Nonalcoholic Fatty Liver Disease

Front 1

What is nonalcoholic FLD associated with the epidemic of in the US?

Back 1

Obesity

Front 2

What two conditions are associated with nonalcoholic fatty liver disease?

Back 2

Front 3

What is the clinical definition of obesity?

How do you calculate BMI?

Back 3

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Front 6

What percent of normal individuals have fatty liver? What percent of obese?

What percent of normal have NASH?

What percent of morbidly obese have NASH?

Back 6

BMI > 35 = morbidly obese only if there is another associated disease

BMI > 40 = morbidly obese if no other associated disease

Front 7

Guess what these are all associated with...

Back 7

NAFLD

Front 8

Which race has highest rates of NAFLD? Race with lowest?

Which sex?

Back 8

Front 9

What is the leading cause of pediatric liver disease?

Median age?

Back 9

Front 10

What are some nutritional abnormalities and metabolic disease that can cause NAFLD?

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Front 11

What are some drugs that can cause NAFLD?

Back 11

Don't have to memorize these medications!

Front 12

Two surgeries that can cause NAFLD?

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Front 13

What is an increasing cause of hepatocellular carcinoma?

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Front 14

What is the pathogenesis of NAFLD?

Use trigylcerides, chylomicrons, lymphatics, free fatty acids, mitochondria

What is a result of disturbed balance (more lipogenesis and increased FFA)?

Back 14

Front 15

Insulin resistance:

Insulin promotes the uptake of _____
Stored as _____
Inhibits _____
Increased levels of insulin lead to increased lipogenesis, increased _____
Increased mitochondrial ____ oxidation
Free radical formation and damage

Back 15

Insulin resistance:

Insulin promotes the uptake of glucose
Stored as glycogen
Inhibits lipolysis
Increased levels of insulin lead to increased lipogenesis, increased FFA
Increased mitochondrial fatty acid oxidation
Free radical formation and damage

Front 16

How does obesity affect the synthesis of FFA?

How does it affect the oxidation of FFA?

How does insulin effect adipose tissue lipolysis? This leads to increased or decreased FFA?

Back 16

Front 17

What does an increase in FFA lead to in the liver? Increased or decreased oxidative stress?

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Front 18

What is the two hit hypothesis of NAFLD?

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Front 19

Draw the pathway of insulin resistance:

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Front 21

What are the clinical signs or symptoms of NAFLD? What is one nonspecific symptom?

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Front 22

What are the four signs on physical exam for NALD?

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Front 23

What percent of patients with NASH have elevated liver enzymes?

Is AST 2x ALT like in alcoholic fatty liver disease?

What is the alkaline phosphatase level?

Back 23

Front 24

What is shown on ultrasound?

Back 24

US: homogeneously fatty infiltrated liver, increased echogenicity throughout

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Front 26

Does a fatty appearance on ultrasound or CT make the diagnosis?

What is the only way to DEFINITELY diagnose and stage the disease?

Back 26

Nope

Biopsy (controversial)

Front 27

What is macrovesicular fat?

Back 27

Steatosis

Front 28

Inflammation, hepatocyte degeneration, ballooning, and Mallory bodies on histology. What is it?

Back 28

Steatohepatitis

Front 29

Pericellular then bridging on histology. Diagnosis?

Back 29

Fibrosis

Front 30

NAFLD:

What percent of patients in 10 years will develop cirrhosis?

Back 30

20%

Front 31

Which shows perivunular and perisinusoidal fibrosis

"chicken wire appearance"?

Which shows macro vesicular steatosis, Mallory hyaline, and hepatocyte ballooning?

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Front 32

What is the number one lifestyle change for NAFLD?

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Front 34

What is felt to be a major cause of cryptogenic cirrhosis?

What are two increasing causes of cirrhosis and HCC?

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Front 36

What are the five components metabolic disease (which is strongly associated with NAFLD)?

Diabetes mellitus

Hypertension

Dyslipidemia

Central obesity

Microalbuminuria

Back 36

Diabetes mellitus

Hypertension

Dyslipidemia

Central obesity

Microalbuminuria

Front 37

What are the two major forms of NAFLD?

What is the subset of NAFLD with over clinical features of liver injury, such as elevated serum transminases, and histologic features of hepatocyte injury?

What disease contributes to the progression of other liver disease such as HCV and HBV?

What increases the risk for hepatocellular carcinoma in the absence of significant scarring unlike chronic viral hepatitis and alcoholic liver disease

Back 37

Steatotis

Nonalcoholic steatohepatitis

NASH

NAFLD

NAFLD

Front 38

Hepatic steatosis, like obesity in general, arises from an overabundance of _____, diminished exercise, and genetic/epigenetic mechanisms. Individuals with NAFLD eat more fast food and exercise less. _____, a nearly ubiquitous, inexpensive sweetener in manufactured foods, also appears to promote insulin resistance.

