Cancer Therapy Vol 3, 189-192, 2005

A summary on lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HBsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy

Research Article

Viroj Wiwanitkit

Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok Thailand 10330

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*Correspondence: Viroj Wiwanitkit, M.D., Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 10330; Tel: 662 256 4136; Fax: 662 218 3640; e-mail: Viroj.W@Chula.ac.th

Key words: lamivudine, primary prevention, chemotherapy, Hodgkin’s lymphoma

Abbreviations: hepatitis B virus surface antigen, (HbsAg); hepatitis B virus, (HBV)

Received: 1 March 2005; Revised: 10 March 2005

Accepted: 07 April 2005; electronically published: April 2005

Summary

Several hepatitis viruses have been mentioned as a risk factor for development of Hodgkin’s lymphoma. In addition, the reactivation of hepatitis in Hodgkin’s lymph patients co-infected with hepatitis virus treated with chemotherapy is reported. It is noted that hepatitis B virus (HBV) reactivation of various degrees of severity. Lamivudine , a nucleoside analogue that can directly suppress HBV replication, is tried as a prophylaxis and treatment of the HBV reactivation. Here, the author summarized the recent report on using lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HbsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy. A literature review to find the previous reports about using lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HbsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy was performed. According to this study, there are 4 recruited reports covering 31 cases of using lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HBsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy. Of these cases, 10 cases were prescribed for lamivudine primary prophylaxis and the results showed no reactivation of fulminant hepatitis while in the other 21 cases without prophylaxis the reactivation were noted in 15 cases. Therefore, the preventive effect of having lamivudine primary prophylaxis is 100 % (odds ratio is uncountable high). Here, the author concluded that lamivudine prophylaxis might be effective, when chemotherapy is given to an HBsAg-positive patient with non-Hodgkin's lymphoma. However, before further implication, a larger case-control study is required for making a final conclusion.

I. Introduction

Keresztes et al, (2003) said that numerous observations implied that the pathogenesis of malignant lymphomas is multifactorial and that viruses probably play an important etiologic role (Keresztes et al, 2003). Lymphoma is a common hematological malignancy. Fisher and Fisher said that several pathogens have been linked to the risk of lymphoma, including Epstein-Barr virus, human immunodeficiency virus, hepatitis virus, and simian virus 40 (Fisher and Fisher, 2004). Several hepatitis viruses have been mentioned as a risk factor for development of Hodgkin’s lymphoma (Chow, 1993; Takada, 1999). In addition, the reactivation of hepatitis in Hodgkin’s lymph patients co-infected with hepatitis virus treated with chemotherapy is reported (Rossi et al, 2001).

Rossi et al noted that hepatitis B virus (HBV) reactivation of various degrees of severity, including fulminant hepatitis, might develop in 20-50% of hepatitis B virus surface antigen (HbsAg)-positive patients undergoing immunosuppressive or cytostatic treatment (Rossi et al, 2001). Management of the reactivation of HBV becomes a new insight for the present therapy of any cases with Hodgkin’s lymphoma. Lamivudine, a nucleoside analogue that can directly suppress HBV replication, is tried as a prophylaxis and treatment of the HBV reactivation. Here, the author summarized the recent report on using lamivudine primary prophylaxis of

Table 1. Previous reports on using lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HbsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy

Reports	Number of patients	Dosage lamivudine regimen	Number of patients with reactivation/ number of patients receive prophylaxis
Tsutsumi et al, 2004a Silvestri et al, 2000 Nakagawa et al, 2002	4 4 2	100 mg/day 100 mg/day 100 mg/day	0 / 1 0 / 4 0 / 2

* Indeed, there is another additional report (Shibolet et al, 2002;) on using lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HBsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy, however, there is no complete data on the outcome specifically to non Hodgkin’s lymphoma in this study.

hepatitis B virus reactivation in chronic HbsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy.

II. Materials and methods

A literature review to find the previous reports about using lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HBsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy was performed. The author used the electronic search engine PubMed in searching for the literatures. Any reports that did not present complete details or contain English details were excluded. The available reports were collected and extracted for the clinical data. Those primary data were used for further metanalysis study. Concerning the metanalysis study, the summative descriptive analysis was performed where appropriate. The SPSS 11.0 for Windows was used for statistical analysis in this study.

