Hepatobiliary - non-neoplastic liver conditions

Question 1

hepatic diseases (6)

Answer 1

1. Infectious disorders
   - Viral hepatitis
   - Bacterial, parasitic and helminthic
2. Drug- and toxin induced liver injury (DILI)
   - Alcoholic liver disease
3. Cholestatic / biliary diseases
   - Large bile duct obstruction
   - Neonatal cholestasis
   - Autoimmune cholangiopathies
4. Autoimmune hepatitis
5. Metabolic diseases
   - Non-alcoholic fatty liver disease (NAFLD)
   - Haemochromatosis
   - Wilson disease
   - a1-antitrypsin deficiency
   - Neonatal hepatitis
6. Circulatory disorders
   - Hepatic venous outflow obstruction

Question 2

acute hepatitis symptoms

Answer 2

• Jaundice
• Poor appetite
• Dark-coloured urine
• Nausea and vomiting
• Fever
• Abdominal pain
• Fatigue

Question 3

causes of viral hepatitis

Answer 3

Hepatotropic: Hepatitis A, B, C, D, E

Non-hepatotropic (no effect on liver): EBV, CMV

Question 4

hepatitis A

• mode of transmission
• where does it affect
• malignancy

Answer 4

• fecal-oral transmission
• affects countries w/ poor hygiene/ sanitation, close quarters
• consumption of raw shellfish
• benign: self-limiting,
  gives lifelong immunity

Question 5

hepatitis B

• modes of transmission **
• pathogenesis
• diagnosis
• malignancy
• carrier state
• histo features

Answer 5

global health problem:

• Vertical transmission
• Horizontal transmission esp. early childhood
• Sexual and IV drug abuse
• injury to hepatocytes caused by immune response -> CD8+ cytotoxic T cells attacking infected cells
• HBsAg (acute), HBcAg (chronic) postive**
• risk of causing hepatocellular carcinoma
• healthy carrier w/ no inflammation -> normal ALT/AST
• ‘ground-glass’ hepatocyte

Question 6

hepatitis C

• modes of transmission **
• pathogenesis
• carrier state
• histo features
• diagnosis**

Answer 6

• IVDA, sexual, needle-stick injury, vertical
  but 1/3 have no identifiable risk factors
• HCV is genomically unstable + has multiple strategies to evade host anti-viral immunity
• > causes hepatic damage (persistent infection and chronic hepatitis)
• no carrier state - all presents as chronic hepatitis
• no lifelong immunity - HCV RNA (RT-PCR) very persistent **
• histo features:
  lymphoid follicle
  fatty change

Question 7

hepatitis D

• mode of transmission
• where does it affect
• pathogenesis
• diagnosis
• vaccine/ treatment

Answer 7

• blood-borne (IVDA, blood transfusions)
• prevalence highest in Amazon basin, Middle East, Mediterranean and central Africa
• Superinfection:
  severe acute hepatitis in a HBV carrier/
  exacerbation of preexisting chronic Hep B infection
• diagnosis: IgM anti-HDV antibody
• vaccine: prevent HBV infection also prevents HDV cause HDV is developed from HBV
  self-limiting (like HBV)

Question 8

hepatitis E

• mode of transmission
• who should take special caution
• diagnosis
• vaccine/ treatment

Answer 8

• fecal oral transmission
• zoonosis: monkeys, cats, pigs, dogs
• immunocompromised pts - chronic infection
• pregnancy: high mortality rate
• diagnosis: HEV RNA and virions can be detected by PCR in stool and serum
• self-limiting disease

Question 9

acute vs chronic viral hepatitis

Answer 9

difference is the pattern of injury
both are mononuclear T cells
acute: lobular hepatitis
chronic: portal hepatitis

Question 10

lobular hepatitis (acute) 
histo features

Answer 10

• Hepatocyte degeneration (hydropic swelling)
• Apoptosis, spotty necrosis with hepatocyte dropout to confluent necrosis
  (perivenular, bridging)
• Kupffer cell (macrophage) hypertrophy
• Lymphoplasmacytic infiltrate
• Cholestasis (cause of bile duct obstruction)

Question 11

portal hepatitis (chronic) histo features

Answer 11

• Lymphoplasmacytic portal infiltration
• Portal and periportal (interface) hepatitis to bridging hepatic necrosis
• Fibrosis to cirrhosis; regression may occur

