Lamivudine prophylaxis for prevention of chemotherapy‐induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies

Abstract

Although hepatitis B virus (HBV) reactivation in HBV carriers undergoing immunosuppressive therapy is clearly documented, the role of antiviral prophylaxis in such individuals is still controversial. The aim of this study was to determine the efficacy of lamivudine prophylaxis in HBV carriers with haemato/oncological malignancies, who receive chemotherapy. Eighteen HBV carriers with malignancy, who were candidates for chemotherapy, were enrolled. Eight subjects (three with leukaemia, four with lymphoma and one with multiple myeloma) were enrolled for prophylactic lamivudine therapy. The remaining 10 patients (six with leukaemia, three with lymphoma and one with breast cancer) were not treated with lamivudine and were used as a control. Lamivudine was administered beginning on the same day as the chemotherapy and was maintained for a year after chemotherapy was discontinued. No HBV-related mortality was observed in either group. In the lamivudine-treated group, none of the subjects had clinical, biochemical or serological evidence of HBV reactivation during the time they were receiving chemotherapy and after their chemotherapy was discontinued. In contrast, five of the 10 HBV carriers not receiving lamivudine therapy experienced a reactivation of HBV infection. This reactivation of HBV was observed during the chemotherapy in four with one individual experiencing a HBV activation 12 months after chemotherapy was discontinued. No lamivudine-related major adverse effects were observed. Hence prophylactic lamivudine treatment in HBV carriers with haemato/oncological malignancy receiving chemotherapy prevents chemotherapy-induced HBV reactivation.

Hepatitis B reactivation after chemotherapy: two decades of clinical research

“…This will lead to the development of lamivudine resistance caused by point mutations, with substitution of either valine or isoleucine for the amino acid position 204 methionine (rtM204V or rtM204I, respectively) in the HBV DNA polymerase gene (tyrosinemethionine-aspartate-aspartate [YMDD] motif) [67]. Its risk increases as the therapy is prolonged, reaching a level of 67% after 4 years in nonimmunocompromised patients Jang et al 88 Lim et al 127 Yeo et al 119 Lee et al 118 Idilman et al 117 Yeo et al 116 Leaw et al 115 Ozguroglu et al 114 Lau et al 85 Persico et al 113 Shibolet et al 112 Dai et al 111 Nagamatue et al 58 0.001 0.01 0.1 1 10 100 1000…”

“…On the other hand, prolonged therapy with nucleos(t)ide analogues is associated with an increased likelihood of developing lamivudine-resistant mutants. Hence, most cancer centers would aim at discontinuing or withdrawing preemptive lamivudine as soon as possible to limit the duration of antiviral therapy [57,85,86,[111][112][113][114][115][116][117][118][119]127]. However, at the moment there is no available consensus on the optimal duration of lamivudine therapy.…”

Hepatitis B prophylaxis in patients undergoing chemotherapy for lymphoma: A decision analysis model

“…Data from 14 studies published from various parts of the world between 1990 and 2006 that examined HBV reactivation in lymphoma patients undergoing chemotherapy were collected (Table 1). [12][13][14][15][16][17][19][20][21][22][23][24][25][26] Seven of these studies compared the prophylactic use of lamivudine during chemotherapy to the empiric use of the drug, [12][13][14][15][16][17]26 6 studies restricted lamivudine to the treatment of reactivation, [20][21][22][23][24][25] and 1 study examined only the prophylactic use of lamivudine. 19 Lymphoma and Chemotherapy.…”

“…11 The use of prophylactic lamivudine can decrease the incidence of HBV reactivation from 30%-80% to 0%-17%. [12][13][14][15][16][17] The aim of this study was to compare the efficacy and costs of 2 management strategies in patients with hepatitis B undergoing chemotherapy: (1) lamivudine prophylaxis and (2) lamivudine use only in patients with evidence of an HBV reactivation. Because lamivudine has been shown to be effective in preventing HBV reactivation, is inexpensive, and is associated with few adverse effects, we believed that the use of lamivudine prophylaxis would be most cost-effective.…”

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

“…In a single study, lamivudine was given before the onset of chemotherapy and for 1 month after its withdrawal in 20 patients with lymphoid malignancies, and it showed similar results without any adverse effects [8]. There are also three studies in which lamivudine was given to 39 patients with various malignancies, prior to the commencement of chemotherapy, and was continued for 6-12 months after its completion; no hepatitis B flare-ups occurred [7,24,40]. In a recent report, lamivudine showed similar results when administered to 10 children with hematologic malignancies who had suffered in the past immunosuppressive-induced hepatitis B virus reactivation [41].…”