What is the management of hepatitis B?

Management of Hepatitis B

Immediate Treatment Indications

All patients with life-threatening liver disease—acute liver failure, decompensated cirrhosis, or severe hepatitis B exacerbation—must start antiviral therapy immediately with entecavir or tenofovir, regardless of HBV DNA or ALT levels. 1, 2

• Patients requiring liver transplantation need viral suppression to reduce post-transplant HBV recurrence risk 1
• Decompensated cirrhosis patients require immediate treatment and must be evaluated for liver transplantation 1, 2
• Pegylated interferon is absolutely contraindicated in decompensated disease 1, 2

Treatment Indications by Disease Stage

Compensated Cirrhosis

• Treat all patients with compensated cirrhosis who have HBV DNA >2,000 IU/mL, regardless of ALT level 1, 2
• EASL guidelines recommend treatment with any detectable HBV DNA in cirrhotic patients 1, 2
• Long-term nucleos(t)ide analogue therapy prevents disease progression and can reverse fibrosis—74% of cirrhotic patients showed regression after 5 years of tenofovir 1

Non-Cirrhotic Chronic Hepatitis B

For HBeAg-positive patients:

• Treat when HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal 1, 3
• Treat when HBV DNA >20,000 IU/mL with moderate-to-severe inflammation or fibrosis on biopsy, even with normal ALT 1
• Patients >30 years with HBV DNA >1,000 IU/mL should be considered for treatment even with normal ALT 3

For HBeAg-negative patients:

• Treat when HBV DNA >2,000 IU/mL AND ALT >2× upper limit of normal 1, 3
• Treat when HBV DNA >2,000 IU/mL with at least moderate fibrosis on biopsy 1, 2

First-Line Treatment Selection

Entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) are the only recommended first-line agents due to high potency and high genetic barrier to resistance. 2, 3

• After 8 years of TDF treatment, no resistance has been detected 2
• Entecavir resistance remains <1% after 5 years 2
• First-generation nucleos(t)ide analogues (lamivudine, adefovir) are not recommended due to high resistance rates 2

Drug Selection for Special Circumstances

Pregnancy:

• Tenofovir DF is the preferred agent (FDA pregnancy category B) 1, 4, 2
• Prophylactic tenofovir starting at 24-32 weeks gestation is recommended for mothers with HBV DNA >200,000 IU/mL to prevent mother-to-child transmission 2, 3
• Pegylated interferon is contraindicated during pregnancy 1

Renal dysfunction or bone disease:

• Entecavir, TAF, or besifovir are preferred over TDF 3
• TAF demonstrates less renal tubular dysfunction and bone mineral density loss compared to TDF through 96 weeks 2
• Avoid TDF with concurrent nephrotoxic agents (e.g., high-dose NSAIDs) 5

HIV-HBV coinfection:

• All coinfected patients must start antiretroviral therapy regardless of CD4 count 2
• TDF- or TAF-based ART regimens are mandatory 1, 2

Healthcare workers:

• Those with HBV DNA ≥2,000 IU/mL performing exposure-prone procedures should receive entecavir or tenofovir to reduce viral load to undetectable or <2,000 IU/mL 1

Treatment Duration and Monitoring

Long-term, potentially indefinite treatment is required with nucleos(t)ide analogues until HBsAg loss occurs, which is rarely achieved. 2, 3

Monitoring Schedule

• HBV DNA levels every 3-6 months during treatment 2, 3
• Liver function tests every 3-6 months 2, 3
• For compensated patients not on treatment: ALT every 3 months, HBV DNA every 6-12 months, fibrosis assessment every 12 months 2
• For decompensated patients: monitoring every 1-3 months 2

Treatment Goals

• Short-term: Undetectable HBV DNA by sensitive PCR assay, ALT normalization, HBeAg seroconversion (in HBeAg-positive patients) 2, 3
• Long-term: Prevention of cirrhosis, hepatic decompensation, and hepatocellular carcinoma 3
• Optimal endpoint: HBsAg loss (functional cure) 2, 3

Stopping Criteria (Selected Patients Only)

• HBeAg-positive patients who achieve HBeAg seroconversion with undetectable HBV DNA and complete at least 12 months of consolidation therapy may consider stopping 2
• Sustained off-therapy virological response is defined as HBV DNA <2,000 IU/mL for at least 12 months after therapy ends 2

Critical Warnings and Pitfalls

Severe acute exacerbations of hepatitis B can occur after discontinuing treatment—never stop nucleos(t)ide analogues without close hepatic function monitoring for at least several months. 5, 6

• Patients must be counseled to never let their medication run out 5
• If treatment is stopped, monitor liver function and HBV DNA frequently 5

Common pitfalls to avoid:

• Do not rely on traditional ALT cutoffs to exclude liver disease—normal ALT does not exclude significant necroinflammation or fibrosis 2
• Distinguish between true acute hepatitis B and reactivation of chronic hepatitis B, as both require treatment but have different implications 1, 4
• Non-adherence is a more common cause of virological breakthrough than true resistance 4
• Do not use entecavir in HIV-HBV coinfected patients unless they are receiving highly active antiretroviral therapy, as entecavir monotherapy can lead to HIV resistance 6

Hepatocellular Carcinoma Surveillance

HCC surveillance is mandatory for all cirrhotic patients and those with moderate-to-high HCC risk scores, even under effective nucleos(t)ide analogue therapy. 2

• HBV replication is an independent predictor of cirrhosis, HCC, and liver-related deaths 1
• Other risk factors include male sex, older age, HBV genotype, coinfection with HIV/HCV/HDV, elevated ALT, alcohol, and tobacco use 1

Acute Hepatitis B Management

More than 95% of adults with acute HBV infection recover spontaneously without antiviral therapy. 1, 4

• Antiviral therapy with entecavir or tenofovir is indicated only for patients with severe acute hepatitis B (total bilirubin >3 mg/dL, INR >1.5, encephalopathy, or ascites) 4
• For fulminant hepatitis B, evaluate for liver transplantation and start nucleos(t)ide analogues 1, 4
• If treatment is given, continue for at least 3 months after anti-HBs seroconversion or at least 12 months after anti-HBe seroconversion without HBsAg loss 1, 4