W10.3_Liver Diseases

Question 1

Explain the characteristics and current trends of liver diseases. What are the main and other causes of liver diseases (3/5)?

Answer 1

• Major, under-recognised, yet highly preventable chronic conditions with increasing death rate
• Liver’s ability to regenerate causes no symptoms -> difficult to identify
• Main causes: alcohol, non-alcoholic fatty liver disease (NAFLD), viral hepatitis
• Other causes: drugs, toxins, metabolic/immune diseases, vascular/biliary abnormalities, cancer

Question 2

Explain how alcohol causes liver diseases and the guidelines surrounding it.

Answer 2

• Alcohol: most common cause
• Recommended guidelines: ≤14 units/week, spread across ≥3 days (but no completely safe level)
• Liver being unable to process alcohol quickly enough -> inflammation and scarring (may not show symptoms until significant damage) -> cirrhosis and death

Question 3

Define and explain the formation of non-alcoholic fatty liver disease (NAFLD). What are its risk factors?

Answer 3

• NAFLD: build-up of fat in liver
• Fat (triglycerides) metabolised in liver form lipoproteins -> released to circulation
• Excess triglycerides or blocking in release of lipoproteins cause build-up of fat in liver cells
• Accumulation of fat in liver cells -> inflammation (NASH) -> scarring/fibrosis of liver -> cirrhosis (irreversible liver damage)
• Risk factors: obesity, increased visceral fat, insulin resistance/diabetes, lack of exercise

Question 4

Define viral hepatitis. Explain the characteristics of the different types of hepatitis (A/B/C/D/E).

Answer 4

• Viral hepatitis: causes acute/chronic liver inflammation
• Hepatitis A (HAV): common, enterically transmitted (through contaminated water/food), often mild, X progress to chronic/carrier status
• Hepatitis B (HBV): DNA virus, highly contagious, transmitted through body fluids, acute infection can cause chronic/carrier status, leading cause of hepatocellular carcinoma (HCC)
• Hepatitis D (HDV/δ virus): can only replicate in presence of HBV, combination of both increase risk of progression in liver disease
• Hepatitis C: RNA virus, blood-borne, acute/chronic, often undiagnosed cause of asymptomatic, slow and progressive disease yet could get rid of through effective treatment
• Hepatitis E: similar course and properties to HAV

Question 5

Why would drug induced liver injury (DILI) occur? Explain how it is observed in patients with liver disease.

Answer 5

• Majority of drugs are hepatotoxic (in wide spectrum of damage), some have to be withdrawn due to concerns, need to identify DILI and potential causes
• Patients with liver disease do not have increased susceptibility to hepatotoxicity but effects may be more severe

Question 6

Define and explain intrinsic reactions and idiosyncratic reactions in DILI.

Answer 6

• Intrinsic reactions: predictable, reproducible, dose dependent, occur rapidly and cause necrosis/acute liver failure (ex. paracetamol overdose)
• Idiosyncratic reactions: not predictable nor reproducible, not dose dependent, take weeks/months to occur, can result from metabolic idiosyncrasy/immunoallergic reactions (ex. NSAIDs, anti-epileptics)

Question 7

Categorise liver diseases into different types (7) by the length and pattern of damage.

Answer 7

• Acute: ≤6 months, usually caused by viral hepatitis A/E and intrinsic DILI, self-limiting with spontaneous recovery, can progress to acute liver failure/chronic liver disease
• Chronic: >6 months, progressive with permanent structural damages, usually caused by alcohol and chronic viral hepatitis
• Cholestatic: disruption of bile flow caused by stagnation of bile in bile ducts
• Hepatocellular: steatosis (fatty infiltration) or hepatitis (inflammation)
• Fibrosis: active deposition of collagen formation of scar tissue (regeneration) -> extensive hepatocyte damage, disruption of blood flow
• Cirrhosis: irreversible liver damage, erratic regeneration and nodules can form
• Decompensated cirrhosis: not enough hepatocyte capacity to perform required liver functions

Question 8

What are the initial symptoms of liver diseases? What are the severe symptoms of it?

Answer 8

• Mostly asymptomatic initially (long time interval between occurrence and detection)
• Initial symptoms (unspecific): fatigue, general malaise, fever, nausea and vomiting
• Accumulation of bilirubin: jaundice (yellow eyes/skin), pale stools and dark urine
• Accumulation of hormones: pruritus (itching), spider naevi, gynaecomastia (breast in men)
• Reduced clotting factors: bruising and bleeding, liver palms, finger clubbing
• Severe symptoms: ascites (abdominal fluid buildup), encephalopathy (confusion), varices (development of new and week hepatic blood vessels) and portal hypertension

Question 9

Explain the different markers in liver function tests (LFT) (6).

Answer 9

• Bilirubin: product of RBC breakdown -> transported to liver in serum attached to albumin -> transformed into water-soluble conjugate -> excreted via bile to intestines
• Levels increased could indicate (haemolysis), hepatocellular damage, cholestasis
• Albumin: proteins produced in liver with long half-life
• Levels decreased could indicate (oedema) and chronic liver disease
• Transaminases: AST (aspartate transferase) found in liver/heart/skeletal muscle/pancreas/kidneys/RBC, ALT (alanine transferase) found in liver
• Levels increased could indicate hepatitis, (drugs, sepsis), decreased could indicate severe cirrhosis (unable to produce proteins)
• ALP (alkaline phosphatase): found in liver/bone/intestine/placenta
• Levels increased could indicate cholestasis, (damage to biliary tree)
• GGT (γ-glutamyltransferase): found in liver/biliary epithelial cells/pancreas/kidneys/prostate/intestine
• Levels increased could indicate alcohol, cholestasis, (carcinoma of pancreas/GI tract)
• PT (prothrombin time)/INR (international normalised ratio): blood clotting factors produced by liver with short half-life
• Levels increased could indicate acute/chronic liver disease

Question 10

How is liver impairment diagnosed from LFTs? Describe the Child’s Pugh Scoring System. Are there any other assessments that may be required?

Answer 10

• Abnormal = 2-3 indicators above upper limits (but not necessarily due to liver dysfunction)
• Child’s Pugh Scoring System: to assess prognosis of cirrhosis
• Other assessments:
• Fibroscan: non-invasive method to assess liver stiffness, quick and painless
• Imaging: liver ultrasound/CT or MRI scan/ERCP and MRCP
• Liver biopsy
• Specific tests (ex. viral cultural tests for suspected hepatitis)