6 - Alcoholic and Nonalcoholic Fatty Liver Disease Flashcards Preview

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Flashcards in 6 - Alcoholic and Nonalcoholic Fatty Liver Disease Deck (57)
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1

Primary place of lipid metabolism

Liver

2

What leads to fatty changes?

"Stressors"

3

What are the two categories of Fatty Liver?

Alcoholic
Non-Alcoholic

4

Secondary Steatosis - Fatty Liver

Alcohol
Overnutrition (Obesity, metabolic syndrome)
Starvation
TPN (Total parenteral nutrition)
Drugs (Amiodarone, methotrexate, tamoxifen, steroids)
Infections (HIV, HCV)
Celiac Disease
Genetic Causes (Abetalipoproteinemia, Wilson's)

5

Alcohol-Induced Steatosis

(+/-)Alcoholic Hepatitis
Fibrosis
Cirrhosis

6

Non-Alcohol-Induced Steatosis

(+/-)Non-alcoholic Steatohepatitis
Fibrosis
Cirrhosis

7

Spectrum of Alcoholic Liver Disease

Alcoholic Fatty Liver Disease
Fibrosis
Alcoholic Hepatitis
Cirrhosis

8

Cutoff for how much fat the liver can handle as "normal"

5% of volume as fat

9

CDC definition of "moderate drinking"

2 drinks per day for men
1 drink per day for women

10

Risk factors for ALD

Amount of alcohol ingested:
Non-linear
Drinking outside of mealtime increases risk by 2.7 fold
Syngergistic relationship between viral hepatitis and alcohol in terms of advancing liver disease

11

How many grams in a standard drink?

12oz beer
8oz malt liquor
5oz wine
1.5oz distilled spirits

12

Risk of cirrhosis increases (men)

>60 - 80g/day for at least 10 years

13

Risk of cirrhosis increases (women)

>20g/day for at least 10 years

14

CAGE Criteria

Tried to CUT down
People ANNOYED you by criticizing drinking
Felt GUILTY about drinking
Needed an EYE OPENER

Score of 2 is clinically significant

15

Damage done in alcoholic hepatitis

NAD accepts proton from alcohol dehydrogenase
Forms acetaldehyde
Free-reactive species of acetaldehyde forms adducts
Increases ROS formation
Increases NADH/NAD+ ratio

Acetaldehyde build up causes majority of damage

16

CYP2E1 Pathway in Alcohol Metabolism

ROS species increases
Outbalances reduction
Inflammation ensues

17

LPS's Role in Alcohol-Induced Liver Injury

Ethanol promotes translocation of LPS
Lumen of small intestine to Portal vein to liver

In Kupffer cell, LPS stimulates activation through promotion of cytokine and ROS release

18

Alcoholic Hepatitis

Clinical syndrome of acute jaundice and liver failure
Occurs after DECADES of alcohol abuse
Inflammatory
Fibrosis MAYBE but generally not cirrhotic

Scariest consequence:
Portal hypertension (due to microvascular occlusion secondary to hepatic swelling)

19

Alcoholic Hepatitis - Presentation

Rapid onset of jaundice
Fever
Ascites
Proximal muscle loss
Encephalopathy
Liver is enlarged & tender

20

Alcoholic Hepatitis - Physical Exam

Signs of Chronic Alcohol Use:
Parotid enlargement
Dupuytren's Contracture
Gynecomastia (relative depletion of testosterone)

Signs of Severe Liver Disease:
Visible veins across the abdominal wall
Edema
Ascites
Spider telangiectasia

21

Alcoholic Hepatitis - Histo

Ballooned Hepatocytes
Mallory bodies (alcoholic hyaline) surrounded by PMNs
Amorphous eosinophilic inclusion bodies
Large fat globules (macro-steatosis) in hepatocytes

22

Alcoholic Hepatitis - Labs

Elevation of serum aminotransferases (hallmark of hepatitis)
AST/ALT ratio > 2

Maddrey Discriminant Function:
Poor prognosis >= 32 (very high risk of dying, 30 - 50 % 28 day mortality)

Lille Model:
Helps predict mortality to guide therapy

23

Alcoholic Hepatitis - Treatment

Abstinence (though risk of progressing to cirrhosis remains)
Treat nutritional deficiencies

Steroids (1st line):
Prednisolone 40 mg/day for one month, then discontinue or taper over 3w
Appropes for those with MDF >= 32
15 - 30% risk reduction in short term (28d) mortality in early studies, 4% in more recent studies

24

Alcoholic Hepatitis - Other treatments

Anti-cytokine therapy:
Mitigates the effects of dysregulatd cytokines (TNF-α)

Pentoxifylline:
Inhibits production of TNF-α and other cytokines
STOPAH trial showed NO mortality benefit

25

Transplantation and CIrrhosis

Longstanding alcohol use and/or alcoholic hepatitis leads to fibrosis/cirrhosis

Alcoholic hepatitis and active drinking are absolute contraindications to consideration for liver transplantation

Require at least 6 months abstinence from drinking prior to transplant evaluation

26

Nonalcoholic Fatty Liver Disease

Entire spectrum of fatty liver disease without significant alcohol use, ranges from fatty liver to steatohepatitis to cirrhosis

27

Nonalcoholic Fatty Liver (NAFL)

Hepatic steatosis
No evidence of hepatocellular injury (ballooning)
No fibrosis

28

Nonalcoholic Steatohepatitis (NASH)

Hepatic steatosis
Inflammation
Hepatocyte injury (ballooning)
(+/-) fibrosis

29

NASH Cirrhosis

Cirrhosis
Previous histological evidence of steatosis or steatohepatitis

30

Metabolic Syndrome - Definition

Abdominal obesity
Hypertension
Diabetes
Dyslipidemia