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Hepatitis B reactivation due to cancer chemotherapy
Submit responseWe would like to thank Dr. Hsu and colleagues for their comments on our meta-analysis dealing with the beneficial role of preventive lamivudine in reducing hepatitis B reactivation during cancer chemotherapy (1). We agree that corticosteroids play an important role in chemotherapy-induced HBV reactivation and this was the reason to list the use of corticosteroids in a dedicated column in Table 1. Unfortunately, as apparent from the adjacent chemotherapy column showing administration of CHOP (where P stands for prednisone), patients from the study of Lau et al. (2) and Hsu et al. (3) were both erroneously labeled as respectively “not receiving” and “not reported” receiving corticosteroids. We also acknowledge that, instead of randomized clinical trial with therapeutic (deferred) lamivudine controls, the study by Hsu et al. (3) was inadvertently classified as prospective with historical controls in the tables 1 and figures. It should be noted, however, that we quoted the meeting abstract of the study published by the authors (3) and not the paper they reference as being quoted (4). Their full manuscript with the cited clinical trial identifier was not yet published until after the acceptance of our meta-analysis. Additionally, the corresponding authors of all the published studies and abstracts included in our meta-analysis were contacted via email for further clarifications but we were unsuccessful in getting a response. Authors may also recall that their meeting abstract title did not mention that their study was a randomized-controlled study (3) and the title was reworded only later when published in its entirety (4). Because our research synthesis did not pool data from various studies, the apparent misclassification of this study has no effect on the conclusions.
On the other hand, the statement in our Discussion section about the duration of prophylactic lamivudine was based upon a direct quote from the Conclusion section of the abstract by Hsu et al. (3): “The duration of lamivudine prophylaxis, which can reduce the incidence and severity of HBV reactivation and hepatitis during chemotherapy, may have to be no less than 8 months after completion of chemotherapy.” That is, the authors indeed did recommend a specific duration (at least 8 months) of prophylactic lamivudine after discontinuation of chemotherapy (3).
References:
1. Loomba R, Rowley A, Wesley R, Liang J, Hoofnagle JH, Pucino F, et al: Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Int Med 2008; 148: 519-528
2. Lau GK, Yiu HH, Fong DY, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 2003; 125(6):1742-9.
3. Hsu C HC, Su IJ, Hwang WS, Wang MC, Lin SF, Lin TH, et al. A prospective comparative study of prophylactic or therapeutic use of lamivudine for chemotherapy-associated hepatitis B (HBV) reactivation in non-Hodgkin's lymphoma patients. Gastroenterology 2006; 131:S 297; 788 A (American Gastroenterology Association Meeting Abstracts 2006).
4. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, et al: A revisit for prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology 2008; 47: 844-853
Conflict of Interest:
None declared
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Prophylactic lamivudine for chemotherapy-induced hepatitis B reactivation
Submit responseWe read with great interest the systematic review done by Loomba et al for chemotherapy-induced hepatitis B (HBV) reactivation in cancer patients who tested positive for HBV surface antigen (1). However, some of the information as quoted in that paper needs clarification.
In table 1, regarding the use of corticosteroids as one of the most important risk factors of chemotherapy-induced HBV reactivation (2), our study and the study by Lau et al were mistakenly categorized as either not reported or not using corticosteroids. In fact, both studies enrolled patients with lymphoma, and corticosteroid was an integral component of most standard chemotherapy for lymphoma. Therefore, both studies used corticosteroids for the treatment of their subjects.
In table 1, our study was in the category of prospective cohort study with historical control. In fact, our study was a randomized controlled clinical trial (ClinicalTrials.gov Identifier: NCT00201318)(3). Our study enrolled patients with newly diagnosed non-Hodgkin's lymphoma and randomized the patients to either prophylactic lamivudine during chemotherapy or therapeutic lamivudine upon hepatitis flare. The incidence of both HBV reactivation and HBV-related hepatitis flare were significantly reduced by prophylactic lamivudine. Our paper also indicated that therapeutic lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation.
In the discussion section the authors mentioned that we proposed a duration of prophylactic lamivudine for at least 8 months after completion of chemotherapy. Although our study indicated that HBV reactivation may occur more than 6 months after completion of chemotherapy, we did not recommend a specific duration of prophylactic lamivudine. The optimal duration of prophylactic lamivudine is still unknown. Most previous studies continued lamivudine prophylaxis for 1 to 3 months after completion of chemotherapy, and the current guidelines by the American Association for the Study of Liver Diseases (AASLD) recommended prophylactic lamivudine for at least 6 months after completion of chemotherapy, based on expert consensus (4). The potential benefit of longer-term anti-viral therapy must be judged against the risk of inducing viral mutants and drug resistance. Further clinical trials to determine the optimal duration and agents of anti-viral therapy are definitely warranted.
References:
1. Loomba R, Rowley A, Wesley R, Liang J, Hoofnagle JH, Pucino F, et al: Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Int Med 2008; 148: 519-528
2. Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, et al. Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology 2003; 37: 1320-1328
3. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, et al: A revisit for prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology 2008; 47: 844-853
4. Lok ASF, McMahon BJ: Chronic hepatitis B. Hepatology 2007; 507-39
Conflict of Interest:
None declared