What is the treatment protocol for Hepatitis B (Hep B)?

From the Guidelines

The standard treatment protocol for chronic hepatitis B involves antiviral medications, with first-line options including entecavir (0.5-1mg daily) or tenofovir disoproxil fumarate (300mg daily) or tenofovir alafenamide (25mg daily), as recommended by the most recent guidelines 1.

Treatment Indications

The primary goal of treatment is to suppress HBV replication, prevent progression of liver disease, and improve quality of life. Treatment is generally indicated for patients with:

• Elevated ALT levels
• High HBV DNA levels (>2,000 IU/mL)
• Evidence of liver fibrosis
• Compensated or decompensated cirrhosis with detectable HBV DNA

Treatment Options

The preferred first-line treatments for CHB are:

• Entecavir
• Tenofovir disoproxil fumarate
• Tenofovir alafenamide
• Peginterferon alfa-2a (for patients with mild to moderate chronic hepatitis B)

Monitoring and Follow-up

Regular monitoring is essential during treatment, including:

• Liver function tests every 3-6 months
• HBV DNA levels to assess viral suppression
• Periodic screening for hepatocellular carcinoma with ultrasound every 6 months, especially for patients with cirrhosis or family history of liver cancer

Rationale

These antivirals work by inhibiting HBV polymerase, preventing viral replication, and reducing liver inflammation and damage. While they effectively control the virus, they rarely achieve complete cure (HBsAg clearance), which is why long-term therapy is typically necessary 1.

From the FDA Drug Label

The mean age of subjects was 39 years, 76% were male, 37% were Asian, 62% were Caucasian and 52% had previously received interferon-α. The mean duration of prior lamivudine therapy was 2. 7 years, and 85% had lamivudine resistance substitutions at baseline by an investigational line probe assay. At baseline, subjects had a mean Knodell Necroinflammatory Score of 6.5, mean serum HBV DNA as measured by Roche COBAS Amplicor PCR assay was 9. 36 log 10 copies/mL, and mean serum ALT level was 128 U/L. Entecavir was superior to lamivudine on a primary endpoint of Histologic Improvement (using the Knodell Score at Week 48). Table 10: Histologic Improvement and Change in Ishak Fibrosis Score at Week 48, Lamivudine-Refractory Subjects in Study AI463026 Entecavir 1 mg n=124 a Lamivudine 100 mg n=116 a Histologic Improvement (Knodell Scores) Improvement b 55% 28% No improvement 34% 57% Ishak Fibrosis Score Improvement c 34% 16% No change 44% 42% Worsening c 11% 26%

The treatment protocol for Hepatitis B (Hep B) using entecavir is as follows:

• Dosing: 1 mg once daily for lamivudine-refractory subjects, and 1 mg once daily for subjects with decompensated liver disease.
• Key endpoints:
  • Histologic Improvement
  • HBV DNA proportion undetectable (<300 copies/mL)
  • ALT normalization (≤1 x ULN)
  • HBeAg seroconversion
• Study results: Entecavir was superior to lamivudine in achieving Histologic Improvement and had a higher proportion of subjects with undetectable HBV DNA and ALT normalization. 2

From the Research

Treatment Protocol for Hepatitis B

The treatment protocol for Hepatitis B (Hep B) typically involves the use of nucleos(t)ide analogs (NAs) [ 3, 4, 5, 6, 7 ].

First-Line Treatment Options

• Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line treatment options due to their excellent tolerability, antiviral potency, and high genetic barrier to resistance [ 3, 4, 5, 6 ].
• Tenofovir alafenamide (TAF) is also considered a first-line treatment option, particularly in patients with a risk of osteoporosis or renal abnormalities [ 7 ].

Treatment Duration

• Treatment with NAs is often required over a prolonged period to achieve durable virologic suppression [ 3, 6 ].
• The decision to stop NA therapy is based on various factors, including the patient's disease status, treatment response, and risk of relapse [ 5, 6 ].

Safety and Efficacy

• Long-term use of NAs has been associated with low rates of serious adverse events, including lactic acidosis, renal function impairment, osteopenia, and osteoporosis [ 3 ].
• TAF has been shown to be at least as effective as TDF, with higher rates of ALT normalization and significantly fewer kidney disturbances and changes in bone mineral density [ 7 ].

Patient Selection

• The choice of treatment should be individualized based on the patient's characteristics, disease status, and treatment history [ 4, 6, 7 ].
• Patients with advanced liver disease, decompensated cirrhosis, or a history of lamivudine resistance may require special consideration when selecting a treatment regimen [ 4, 6, 7 ].