What are the treatment criteria for a patient with chronic hepatitis B?

Hepatitis B Treatment Criteria

Treat chronic hepatitis B when HBV DNA ≥2,000 IU/mL with elevated ALT and/or at least moderate liver inflammation/fibrosis; all cirrhotic patients with any detectable HBV DNA require treatment regardless of ALT levels. 1

Core Treatment Indications

HBeAg-Positive Chronic Hepatitis B

• Initiate treatment when HBV DNA ≥20,000 IU/mL AND ALT >2× upper limit of normal (ULN), even without liver biopsy. 1, 2
• For patients with HBV DNA ≥20,000 IU/mL and ALT between 1-2× ULN, obtain liver biopsy or non-invasive fibrosis assessment; treat if at least moderate necroinflammation or fibrosis is present. 1
• Treatment can be delayed 3-6 months in compensated disease to allow for potential spontaneous HBeAg seroconversion, but not in patients with signs of liver failure. 1
• Consider treatment in patients >30 years old with persistently normal ALT if family history of hepatocellular carcinoma or cirrhosis exists. 1

HBeAg-Negative Chronic Hepatitis B

• Treat when HBV DNA ≥2,000 IU/mL AND ALT >2× ULN, with or without biopsy confirmation. 1, 2
• For HBV DNA ≥2,000 IU/mL with ALT 1-2× ULN, liver biopsy or non-invasive markers should demonstrate at least moderate fibrosis before initiating therapy. 1
• These patients typically require indefinite treatment, as HBsAg loss occurs in only 1-12% even after years of therapy. 2

Cirrhosis (Compensated)

• All cirrhotic patients with HBV DNA ≥2,000 IU/mL must be treated immediately, regardless of ALT level. 1, 2
• ALT should not be used as a treatment criterion in cirrhosis, as these patients already have significant fibrosis and frequently have near-normal ALT despite active disease. 3
• Even lower levels of detectable HBV DNA warrant treatment in this population to prevent hepatic decompensation. 1

Cirrhosis (Decompensated)

• Treat immediately with entecavir or tenofovir regardless of HBV DNA level; pegylated interferon is absolutely contraindicated due to risk of precipitating liver failure. 3, 2, 4
• Coordinate treatment with transplant centers and refer for liver transplantation evaluation. 3

Special Clinical Scenarios Requiring Treatment

Normal ALT with Elevated HBV DNA

• Patients with HBV DNA ≥2,000 IU/mL and persistently normal ALT should undergo liver biopsy or non-invasive fibrosis assessment. 1
• Approximately 20-25% of these patients have significant fibrosis and warrant treatment. 1
• Consider treatment without biopsy in patients >40 years old, particularly Asians (men >40, women >50) or Africans >20 years old due to higher HCC risk. 1

Pregnancy

• Treat pregnant women with high viremia (typically HBV DNA >200,000 IU/mL) to prevent mother-to-child transmission, using tenofovir as the preferred agent. 3, 2
• Tenofovir disoproxil fumarate or tenofovir alafenamide have pregnancy category B status with known safety experience. 1

Immunosuppression or Chemotherapy

• Initiate prophylactic antiviral therapy before starting immunosuppression or chemotherapy in all HBsAg-positive patients, regardless of HBV DNA or ALT levels, to prevent potentially fatal HBV reactivation. 3, 2
• Lamivudine reduces frequency and severity of hepatitis flares in this population, though entecavir or tenofovir are preferred for longer-term use. 3

First-Line Treatment Selection

Monotherapy with entecavir 0.5 mg daily, tenofovir disoproxil fumarate 300 mg daily, or tenofovir alafenamide 25 mg daily is the preferred approach due to high genetic barriers to resistance and potent antiviral efficacy achieving >90% viral suppression. 3, 2

Nucleos(t)ide Analogue Selection

• Entecavir demonstrates 1.2% resistance after 5 years in treatment-naïve patients. 1
• Tenofovir (TDF or TAF) shows no resistance after 1.5 years and maintains high efficacy long-term. 1
• Tenofovir alafenamide has superior renal and bone safety compared to tenofovir disoproxil fumarate with equivalent antiviral efficacy. 3, 2
• Never use entecavir in patients with any prior lamivudine exposure, even if brief, due to archived resistance mutations. 2

Pegylated Interferon Alternative

• Pegylated interferon alfa-2a can be considered in mild to moderate chronic hepatitis B without cirrhosis, offering finite 48-week treatment duration without drug resistance. 1, 3
• Response rates are lower than nucleos(t)ide analogues, but sustained responders may achieve HBsAg loss in 30-50% over time. 5
• Contraindicated in decompensated cirrhosis, pregnancy, autoimmune disease, and severe psychiatric conditions. 4

Treatment Duration

• HBeAg-positive patients require treatment for at least 1 year after HBeAg seroconversion, then an additional 3-6 months of consolidation therapy. 2
• HBeAg-negative patients and those with cirrhosis require indefinite therapy, as relapse rates reach 80-90% if stopped within 1-2 years. 1, 2
• The optimal duration remains unknown; most patients require long-term or lifelong therapy to maintain viral suppression. 3, 6

Critical Monitoring Parameters

• Measure HBV DNA and ALT every 3-6 months during therapy to assess virological and biochemical response. 3
• Assess renal function (creatinine, estimated GFR, serum phosphorus) periodically with tenofovir-based therapy, particularly in patients with pre-existing renal disease or concurrent nephrotoxic agents. 3, 6
• Monitor for HCC development with ultrasound and AFP every 6 months in all cirrhotic patients and high-risk non-cirrhotic patients (Asian men >40, Asian women >50, Africans >20, family history of HCC). 1

Common Pitfalls to Avoid

• Do not discontinue therapy prematurely in HBeAg-negative patients or those with cirrhosis, as severe hepatitis flares with potential liver failure can occur. 2, 6
• Avoid using lamivudine as first-line therapy except for short-term prophylaxis during chemotherapy or pregnancy, as resistance develops in up to 70% within 5 years. 1
• Do not use ALT as the sole criterion for treatment decisions in cirrhotic patients, as they often have normal or minimally elevated ALT despite active viral replication. 3
• Never combine tenofovir disoproxil fumarate with adefovir or use multiple tenofovir-containing products simultaneously. 6