Screening and Management of Hepatitis B Virus before the First Rituximab Infusion: We Must Do Better!

Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen is widely used for the treatment of B-cell malignancies and others auto immune pathologies.

HBV reactivation is a well known life-threatening complication of rituximab. In 2004, US FDA recommended HBV screening of high risk patients before the first Rituximab infusion and treatment of patients with positive hepatitis B surface antigen or antibody to hepatitis B core. Then in 2008, CDC recommended screening of all patients. EASL in 2012 recommended treating patients with positive HBsAg or anti-HBc.

The aim of this study was to evaluate HBV screening and management before the initiation of rituximab.

We conducted a retrospective monocentric study in Argenteuil Hospital, located in the neighborhood of Paris, France. All patients who received rituximab between January 1, 2008 and December 31, 2013 were included. The list was exhaustive through the Pharmacy Informatics. Laboratory Informatics gave test dates and results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antibody (anti-HBc) and antibody to hepatitis B surface (anti-HBs). We investigated for medical record when serology was missing. We considered serology as not done when no result was found.

The data are described as number and percentages for categorical variables and mean ± standard deviation or median for continuous variables. Between-group comparisons were done using the chi-square test for categorical data and Student t-test for continuous data. P values <0.05 were considered statistically significant. Statistical analysis was performed with R software (http://cran-project.org).

We included 509 patients with a mean age of 65.5 when rituximab treatment was initiated. Men represented 58% and 33% of patients were born outside of France, mainly in Africa or in Asia. Rituximab was mainly used in cancer treatment (91%) and chemotherapy was associated in 82% of cases.

Five medical records were lost, so the study was conducted for 504 patients. The rate of assessment for HBV serology was 79.4% (104 not done among the 504). Sex, country of origin, indication for treatment or cancer were not statistically significant for the quality of screening. No difference was found depending on the period. A trend in favor a worst screening for older patients was seen: median age for screening patients was 64.8 versus 68.1 (p=0.053).

Among the 9 patients who were HBsAg+, 8 received analogue nucleoside and did not reactivate HBV. These patients have also been screened for Hepatitis Delta virus. The patient who did not receive a preemptive therapy reactivated HBV. This patient was initially treated in another center without HBV screening. When he was referred to us an important hepatic flare secondary to HBV reactivation was found. Six among the 11 patients who were anti-HBc+ /antiHBs- received preemptive therapy and no reactivation was seen. Adenofovir then tenofovir was chosen preferentially. None of the patients with anti-HBc and anti-HBs received preemptive antiviral therapy as recommended since 2004. Among them, one patient treated with rituximab and chlorambucil for CLL reactivated HBV. Evolution was favorable on entecavir.

To summarize, our HBV management before Rituximab first infusion must be improved. All patients with HBc with or without HBs antibody are of risk of HBV reactivation. Pre-emptive treatment should be proposed to all patients with HBc positive antibody.