From the Guidelines
Medications with a high risk of hepatitis B reactivation include B-cell depleting agents, high-dose corticosteroids, anthracycline derivatives, and potent TNFα inhibitors, as stated in the most recent guidelines 1. These medications can cause reactivation in HBsAg-positive patients, with risks ranging from 10% to over 30% depending on the specific medication and patient population.
- B-cell depleting agents, such as rituximab and ofatumumab, are associated with a high risk of reactivation in both HBsAg-positive and HBsAg-negative/anti-HBc-positive patients.
- High-dose corticosteroids, such as prednisone ≥20 mg/day for ≥4 weeks, also pose a significant risk of reactivation.
- Anthracycline derivatives, such as doxorubicin and epirubicin, are associated with a high risk of reactivation, particularly in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) therapy.
- Potent TNFα inhibitors, such as infliximab and adalimumab, carry a moderate to high risk of reactivation, depending on the specific medication and patient population. Other medications, such as cytokine-based therapies, immunophilin inhibitors, tyrosine-kinase inhibitors, and proteasome inhibitors, may also pose a risk of reactivation, although the risk is generally lower than with the medications listed above. Patients requiring these therapies should undergo HBV screening before treatment initiation, and those with evidence of current or past infection should receive prophylactic antiviral therapy, typically entecavir 0.5 mg daily or tenofovir 300 mg daily, starting 1-2 weeks before immunosuppression and continuing for 6-12 months after discontinuation to prevent potentially fatal hepatitis flares 1.
From the FDA Drug Label
5.3 Hepatitis B Virus (HBV) Reactivation Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including RITUXAN 5.6 Hepatitis B Reactivation Reactivation of hepatitis B in patients who were previously infected with the hepatitis B virus (HBV) and had received concomitant TNF-blocking agents, including very rare cases (< 0.01%) with Enbrel, has been reported.
- Medications with high risk of hepatitis B reactivation:
- Key points:
- HBV reactivation can occur in patients treated with these medications, even if they are HBsAg negative but anti-HBc positive.
- Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating therapy.
- Prescribers should exercise caution in prescribing these medications in patients previously infected with HBV.
- Patients who develop HBV reactivation should be considered for discontinuation of the medication and initiation of anti-viral therapy.
From the Research
Medications with High Risk of Hepatitis B Deactivation
- Rituximab is a medication that carries a high risk of hepatitis B virus (HBV) reactivation in patients with chronic or resolved hepatitis B, as shown in studies 4, 5, 6, 7, 8.
Risk Factors for HBV Reactivation
- HBsAg positivity and isolated anti-HBc positivity are risk factors for HBV reactivation in patients receiving rituximab 5.
- A higher baseline HBV DNA level (≥20 IU/mL) is an independent predictor for HBV reactivation and HBV-associated hepatitis 4.
- The cumulative rituximab dose may also play a role in HBV reactivation, with a higher dose tend to be associated with reactivation 5.
Incidence of HBV Reactivation
- The incidence of HBV reactivation in patients receiving rituximab is estimated to be around 21-64% 4, 5, 8.
- The risk of HBV reactivation continues to increase even 2 years after rituximab therapy 4.
Clinical Implications
- Prophylactic antiviral therapy is recommended for all patients with resolved HBV infection who are undergoing rituximab therapy, regardless of the indication 6, 8.
- Enhanced monitoring alone may be reasonable for patients receiving non-rituximab biologics or direct-acting antivirals (DAAs) for hepatitis C 8.