What is the management approach for a patient with chronic Hepatitis B (HBV) infection?

Management of Chronic Hepatitis B Infection

The management of chronic Hepatitis B (HBV) infection should be based on high-genetic-barrier antiviral drugs such as entecavir or tenofovir as first-line therapy, with treatment decisions guided by HBV DNA levels, ALT levels, and the severity of liver disease. 1

Diagnostic Evaluation

Initial evaluation of HBsAg-positive patients should include:

• Complete serologic testing (HBeAg, anti-HBe, anti-HBc, anti-HBs)
• Liver function tests (ALT, AST, bilirubin, albumin, PT/INR)
• HBV DNA quantification
• Assessment of liver fibrosis (biopsy or non-invasive methods like Fibroscan)
• Screening for coinfections (HIV, HCV, HDV)
• Hepatitis A immunity testing

Treatment Indications

Treatment should be initiated in patients with:

• HBV DNA >2000 IU/mL AND ALT above upper limit of normal (ULN) AND moderate-to-severe necroinflammation or at least moderate fibrosis 2
• HBV DNA >2000 IU/mL AND significant fibrosis regardless of ALT levels 2
• Compensated cirrhosis with any detectable HBV DNA, regardless of ALT levels 2
• Decompensated cirrhosis with any detectable HBV DNA (urgent treatment required) 2

Special populations requiring treatment:

• Patients with extrahepatic manifestations and active HBV replication 2
• Patients receiving immunosuppression/chemotherapy (prophylaxis) 2
• Pregnant women with high viral load (third trimester treatment to prevent vertical transmission) 1
• HBV-related liver transplant recipients (to prevent recurrence) 1

First-Line Treatment Options

Preferred agents:

1. Entecavir (0.5 mg daily; 1 mg daily for lamivudine-resistant patients) 1
2. Tenofovir disoproxil fumarate (300 mg daily) 1
3. Tenofovir alafenamide (25 mg daily) - preferred in patients with or at risk for renal/bone disease 1
4. Pegylated interferon alpha (180 μg weekly for 48 weeks) - for selected patients 2

Treatment efficacy (HBeAg-positive patients at 48 weeks):

Agent	HBV DNA <60-80 IU/mL	ALT normalization	HBeAg seroconversion	HBsAg loss
PEG-IFN-2a	14%	41%	32%	3%
Entecavir	67%	68%	21%	2%
Tenofovir	76%	68%	21%	3%

2

Monitoring During Treatment

• HBV DNA levels: Every 3-6 months
• ALT and AST: Every 3-6 months
• HBeAg/anti-HBe (in HBeAg-positive patients): Every 6-12 months
• Renal function: Every 6-12 months (especially with tenofovir)
• Non-invasive fibrosis assessment: Annually

1

Management of Special Patient Groups

Immunotolerant patients (HBeAg-positive, normal ALT, high HBV DNA)

• Under 30 years without evidence of liver disease: Monitor every 3-6 months without immediate treatment
• Over 30 years or with family history of HCC/cirrhosis: Consider liver biopsy or treatment 2

HBeAg-negative patients with normal ALT and low-moderate viral load

• HBV DNA 2000-20,000 IU/mL: Close monitoring with ALT every 3 months and HBV DNA every 6-12 months
• Consider non-invasive fibrosis assessment (Fibroscan) 2

Patients with decompensated cirrhosis

• Urgent antiviral treatment with entecavir or tenofovir
• Consider liver transplantation evaluation simultaneously 2

Patients with renal impairment

• Dose adjustment required for nucleos(t)ide analogues
• For creatinine clearance 30-49 mL/min: Tenofovir every 48 hours or switch to entecavir
• For creatinine clearance 10-29 mL/min: Tenofovir every 72-96 hours or switch to entecavir
• Monitor renal function closely 3

Management of Resistance

• For lamivudine/telbivudine resistance: Switch to tenofovir or add adefovir 1
• For adefovir resistance: Add lamivudine or switch to tenofovir + emtricitabine, or add entecavir 1
• For multidrug resistance: Combine tenofovir and entecavir 1

Duration of Treatment

• HBeAg-positive patients: Continue treatment until HBeAg seroconversion and undetectable HBV DNA, then consolidation therapy for at least 12 months
• HBeAg-negative patients: Long-term (indefinite) treatment is usually required
• Cirrhotic patients: Lifelong treatment is recommended

Important Considerations

• Never discontinue treatment abruptly as this may cause severe acute exacerbations of hepatitis 3
• Monitor for at least several months after stopping treatment 3
• Patients on tenofovir should be monitored for renal impairment and bone density loss 3
• Counsel patients on preventing transmission, including notifying household and sexual contacts for testing and vaccination 1
• Advise patients to limit or avoid alcohol consumption 1

Potential Complications and Management

• Severe acute exacerbations after treatment discontinuation: Close monitoring required; may need to restart antiviral therapy 3
• Nephrotoxicity with tenofovir: Monitor renal function; consider dose adjustment or switching to entecavir or tenofovir alafenamide 3
• Lactic acidosis: Rare but serious; suspend treatment if suspected 3
• Resistance development: Perform resistance testing and adjust therapy accordingly 1

The management of chronic HBV requires long-term commitment to therapy and regular monitoring to ensure viral suppression and prevent complications such as cirrhosis and hepatocellular carcinoma.