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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
What does the biomarker ELF measure?
Markers of extracellular matrix: tissue inhibitor of TIMP-1, PIIINP and hyaluronic acid
26
NICE guidelines for diagnosing advanced liver fibrosis
ELF ≥10.5 and NAFLD
27
True or false: The liver produces all main plasma proteins
False - it doesn't produce gamma globulins
28
What does albumin do?
Transport fatty acids, bilirubin and drugs
29
What do alpha-globulins do?
Transport lipoproteins, insulin
30
What do bile acids do?
Emulsify lipids in the intestines
31
Where are most bile acids stored?
Gallbladder
32
Where is the main point of bile acid reabsorption?
Ileum
33
What percentage of hepatocytes need to have steatosis for a diagnosis of NAFLD?
>5%
34
What type of diet is associated with weight gain and obesity?
Western diet
35
Why is a Western lifestyle associated with weight gain?
Excess calorie intake Excess saturated fat High fructose intake Sedentary behaviour
36
What organs are hypothesised to be affected by NAFLD?
Adipose tissue Pancreas Gut Liver
37
What percentage of patients with NAFLD first present with liver failure?
70%
38
Visceral fat is more/less pathogenic than subcutaneous fat
More pathogenic
39
How does fat drive pro-inflammatory signals?
By changing how hepatocyte behave
40
What is ceramide produced from?
Serine/sphingosine
41
What does ceramide do?
Induces beta oxidation leading to less efficient insulin signalling, further leading to insulin resistance
42
Function of phosphokinase C
Proinflammatory mediator
43
How is insulin signalling an implicated pathway in NAFLD?
Increased lipolysis Enhanced de novo lipogenesis Increased gluconeogenesis
44
True or false: Unhealthy, calorie dense, poor-fibre diets can lead to changes in the gut microbiota?
True
45
How is mitochondrial dysfunction a pathological process in NAFLD?
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
What is NLRP3?
An inflammasome which is involved in normal homeostasis and infection control
47
True or false: NLRP3 is downregulated in NASH
False, it is upregulated
48
What is NRF2?
A key antioxidant
49
What is the recommended weight loss for people with NAFLD?
7-10%
50
Lifestyle changes: Fructose intake Alcohol consumption
Try to avoid fructose intake Alcohol consumption strictly <30g/day for men and <20g/day for women
51
Describe the macronutrient composition for lifestyle changes
Low to moderate fat Moderate to high carbohydrate Or low carbohydrate diets/ketogenic diets with high protein
52
How does coffee consumption affect the liver?
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
PPAR-receptor agonists: - Examples - What do they do? - How does it improve NASH?
- Pioglitazone, saroglitazar, permafibrate - They bind a wide range of fatty acids - Improve all histological features except fibrosis
54
Describe the use of antioxidants for the treatment of NAFLD
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
Do statins or ezetimibe help treat NAFLD?
They have no effects on the liver but they can prevent the CV risk
56
How do bile acid modulators work in NAFLD?
The agonism of FXR (bile acid receptor) decreases hepatic gluconeogenesis and improves peripheral insulin sensitivity
57
What may prescribed alongside bile acid modulators and why?
Statins because bile acid modulators cause a paradoxical increase in cholesterol synthesis
58
Role of DPP-4 antagonists in NAFLD
Modest decrease of liver fat content after 24 week treatment with sitagliptin
59
Is anti-TNF a good option for treating NAFLD?
No, it may worsen fibrosis

CVDM (16 decks)

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