Hepatitis B Antiviral Therapy

Hepatitis B antiviral therapy suppresses viral replication to prevent cirrhosis, decompensation and hepatocellular carcinoma. It rarely cures infection, so treatment is usually long term.

Classification. Nucleotide and nucleoside analogues (tenofovir disoproxil, tenofovir alafenamide, entecavir) and pegylated interferon.

• Tenofovir disoproxil fumarate 300 mg once daily.
• Tenofovir alafenamide 25 mg once daily with food.
• Entecavir 0.5 mg once daily on an empty stomach; 1 mg daily in lamivudine-experienced patients and in decompensated cirrhosis.
• Pegylated interferon alfa-2a 180 microgram subcutaneously weekly for 48 weeks in selected patients.
• Lamivudine, telbivudine and adefovir are obsolete because of resistance.

Differences. Tenofovir and entecavir have a high barrier to resistance. Tenofovir alafenamide is kinder to kidney and bone than tenofovir disoproxil.

• Treat: cirrhosis with any detectable HBV DNA; HBV DNA over 2,000 IU/mL with ALT over the upper limit of normal and significant fibrosis or inflammation; HBV DNA over 20,000 IU/mL with ALT over twice the upper limit of normal; family history of hepatocellular carcinoma or cirrhosis; extrahepatic disease; acute liver failure.
• Prophylaxis during immunosuppression: start before chemotherapy, rituximab or high-dose corticosteroids in anyone with positive HBsAg, and in those with isolated anti-HBc at high risk; continue for 6 months after chemotherapy and for 12 to 18 months after rituximab.
• Prevention of mother-to-child transmission: tenofovir disoproxil from 28 to 32 weeks when HBV DNA is over 200,000 IU/mL, stopping at delivery to 3 months postpartum; give the infant hepatitis B vaccine within 24 hours of birth, plus hepatitis B immunoglobulin 100 IU intramuscularly when available.
• HIV coinfection: use a tenofovir-containing antiretroviral regimen; never lamivudine alone.
• Stopping: not in cirrhosis. In non-cirrhotic HBeAg-negative patients, consider after at least 3 years of undetectable HBV DNA, with monitoring for flares.

Selection. Prefer tenofovir alafenamide or entecavir in older adults, bone disease or kidney impairment.

Contraindications. Pegylated interferon in decompensated cirrhosis, autoimmune disease, severe psychiatric disease and pregnancy.

Adverse effects. Tenofovir disoproxil: proximal tubular injury with phosphate wasting, reduced bone density. Tenofovir alafenamide: weight gain, lipid rise. Entecavir: lactic acidosis in decompensated disease. Severe flares of hepatitis after stopping any nucleotide or nucleoside analogue.

Interactions. Tenofovir disoproxil with NSAIDs, aminoglycosides and other nephrotoxic drugs.

Special groups.

• Pregnancy: tenofovir preferred; avoid entecavir.
• Breastfeeding: tenofovir acceptable.
• Children: tenofovir disoproxil from 2 years and tenofovir alafenamide from 6 years (25 kg or more) with weight-based dosing.
• Older adults: monitor kidney function and bone density.
• Kidney impairment, tenofovir disoproxil: 300 mg every 48 hours when creatinine clearance is 30 to 49 mL/min; every 72 to 96 hours at 10 to 29 mL/min; avoid below 10 mL/min unless on haemodialysis (every 7 days). Tenofovir alafenamide needs no change down to 15 mL/min.
• Kidney impairment, entecavir: 0.25 mg daily or 0.5 mg every 48 hours at 30 to 49 mL/min; 0.15 mg daily or 0.5 mg every 72 hours at 10 to 29 mL/min; 0.05 mg daily or 0.5 mg weekly below 10 mL/min.

Monitoring. ALT and HBV DNA every 3 to 6 months in the first year, then every 6 months; HBsAg and HBeAg yearly; creatinine and phosphate every 3 to 6 months with tenofovir disoproxil. Ultrasound for hepatocellular carcinoma every 6 months in cirrhosis and in high-risk non-cirrhotic patients; start earlier in people of African ancestry and with a family history.

Referral and escalation. Decompensation, ALT over 10 times the upper limit of normal with jaundice, rising HBV DNA on therapy (check adherence), or a liver mass.