Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma

Abstract

Reactivation of hepatitis is one of the most serious complications of chemotherapy in lymphoma patients who are carriers of the hepatitis B virus (HBV). Glucocorticoids are linked to increased risk of HBV reactivation. This study seeks to clarify whether removal of glucocorticoids from chemotherapy regimens may decrease the risk of HBV reactivation. Eligible patients were seropositive for hepatitis B surface antigen (HBsAg) and had histologically proven non-Hodgkin's lymphomas for which intensive chemotherapy was indicated. Patients were randomized to receive either ACE (epirubicin, cyclophosphamide, and etoposide) or PACE (prednisolone ؉ ACE). A total of 50 patients were enrolled, 25 each for the ACE and PACE arms. The cumulative incidence of HBV reactivation at 9 months after starting chemotherapy was 38% and 73% for ACE and PACE arm, respectively (P ‫؍‬ .03). The degree of clinical hepatitis was significantly more severe in the PACE arm: 11 patients (44%) in the PACE and 3 patients (13%) in the ACE arm had ALT elevation more than 10-fold of normal (P ‫؍‬ .025), and 7 patients (28%) in the PACE and 1 patient (4%) in the ACE arm had icteric hepatitis (P ‫؍‬ .049). Complete remission of tumors occurred in 11 (46%) patients in the PACE and 8 (35%) patients in the ACE arm (P ‫؍‬ .556). The estimated overall survival rate at 46 months was 68% in the PACE arm and 36% in the ACE arm, respectively (P ‫؍‬ .18). In conclusion, steroid-free chemotherapy decreases the incidence and severity of HBV reactivation in HBsAg-positive lymphoma patients. However, further research is needed to evaluate whether steroid-free chemotherapy may confer a less satisfactory control of lymphoma. (HEPATOLOGY 2003;37:1320-1328

Prevention of hepatitis B reactivation with lamivudine in hepatitis B virus carriers with hematologic malignancies treated with chemotherapy—A prospective case series

“…The majority of our patients was treated with secondor third-line chemotherapy regimens, due to lack of response to the first-line ones; nevertheless, the intensification of cytostatic treatment, a known risk factor for HBV reactivation [1][2][3][4][5][6][7][8][9][10][11], did not lead to flare-ups, further supporting the efficacy of lamivudine in this setting. Finally, 4 patients were treated with rituximab, the administration of which has been recently associated with the occurrence of fulminant hepatitis caused by HBV reactivation [42].…”

“…Asymptomatic reactivation was defined as the virologic reactivation with less than a 10-fold increase of aminotransferase activity compared to baseline levels without any clinical signs of liver disease. Virologically, reactivation was defined as an increase in HBV-DNA levels more than 400 copies/mL for patients with undetectable viral load prior to the exacerbation or as a more than 10 times increase compared to pre-exacerbation levels [25].…”

“…Corticosteroids are the most significant predisposing factor to HBV reactivation, because they promote viral replication both directly and indirectly by causing immunosuppression [4]. In a comparative trial, flare-ups occurred in 47.4% compared 8.3% in HBV carriers with nonHodgkin lymphoma treated with corticosteroidscontaining and corticosteroids-free chemotherapy, respectively [9].…”

“…This complication is more frequent in patients with hematologic malignancies because administration of corticosteroids, the mainstay of treatment of these patients, is an independent risk factor for HBV reactivation [2,4,9,10]. The administration of more intensive chemotherapy in order to treat the non-responders also increases the frequency of hepatitis B flare-up [1,11].…”

“…Hepatitis B is a major health problem with 350 million people infected worldwide, while in endemic areas the carrier rate of the population is as high as 15-20% [7,9]. Therefore, patients with hematologic malignancies might also be HBV carriers with a frequency as high as 26% [3].…”