GIS21 Hepatitis And Cirrhosis

Question 1

Liver functions

Answer 1

1. Processing of dietary amino acids, carbohydrates, lipids
2. Synthesis of Serum **albumin + **Coagulation factors (I, II, V, VII, IX, X)
3. ***Detoxification of drugs and chemicals
4. ***Bilirubin / bile formation
5. Glycogen storage
6. Blood storage —> sustain circulation
7. Uptake, storage and distribution of nutrients and vitamins
8. Maintain blood glucose level
9. Regulate circulating levels of ***VLDL
10. ***Iron storage, metabolism and homeostasis
11. ***Endocrine function:
    - convert Vit D3 to 25-hydroxycholecalciferol
    - convert T4 to T3

Question 2

Histological functional unit of liver

Answer 2

Old classification: ***Lobules
- central vein surrounded by portal space (branches of portal vein, hepatic artery, bile duct)

New classification: ***Acini

• portal space in middle of 2 central veins
• zone 1, 2, 3 (zone 3 nearest to central veins —> least oxygenated, least nutrient-supplied, prone to damage by e.g. shock)

Question 3

Etiology of hepatitis

Answer 3

• ***Hepatitis virus
• ***Alcoholism
• ***Drugs
• ***Obesity
• ***Autoimmune diseases (autoimmune hepatitis)
• ***Metabolic diseases (Wilson’s disease)
• Non-hepatitis virus

Question 4

***Acute hepatitis symptoms (三寶)

Answer 4

Similar clinical features irrespective of causes

1. ***Jaundice: yellowing of skin and eye (sclera)
2. ***Anorexia: loss of appetite
3. ***Malaise: generalised weakness

記: JAM

Question 5

Histopathology of acute hepatitis

Answer 5

Hepatitis —> cell death/necrosis

1. Acidophil bodies (apoptosis, apoptotic bodies - individual cell death)
   —> acute viral hepatitis
2. Zonal necrosis (death of hepatocytes involving an acinar zone)
   —> toxic / haemodynamic e.g. paracetamol
3. Bridging necrosis (across acinar zones)
   —> severe viral hepatitis
4. Panacinar necrosis (all acinar zones)
   —> severe viral hepatitis / toxins

Question 6

Chronic hepatitis

Answer 6

Necro-inflammatory disease of liver for ***>6 months

Clinical features:
repeated attacks of hepatitis, some attacks may be asymptomatic

• **Causes:
  1. Hepatitis viruses (ONLY B, C, D)
  2. Alcohol
  3. Drugs
  4. Autoimmune
  5. NASH (obesity, diabetes)

Histology:
- ***Inflammatory cells in portal tracts

Question 7

Human hepatitis viruses

Answer 7

HAV - RNA unenveloped
HBV - ***DNA enveloped
HCV - RNA enveloped
HDV - RNA enveloped
HEV - RNA unenveloped

記:
Chronic: enveloped
Acute: unenveloped
ONLY HBV is DNA virus

Question 8

Hepatitis A virus

Answer 8

• Faecal-oral route (not well-cooked shellfish food; infected subject to food/ subject)
• incubation period 15-40 days
• direct ***cytopathic effect on hepatocytes
• mild illness with full recovery usually (99% recovery)
• ***no chronicity / carrier state
• ***vaccine available
• 4 types: Cholestatic, Relapsing, Protracted, Fulminant

Question 9

Hepatitis B virus

Answer 9

Small DNA virus of 3200 nucleotides
4 proteins:
- P (Polymerase / reverse transcriptase)
- S (HBsAg)
- C (HBcAg + HBeAg)
- X (HBx)

Route: Parenteral

• blood and blood product
• sexual contact
• **- vertical transmission
• acute and chronic
• carrier state exists
• Vaccine available
• Curative anti-viral drug NOT available (***only effective suppressive drugs)

HBV infects liver cells
—> ***Cell-mediated immune defence of the host attacks HBV then damage liver cells
—> Hepatitis

• Clinical sequelae
  1. Acute hepatitis B
  —> fulminant hepatitis / persistent hepatitis / recovery

