hepatitis Predictors of Survival

-Maddrey Score
-Glasgow Alcoholic Hepatitis Score
-Model for End-Stage Liver Disease (MELD)

14

Advanced Liver disease in Alcoholics

-Hep C
-Hemochromatosis
-Alpha one antitrypsin deficiency

15

Ethanol + Hepatitis C

42% HCV
22% HCV + Ethanol
8% Ethanol

16

Ethanol + Hemochromaosis

-15% of patients with hemochromatosis had ethanol abuse (>80gm/d)
-ethanol abuse associated with advanced fibrosis with hemochromatisos
-inc. cirrhosis and shorter survival than those without ethanol abuse

17

Ethanol + HFE mutations

conflicting data
-patients with ALD + C282Y mutations had more advanced fibrosis and cirrhosis
-HFE Heterozygousity "likely play some role in inc. iron loading and liver injury"

18

Ethanol + HFE

-alcoholic cirrhotic patients with heterozygous C282Y mutations had increased hepatic iron scores and higher rates of HCC

19

Ethanol + A1AT deficiency

-2.7% with phenotype (Caucasian Americans)

20

Alpha one Antitrypsin Deficiency

MZ or ZZ
-chronic hepatitis (8% alcoholic)
-cirrhotic (41% alcoholic)

21

Ethanol + Obesity

-ethanol patterns, obesity and associated hyperglycemia are the most important environmental factors determining ALD risk

22

Treatment of Alcoholic Liver Disease

-abstinence
-optimize nutrition
-pentoxifylline (TNF alpha inhibitor)
-immunosuppression with corticosteroids in select patients
-LIVER TRANSPLANT

23

Spectrum of Alcoholic Liver Disease

-steatosis
-perivenular fibrosis (central vein)
-alcoholic hepatitis
-sub-sinusoidal fibrosis
-cirrhosis
-hepatocellular carcinoma

24

Macrovesicular

-lipid filled vesicle is larger than the nucleus

25

Nonalcoholic Fatty Liver Disease

-acquired liver disease in children & adults
-inc. w/epidemic of obesity in US
-macrovesicular hepatic steatosis
-ethanol <20gm per day

26

2 conditions of Nonalcoholic fatty liver disease

1. Steatosis
2. Non-Alcoholic Steatohepatitis (NASH)
-fatty liver, fibrosis and cirrhosis described in obease patients, (NASH was originally separate)

27

Obesity

-excess body fat in relation to lean body mass
-BMI > 30
-BMI = weight/height^2

28

Nonalcoholic Fatty Liver Disease: Prevalence

-NAFLD: 20-30% of adults, 10% kids
-by 2025, over 25 million Americans are predicted to have NAFLD related to liver disease
-next epidemic for liver disease
Fatty Liver: 10-15% of normal individuals
-70-80% of obese
NASH: 3% of normal, 15-20% of morbidly obese (BMI>35)

29

NAFLD associated with?

-obesity
-Type 2 Diabetes
-Hyperlipidemia
-Metabolic Syndrome

30

Nonalcoholic Fatty Liver Disease: Epidemiology

-Race/Ethnicity: mexican americans have the highest africans lowest
-Gender: initially more women, now 50/50
-Familial component: diet, genetics