Hepatits B, Chronic

4 stages

Variable duration and severity at each stage, progression can be reversible

1. Immune Tolerance
2. Immune Active/Clearance
3. Inactive Carrier State
4. Reactivation (HBeAg-negative CHB)

• HBeAg positivity with DNA levels at or above 20,000 IU/mL and no significant immune response to the virus (thus - persistently normal ALT)
• Biopsies of immune tolerant patients are typically benign without inflammation or fibrosis (minimal)
• Perinatally infected patients typically remain in the immune tolerant phase until adolescence (genotype C patients will remain in this stage the longest)
• Highly contagious due to high levels of viremia

• Immune activity can have fluctuating ALT levels, HBV DNA levels, and histologic activity on Bx suggesting inflammation and injury
• If activity is successful, clearance occurs (decrease in HBeAg, increase in Anti HBe) - transition to inactive carrier state
• If Clearance does not occur, damage may occur - leading to fibrosis, cirrhosis, and higher risk of hepatocellular carcinoma, HCC

• Clearance of HBeAg and increase in Anti-HBe aka HBeAb (HBeAg seroconversion)

• Emergence of precore/basal core promoter mutations allowing viral replication and reactivation

Work up:

• HBeAg, ALT and HBV DNA q3mo
• Surveillance for HCC via Ultrasound and Alpha-fetoprotein q6mo (q3mo if cirrhosis present)
• HBeAg status:
  
• If HBeAg negative w/ normal ALT and low (<2000) HBV DNA, then get labs q3-6mo
  
• If HBeAg negative w/ ALT >2x ULN >3mo and HBV DNA >2000, Antiviral Tx w/o Liver Bx
• If HBeAg negative w/ ALT 1-2x ULN >3-6mo and HBV DNA>2000, r/o other diseases and Bx liver prior to antiviral Tx
• If HBeAg negative w/ ALT elevated >3mo and HBV DNA <2000, and Liver Bx shows mod/devere inflammation and significant fibrosis, then Tx with Antivirals
  
• If HBeAg positive w/ high (>20,000) HBV DNA and ALT >2x ULN >12mo and HBeAg seroconversion does not occur, Tx with antiviral recommended without liver Bx
• If HBeAg positive w/ high (>20,000) HBV DNA and ALT elevated 1-2x ULN for 12mo, Bx Liver to determine indication for antiviral Tx
• If HBeAg positive w/ low or  intermediate (<20k) HBV DNA and ALT levels are persistently elevated for any length of time, r/o other diseases and Bx liver prior to antiviral Tx
• The 2015 APASL guidelines recommend that children with either decompensated cirrhosis or compensated cirrhosis should be treated. Analysis of the liver histology is not needed to initiate antiviral treatment in children with decompensated cirrhosis.