Back 38

Hepatic steatosis, like obesity in general, arises from an overabundance of calorie rich food, diminished exercise, and genetic/epigenetic mechanisms. Individuals with NAFLD eat more fast food and exercise less. High fructose corn syrup, a nearly ubiquitous, inexpensive sweetener in manufactured foods, also appears to promote insulin resistance.

Front 39

In individuals with established insulin resistance and metabolic syndrome, the visceral adipose tissue not only _____, but also becomes dysfunctional, with reduced production of the _____ hormone, adiponectin, and increased production of inflammatory cytokines such as TNF-α and _____. These changes in turn promote hepatocyte apoptosis. Fat laden cells are highly sensitive to lipid _____ products generated by oxidative stress which can damage mitochondrial and plasma membranes, causing apoptosis.

Diminished autophagy also contributes to mitochondrial injury and formation of _____ bodies.

Back 39

In individuals with established insulin resistance and metabolic syndrome, the visceral adipose tissue not only increases, but also becomes dysfunctional, with reduced production of the lipid hormone, adiponectin, and increased production of inflammatory cytokines such as TNF-α and IL-6. These changes in turn promote hepatocyte apoptosis. Fat laden cells are highly sensitive to lipid peroxidation products generated by oxidative stress which can damage mitochondrial and plasma membranes, causing apoptosis.

Diminished autophagy also contributes to mitochondrial injury and formation of Mallory-Denk bodies.

Front 40

Kupffer cell production of ___ and ____ activate stellate cells directly leading to deposition of scar tissue. Stellate cell activation also occurs through the _____ signaling pathway in part through natural killer T-cell activation. In fact, the level of _____ pathway activity correlates with stage of fibrosis in NAFLD.

Back 40

Kupffer cell production of TNF-α and TGF-β activate stellate cells directly leading to deposition of scar tissue. Stellate cell activation also occurs through the hedgehog signaling pathway in part through natural killer T-cell activation. In fact, the level of hedgehog pathway activity correlates with stage of fibrosis in NAFLD.

Front 41

True or false:

NASH almost completely overlaps in its histologic features with alcoholic hepatitis.

Back 41

TRUE

Front 42

At the most clinically benign end of the spectrum, there is no appreciable hepatic inflammation, hepatocyte death, or scarring, despite persistent elevation of serum liver enzymes. In NASH, compared with alcoholic hepatitis, _____ cells may be more prominent than neutrophils and _____ bodies are often less prominent.

Steatofibrosis in NAFLD shows precisely the same features and progression as it does in alcoholic liver disease, although _____ may be more prominent.

Cirrhosis may develop, is often subclinical for years, and, when established, the steatosis or steatohepatitis may be ___ or ___.

Back 42

At the most clinically benign end of the spectrum, there is no appreciable hepatic inflammation, hepatocyte death, or scarring, despite persistent elevation of serum liver enzymes. In NASH, compared with alcoholic hepatitis, mononuclear cells may be more prominent than neutrophis and Mallory-Denk bodies are often less prominent.

Steatofibrosis in NAFLD shows precisely the same features and progression as it does in alcoholic liver disease, although portal fibrosis may be more prominent.

Cirrhosis may develop, is often subclinical for years, and, when established, the steatosis or steatohepatitis may be reduced or absent.

Front 43

What is 90% of previously described "cryptogenic cirrhosis" now thought to represent?

How does pediatric NALD differ from that in adults? (steatosis, portal vs. central, and mononuclear vs. parenchymal)?

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Front 44

Is NAFLD a diagnosis of exclusion?

Back 44

Yes!

Front 45

Individ­uals with simple steatosis are generally _____ (symptomatic or asymptomatic). Imaging studies may reveal ___ accumulation in the liver.

_____ is the most reliable diagnostic tool for NAFLD and NASH, and for assessment of scarring.

NAFLD is a diagnosis of exclusion! Viral, autoimmune and other metabolic diseases of the liver must be excluded before the diagnosis can be made.

Serum AST and ALT are _____ in about 90% of patients with NASH.

Despite the enzyme elevations, patients may be _____. Others have general symptoms such as fatigue or _____-sided abdominal discomfort caused by hepatomegaly.

Because of the association between NASH and the metabolic syndrome, _____ disease is a frequent cause of death in patients with NASH.

Back 45

Individ­uals with simple steatosis are generally asymptomatic. Imaging studies may reveal fat accumulation in the liver.

Liver biopsy is the most reliable diagnostic tool for NAFLD and NASH, and for assessment of scarring.

NAFLD is a diagnosis of exclusion! Viral, autoimmune and other metabolic diseases of the liver must be excluded before the diagnosis can be made.

Serum AST and ALT are elevated in about 90% of patients with NASH.

Despite the enzyme elevations, patients may be asymptomatic. Others have general symptoms such as fatigue or right-sided abdominal discomfort caused by hepatomegaly.

Because of the association between NASH and the metabolic syndrome, cardiovascular disease is a frequent cause of death in patients with NASH

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