Question 12

grading and staging of liver disease

Answer 12

grading: extent of injury and inflammation
staging: progression of fibrosis

Question 13

Non-hepatotropic viral hepatitis

- viral types

Answer 13

multi organ involvement

• opportunistic infection:
• CMV, HSV, EBV, adenovirus

Question 14

localised diseases caused by bacterial, parasitic and helminthic infections (2)

Answer 14

• Abscess (bacterial or amoebic)

- Hydatid cyst

Question 15

diffused diseases caused by bacterial, parasitic and helminthic infections (3)

Answer 15

• Mild hepatic inflammation w/ varying hepatocellular cholestasis
• Granulomatous disseminated disease (Schistosoma – ‘pipe stem fibrosis’, miliary TB)
• Dilated intrahepatic ducts (liver flukes: high rate of cholangiocarcinoma)

Question 16

amoebic abscess (localised liver disease)

Answer 16

Large cavity lined by necrotic shaggy tissue

• Abscess contents have lack of inflammatory cells due to process of liquefactive necrosis
• caused by protozoa

Question 17

miliary TB of liver

• histo features
• diagnosis

Answer 17

• granuloma: Epithelioid histiocytes, lymphocytes and multinucleated giant cells
• Ziehl-Neelsen stain for acid-fast bacilli
• Culture and sensitivity for Mycobacterium tuberculosis

Question 18

autoimmune hepatitis

• antibodies present
• affect who more

Answer 18

Chronic progressive disease

• autoantibodies: ANA, SMA, anti-SLA/LP, AMA, anti-LKM1

genetic association: HLA genotype
affects females more

Question 19

autoimmune hepatitis

• diagnosis
• histo features

Answer 19

• presence of autoantibodies
• elevated IgG level

histo:
1. interface hepatitis with lymphoplasmacytic predominance
2. Emperipolesis
3. Hepatic rosette formation

Question 20

Drug- and toxin induced liver injury (DILI)

- pathogenesis

Answer 20

• Direct toxicity
• hepatic conversion of xenobiotic -> active toxin
• immune-mediated mechanisms

Question 21

DILI (Drug- and toxin induced liver injury) diagnostic criteria

Answer 21

• temporary liver damage upon drug/toxin exposure

- recovery upon stopping the drug

Question 22

alcoholic liver disease

- factors determining severity of ALD

Answer 22

• Dosage and duration: 6 beers/day + > 10-20 yrs
• Gender: females more susceptible
• Ethnic and genetic differences (in production of detoxifying enzymes)
• Comorbid conditions (viral hepatitis)

Question 23

alcoholic liver disease

- complications

Answer 23

• steatosis
• Dysfunction of mitochondrial and cellular membranes
• Hypoxia and oxidative stress
• increase in inflammatory response
• decrease hepatic sinusoids perfusion

Question 24

alcoholic liver disease

- histo features (6)

Answer 24

• Centrilobular steatosis (reversible with abstention)
• Hepatocyte swelling (ballooning degeneration) and necrosis
• Mallory-Denk bodies
• Neutrophilic reaction
• Pericellular/perisinusoidal fibrosis (“Chicken-wire fence” pattern)
• Cirrhosis (micronodular)

Question 25

Non-alcoholic fatty liver disease (NAFLD) [metabolic disease] - progression

Answer 25

only for individuals who drink very little alcohol healthy -> steatosis -> NASH (steatohepatitis) -> NASH w/ fibrosis -> cirrhosis NASH: hepatocyte injury

Question 26

2 causes of NAFLD

Answer 26

metabolic diseases: - Insulin resistance -> decreased lipid metabolism + increased production of inflammatory cytokines - Oxidative injury -> liver cell necrosis as fat laden cells are highly sensitive to lipid peroxidation products

Question 27

haemochromatis definition

Answer 27

Caused by excessive iron absorption, depositing in parenchymal organs (liver, pancreas, heart, joints, endocrine organs, skin)

Question 28

wilson's disease definition

Answer 28

Autosomal recessive disorder caused by ATP-7B gene mutation (chr 13) - > impaired copper excretion into bile + failure to secrete copper into blood - > accumulation of copper in the tissues and organs

Question 29

A1-antitrypsin deficiency

Answer 29

Autosomal recessive: disorder of protein folding -> impaired secretion and very low serum α1AT (α1AT is important in inhibition of proteases, particularly those released from neutrophils) -> so high protease activity