| Patient Population | Key Issues | Recommendations |
|---|---|---|
| Decompensated liver disease* | ∙ Higher risk of cirrhosis, HCC, and mortality ∙ Often associated with comorbidities such as renal dysfunction, protein malnutrition, or vitamin deficiencies | ∙ Treatment is indicated irrespective of HBV DNA levels to improve clinical status ∙ Recommended agents: ETV and TDF (well tolerated and shown to improve liver status) ∙ Regular monitoring of renal function and lactic acidosis recommended during ETV or TDF therapy ∙ IFNs contraindicated; they may increase risk of sepsis and decompensation |
| HCV, HDV, or HIV coinfection | ∙ Multiple viruses to be managed ∙ Higher risk of cirrhosis, HCC, and mortality | ∙ Treatment should target the dominant virus ∙ In HIV coinfection, LVD and TDF are active against both HBV and HIV; ETV is not recommended unless the patient also receives HAART ∙ Peg-IFN only drug effective against HDV ∙ Some reports of renal toxicity with TDF in HBV/HIV-coinfected patients |
| LT recipients | ∙ Risk of HBV reactivation | ∙ Anti-HBV prophylaxis before and/or after LT recommended ∙ HBIg with or without LVD historically is the most common approach; however, there is no consensus on HBIg dose and duration (that is, long-term low dose vs. short-term high dose; HBIg withdrawal; on-demand HBIg on NUC maintenance) ∙ Alternative prophylactic regimens: ETV or TDF, alone or combined with HBIg |
| Immune-suppressive or chemotherapy | ∙ Risk of HBV reactivation | ∙ In HBsAg-positive patients, preemptive NUC therapy should be initiated at the onset of immunesuppressive or chemotherapy to prevent HBV reactivation ∙ In anti-HBc-positive patients receiving rituximab, anti-HBV prophylaxis is recommended |
| Pregnancy | ∙ Risk of perinatal infection from highly viremic mothers ∙ Risk of fetal damage | ∙ IFN-based therapy is contraindicated because of its antiproliferative effect ∙ LdT and TDF are classified as category B (no risk in animal studies but unknown in humans) ∙ LVD, ADV, and ETV are classified as category C (teratogenic in animals, unknown in humans) |
| Pediatric patients | ∙ Infection at an early age is associated with an increased risk of long-term complications ∙ Long-term safety and drug resistance are important concerns | ∙ Recommended to initiate treatment if ALT persistently >2× ULN ∙ IFNs given parenterally and associated with temporarily disrupted growth43 |
Data compiled from refs. 10–12.
↵* Defined as child B or C cirrhosis, or Child–Turcotte–Pugh score ≥7.
ADV, adefovir; ALT, alanine aminotransferase; ETV, entecavir; HAART, highly active antiretroviral therapy; HBc, hepatitis B core antigen; HBIg, hepatitis B immunoglobulin; HBsAg, hepatitis B s antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDV, hepatitis D virus; HIV, human immunodeficiency virus; IFN, interferon; LdT, telbivudine; LT, liver transplant; LVD, lamivudine; NUC, nucleo(s)tide analog; Peg-IFN, pegylated interferon; TDF, tenofovir; ULN, upper limit of normal.