What is the recommended treatment protocol for a patient with Hepatitis B (HBV) infection?

Treatment Protocol for Hepatitis B Infection

For chronic hepatitis B, initiate first-line treatment with entecavir 0.5 mg daily or tenofovir (DF 300 mg or AF 25 mg) daily, as these agents achieve >90% virologic suppression with minimal resistance and are strongly preferred over all other options. 1, 2

First-Line Treatment Selection

Entecavir and tenofovir are the only recommended first-line agents due to their superior potency and high genetic barrier to resistance 1, 2:

• Entecavir 0.5 mg daily achieves 83% virologic suppression (HBV DNA <50 IU/mL) at 96 weeks, with no genotypic resistance detected after 8 years in treatment-naïve patients 1
• Tenofovir DF 300 mg daily demonstrates 93% virologic suppression at 48 weeks with no resistance after 8 years, maintaining efficacy even with baseline viral loads ≥9 log10 copies/mL 1
• Tenofovir AF (TAF) is equally effective as tenofovir DF but with improved renal and bone safety profile 1

Never use lamivudine, adefovir, or telbivudine as first-line therapy - lamivudine has resistance rates up to 70% after 5 years, and adefovir has inferior efficacy compared to tenofovir 1, 2

Treatment Indications by Clinical Scenario

HBeAg-Positive Chronic Hepatitis B

Initiate treatment when HBV DNA >20,000 IU/mL AND ALT >2× ULN 3, 1:

• Patients also require increased ALT levels or evidence of hepatitis on liver biopsy 3
• Consider treatment even if ALT <2× ULN when family history of HCC or cirrhosis exists 1

HBeAg-Negative Chronic Hepatitis B

Initiate treatment when HBV DNA >2,000 IU/mL AND ALT >2× ULN 3, 1:

• Lower HBV DNA threshold reflects the natural history of HBeAg-negative disease 3

Compensated Cirrhosis

Treat if HBV DNA ≥2,000 IU/mL, regardless of ALT level 3, 1:

• Entecavir and tenofovir are strongly preferred over lamivudine due to high resistance rates that could precipitate decompensation 1

Decompensated Cirrhosis

Immediately treat all patients with any detectable HBV DNA, regardless of viral load level, HBeAg status, or ALT 1, 2:

• Consider combination therapy with tenofovir plus lamivudine or entecavir monotherapy to minimize resistance risk 1
• Peginterferon is absolutely contraindicated due to risk of further decompensation 1

Acute Hepatitis B

Treatment is only indicated for fulminant hepatitis B or protracted severe acute hepatitis B (total bilirubin >3 mg/dL, INR >1.5, encephalopathy, or ascites) 3:

• Use lamivudine, telbivudine, or entecavir for rapid onset of action 3

Special Populations

Immunosuppression/Chemotherapy

All HBsAg-positive patients should receive prophylactic entecavir or tenofovir at the onset of chemotherapy or immunosuppressive therapy 3:

• HBsAg testing must be performed prior to initiation in high-risk patients 3
• Patients with HBV DNA >2,000 IU/mL pre-chemotherapy should continue antiviral therapy until reaching therapeutic endpoints for chronic hepatitis B 3
• Lamivudine or telbivudine are reasonable for short-term prophylaxis given safety and rapid action 3
• IFN-α is contraindicated due to bone marrow suppressive effects and risk of hepatitis flares 3

Transplant Recipients

All HBsAg-positive solid organ and HSCT recipients should start prophylactic antiviral treatment at time of transplantation 3:

• Entecavir or tenofovir DF is preferred for long-term treatment 3
• HBsAg-negative, anti-HBc-positive recipients need regular monitoring for HBV reactivation 3

HIV Coinfection

Initiate tenofovir-based HAART regimen combined with emtricitabine or lamivudine for simultaneous treatment of both viruses 3:

• All HIV-HBV coinfected patients should be treated regardless of CD4 count 3
• Never use entecavir monotherapy as it increases risk of HIV resistance 3
• Patients should be offered HIV testing before starting entecavir therapy 4

Pregnancy

For women with HBV DNA ≥10^7 copies/mL and elevated ALT, or who already have an HBsAg-positive child, antiviral therapy with lamivudine, telbivudine, or tenofovir during the third trimester is recommended 3:

• For most young women with mild liver disease, postponement until after pregnancy is prudent 3

Lamivudine-Experienced Patients

Avoid entecavir due to increased risk of resistance from archived mutations in HBV covalently closed circular DNA 1:

• Use tenofovir (DF or AF) instead 1
• If already on entecavir with lamivudine resistance, switch to tenofovir or add tenofovir 1

Treatment Duration

HBeAg-Positive Patients

Continue treatment for at least 1 year after HBeAg seroconversion, then an additional 3-6 months 1:

• Long-term therapy is typically required for cirrhotic patients until HBsAg loss occurs 1

HBeAg-Negative Patients

Long-term or indefinite treatment is required, as relapse rates reach 80-90% if stopped within 1-2 years 1:

• Continue until HBsAg loss is achieved and maintained for 6-12 months 5

Cirrhotic Patients

Therapy should be long-term, continuing until HBsAg loss occurs 1:

• Do not discontinue even after HBeAg seroconversion due to ongoing risk of HCC and disease progression 1

Monitoring During Treatment

Check HBV DNA and ALT levels at baseline and every 3-6 months during therapy 1, 5:

• Monitor HBeAg status regularly in HBeAg-positive patients 1
• Monitor renal function, particularly with tenofovir DF 1, 5
• Consider bone density monitoring in patients on tenofovir DF with risk factors 1
• Perform ultrasound every 6 months for HCC surveillance in all cirrhotic patients 2

Managing Inadequate Response

First verify medication adherence - this is the most common cause of breakthrough rather than true resistance 1:

• For partial virologic response on lamivudine or telbivudine, switch to tenofovir 1
• For drug resistance, switch to tenofovir or combine entecavir with tenofovir 1

Critical Pitfalls to Avoid

Never use entecavir in patients with any prior lamivudine exposure, even if brief, due to risk of archived resistance mutations 1, 2:

• This includes patients who received lamivudine as part of HIV therapy 3

Never discontinue therapy prematurely in HBeAg-negative patients or those with cirrhosis, as this can lead to severe hepatitis flares 1, 4:

• Monitor hepatic function closely for at least several months after discontinuation 4

Never use combination therapy as initial treatment in treatment-naïve patients unless decompensated cirrhosis is present 1:

• Monotherapy with entecavir or tenofovir is equally effective and reduces cost and potential toxicity 1

Never assume virologic breakthrough represents resistance without first confirming medication adherence 1

Never use peginterferon in decompensated cirrhosis due to risk of further hepatic decompensation 1

Treatment Goals

The primary goal is sustained suppression of HBV DNA to undetectable levels to prevent progression to cirrhosis, liver failure, and hepatocellular carcinoma 1, 5:

• Secondary goals include ALT normalization and histologic improvement 1, 5
• The ideal endpoint is HBsAg loss with or without anti-HBs seroconversion 1, 5

Long-Term Considerations

Continue lifelong HCC screening even after HBsAg loss if significant fibrosis or cirrhosis was present at baseline 5, 2:

• Entecavir does not cure HBV but may lower viral load, reduce ability to multiply, and improve liver condition 4
• Treatment has not been shown to reduce transmission risk through sexual contact or blood contamination 4