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CVDM > NAFLD > Flashcards

NAFLD Flashcards

1
Q

Causes of NAFLD

A

Obesity
T2DM
Hyperlipidaemia
Insulin-resistance
Surgical procedures
Rapid changes in weight
Drugs/toxins
Coeliac disease

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2
Q

At what definition is alcohol not a causative factor FLD?

A

Exclusion of both secondary causes of a daily alcohol consumption >30g per day for men and >20g per day for women

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3
Q

Is NAFLD symptomatic or asymptomatic?

A

Mainly asymptomatic

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4
Q

If a patient were to have symptoms of NAFLD what symptoms would they experience?

A

Fatigue
Malaise
RUQ discomfort/tenderness

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5
Q

What are the physical findings of NAFLD?

A

Hepatomegaly

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6
Q

How may NAFLD be diagnosed?

A

Abnormal ALT or GGT
Bright liver on USS
Negative liver screen
Features of metabolic syndrome
Liver biopsy

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7
Q

What AST/ALT ratio helps distinguish NAFLD from AFLD?

A

AST/ALT <1

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8
Q

What AST/ALT ratio suggests advanced fibrotic stage?

A

AST/ALT >1

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9
Q

Histological findings in NAFLD

A

Accumulation of fat in liver

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10
Q

Histological findings in NASH

A

Accumulation of fat in liver combined with inflammation and cell damage

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11
Q

Histological findings of fibrosis

A

Scarring in inflamed liver

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12
Q

Histological findings of cirrhosis

A

Nodules of damaged cells surrounded by scarring

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13
Q

Up until what stage is NAFLD reversible?

A

Up until cirrhosis

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14
Q

Pathology of cirrhosis

A

Chronic injury → inflammation, damage, matrix deposition, parenchymal death, angiogenesis → disrupted architecture, loss of function → liver failure, portal hypertension (→ hepatocellular carcinoma)

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15
Q

What determines how long it takes NAFLD to progress to cirrhosis?

A

Genetics and environmental factors

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16
Q

Aims of diagnosis in NAFLD?

A

Reduce CV and cancer risk
Reduce risk of cirrhosis
Reduce complications

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17
Q

How is steatosis diagnosed?

A

MRS
USS
Biopsy

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18
Q

How is NASH diagnosed?

A

Biopsy

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19
Q

How is fibrosis diagnosed?

A

Biopsy
Fibroscan
Fib-4 score
Biomarkers

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20
Q

What biomarkers are available to detect fibrosis?

A

ELF, Fibrotest

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21
Q

Histological stages of NAFLD

A

Fatty liver
Fat accumulation and lobular inflammation
Fat accumulation and ballooning degradation
Fat accumulation, ballooning, degradation and either Mallory hyaline or fibrosis

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22
Q

Troubles with liver biopsy

A

Invasive
Costly
Observer variability
Sampling error
Morbidity and Mortality

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23
Q

True or false:
Fibroscan is good at detecting all stages of fibrosis?

A

False - good at picking out severe fibrosis and cirrhosis and normals but not good at middle ranges

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24
Q

What does the biomarker ELF look at?

A

Markers of collagen deposition

25
Q

What does the biomarker ELF measure?

A

Markers of extracellular matrix: tissue inhibitor of TIMP-1, PIIINP and hyaluronic acid

26
Q

NICE guidelines for diagnosing advanced liver fibrosis

A

ELF ≥10.5 and NAFLD

27
Q

True or false:
The liver produces all main plasma proteins

A

False - it doesn’t produce gamma globulins

28
Q

What does albumin do?

A

Transport fatty acids, bilirubin and drugs

29
Q

What do alpha-globulins do?

A

Transport lipoproteins, insulin

30
Q

What do bile acids do?

A

Emulsify lipids in the intestines

31
Q

Where are most bile acids stored?

A

Gallbladder

32
Q

Where is the main point of bile acid reabsorption?

A

Ileum

33
Q

What percentage of hepatocytes need to have steatosis for a diagnosis of NAFLD?

A

> 5%

34
Q

What type of diet is associated with weight gain and obesity?

A

Western diet

35
Q

Why is a Western lifestyle associated with weight gain?

A

Excess calorie intake
Excess saturated fat
High fructose intake
Sedentary behaviour

36
Q

What organs are hypothesised to be affected by NAFLD?

A

Adipose tissue
Pancreas
Gut
Liver

37
Q

What percentage of patients with NAFLD first present with liver failure?

A

70%

38
Q

Visceral fat is more/less pathogenic than subcutaneous fat

A

More pathogenic

39
Q

How does fat drive pro-inflammatory signals?

A

By changing how hepatocyte behave

40
Q

What is ceramide produced from?

A

Serine/sphingosine

41
Q

What does ceramide do?

A

Induces beta oxidation leading to less efficient insulin signalling, further leading to insulin resistance

42
Q

Function of phosphokinase C

A

Proinflammatory mediator

43
Q

How is insulin signalling an implicated pathway in NAFLD?

A

Increased lipolysis
Enhanced de novo lipogenesis
Increased gluconeogenesis

44
Q

True or false:
Unhealthy, calorie dense, poor-fibre diets can lead to changes in the gut microbiota?

A

True

45
Q

How is mitochondrial dysfunction a pathological process in NAFLD?

A

Excessive and regulated ROS production within mitochondrial matrix can damage constituent structures including membrane and DNA and may induce pro-apoptotic pathways including mitochondrial autophagy

46
Q

What is NLRP3?

A

An inflammasome which is involved in normal homeostasis and infection control

47
Q

True or false:
NLRP3 is downregulated in NASH

A

False, it is upregulated

48
Q

What is NRF2?

A

A key antioxidant

49
Q

What is the recommended weight loss for people with NAFLD?

A

7-10%

50
Q

Lifestyle changes:
Fructose intake
Alcohol consumption

A

Try to avoid fructose intake
Alcohol consumption strictly <30g/day for men and <20g/day for women

51
Q

Describe the macronutrient composition for lifestyle changes

A

Low to moderate fat
Moderate to high carbohydrate
Or low carbohydrate diets/ketogenic diets with high protein

52
Q

How does coffee consumption affect the liver?

A

There are no liver-related limitations
It is recommended to have 3-5 cups of coffee a day (doesn’t need to be black but be aware of caffeine intake

53
Q

PPAR-receptor agonists:
- Examples
- What do they do?
- How does it improve NASH?

A
  • Pioglitazone, saroglitazar, permafibrate
  • They bind a wide range of fatty acids
  • Improve all histological features except fibrosis
54
Q

Describe the use of antioxidants for the treatment of NAFLD

A

Vitamin E may improve steatosis and ballooning and resolve NASH in some patients but no improvement in fibrosis scores
Concerns about long-term safety

55
Q

Do statins or ezetimibe help treat NAFLD?

A

They have no effects on the liver but they can prevent the CV risk

56
Q

How do bile acid modulators work in NAFLD?

A

The agonism of FXR (bile acid receptor) decreases hepatic gluconeogenesis and improves peripheral insulin sensitivity

57
Q

What may prescribed alongside bile acid modulators and why?

A

Statins because bile acid modulators cause a paradoxical increase in cholesterol synthesis

58
Q

Role of DPP-4 antagonists in NAFLD

A

Modest decrease of liver fat content after 24 week treatment with sitagliptin

59
Q

Is anti-TNF a good option for treating NAFLD?

A

No, it may worsen fibrosis

CVDM (16 decks)

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