2. Chronic hepatitis B
—> inactive carrier / chronic hepatitis
(chronic hepatitis)
—> ***Cirrhosis
—> ***HCC

Question 10

Hepatitis C virus

Answer 10

Route: Parenteral

• ***blood / body fluid
• NOT through gut
• vertical transmission
• Vaccine NOT available
• ***Curative anti-viral drug available
• <1% population in HK infected (Anti-HCV +ve)
• acute and chronic
• carrier state exists
• serological markers: ***Anti-HCV, HCV RNA
• Anti-HCV is NOT protective
• Clinical sequelae
  1. Acute hepatitis
  2. Carrier state
  3. End-stage liver
  4. Liver cancer

Question 11

Hepatitis D virus

Answer 11

• Defective RNA virus
• requires ***HBsAg (i.e. presence of HBV) to be infective
• ***aggravate consequence of HBV infection

Route: parenteral

• Co-infection: simultaneous introduction of HDV and HBV
• Super-infection: introduction of HDV into HBsAg +ve host

Question 12

Hepatitis E virus

Answer 12

• Faecal-oral route
• low risk of chronicity
• full recovery expected
• rising incidence in HK —> ***major cause of acute hepatitis

Question 13

Viral hepatitis route of transmission

Answer 13

Faecal-oral route:
A, E

Parenteral route:
B, C, D

Chronicity:
B, C, D

Question 14

***Alcoholic liver diseases

Answer 14

1. Alcoholic hepatitis
2. **Steatosis (Fatty liver) —> reversible
   - **Fat + **Inflammation + **Scarring
   - end-stage: scar tissue replaces liver cells
3. Liver fibrosis —> irreversible
4. Cirrhosis —> irreversible

Question 15

Drug-induced hepatitis

Answer 15

Examples:

• Anti-TB drugs
• Paracetamol
• Weight-reducing drugs
• Herbs
• acute / chronic

Pathogenesis:

1. dose-related (predictable) e.g. alcohol, paracetamol
2. idiosyncratic (unpredictable) e.g. Halothane, Isoniazid, Chlorpromazine

Mechanism:

• ***direct toxicity
• hepatic ***conversion from xenobiotic to active toxin
• immune mechanisms

Question 16

***Non-alcoholic fatty liver disease (NAFLD) / Non-alcoholic steatohepatitis
(NASH)

Answer 16

• Fatty liver disease
• inflammation with concurrent fat accumulation in liver
• due to ***Metabolic syndrome e.g. obesity, hypertension, diabetes

Question 17

Autoimmune hepatitis

Answer 17

• AutoAb-mediated disease in liver
• acute and chronic
• ***Plasma cell-rich infiltrate in the portal tracts
• Circulating antibodies
  —> Type 1: anti-nuclear (ANA), anti-smooth muscle (SMA), anti-actin (AAA), anti-soluble liver antigen/liver-pancreas antigen (anti-SLA/LP) antibodies
  —> Type 2: anti-liver kidney microsome-1 (anti-LKM-1) antibodies

Question 18

***Cirrhosis

Answer 18

• ***Diffuse process affecting entire liver
• **Regenerative nodules of hepatocytes surrounded by **Fibrous CT (Fibrosis)
• end-stage liver disease —> irreversible
• only current treatment: liver transplantation

Question 19

Cirrhosis etiology

Answer 19

1. Hepatitis virus (post-viral cirrhosis)
   —> ***B, C, D
2. Alcohol / drugs / toxins
3. NASH
4. Autoimmune
5. Primary biliary cirrhosis
   —> autoimmune disease against bile ducts
6. Hereditary diseases
   —> Wilson’s disease, α1-antitrypsin deficiency
7. Cryptogenic cirrhosis (unknown)

Question 20

***Cirrhosis complications

Answer 20

1. Portal hypertension (fibrosis and regeneration causes structural changes: Sinusoidal + Post-sinusoidal block —> ↑ hepatic vascular resistance —> hypertension)

***- Esophageal varices
—> Porto-systemic shunting

***- Hepatic encephalopathy
—> Porto-systemic shunting
—> CNS syndrome (confusion, coma, flapping tremor) due to failure of liver to remove nitrogen-metabolite e.g. NH3 and other toxic substances from GI tract (e.g. Hyperammonemia)

***- Ascites
—> accumulation of extracellular fluid in peritoneal cavity due to
—> 1. Portal hypertension
—> 2. Low serum albumin (low osmotic pressure in blood)

***- Splenomegaly / Hypersplenism
—> lead to consequent sequestration RBC / WBC / platelets
—> mild pancytopenia / thrombocytopenia

2. Portal vein thrombosis
3. Liver failure
4. ***Hepatocellular carcinoma