Lecture 7.1 - Viral Hepatitis

Hepatitis Viruses

• Hepatitis definition: Acute vs Chronic
• 5 main strains of hepatitis viruses: A, B, C, D, and E
• Each virus can cause similar symptoms, but they are transmitted differently and can affect the liver in different ways

Importance of Hepatitis

• Estimated 325 million people worldwide live with hepatitis B and/or C
• Disease burden and economic burden due to chronic hepatitis related liver cirrhosis, liver cancer, liver transplant, and mortality
• Hepatitis B is preventable due to vaccine, and universal vaccination was introduced to the UK infant schedule in 2017
• Hepatitis C is treatable with direct-acting antiviral drugs, and WHO set a target to eliminate viral hepatitis by 2030

Viral Structure

• Hepatitis A virus: non-enveloped RNA virus in the Picornavirus family
• Hepatitis B virus: enveloped partially double-stranded DNA virus in the Hepadnavirus family
• Hepatitis C virus: enveloped single-stranded RNA virus in the Flavivirus family
• Hepatitis D virus: defective virus that can't infect a hepatocyte unless already infected with HBV
• Hepatitis E virus: non-enveloped RNA virus in the Hepeviridae family

Hepatitis A

• RNA virus in the Picornaviridae family
• Oral-fecal route (contaminated water, bad hygiene areas, food, etc.)
• 114 million affected worldwide
• Incubation: 2-6 weeks
• Vaccine available
• Self-limiting, complications rare
• HAV IgM: active infection (primary infection)
• HAV IgG: recovery/vaccination

Hepatitis E

• RNA virus in the Hepeviridae family
• Oral-fecal route
• 28 million affected worldwide
• Incubation: 40 days
• Dangerous in pregnant women
• Self-limiting, off-licence Ribavarin (antiviral agent)
• HEV IgM: active infection
• HEV IgG: recovery

Hepatitis B

• Vertical transmission (75% globally)
• Sexual contact, IVDU, blood products, needlestick injuries
• Incubation: 6 weeks to 6 months
• Chronicity: 90% in infancy, 20% in older children, and <10% in adults
• Vaccine available

Hepatitis C

• IVDU (90%), sexual contact (<1%), infants born to HCV +ve, blood products prior to 1991, needlestick injuries
• Incubation: 2 weeks to 6 months
• Chronicity: 80%
• No vaccine available

Pathophysiology

• Acute infection after inoculation/ingestion of virus
• Virus enters hepatocytes, which are the main site of replication
• Triggers cellular immune response by the host's defence mechanisms
• Release of cytotoxic cytokines and natural killer cells
• Attack infected hepatocytes, leading to destruction and release of liver enzymes
• Oedema, necrosis, cholestasis, fibrosis, cirrhosis, and carcinoma

Signs and Symptoms

• No symptoms, malaise, lethargy, fever, nausea, anorexia, abdominal pain, jaundice, pruritis, dark urine, pale stools, hepatomegaly, tender
• Later signs of liver cirrhosis: palmar erythema, spider naevi, gynaecomastia, abdominal distension, caput medusae, encephalopathy

Investigations

• Blood tests
• Liver function tests: liver transaminases (ALT, AST), alkaline phosphatase, albumin, coagulation tests (INR, PT)
• Immunology: look for viral RNA via PCR or antigens/antibodies in the blood (IgM or IgG)
• Imaging: not usually required for diagnosis, but can use ultrasound, CT scan, and liver biopsy

Hepatitis B Serology

• Hepatitis B markers: HB surface antigen, HB surface antibody, HB core antibody, E antigen
• HB surface antigen: found in the blood of a person who is infected with HBV

Hepatitis B Management

• Refer anyone who is HBsAg positive to a gastroenterologist or Infectious disease specialist
• Anti-virals: suppress viral replication, e.g. entecavir, tenofovir, lamivudine
• Education regarding transmission

Hepatitis B Vaccination

• Genetically engineered surface Ag of the virus
• 3 doses + boosters if required
• Produces antibody response to surface antigen
• Universal UK infant schedule in 2017: 6 in 1 vaccine, given at 2, 3, and 4 months
• At-risk population: babies born to infected mothers, close family or sexual partner, receive regular blood transfusions or products, people whose work puts them at risk, prisoners, IVDU, and MSM