Non-Alcoholic Fatty Liver Disease

Question 1

What is non-alcoholic fatty liver disease (NAFLD)?

Answer 1

Refers to excess fat (triglyceride) accumulation in the liver (steatosis), where hepatocytes contain more than 5% of triglycerides, which is not the result of excessive alcohol consumption or other secondary causes.

Question 2

Briefly describe the pathological classification of NAFLD

Answer 2

Type 1

• Simple steatosis (felt to be non-progressive).

Type 2

• Steatosis plus lobular inflammation (probably benign, not considered to be NASH).

Type 3

• Steatosis, lobular inflammation, and ballooning degeneration. This is NASH without fibrosis (may progress to cirrhosis and liver failure).

Type 4

• Steatosis, ballooning degeneration, and fibrosis or Mallory bodies. This is NASH with fibrosis (may progress to cirrhosis and liver failure).

Question 3

What is steatosis?

Answer 3

Macrovesicular or mixed predominantly macro-/microvesicular without evidence of inflammation or fibrosis (bland).

Question 4

What is Steatohepatitis (non-alcoholic steatohepatitis or NASH)?

Answer 4

Macrovesicular or mixed predominantly macro-/microvesicular steatosis with evidence of hepatocyte ballooning degeneration, mild diffuse lobular mixed acute and chronic inflammation, and perivenular perisinusoidal collagen deposition.

Question 5

What is NASH-associated fibrosis?

Answer 5

Wound healing response in which damaged regions of chronic inflammatory disease are encapsulated by extracellular matrix or scar tissue. In its initial stages, fibrosis is thought to be reversible to some degree, but in the late stages it is felt to be irreversible.

Question 6

What is NASH associated cirrhosis?

Answer 6

Histological definition connoting the last stage of progressive hepatic fibrosis. Characterised by the distortion of hepatic architecture and the formation of regenerative nodules. It is traditionally believed to be an irreversible condition.

Question 7

What is NASH associated end-stage liver disease?

Answer 7

Term used to describe the stage at which patients with cirrhosis develop clinical complications. A majority of the complications are sequelae and manifestations of advanced fibrosis, with portal hypertension and decreased synthetic function of the liver. They include ascites, portosystemic encephalopathy, variceal bleeding, hepatocellular carcinoma, and the hepatorenal and hepatopulmonary syndromes.

Question 8

What are the risk factors for NAFLD?

Answer 8

• Obesity
• Insulin resistance
• Dyslipidemia
• Hypertension
• Metabolic syndrome
• Hepatotoxic medications

Question 9

Give examples of hepatoteoxic medications that can predispose to NAFLD

Answer 9

Medications associated with the development of non-alcoholic fatty liver disease include:

• Oestrogens (tamoxifen)
• Corticosteroids
• Diltiazem
• Methotrexate
• Valproate
• Amiodarone

Question 10

What are the signs of NAFLD?

Answer 10

• Hepatosplenomegaly

Question 11

What are the symptoms of NAFLD?

Answer 11

• Fatigue and malaise
• RUQ pain

Question 12

What investigations should be ordered for NAFLD?

Answer 12

• Serum AST and ALT
• AST: ALT ratio
• Total bilirubin
• Alkaline phosphatase
• Gamma glutamyl transderase
• FBC
• Metabolic panel
• Lipid panel
• Prothrombin time and INR
• Serum albumin

Question 13

Why investigate serum AST and ALT? And what may this show?

Answer 13

• Usually mildly elevated at 1-4 times upper limit of normal values. Elevations occur in 50% to 90% of cases; ALT is usually higher than AST; reverses with more advanced disease.
• Elevated

Question 14

How does the AST:ALT ratio differ in NAFLD and alcoholic liver disease?

Answer 14

The AST:ALT ratio (AAR) in non-alcoholic steatohepatitis (NASH) is typically <1.

This differs from acute alcoholic hepatitis, where the ratio is usually >2.

Question 15

Why investigate total bilirubin? And what may this show?

Answer 15

• Usually only begins with decompensated disease
• Elevated

Question 16

Why investigate alkaline phosphatase? And what may this show?

Answer 16

• Alkaline phosphatase is an enzyme found in liver and bone tissue
• Elevated

Question 17

Why ivnestigate gamma glutamyl transferase? And what may this show?

Answer 17

• Elevation increases the risk for presence of advanced fibrosis in non-alcoholic fatty liver disease
• Elevated

Question 18

Why investigate FBC? And what may this show?

Answer 18

• Anaemia and thrombocytopenia due to hypersplenism usually seen after the development of cirrhosis and portal hypertension
• Anaemia or thrombocytopenia

Question 19

Why investigate metabolic panel? And what may this show?

Answer 19

• Tests:
  
  • Mild hyponatraemia is commonly seen in patients with cirrhosis (due to increased levels of antidiuretic hormone)
  • Serum creatinine and urea may be elevated because renal function declines as liver disease advances
  • Serum glucose may be elevated
• Abnormal

Question 20

Why investigate lipid panel? And what may this show?

Answer 20

• Fasting lipid panel shows hypertriglyceridaemia in 20% to 80% of patients; many patients with non-alcoholic steatohepatitis will have low HDL as part of the metabolic syndrome. As liver disease becomes more severe, it is not uncommon for cholesterol levels to decrease.
• Elevated total cholesterol, LDL, triglyceride, and low HDL

Question 21

Why investigate prothrombin time and INR? And what may this show?

Answer 21

• Indication of impaired or decompensated liver synthetic function
• Elevated

Question 22

Why investigate serum albumin? And what may this show?

Answer 22

• Low albumin is an indication of impaired liver synthetic function
• Decreased

Question 23

Briefly describe the treatment for NAFLD without end-stage liver disease

Answer 23

• Diet and exercise
• Adjunct: vitamin E, weight loss pharmacology and roux-en-Y gastric bypass

Question 24

Briefly describe diet and exercise advice for patients with NAFLD

Answer 24

ifestyle modification must form the basis for first-line therapy in patients with non-alcoholic fatty liver disease.

Weight loss in obese and overweight patients through reduced caloric intake, increased exercise, or a combination of both causes a loss of adipose tissue that leads to reduced insulin resistance and improved muscular insulin sensitivity.

Question 25

Briefly describe the treatment for NAFLD with end-stage liver disease

Answer 25

• Liver transplantation
• Transjugular intrahepatic portosystemic shunt

Question 26

What complications are associated with NAFLD?

Answer 26

• Ascites
• Variceal haemorrhage
• Portosystemic encephalopathy
• Hepatocellular carcinoma (HCC)

Question 27

What differentials should be considered for NAFLD?

Answer 27

1. Alcoholic liver disease
2. Autoimmune hepatitis

Question 28

How does NAFLD and alcoholic liver disease differ?

Answer 28

• Differentiating signs and symptoms:
  
  • No specific differentiating signs or symptoms
  • Quantification of alcohol intake
• Differentiating investigations:
  
  • AST: ALT ratio typically >2 in alcoholic liver disease

Question 29

How does NAFLD and autoimmune hepatitis differ?

Answer 29

• Differentiating signs and symptoms: no specific differentiating signs or symptoms
• Differentiating investigations: circulating autoantibodies, hyperglobulinaemia and inflammatory changes on liver histology