Alcohol as a Risk Factor

Question 1

List the common diseases of the gall bladder.

Answer 1

• Gallstone disease (cholelithiasis).
• Cholecystitis: acute and chronic.
• Choledo-cholithiasis.
• Gallbladder cancer.
• Gangrene of the gallbladder.
• Abscess of the gallbladder.
• Gallbladder polyps.
• Acalculous gallbladder disease.
• Biliary dyskinesia.
• Sclerosing cholangitis.

Question 2

Describe the production of bile and explain how gallbladder disease affects this.

Answer 2

• Bile is produced by the liver, stored in the gallbladder and transported through ducts.
• Contains cholesterol, bile salts and bilirubin (a breakdown product of Hb).
• Gallbladder disease is one of the most common disorders of the biliary system.
• Interaction of genetic and environmental causes.

Question 3

Describe cholethiasis.

Answer 3

• Gallstones
• Hard deposits ot stones that develop in the gallbladder and the biliary tract if:
  
  • The bile contains unusually high levels of cholesterol or bilirubin or low levels of bile salts.
  • The gallbladder is dysfunctional.
  • The release of bile is impaired.
• Having gallstones increases the risk of developing gallbladder cancer.

Question 4

What is the role of lifestyle in cholethiasis?

Answer 4

• Pigment (bilirubin) stones (~1/5) - main type in chronic haemolytic disorders or cirrhosis.
• Cholesterol stones (~4/5) - influenced by effects of metabolic syndrome.

Question 5

What is the role of body weight in the development of gallstones?

Answer 5

• Obesity
  
  • ​Acts on most mechanisms of formation (e.g. super-saturation of bile with cholesterol).
    
    • Also via obesity associated factors (dyslipidaemia, gallbladder stasis, diet, sedentary lifestyles).
• Rapid weight loss
  
  • ​Cholecystectome in up to 1/3 bariatric patients by 3y post-surgery.
    
    • Risk minimised by ursodeoxycholic acid (UCDA) until weight stabilised, and appropriate fat content (≥7g/d) of very low calorie diets.

Question 6

What is the role of physical activity in the development of gallstones?

Answer 6

• Regular physical activity protects against formation, and limits symptomatic stones up ~30%.
  
  • Sedentary lifestyles increase risk.
• Mechanisms include physical activity effect on:
  
  • ​Decreased insulin resistance, triglyceridaemia.
  • Increased plasma HDL during physical activity suggesting increase in cholesterol transport back to the liver.
  • Stimulating gallbladder contraction.

Question 7

What are the dietary recommendations for patients with / at risk of gallstones?

Answer 7

• Regular eating patterns - increase gallbladder emptying.
• Fibre and calcium - high intakes decrease biliary hydrophobic bile acids.
• PUFA / MUFA (and nuts) - may be protective.
• Fruit and veg - may be protective.
• Vitamin C - may be protective. Role in conversion of cholesterol to bile acids.

Question 8

Describe what happens as a result of damage to liver cells.

Answer 8

• Hepatitis (inflammation) - chronic if >6months. Part of the repair process.
• Fibrosis (scarring) - when ‘temporary’ fibrous ‘scaffold’ remains if new cells cannot regenerate fast enough.
• Cirrhosis (spread of inflammation and fibrosis) - affects function and shape. ‘Compensated’ then ‘decompensated’ as function decreases.
• Cirrhosis increases the risk of hepatocellular carcinoma (HCC).

Question 9

Describe the common natural history of alcohol-related and non-alcoholic fatty liver disease.

Answer 9

Question 10

Describe non-alcoholic fatty liver disease.

Answer 10

• Significant fat accumulation of hepatocytes in absence of excessive alcohol intake or other causes of liver disease.
• Risk factors:
  
  • Obesity is the main phenotype and risk factor, driven by insulin resistance (also increased risk of advanced disease).

Question 11

What is the role of lifestyle in NAFLD?

Answer 11

• Unhealthy Western lifestyles leading to obesity play a role in the development and progression of NAFLD.
• Assessment of diet and physical activity should be part of screening.
• NAFLD should always be suspected in obese children.

Question 12

Describe the treatment of NAFLD with respect to diet nd lifestyle.

Answer 12

• If overweight / obese
  
  • Modest weight loss (>/= 7%) reduces liver fat, improves hepatic insulin resistance and can resule in non-alcoholic steatohepatitis (NASH) regression.
  • Structured lifestyle programmes are advisable.
• A pragmatic, individually tailored approach is required:
  
  • Dietary restriction PLUS
  • Progressive increase in aerobic exercise / resistance training.

Question 13

How can alcohol increase risk of malnutrition?

Answer 13

Question 14

Describe the malnutrition and sarcopenia associated with liver disease.

Answer 14

• Malnutrition
  
  • Weight loss common in heavy drinkers.
  • Frequent in cirrhosis (20% in compensated, >50% in decompensated).
  • Associated with progression of liver failure and poorer prognosis.
  • Both adipose tissue and muscle tissue can be delpeted.
• Malnutrition and muscle mass loss (sarcopenia)
  
  • ​Preferential use of lipids as a fuel (fat loss) and decreased protein synthesis (muscle atrophy) in heavy drinkers.
  • More complications e.g. susceptibility to infections, ascites.
  • Independent predictors of lower survival in NASH, cirrhosis and liver transplant.
• Overweight / obese cirrhotic increasing due to increase in NASH
  
  • ​Sarcopenia may be overlooked.
  • Obesity and sarcopenic obesity may worsen prognosis.

Question 15

What happens to levels of thiamine (B₁) in alcoholic liver disease?

Answer 15

• Thiamine is commonly deficient in ALD.
• Water soluble essential nutrient.
• Phosphorylated in the gut to active coenzyme form, important in:
  
  • ATP production
  • Normal nerve conduction
  • Maintenance of neural membranes
• In chronic alcohol use, levels rapidly reduce due to:
  
  • Poor intake
  • Decreased conversion to coenzyme
  • Decreased storage in fatty liver
  • Inhibited intestinal absorption
  • Increased metabolic demand - use of thiamine for ethanol metabolism

Question 16

What are the clinical thiamine deficiency signs?

Answer 16

Question 17

What are the notable deficiencies associated with alcoholic fatty liver disease?

Answer 17

Question 18

How much alcohol is safe?

Answer 18

14 units (men and women).