What is the treatment approach for Hepatitis B?

Treatment Approach for Hepatitis B

The long-term administration of a potent nucleos(t)ide analogue with high barrier to resistance, specifically entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide, represents the treatment of choice for chronic hepatitis B. 1

Patient Selection for Treatment

Treatment decisions should be based on:

1. HBV DNA levels:

   • HBV DNA ≥ 2,000 IU/ml typically requires treatment
   • All cirrhotic patients with detectable HBV DNA should be treated regardless of level

2. ALT levels:

   • Elevated ALT (particularly >2× upper limit of normal)
   • Some patients with normal ALT may still require treatment based on other factors

3. Liver disease severity:

   • At least moderate histological lesions
   • All patients with cirrhosis and detectable HBV DNA

Treatment Algorithm

Clinical Scenario	Treatment Recommendation
Compensated cirrhosis with detectable HBV DNA	Treat regardless of ALT level [1]
Decompensated cirrhosis with detectable HBV DNA	Immediate treatment required [2]
HBV DNA >20,000 IU/mL and ALT >2× ULN	Treat regardless of histology [1,3]
HBV DNA >2,000 IU/mL with moderate/severe histological lesions	Treat regardless of ALT [1]
Immune tolerant phase (high HBV DNA, normal ALT)	Generally monitor rather than treat [1]
Inactive carrier phase (low HBV DNA, normal ALT)	Generally monitor rather than treat [1]

First-Line Treatment Options

1. Nucleos(t)ide Analogues (NAs)

• Entecavir (0.5 mg daily for treatment-naïve; 1 mg daily for lamivudine-resistant or decompensated cirrhosis) 1, 4
• Tenofovir disoproxil fumarate (300 mg daily) 1, 5
• Tenofovir alafenamide (25 mg daily) 2

These medications have high genetic barriers to resistance and excellent safety profiles. They require long-term or indefinite administration for most patients.

2. Pegylated Interferon-alfa

• Can be considered in mild to moderate chronic hepatitis B patients 1
• Administered for a finite duration (typically 48 weeks)
• Contraindicated in decompensated cirrhosis 2
• Offers potential for immune-mediated control and sustained off-treatment response

Monitoring During Treatment

• HBV DNA levels: Every 3-6 months
• ALT/AST: Every 3-6 months
• HBeAg/anti-HBe status: Every 6-12 months
• Renal function: Every 6-12 months (particularly with tenofovir disoproxil fumarate)
• Assessment for hepatocellular carcinoma: Regular surveillance required

Special Populations

Decompensated Cirrhosis

• Prompt antiviral therapy with entecavir (1 mg daily) or tenofovir (300 mg daily) is required 2
• Peginterferon-α is absolutely contraindicated 2
• Consider liver transplantation concurrently with antiviral therapy 2

Pregnant Patients

• Consider tenofovir in the third trimester for pregnant women with high viral load to prevent vertical transmission 2

HIV Co-infection

• Include tenofovir in the antiretroviral regimen 2
• Avoid lamivudine monotherapy due to high resistance rates 2

Patients Requiring Immunosuppression

• Prophylactic antiviral therapy is indicated to prevent HBV reactivation 1, 2
• Use high-genetic-barrier drugs (entecavir or tenofovir) 2

Treatment Goals and Outcomes

The main goal of therapy is to improve survival and quality of life by preventing disease progression and hepatocellular carcinoma development 1. This is achieved through:

1. Long-term suppression of HBV replication (HBV DNA undetectable by PCR)
2. ALT normalization
3. Improvement in liver histology
4. Prevention of cirrhosis and hepatocellular carcinoma

HBsAg loss represents an optimal endpoint but is rarely achieved with current therapies 1.

Common Pitfalls to Avoid

1. Using first-generation antivirals: Lamivudine, adefovir, and telbivudine should be avoided due to their low potency and high frequency of drug resistance 2

2. Stopping treatment prematurely: Most patients require long-term or indefinite treatment, especially those with cirrhosis 2

3. Inadequate monitoring: Regular assessment of viral load, liver function, and complications is essential 1

4. Overlooking renal function: Dose adjustment is required for all nucleos(t)ide analogues in patients with creatinine clearance <50 ml/min 2

5. Failing to screen for hepatocellular carcinoma: HCC remains a major concern even for treated chronic hepatitis B patients 1