MAFLD

Question 1

Definition

Answer 1

Metabolic dysfunction-associated steatotic liver disease: Excessive hepatic fat accumulation associated with insulin resistance and evidence of steatosis

Question 2

How is MAFLD defined histologically?

Answer 2

Fat accumulation in >5% of hepatocytes in the absence of significant alcohol consumption and associated with metabolic dysfunction.

Question 3

What alcohol consumption threshold must be excluded in the diagnosis of MAFLD?

Answer 3

> 21 drinks/week in men or >14 drinks/week in women over two years.

Question 4

What conditions must be present for MAFLD diagnosis when steatosis is detected?

Answer 4

Overweight/obesity, type 2 diabetes, or metabolic syndrome.

Question 5

What is the disease spectrum of MAFLD?

Answer 5

Simple steatosis

Steatohepatitis (MASH)

Fibrosis

Cirrhosis

Hepatocellular carcinoma (HCC)

Question 6

How does simple hepatic steatosis differ from steatohepatitis?

Answer 6

Steatosis → fat accumulation without hepatocellular injury
Steatohepatitis → steatosis with inflammation and hepatocellular injury.

Question 7

What histologic feature characterizes steatohepatitis?

Answer 7

Inflammation and hepatocyte injury (ballooning degeneration) with or without fibrosis.

Question 8

What inclusion bodies may appear in steatohepatitis?

Answer 8

Mallory-Denk bodies.

Question 9

What is the approximate global prevalence of MAFLD?

Answer 9

Around 20–30% of the population.

Question 10

Why is MAFLD considered a major global health problem?

Answer 10

It is the most common cause of chronic liver disease worldwide.

Question 11

What is the approximate prevalence of MAFLD in patients with type 2 diabetes?

Answer 11

Approximately 69%.

Question 12

What percentage of patients with MAFLD develop steatohepatitis?

Answer 12

About 10–20%

Question 13

What percentage of patients with steatohepatitis progress to cirrhosis?

Answer 13

Approximately 10–29%

Question 14

What is the most common cause of death in patients with MAFLD?

Answer 14

Cardiovascular disease

Question 15

What metabolic conditions strongly increase the risk of MAFLD?

Answer 15

Obesity

Type 2 diabetes

Dyslipidemia

Metabolic syndrome

Question 16

What cardiovascular risk factors are associated with MAFLD?

Answer 16

Obesity

Hypertension

Hypertriglyceridemia

Insulin resistance.

Question 17

What anthropometric measurement reflects central obesity risk for MAFLD?

Answer 17

Waist circumference

Question 18

What histologic feature characterizes hepatic steatosis?

Answer 18

Accumulation of triglyceride droplets within hepatocytes.

Question 19

What genetic variants are associated with MAFLD susceptibility?

Answer 19

PNPLA3

MBOAT7

TM6SF2

Question 20

What additional risk factors may contribute to MAFLD development?

Answer 20

Smoking, viral hepatitis, hypothyroidism, obstructive sleep apnea, and age >40–50 years

Question 21

What is the central metabolic abnormality in MAFLD pathogenesis?

Answer 21

Insulin resistance

Question 22

How does insulin resistance promote hepatic steatosis?

Answer 22

Increased lipolysis in adipose tissue → elevated circulating free fatty acids → hepatic triglyceride accumulation

Question 23

What are the major sources of hepatic fatty acids contributing to steatosis?

Answer 23

Adipose tissue lipolysis (~60%)
De novo lipogenesis (~25%)
Dietary fats (~15%).

Question 24

What early symptoms may occur in MAFLD?

Answer 24

Fatigue and right upper quadrant discomfort.

Question 25

What cellular metabolic processes contribute to triglyceride accumulation in hepatocytes?

Answer 25

Increased fatty acid supply Increased hepatic lipogenesis Reduced β-oxidation Reduced VLDL secretion.

Question 26

What causes increased Hepatic De Novo Lipogenesis (DNL)?

Answer 26

High intake of refined carbohydrates, frucose and sugary beverages.

Question 27

What is the two hit hypothesis?

Answer 27

Two sequential mechanisms that lead from simple steatosis to inflammatory injure and fibrosis:

Question 28

What represents the first hit in MAFLD pathogenesis?

Answer 28

Insulin resistance causing hepatic fat accumulation.

Question 29

What represents the second hit in MAFLD pathogenesis?

Answer 29

Oxidative stress and inflammatory cytokine release

Question 30

What inflammatory mediators contribute to hepatic injury in MAFLD?

Answer 30

TNF-α and IL-6.

Question 31

What liver cell type drives fibrosis development in MAFLD?

Answer 31

Hepatic stellate cells.

Question 32

What cellular stress mechanisms contribute to hepatocyte injury in MAFLD?

Answer 32

* Oxidative stress * Mitochondrial dysfunction * Endoplasmic reticulum stress.

Question 33

What immune pathway contributes to inflammation in MAFLD progression?

Answer 33

Inflammasome activation

Question 34

What is the typical clinical presentation of MAFLD?

Answer 34

Most patients are asymptomatic.

Question 35

What is the most common physical examination finding in MAFLD?

Answer 35

Hepatomegaly.

Question 36

What signs may appear in advanced disease or cirrhosis?

Answer 36

* Ascites * Jaundice * Splenomegaly.

Question 37

What is the typical transaminase pattern in MAFLD?

Answer 37

ALT higher than AST (usually they rarely excede more than 10X the NUL, and are less than 1X the NUL)

Question 38

What AST/ALT ratio may indicate advanced fibrosis or cirrhosis?

Answer 38

AST higher than ALT (more damage)

Question 39

What metabolic laboratory abnormalities are often associated with MAFLD?

Answer 39

Hyperglycemia and dyslipidemia.

Question 40

What imaging modalities can detect hepatic steatosis?

Answer 40

* Ultrasound * CT * MRI * Controlled attenuation parameter (CAP).

Question 41

What noninvasive clinical tests are used to evaluate fibrosis in MAFLD?

Answer 41

* NAFLD fibrosis score * FIB-4 * Hepamet

Question 42

What imaging technique is particularly useful to exclude advanced fibrosis?

Answer 42

Transient elastography (FibroScan).

Question 43

What is the gold standard diagnostic test for distinguishing steatosis from steatohepatitis?

Answer 43

Liver biopsy.

Question 44

What is the most effective therapy for MAFLD?

Answer 44

Weight loss through lifestyle modification (diet and exercise).

Question 45

What degree of weight loss may improve hepatic confitions?

Answer 45

≥10% for hepatic fibrosis, ≥7% for steatohepatitis, ≥5% hepatic steatosis

Question 46

What dietary pattern is recommended for MAFLD management?

Answer 46

Mediterranean diet with reduced carbohydrate intake.

Question 47

What pharmacologic therapy improves insulin sensitivity in diabetic patients with MAFLD?

Answer 47

Thiazolidinediones (PPAR-γ agonists).

Question 48

What antioxidant therapy has been used to improve steatohepatitis?

Answer 48

Vitamin E (800 IU/day) - cardiovascular risk

Question 49

What complications may occur in MAFLD-related cirrhosis?

Answer 49

* Portal hypertension * Hepatocellular carcinoma * Liver failure.

Question 50

What cellular mechanism leads to fibrosis progression in MAFLD?

Answer 50

Activation of hepatic stellate cells with collagen deposition.