Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation

Abstract

Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4-to 8-week intervals for the first year and then 4-to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P < .008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P ‫؍‬ .002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P ‫؍‬ .021). I n an endemic area for chronic hepatitis B infection, exacerbation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. 1,2 Careful prospective serologic testing has shown that liver damage due to exacerbation of hepatitis B virus (HBV) is a 2-stage process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterized by enhanced viral replication, as reflected by increases in serum levels of HBV DNA, hepatitis B e antigen, and HBV DNA polymerase, which presumably results in widespread infection of hepatocytes. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this may lead to hepatitis, hepatic failure, and even death. [3][4][5] In keeping with these observations, our recent data suggest that a high pretreatment level of serum HBV DNA is the single most important factor for exacerbation of HBV after intense immunosuppression. 6 In the past few decades, hematopoietic cell transplantation has been established as the standard treatment of various hematologic and oncologic problems. 7 In areas such as Southeast Asia, where HBV infection is prevalent, hematopoietic cell transplantation might be complicated by HBV-related morbidity and mortality. 8 The pre-heAbbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; anti-HBV, antibody to hepatitis B virus; PCR, polymerase chain ...

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.…”

A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization

“…Earlier studies have suggested that preemptive antiviral therapy significantly reduced the risk of HBV reactivation during cytotoxic chemotherapy. 4,6,8,11 Although the concept of preemptive therapy appears appealing, it has never been investigated prospectively in HCC patients. Moreover, transarterial chemotherapy seems to be different from systemic chemotherapy in terms of the route of administration and the toxicity of the treatment itself.…”

A comparison of lamivudine vs entecavir for prophylaxis of hepatitis B virus reactivation in allogeneic hematopoietic stem cell transplantation recipients: a single-institutional experience

“…18,19 In this study, faster reduction of HBV viral loads to undetectable levels in the entecavir group also suggests that entecavir possesses better antiviral activity than lamivudine, and this may be another reason for the lower incidence of HBV reactivation seen in the entecavir group vs the lamivudine group. [20][21][22] In this study, in patients receiving transplants from donors with a natural immunity to HBV (HBsAb and HBcAb positive), both entecavir and lamivudine produced higher rates of HBsAg seroclearance and shorter times to HBsAg seroclearance than those reported in chronic HBV-infected patients. 23 These results were similar to findings of several previous studies that reported a HBsAg seroclearance rate of ∼ 70% and a median onset time of ∼ 2.4 months (range: 1.5-3.5 months) in allo-HSCT recipients.…”