Hepatitis B Virus

Snapshot

A 35-year-old presents to the emergency department due to abdominal pain and malaise. He also reports “yellow-ing” of his skin. Medical history is noncontributory. Social history is notable for intravenous drug use and having multiple sexual partners. Physical examination is remarkable for right upper quadrant tenderness, generalized jaundice, and scleral icterus. Laboratory studies demonstrate the presence of HBsAg and significantly elevated IgM anti-HBc, and HBeAg.

Introduction

Classification
- a Hepadnavirus in the Hepadnaviridae family
  - circular, partially double-stranded DNA virus
Epidemiology
- risk factors
  - not receiving hepatitis B virus (HBV) vaccine
  - sexual contact with a person with HBV
  - illicit drug use
  - having HIV and hepatitis C virus
Transmission
- perinatal transmission
- blood transfusion
- transplant
- sexual contact
- blood exposure
Pathogenesis
- once the HBV is in the bloodstream, it makes its way to the liver, where it replicates within hepatocytes, causing immune-mediated hepatitis via CD8+ T-cells and natural killer cells
- when HBV is inside the hepatocyte, the viral genome enters the hepatocyte nucleus
  - the positive strand of the HBV DNA is synthesized and is converted to covalently closed, circular DNA (cccDNA)
    - the HBV genome undergoes reverse transcription, creating a pre-genomic RNA, which becomes encapsidated
      - a new negative and subsequent positive strand of the HBV DNA is eventually synthesized
        the partially double-stranded HBV DNA nucleocapsid can enter more hepatocytes to produce more cccDNA
Prognosis
- most immunocompetent adult patients spontaneously recover
  - 90% of infected adults recover, 10% progress to chronic infection
- most neonates progress to chronic infection
worse prognosis with coinfection with hepatitis D or hepatitis C infection

Presentation

Studies

Liver function tests
- Alanine/aspartate aminotransferases (ALT/AST)
  - Elevation in the acute phase of up to 1,000 to 2,000 U/L
  - Milder elevations or can be normal in the chronic phase
Serologic studies
- HBsAg
  - indicates that there is an HBV infection
- anti-HBs
  - indicates immunity to HBV infection via
    - prior infection
    - vaccination
- HBcAg
  - an antigen associated with the core of the HBV
- anti-HBc
  - IgM antibodies against HBc suggests an acute or recent infection
  - IgG antibodies against HBc suggest a previous exposure or chronic infection
  - during the window period, may be the only positive serologic test suggesting infection
- HBeAg
  - infected hepatocytes secrete this antigen, suggesting active replication, thus having high transmissibility
- anti-HBe
suggest low transmissibility

Differential

Hepatitis A infection
- differentiating factor
  - presence of anti-hepatitis A antibodies in serological testing
Hepatitis C infection
- differentiating factor
presence of anti-hepatitis C antibodies in serological testing

Treatment

Medical
- vaccination
  - indication
    - as a preventative measure against HBV infection
      - all neonates
      - all unvaccinated infants, children, and adolescents
      - all unvaccinated adults with an increased risk of contracting the infection
        healthcare personnel
        a sexually-active person with multiple sexual partners
        end-stage renal disease
        HIV infection
        chronic liver disease
- tenofovir or entecavir
  - indication
    - monotherapy for acute HBV infection in patients with fulminant infection or severe acute hepatitis (e.g., increased INR)
    - monotherapy for chronic HBV infection with immune-active chronic hepatitis
      - HBeAg-positive
      - HBeAg-negative with elevated viral DNA levels and a transaminitis
    - patients with hepatocellular carcinoma
  - comments
acute HBV infection is usually symptomatically treated as most cases self-resolve

Complications