When is treatment indicated for hepatitis B?

Treatment Indications for Hepatitis B

Treatment for chronic hepatitis B should be initiated in patients with HBV DNA ≥ 2,000 IU/mL and ALT > 2× ULN, or those with moderate to severe inflammation or significant fibrosis on liver biopsy, regardless of ALT levels. 1

Treatment Decision Algorithm

HBeAg-positive patients:

1. Definite treatment indications:

   • HBV DNA ≥ 20,000 IU/mL AND ALT ≥ 2× ULN 1
   • HBV DNA ≥ 20,000 IU/mL AND moderate/severe inflammation or significant fibrosis on biopsy 1
   • Any detectable HBV DNA in patients with compensated or decompensated cirrhosis 1

2. Consider treatment:

   • HBV DNA ≥ 20,000 IU/mL AND ALT 1-2× ULN: Liver biopsy recommended; treat if moderate/severe inflammation or significant fibrosis 1
   • Age > 30 years with high HBV DNA, even with normal ALT (no longer considered immune tolerant) 1

3. Not indicated for treatment:

   • Immune tolerant phase (HBeAg-positive with persistently normal ALT) under age 30 1

HBeAg-negative patients:

1. Definite treatment indications:

   • HBV DNA ≥ 2,000 IU/mL AND ALT ≥ 2× ULN 1
   • HBV DNA ≥ 2,000 IU/mL AND moderate/severe inflammation or significant fibrosis on biopsy 1
   • Any detectable HBV DNA in patients with compensated or decompensated cirrhosis 1

2. Consider treatment:

   • HBV DNA ≥ 2,000 IU/mL AND ALT < 2× ULN: Liver biopsy recommended; treat if moderate/severe inflammation or significant fibrosis 1

Special populations requiring treatment regardless of standard criteria:

• Cirrhotic patients:

  • Compensated cirrhosis: Treat if HBV DNA ≥ 2,000 IU/mL regardless of ALT 1
  • Decompensated cirrhosis: Treat if any detectable HBV DNA 1

• Other indications:

  • Family history of HCC or cirrhosis 1
  • Extrahepatic manifestations of HBV 1

Treatment Options

Once the decision to treat is made, preferred first-line therapies include:

• Entecavir
• Tenofovir
• Pegylated interferon-α

These agents are preferred due to their potent viral suppression and high genetic barrier to resistance 1.

Monitoring During Treatment

• Regular monitoring of HBV DNA levels (every 3-6 months)
• ALT monitoring every 3-6 months
• For HBeAg-positive patients: HBeAg/anti-HBe testing every 6 months
• Assessment for treatment response and potential resistance

Common Pitfalls to Avoid

1. Delaying treatment in patients with active disease: Patients with high viral loads and elevated ALT should be treated promptly to prevent disease progression.

2. Treating immune tolerant patients unnecessarily: Young patients (<30 years) in the immune tolerant phase generally don't benefit from treatment unless they have other risk factors.

3. Overlooking cirrhotic patients with low viral loads: Patients with cirrhosis should be treated even with low-level viremia.

4. Discontinuing treatment prematurely: Abrupt discontinuation can lead to severe hepatitis flares. Treatment duration decisions should be based on HBeAg status, HBsAg loss, and degree of liver disease.

5. Ignoring drug resistance: Using agents with low genetic barriers to resistance (like lamivudine) as first-line therapy increases the risk of treatment failure.

The goal of treatment is to prevent progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma by achieving sustained viral suppression, which improves long-term outcomes and quality of life 2.