NAFLD Flashcards
Causes of NAFLD
Obesity
T2DM
Hyperlipidaemia
Insulin-resistance
Surgical procedures
Rapid changes in weight
Drugs/toxins
Coeliac disease
At what definition is alcohol not a causative factor FLD?
Exclusion of both secondary causes of a daily alcohol consumption >30g per day for men and >20g per day for women
Is NAFLD symptomatic or asymptomatic?
Mainly asymptomatic
If a patient were to have symptoms of NAFLD what symptoms would they experience?
Fatigue
Malaise
RUQ discomfort/tenderness
What are the physical findings of NAFLD?
Hepatomegaly
How may NAFLD be diagnosed?
Abnormal ALT or GGT
Bright liver on USS
Negative liver screen
Features of metabolic syndrome
Liver biopsy
What AST/ALT ratio helps distinguish NAFLD from AFLD?
AST/ALT <1
What AST/ALT ratio suggests advanced fibrotic stage?
AST/ALT >1
Histological findings in NAFLD
Accumulation of fat in liver
Histological findings in NASH
Accumulation of fat in liver combined with inflammation and cell damage
Histological findings of fibrosis
Scarring in inflamed liver
Histological findings of cirrhosis
Nodules of damaged cells surrounded by scarring
Up until what stage is NAFLD reversible?
Up until cirrhosis
Pathology of cirrhosis
Chronic injury → inflammation, damage, matrix deposition, parenchymal death, angiogenesis → disrupted architecture, loss of function → liver failure, portal hypertension (→ hepatocellular carcinoma)
What determines how long it takes NAFLD to progress to cirrhosis?
Genetics and environmental factors
Aims of diagnosis in NAFLD?
Reduce CV and cancer risk
Reduce risk of cirrhosis
Reduce complications
How is steatosis diagnosed?
MRS
USS
Biopsy
How is NASH diagnosed?
Biopsy
How is fibrosis diagnosed?
Biopsy
Fibroscan
Fib-4 score
Biomarkers
What biomarkers are available to detect fibrosis?
ELF, Fibrotest
Histological stages of NAFLD
Fatty liver
Fat accumulation and lobular inflammation
Fat accumulation and ballooning degradation
Fat accumulation, ballooning, degradation and either Mallory hyaline or fibrosis
Troubles with liver biopsy
Invasive
Costly
Observer variability
Sampling error
Morbidity and Mortality
True or false:
Fibroscan is good at detecting all stages of fibrosis?
False - good at picking out severe fibrosis and cirrhosis and normals but not good at middle ranges
What does the biomarker ELF look at?
Markers of collagen deposition
What does the biomarker ELF measure?
Markers of extracellular matrix: tissue inhibitor of TIMP-1, PIIINP and hyaluronic acid
NICE guidelines for diagnosing advanced liver fibrosis
ELF ≥10.5 and NAFLD
True or false:
The liver produces all main plasma proteins
False - it doesn’t produce gamma globulins
What does albumin do?
Transport fatty acids, bilirubin and drugs
What do alpha-globulins do?
Transport lipoproteins, insulin
What do bile acids do?
Emulsify lipids in the intestines
Where are most bile acids stored?
Gallbladder
Where is the main point of bile acid reabsorption?
Ileum
What percentage of hepatocytes need to have steatosis for a diagnosis of NAFLD?
> 5%
What type of diet is associated with weight gain and obesity?
Western diet
Why is a Western lifestyle associated with weight gain?
Excess calorie intake
Excess saturated fat
High fructose intake
Sedentary behaviour
What organs are hypothesised to be affected by NAFLD?
Adipose tissue
Pancreas
Gut
Liver
What percentage of patients with NAFLD first present with liver failure?
70%
Visceral fat is more/less pathogenic than subcutaneous fat
More pathogenic
How does fat drive pro-inflammatory signals?
By changing how hepatocyte behave
What is ceramide produced from?
Serine/sphingosine
What does ceramide do?
Induces beta oxidation leading to less efficient insulin signalling, further leading to insulin resistance
Function of phosphokinase C
Proinflammatory mediator
How is insulin signalling an implicated pathway in NAFLD?
Increased lipolysis
Enhanced de novo lipogenesis
Increased gluconeogenesis
True or false:
Unhealthy, calorie dense, poor-fibre diets can lead to changes in the gut microbiota?
True
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
What is NLRP3?
An inflammasome which is involved in normal homeostasis and infection control
True or false:
NLRP3 is downregulated in NASH
False, it is upregulated
What is NRF2?
A key antioxidant
What is the recommended weight loss for people with NAFLD?
7-10%
Lifestyle changes:
Fructose intake
Alcohol consumption
Try to avoid fructose intake
Alcohol consumption strictly <30g/day for men and <20g/day for women
Describe the macronutrient composition for lifestyle changes
Low to moderate fat
Moderate to high carbohydrate
Or low carbohydrate diets/ketogenic diets with high protein
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
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
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
Do statins or ezetimibe help treat NAFLD?
They have no effects on the liver but they can prevent the CV risk
How do bile acid modulators work in NAFLD?
The agonism of FXR (bile acid receptor) decreases hepatic gluconeogenesis and improves peripheral insulin sensitivity
What may prescribed alongside bile acid modulators and why?
Statins because bile acid modulators cause a paradoxical increase in cholesterol synthesis
Role of DPP-4 antagonists in NAFLD
Modest decrease of liver fat content after 24 week treatment with sitagliptin
Is anti-TNF a good option for treating NAFLD?
No, it may worsen fibrosis
