Situation: A 45-year-old man with bulky diffuse large B-cell lymphoma is admitted for his first cycle of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Before his first rituximab dose, he was tested for hepatitis B surface antigen and core antibody. What is the reason for this testing?

Rituximab depletes B cells and can reactivate hepatitis B in people with current or past infection, sometimes causing fulminant hepatitis. Screening before the first dose identifies those who need antiviral prophylaxis and monitoring; this is especially important in the Philippines, where hepatitis B is common.

Why hepatitis B testing is required before rituximab

The reason for checking hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before the first dose of rituximab is that rituximab can reactivate a past or current hepatitis B infection, which may progress to severe or fulminant hepatitis. Rituximab is a monoclonal antibody directed against CD20, a protein found on the surface of B lymphocytes. By depleting B cells, rituximab weakens the immune control that normally keeps hepatitis B virus in a dormant state. This loss of immune surveillance allows the virus to resume replication, producing a clinical flare that can be life-threatening.

Key point! The risk of reactivation is not limited to patients who are HBsAg-positive. Patients with resolved hepatitis B — meaning HBsAg-negative but anti-HBc-positive — also carry latent virus in hepatocytes and can reactivate once B-cell immunity is suppressed by rituximab ^[2][4].

Serologic pattern	Interpretation	Reactivation risk with rituximab	Clinical implication
HBsAg (+), anti-HBc (+)	Chronic or active HBV infection	High	Start antiviral prophylaxis before or with rituximab; monitor HBV DNA and liver enzymes
HBsAg (−), anti-HBc (+)	Resolved/past HBV infection	Moderate to high	Consider antiviral prophylaxis; monitor HBV DNA and liver enzymes during and after therapy
HBsAg (−), anti-HBc (−)	No evidence of HBV exposure	Low	No HBV-specific prophylaxis needed; routine monitoring only

The screening strategy therefore identifies two groups that require different levels of protection. Patients with current or past HBV infection need antiviral prophylaxis and close monitoring, because reactivation can occur even months after the last rituximab dose. In the population-based cohort study by Baker et al., HBV screening and antiviral prophylaxis were associated with a reduction in adverse reactivation outcomes among rituximab-treated patients, reinforcing the preventive value of testing before the first infusion . Similarly, Chen et al. found that among DLBCL patients with resolved hepatitis B receiving rituximab-containing chemotherapy, HBV reactivation and hepatitis occurred in a meaningful proportion of cases, and reactivation was linked to poorer survival outcomes ^[2].

Watch out! Do not confuse this screening with vaccination. Hepatitis B vaccine is not given immediately before rituximab to prevent reactivation; the purpose of pre-treatment testing is to detect existing infection and decide whether antiviral prophylaxis is needed. Rituximab itself is not manufactured from plasma that transmits hepatitis B, and hepatitis B infection does not make lymphoma resistant to rituximab.

The clinical sequence is straightforward: test first, then treat. If HBsAg or anti-HBc is positive, antiviral therapy such as entecavir or tenofovir is typically started before rituximab and continued for at least 6–12 months after the last dose, with serial monitoring of HBV DNA and liver function tests. This approach is especially relevant in regions with higher hepatitis B prevalence, where a larger proportion of patients may have unrecognized past infection ^[4]. Quality improvement data also show that systematic screening before rituximab initiation increases detection of at-risk patients and supports timely prophylaxis, reducing preventable reactivation events .