Hepatitis B Antivirals

Hepatitis B antivirals suppress viral replication by inhibiting the HBV polymerase. They do not eradicate covalently closed circular DNA, so HBsAg loss is rare and treatment is usually long-term. Tenofovir (disoproxil and alafenamide) and entecavir are first choice because of high potency and a high barrier to resistance. Pegylated interferon is an immune-modulating alternative.

Pharmacokinetics. Tenofovir and entecavir are renally cleared. Entecavir is taken on an empty stomach (2 hours after and 2 hours before a meal). Lamivudine is well absorbed but has a low barrier to resistance.

• Tenofovir disoproxil fumarate 300 mg daily; tenofovir alafenamide 25 mg daily, with lower renal and bone toxicity.
• Entecavir 0.5 mg daily for nucleoside-naive patients; 1 mg daily if lamivudine-resistant.
• Lamivudine 100 mg daily (HBV dose): low barrier, resistance in the majority within 5 years; used only in combination or short-term.
• Adefovir and telbivudine are obsolete.
• Pegylated interferon alfa-2a 180 micrograms weekly for 48 weeks in selected HBeAg-positive patients with low viral load: finite course, many adverse effects, contraindicated in decompensated cirrhosis.

When to treat. Chronic hepatitis B with:

• Cirrhosis and any detectable HBV DNA.
• HBV DNA over 2000 IU/mL with ALT over the upper limit of normal, or at least moderate fibrosis.
• HBV DNA over 20,000 IU/mL with ALT more than 2 times the upper limit of normal.
• HIV coinfection: treat everyone with a tenofovir-containing regimen.

Prophylaxis before immunosuppression. HBsAg-positive patients, and anti-HBc-positive patients receiving rituximab or intense chemotherapy, start tenofovir or entecavir before treatment and continue for at least 12 months after (18 months after rituximab).

Mother-to-child prevention. Tenofovir from 28 to 32 weeks if HBV DNA is over 200,000 IU/mL (or HBeAg positive), continued to at least delivery and often 4 to 12 weeks afterwards, with infant vaccine within 24 hours of birth and immunoglobulin where available.

Stopping. Finite treatment is considered only in non-cirrhotic HBeAg-positive patients after seroconversion with 12 months of consolidation, or after HBsAg loss. Never stop in cirrhosis. After stopping, check ALT and HBV DNA every 3 months for 12 months because of flares.

Renal adjustment.

• Tenofovir disoproxil: creatinine clearance 30 to 49 mL/min every 48 hours; 10 to 29 mL/min every 72 to 96 hours; haemodialysis once weekly after dialysis.
• Tenofovir alafenamide: no change down to 15 mL/min; use in dialysis.
• Entecavir: 30 to 49 mL/min 0.25 mg daily (or 0.5 mg every 48 hours); 10 to 29 mL/min 0.15 mg daily (or 0.5 mg every 72 hours); under 10 mL/min or dialysis 0.05 mg daily (or 0.5 mg every 7 days).

Region. In East Africa, hepatitis B is highly endemic and often coexists with HIV. Birth-dose vaccination is the main preventive tool. Tenofovir availability is wide, entecavir is limited. Liver cancer surveillance is advised for cirrhosis and for high-risk non-cirrhotic patients, often starting earlier in people of African ancestry.

Contraindications. Hypersensitivity. Interferon in decompensated cirrhosis, autoimmune disease, severe depression, pregnancy.

Serious adverse effects. Hepatitis flare on withdrawal; tenofovir disoproxil nephrotoxicity and bone loss; entecavir and lamivudine lactic acidosis (rare, mostly in decompensated cirrhosis); interferon cytopenias, thyroid disease, depression.

Monitoring. Baseline HBsAg, HBeAg, HBV DNA, ALT, creatinine, phosphate, HIV and hepatitis C and D status, liver stiffness. During treatment: ALT and HBV DNA every 3 to 6 months, creatinine every 3 to 6 months with tenofovir disoproxil, HBsAg yearly, ultrasound every 6 months where surveillance applies.

Special groups.

• Pregnancy: tenofovir is preferred; entecavir is avoided. Breastfeeding: tenofovir compatible.
• Children: tenofovir from 2 years (weight-based or alafenamide from 6 years); entecavir from 2 years by weight.
• Decompensated cirrhosis: entecavir or tenofovir with transplant centre review.
• Hepatitis D coinfection: needs specialist therapy.

Referral and escalation. Refer cirrhosis, hepatocellular carcinoma, flare with jaundice, failure to suppress DNA by month 12, resistance and decompensation.