Hepatitis B e Antibody Positive before Rituximab Combination Chemotherapy Is Associated with a Lower Risk of Hepatitis B Virus (HBV) Reactivation in HBV Carriers with Diffuse Large B-Cell Lymphoma

Background: With antivirus prophylaxis, reactivation of hepatitis B virus (HBV) also occurred in HBV carriers (hepatitis B surface antigen [HBsAg] positive) undergoing rituximab combination chemotherapy. It was reported that most HBV carriers with improved long-term outcomes were seropositive for hepatitis B e antibody (HBeAb). In this study on HBsAg-positive lymphoma patients with prophylaxis, the objectives were to determine the HBV reactivation rate in patients with HBeAb positive compared with the patients with HBeAb negative.

Methods: We retrospectively analyzed the medical records of 113 HBV carriers with CD20(+) diffuse large B-cell lymphoma (DLBCL) received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy with antivirus prophylaxis between August 1, 2002 and November 31, 2011 at Sun Yat-sen University Cancer Center, China.

Results: Among 113 HBV carriers with CD20(+) DLBCL, 68(60.2%) were hepatitis B e antibody (HBeAb) positive. There was no significant difference in terms of sex distribution, age, ECOG PS, stage, baseline HBV DNA detectable rate, or ALT, AST, bilirubin, or LDH between the HBeAb positive group and the HBeAb negative group. However, there were a significantly higher proportion of HBeAg seronegativity (94.1%v 24.4%; P< .001), and HBcAb seropositivity (100.0%v 82.2%; P< .001) in the HBeAb positive group.

All the patients received antiviral therapy before chemotherapy. The antiviral treatments were used as follows: lamivudine in 68 (60.2%) patients, entecavir in 18 (15.2%) patients, others in 27 (23.8%) patients. Other antiviral treatments were including adefovir, lamivudine plus entecavir, lamivudine at beginning and then entecavir, and so on. No significant difference was observed in the antiviral drugs between the two groups.

After R-CHOP chemotherapy, HBV reactivation was found in 23.0% of HBV carriers (26/113). And its incidence rate was lower in HBsAg- positive / HBeAb positive patients than in HBsAg-positive/ HBeAb negative patients (16.1% versus 33.3%; P =.034). Multivariate analysis showed that patients positive for HBeAb before chemotherapy was the only significant and independent protective factor associated with hepatitis due to HBV reactivation after chemotherapy.

Chemotherapy was continued when the serum HBV-DNA level reduced or liver function improved. Survival was not affected by the occurrence of HBV reactivation or the status of HBeAb.

Conclusion: HBeAb positive before rituximab combination chemotherapy was associated with a lower risk of HBV reactivation in HBV carriers with CD20(+) DLBCL. A more effective antivirus prophylaxis may be considered in HBV carriers with HBeAb negative in order to reduce HBV reactivation.