Week 8: Viral Hepatitis

Question 1

Viral hepatitis characteristics and symptoms

Answer 1

• Acute: Jaundice (medical condition with yellowing of skin or whites of eyes, arising from excess of the bilirubin pigment, nausea, abdominal pain, fever
• Destruction of hepatocytes (some regenerate, fibrous tissue build up), small cirrhotic liver
• Liver function tests: elevated serum aminotransferses - ALT (alanine), AST (aspartate)
• Chronic liver disease can lead to liver cancer
• Can be asymptomatic

Question 2

Hepatitis B: Transmission, Clinical manifestations, Pathogenesis, replication, prevention, diagnosis, treatment

Answer 2

Hepatitis B virus Hepadnavirus (ds DNA, enveloped, icosahedral): Humans and chimpanzees. Liver mainly, also kidneys and pancreas.
• Transmission: via blood and blood products, sexual transmission. Also mother to baby at childbirth.
• Clinical manifestations: prodrome phase (vague symptoms e.g. fatigue, vomiting, cough, headache) begins ~2 weeks post exposure, icteric phase (jaundice) - liver cells destroyed due to inflammatory process, bile stasis due to hepatic disfunction), urine dark due to accumulation of blood products, stool clay colour.
Chronic infection most commonly follows asymptomatic infection - leads to liver cirrhosis, failure and cancer but may be passive with no symptoms.
• Pathogenesis: Virus enters through mucosal surfaces. Replication in hepatocytes occurs few days post exposure (HBV DNA integrates into genome of hepatocytes). Cell-mediated response (cytotoxic T cells) cause symptoms but help to resolve infection. Poor CMI response leads to fewer symptoms but also inability to effectively clear infection (chronic infection).
• Replication: HBsAg used to attach to liver cells, uncoats and penetrates core. Partially ds genome is completed to be fully ds and enters nucleus, integrating into host genome.
• Main proteins: HBsAg glycoprotein used to attach to liver cells, HBcAg, HBeAg (soluble secreted Ag), reverse transcriptase, DNA pol.
• Diagnosis: antibodies are detected 4-6 weeks after their specific Ag. Continued presence of HBsAg, HBeAg or both indicates chronic infection.
- Incubation period: HBsAg in circulation
- Prodrome acute phase: more HBsAg but also anti-HBcAg Ab.
• Treatment: interferon therapy helps patients with chronic infection to prevent reactivation, nucleoside analogues (e.g. entecavir)
• Prevention: universal blood and bodily fluid precautions (gloves, protective clothing, disinfection with hypochlorite), screening of blood donors for HBsAg, immunisation (3 doses of genetically engineered HBsAg gives 90% protection)

Question 3

Difference between various types of hepatitis

Answer 3

Hepatitis A and E:

• No carrier state, infection eventually cleared.
• Acquired via faecal-oral route (usually food or person-person)
• Vaccine available for hepatitis A

Hepatitis B, C, D:

• Carrier state, persistent infection, cirrhosis, liver cancer
• Acquired via blood/blood products and through sexual intercourse
• Vaccine available for hepatitis B

Question 4

Diagnosis of viral hepatitis

Answer 4

• Liver function tests: elevation of serum aminotransferses - ALT (alanine), AST (aspartate)
• Serology

Question 5

Hepatitis C

Answer 5

Hep C virus Flavivirus (ssRNA, enveloped, spherical) - several serotypes exist - not crossprotective (vaccine difficult to manufacture)
• Transmission: via blood/blood products. Sexual and vertical transmission is uncommon.
• Clinical presentation: incubation period 2-4 months, most people have subclinical infection. Mild disease in on most other people. About half of infections progress to chronic active hepatitis (risk of cirrhosis and liver cancer)
• Diagnosis: Ab to HCV, Hepatitis C DNA

Question 6

Hepatitis A

Answer 6

Hepatitis A virus Picornavirus (ss RNA, icosahedral): Only one serotype, affects humans only. Replicates in hepatocytes - shed into gut via bile duct. Transmission via faecal-oral route (person-person, anal intercourse, food); high concentration of virus in faeces ~2 weeks before symptoms appear. Resistant to detergents, acid, 60C, survives in water. Incubation period ~30 days with sudden onset. Non-specific symptoms occur after ~1 week (fever, nausea, abdominal pain, loss of appetite, lethargy). Complete recovery (99%), milder in children than adults. Fulminant infection leads to 80% mortality in 3/1000.
Diagnosis: HAV IgM in serum.
Effective vaccine available as only one serotype, given to high risk groups (travellers, sewage workers)