Hepatitis B Virus
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Introduction
Over 2 billion people have been infected with hepatitis B virus (HBV), mostly in Asia and subsaharan Africa. This leads to over 1 million deaths yearly - the 9th leading cause of death worldwide. 400 million people are chronic carriers (0.1-0.3% of North Americans)
Increasing prevalence in North America appears due to immigration, although also high prevalence (4%) in Northern Canada.
The Case of...
Epidemiology
Classification and Characteristics
HBV is a DNA virus which replicates in hepatocytes. Following attachment and uncoating, DNA is trascribed into mRNA, used to make viral proteins.
HBV is the only DNA virus possessing reverse transcriptase, and RNA is returned to DNA for packaging and secretion. Its envelope antigen is a marker of replication, but has an unknown role.
The virus can be present as complete particle, as filaments, or as spheres.
Transmission and Infection
The incubation period ranges from 45-180 days, with 60-90 days the average.
Mother-child transmission is the main source of infection globally, with a high rate of chronicity.
Horizontal transmission, where risk depends on viral load, carries a lower risk of chronicity (less than 20%).
- sex, blood products, IVDU, tattooing, scarification, and acupuncture
Approximately 20% get hepatitis B from needlestick injury.
Clinical Manifesations
Most kids exposed to HBV become infected, but develop fewer symptoms initially; most adults clear infection, but can become very sick or even die.
Almost 2/3 of cases are asymptomatic. Infection may last for months, or a lifetime, representing carrier status. However, carriers can develop chronic active or persistent hepatitis.
Signs and symptoms of acute HBV infection include:
- fever (60-80%)
- jaundice (20-30%)
- flu-like symptoms (over 70%)
- abdominal pain, dark urine, fatigue, weakness, pruritus, arthropathy, nausea, vomiting, anorexia and weight loss, diarrhea/constipation
- fulminant hepatitis
Potential outcomes of chronic HBV:
- no/minimal liver injury
- chronic active hepatitis
- cirrhosis of the liver
- liver failure
- portal hypertension
- hepatocellular carcinoma (0.2% risk/year if non-cirrhosis; 2-3% year if cirrhosis)
stages of infection
stage 1) immune tolerant phase: 2-4 weeks in adults, decades in infected children
stage 2) immune intolerant phase: 3-4 weeks in adults, 10+ years in infected children
- immune attack on infected hepatocytes; DNA levels drop and liver damage enzymes increase
- need treatment to prevent cirrhosis
stage 3) nonimmune/nonreplicative stage: genome integration, with chance of reactivation (stage 2)
stage 4) immune stage: complete viral clearance; no chance of reactivation
Diagnosis
- sAg - surface antigen
- sAb - immune
- cAb IgM - acute infection
- cAb IgG - exposure, past or present
- eAg - marker of replication
- eAb - non-replication
- HBV DNA - marker of replication
- eAg negative, HBVDNA: pre-core mutant, active replication
HB sAg |
Anti HB sAg |
Anti HB cAg |
Interpretation |
|---|---|---|---|
positive |
negative |
positive |
chronic infection (if two +ves 6 months apart) |
negative |
positive (>10 IU) |
negative |
vaccinated; protected |
negative |
positive (>10 IU) |
positive |
previous natural infection; protected |
negative |
positive (<10 IU) |
negative |
vaccinated; unprotected |
Treatment
The hepatitis B vaccine is frequently given to high risk individuals, and increasingly, to high school students in many countries.
Passive immunoglobulin therapy (HB immunoglobulin) is useful after needlestick injuries, to neonates, and after sexual activity
- peginterferon and lamivudine (3Tc - an reverse transcriptase inhibitor) used in chronic infections
- adefovir dipivoxil and entecavir have use with lamivudine-resistant HBV
treat people in stage 2: actively replicating virus, with high viral loads(positive eAg, DNA)
antivirals......
Resources and References
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