Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy

Abstract

Hepatitis B virus (HBV) reactivation is a well-known complication after rituximab therapy in patients with B cell lymphoma. Traditionally, hepatitis B surface antibody (anti-HBs) is a protective antibody, but the effect of rituximab on these antibodies has not been well studied. In 29 B cell lymphoma patients who were positive for anti-HBs before rituximab therapy, anti-HBs serologies before and after rituximab therapy were compared. Anti-HBs titers after rituximab treatment were significantly lower (P < 0.001) than those before treatment. None of the ten cases with pre-treatment anti-HBs titers above 100 mIU/mL became negative for anti-HBs after rituximab therapy. In contrast, 8 of the 19 patients with pre-treatment anti-HBs titers below 100 mIU/mL lost their anti-HBs (P = 0.027). Of these, one patient developed HBsAg seroreversion and HBV reactivation after rituximab therapy. Regarding patients with loss of anti-HBs or not, there was no significant difference in pre- and post-treatment immunoglobulin G levels between both groups. The rate of anti-HBs loss increased with advanced lymphoma stage and international prognostic index (P = 0.002 and <0.001, respectively). Multiple logistic regression analysis showed that pre-treatment anti-HBs titer is the only independent factor influencing the loss of anti-HBs (per one log mIU/mL, odds ratio, 0.003; 95% confidence interval, 0.000-0.302; P = 0.014). In conclusion, we found that anti-HBs titers decreased significantly (P < 0.001) after rituximab treatment. B cell lymphoma patients with low pre-treatment anti-HBs titers (<100 mIU/mL) were more likely to lose anti-HBs antibodies and were at risk of HBV reactivation after rituximab immunochemotherapy.

Hepatitis B virus reactivation with rituximab-containing regimen

“…Although these cases are not completely accurate since we cannot measure titers above 1000 mIU/mL, in these patients, the titers probably did not drop below 1000 mIU/mL. Pei et al [57] reported anti-HBs antibody titers after rituximab therapy and concluded that the risks of HBV reactivation are the reduction of anti-HBs titers, especially low pretreatment anti-HBs titers and the loss of anti-HBs. These results on titer changes might provide an index for preventive lamivudine or entecavir administration in patients who are only anti-HBs-positive.…”

Highly Sensitive Detection of Hepatitis B Virus Surface Antigen by Use of a Semiautomated Immune Complex Transfer Chemiluminescence Enzyme Immunoassay

“…5C). Recently, it was reported that the reduction or the loss of anti-HBs antibody during or after the treatment was followed by HBV reactivation (42,43). Therefore, the ICT-CLEIA assay, which is able to detect HBsAg before the loss of anti-HBs antibody, might be useful for the earlier diagnosis of HBV reactivation.…”

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

“…Pei et al reported that 8 of 10 (80%) HBsAg-positive patients developed HBV reactivation in a retrospective analysis. 26 More recently, Kim et al conducted a multinational retrospective study to evaluate the incidence of HBV reactivation and its risk factors and found that 13 of 22 (59%) HBsAg-positive patients had HBV reactivation without antiviral prophylaxis. 24 …”

“…7,28,29 The incidence of HBV reactivation in HBsAg-positive patients receiving rituximabcontaining chemotherapy without antiviral prophylaxis has been reported to be 59%-80%. 24,26 These patients are considered to constitute a very-high-risk group for HBV reactivation (Figure 1). Of the HBsAg-positive patients, most HBV reactivation occurs during and after chemotherapy, but patients with high HBV DNA levels at baseline potentially suffer HBV reactivation at an early stage of chemotherapy.…”