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GI / Hepatology > 6 - Alcoholic and Nonalcoholic Fatty Liver Disease > Flashcards

6 - Alcoholic and Nonalcoholic Fatty Liver Disease Flashcards

1
Q

Primary place of lipid metabolism

A

Liver

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2
Q

What leads to fatty changes?

A

“Stressors”

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3
Q

What are the two categories of Fatty Liver?

A

Alcoholic

Non-Alcoholic

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4
Q

Secondary Steatosis - Fatty Liver

A

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)

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5
Q

Alcohol-Induced Steatosis

A

(+/-)Alcoholic Hepatitis
Fibrosis
Cirrhosis

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6
Q

Non-Alcohol-Induced Steatosis

A

(+/-)Non-alcoholic Steatohepatitis
Fibrosis
Cirrhosis

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7
Q

Spectrum of Alcoholic Liver Disease

A

Alcoholic Fatty Liver Disease
Fibrosis
Alcoholic Hepatitis
Cirrhosis

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8
Q

Cutoff for how much fat the liver can handle as “normal”

A

5% of volume as fat

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9
Q

CDC definition of “moderate drinking”

A

2 drinks per day for men

1 drink per day for women

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10
Q

Risk factors for ALD

A

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

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11
Q

How many grams in a standard drink?

A

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

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12
Q

Risk of cirrhosis increases (men)

A

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

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13
Q

Risk of cirrhosis increases (women)

A

> 20g/day for at least 10 years

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14
Q

CAGE Criteria

A

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

Score of 2 is clinically significant

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15
Q

Damage done in alcoholic hepatitis

A

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

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16
Q

CYP2E1 Pathway in Alcohol Metabolism

A

ROS species increases
Outbalances reduction
Inflammation ensues

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17
Q

LPS’s Role in Alcohol-Induced Liver Injury

A

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

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18
Q

Alcoholic Hepatitis

A

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)
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19
Q

Alcoholic Hepatitis - Presentation

A 
Rapid onset of jaundice
Fever
Ascites
Proximal muscle loss
Encephalopathy
Liver is enlarged & tender
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20
Q

Alcoholic Hepatitis - Physical Exam

A

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
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21
Q

Alcoholic Hepatitis - Histo

A

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

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22
Q

Alcoholic Hepatitis - Labs

A

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

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23
Q

Alcoholic Hepatitis - Treatment

A

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
Q

Alcoholic Hepatitis - Other treatments

A

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
Q

Transplantation and CIrrhosis

A

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
Q

Nonalcoholic Fatty Liver Disease

A

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

27
Q

Nonalcoholic Fatty Liver (NAFL)

A

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

28
Q

Nonalcoholic Steatohepatitis (NASH)

A

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

29
Q

NASH Cirrhosis

A

Cirrhosis

Previous histological evidence of steatosis or steatohepatitis

30
Q

Metabolic Syndrome - Definition

A

Abdominal obesity
Hypertension
Diabetes
Dyslipidemia

31
Q

Metabolic Syndrome - Associated wtih

A

Impaired glucose metabolism
Impaired fatty acid utilization
Dyslipidemia

32
Q

Metabolic Syndrome and NASH

A

Present in 88% with NASH

54% with NAFLD without NASH

33
Q

Metabolic Syndrome - Hepatic Manifestation Venn Diagram

A

Insulin Resistance
Obesity
Hyperlipidemia

34
Q

How many American Adults are overweight (BMI>25)

A

2/3

35
Q

From 1960 - 2000 What happened to obesity prevalence?

A

DOUBLED

36
Q

Cost of obesity epidemic

A

$117 billion

37
Q

NAFLD - Epidemiology

A

Most common liver diseases in Western, industrialized countries
20 - 40% of general population
More common in men
Majority of cases occur in men between 40 and 60
Hispanics > Caucasians > African Americans

38
Q

NASH - Two Hit Pathogenesis

A

First Hit:
Fat accumulation
Discrepancy between influx/synthesis of hepatic lipids and β-oxidation and export leading to buildup of triglycerides

Second Hit:
Oxidative stress
Lipid peroxidation
Release of cytokines (TNF-α)
Adipocyte derived hormones
39
Q

Main driver for fibrosis

A

Insulin resistance

Leads to cytokines, inflammatory signaling, stellate cell activation, apoptosis, mitochondrial injury, oxidative stress, etc

40
Q

NAFLD Pathology

A

Macrovesicular steatosis
Hepatocyte balooning
Lobular inflammation (Mixed leukocytes)
Mallory bodies (eosinophilic inclusions)

Perivenular & sinusoidal fibrosis - Scarring around central vein
(NOT PRESENT IN ALCOHOLIC)

41
Q

Presentation

A

Asymptomatic - Normal Liver Chemistries
Elevated transaminases
Fibrosis
Cirrhosis

42
Q

Picture of Pediatric Fatty Liver

A

Hepatic steatosis
Portal & lobular inflammation

Improper nutrition
Cardiometabolic risk
Lipid associated (leptin resistance, visceral obesity, etc)

43
Q

NAFLD Comorbidities

A 
Obesity
Type 2 DM
Glucose Intolerance
Dyslipidemia
Metabolic Syndrome
OSA
Hypothyroid
Hypopituitary
PCOS
Hypogonad
44
Q

NAFLD Diagnosis

A

AST & ALT elevation (90% of patients)

AST/ALT:
1 in ASH

No study outside of biopsy can differentiate between simple steatosis & NASH

45
Q

NAFLD Progression

A

Progression from Stage 0 to Stage 4

NAFLD (100%)
Fibrosis Progression (33%)
Rapid Fibrosis Progression (20%)

Annual fibrosis progression rate

  1. 07 stages for NAFL
  2. 14 stages for NASH
46
Q

NASH and End Stage Liver Disease

A

Prevalence of cirrhosis ranges from 3 - 15%
Once cirrhosis sets in, nothing can reverse it
Only cure for decompensated cirrhosis is transplant

47
Q

Histologically learn to tell the difference between

A

Fatty Liver
NASH
NASH with Fibrosis
Cirrhosis

48
Q

How do we diagnose NASH?

A

LIVER BIOPSY

49
Q

NASH vs ASH

A

38 - 50% of patients with ASH progress to cirrhosis (7 years)

8 - 26% of NASH patients progress to cirrhosis

Lower survival rates in ASH:
5 year (38% vs. 67% in NASH)
10 year (15% vs. 59% in NASH)
50
Q

NASH & Cirrhosis

A

Prevalence of obesity increased among cryptogenic cirrhotics

DM prevalence high with cirrhosis

51
Q

How many projected patients have NASH?

A

25 million

52
Q

How many transplants were performed for NASH in 2002

A

160

53
Q

Treatment of NAFLD

A

Mainstay - Lifestyle Intervention:
Diet
Behavior modification
Physical activity (Exercise reduces steatosis even without weight loss)

Weight loss:
Medical
Surgical

54
Q

Pharmacotherapy

A 
Insulin Sensitizers
PPAR-α/δ agonists
FXR agonists
Antioxidants
Caspase Inhibitors
Antifibrotics
55
Q

Current Recommendations - Biopsy proven NASH, nondiabetic, noncirrhotic

A

Vitamin E 800 IU/d

56
Q

Current Recommendations - Biopsy proven NASH, diabetic

A

Pioglitazone (Safety data in NASH limited)

57
Q

Current Recommendations - NAFLD + Hypertriglyceridemia

A

Omega-3 Fatty Acids

GI / Hepatology (28 decks)

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