L41: Patient with jaundice - viral hepatitis

Question 1

Presentation of viral hepatitis

Answer 1

1. Jaundice = increased unconjugated bilirubin (RBCs breakdown, decreased conjugation and excretion by liver)
   - Pre-hepatic: haemolysis
   - Hepatic: failure of conjugation and transport
   - Post-hepatic: biliary system
2. Oedema = decreased albumin production by liver -> lower oncotic pressure -> fluid leaks from vessels
3. Easy bruising = insufficient coagulation protein synthesis by liver

Question 2

What is hepatitis and viral hepatitis?

Answer 2

= inflammation of lover
- Caused by drugs/alcohol, viruses, bacteria (typhoid fever), autoimmune, ischaemic

Viral hepatitis

• Hepatitis viruses are when liver is the main site of replication
• Others can cause hepatic inflammation e.g. EBV, CMV, HIV, mumps, yellow fever

Question 3

HAV - nucleic acid, route and infection

Answer 3

• RNA virus
• Spread via faecal-oral route
• Common in developing world (travel)
• Most infection asymptomatic (esp. children)
• If acute illness: fever, lethargy, jaundice, abnormal liver enzymes, swollen and tender liver
• <1% causes fulminant hep and never chronic
• Testing using antibodies (IgM = current infection, IgG = previous infection)
• Vaccine available
• No treatment, recover spontaneously and will be immune

Question 4

HBV - nucleic acid, route, infection

Answer 4

• DNA virus
• Blood borne and easily transmitted
• Globally distributed, mainly chronic and mother-baby transmission
• V. likely asymptomatic (esp. infant from mother)
• Can cause acute, 0.5% fulminant
• High rate of chronic infection in infants, lower in adults and children
• Fibrosis, cirrhosis, liver failure, cancer
• Vaccine available
• Treatment is suppressive (stop replication with anti-viral drugs)
• Long incubation 3-4mths

Question 5

HCV - nucleic acid, route and infection

Answer 5

• RNA virus
• Blood borne, much less transmitted than HBV
• Areas of eastern europe and russia due to IV drug use
• Infection in adults associated with needle sharing and sex
• Majority asymptomatic
• Can be acute although not often and fulminant rare outside Japan
• Most have chronic infection = cirrhosis, cancer (less than HBV)
• Treatment is curative

Question 6

Hep B virus properties

Answer 6

• Partially double stranded hepatotrophic DNA virus
• Envelope from liver cell
• Hepadnaviridae

Around outside is protein, hep B surface antigen (HBsAg)

• Virus replicates -> excess HBsAg spills into blood
• HBsAg measured in blood to confirmed current active hep B and recombinant used in vaccines

Genomic structure

• Use reverse transcriptase (some drugs for HIV can be used)
• X gene involved in using hepatocyte cell machinery to increase protein synthesis = oncogenic

Question 7

Infection with hep B

Answer 7

• HBsAg binds to receptor on hepatocyte
• Viral DNA moves into nucleus
• Complimentary circular DNA made -> transcribed into mRNA
• Translated with excess HBsAg
• Transcribed mRNA transformed into DNA by reverse transcriptase
• Virus particles assembled and released from liver cell
• Cytotoxic T cell response causes liver damage (symptoms 3mths after infection)
• Some liver cells have hep B DNA rest of life, slightly increased risk of liver cancer and if immunosupressed (chemo) can reactivate hep B

Question 8

Hep C virus properties

Answer 8

• Spherical positive sense RNA virus
• Enveloped
• Not stored in genome of liver cell (only hep B) so does not enter liver cell (nor does hep A)
• Ongoing infection immune system often fails to clear

Question 9

Diagnosis of HAV

Answer 9

IgM positive (no IgG) = current infection 
IgG positive = current illness not HAV (vaccinated or previous infection)
HAV RNA PCR usually not required

Question 10

Diagnosis of HBV

Answer 10

• 1st look at surface antigen = if present then current HBV (does not tell if acute or chronic)
• E antigen = early in infection cycle (if present indicates large amount of HBV replication so high HBV DNA in blood) so marker of infectivity
• Anti-HBE: not usually measured
• Anti-HBS: cured or vaccinated (antibodies to surface antigen)
• Anti-HBC: cured or acute infection (IgM anti-core antibodies would indicate acute)
• Can quantify amount of HBV DNA using PCR: acute will be very high levels of DNA in blood, lower in chronic

Question 11

Diagnosis of HCV

Answer 11

• Antibody against HCV (does not tell you if current or previous infection)
• Then RNA PCR and genotype

Question 12

Chronic HBV

Answer 12

• HBEAg often cleared in 20-30 y/olds (can result in flare of active hepatitis, prognosis improves)
• Surface antigen clearance is uncommon
  Adults after 5 yrs:
• 15% develop cirrhosis
• 20% with cirrhosis decompensate (liver failure)
• 10% with cirrhosis develop hepatocellular carincoma (rarely alive at 5yrs unless curable)

Question 13

Chronic HCV

Answer 13

• Acute -> chronic infection in 6mths in 80%
• Cirrhosis after 20yrs in 10%
• Decompensated hepatocellular carcinoma after another 5yrs in 2-3%

Question 14

Treatment of acute hepatitis

Answer 14

• Not required (can try antivirals for HBV and HCV)
• Supportive care + advice for self-care, transmission, keeping healthy
• Fulminant (rare) = transplant

Question 15

Treatment of chronic hepatitis

Answer 15

• To prevent cirrhosis and cancer and reduce transmission
• HBV: suppress, stop replication with antivirals (those with complications and high ALT 2x normal)
• HCV: curative treatment with drugs