III. Results

According to this study, there are 4 recruited reports (Silvestri et al, 2000; Nakagawa et al, 2002; Persico et al, 2000; Tsutsumi et al, 2004a) covering 31 cases of using lamivudine primary prophylaxis of hepatitis B virus reactivation in chronic HBsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy. Of these cases, 10 cases were prescribed for lamivudine primary prophylaxis and the results showed no reactivation of fulminant hepatitis while in the other 21 cases without prophylaxis the reactivation were noted in 15 cases. Therefore, the preventive effect of having lamivudine primary prophylaxis is 100 % (odds ratio is uncountable high).

IV. Discussion

HBV reactivation has been reported in cancer patients following administration of chemotherapy or immunosuppressive therapy and may result in liver damage of varying degrees of severity (Saif et al, 2001). Vento et al (2002) said that, in carriers of HBV, liver damage due to reactivation of viral replication could occur after withdrawal of immunosuppressive drugs. They also noted that there were difficulties in drug prevention and treatment for the reactivation (Vento et al, 2002). In addition, latent HBV infection in healthy individuals with antibodies to hepatitis B core antigen (anti-HBc) can be seen (Murasawa et al, 2000). Murasawa et al (2000) indicated that the majority of healthy individuals positive for anti-HBc, which had been assumed to denote a past history of transient HBV infection, were latently infected with the episomal form of HBV. This can also be a problem in chemotherapy. Prophylaxis of lamivudine treatment for hepatitis B patients undergoing chemotherapy is therefore recommended. Lau et al (2003) noted that preemptive lamivudine therapy more effectively prevented the development of hepatitis than deferred lamivudine treatment in HBsAg-positive cancerous patients undergoing chemotherapy.

Chemotherapy administration to patients with lymphoproliferative diseases and lymphoma that are carriers of hepatitis B can be complicated by reactivation of Hepatitis B and this may lead to morbidity and mortality due to liver failure (Shtalrid et al, 2001). Shtalrid et al noted that lamivudine inhibited replication of HBV and probably ameliorated the severity of already reactivated hepatitis (Shtalrid et al, 2001). In 1999, Maguire et al said that treatment with lamivudine resulted in rapid loss of hepatitis B virus-DNA, resolution of hepatitis and clinical recovery (Maguire et al, 1999). After administration of lamivudine, the patients gradually recovered from liver failure (Tsutsumi et al, 2004b). Therefore, the lamivudine is recommended for treatment of HBV reactivation in chronic HBsAg carriers with Hodgkin’s lymphoma treated with chemotherapy.

Presently, there is a new attempt to use lamivudine for primary prophylaxis of HBV reactivation in chronic HBsAg carriers with lymphoma treated with chemotherapy. Indeed, there are many reports on the use of lamivudine for treatment of HBV reactivation in chronic HBsAg carriers with lymphoma treated with chemotherapy but there are only a few reports on the use of lamivudine for primary prophylaxis purpose. In addition, there is no previous report on the preventive property of this regimen. A metanalysis to assess the preventive property is warranted. Here the author performed a retrospective study to summarize the previous reports on use lamivudine for primary prophylaxis of HBV reactivation in chronic HBsAg carriers with non Hodgkin’s lymphoma treated with chemotherapy. According to this study, there are some recent studies on this topic. According to the summative analysis, the effectiveness or prophylaxis rate is very high. In addition, the preventive odds ratio is very high (infinity). Of interest, this is the first report proving the good preventive property of the regimen by case-control analysis.

Here, the author concluded that lamivudine prophylaxis might be effective, when chemotherapy is given to an HBsAg-positive patient with non-Hodgkin's lymphoma. However, before further implication, a larger case-control study is required for making a final conclusion. In addition, the problems of the prophylaxis of lamivudine treatment for hepatitis B patients must be discussed. One is resistance to lamivudine, and the other is the treatment duration of the prophylactic administration of lamivudine. Lok et al, (2004) recommended that lamivudine prophylaxis be continued for six months after completion of chemotherapy or immunosuppressive therapy. On the other hand, several durations of the administration of lamivudine prophylaxis, which reportedly delayed hepatitis B reactivation, were observed after lamivudine prophylaxis treatments were discontinued one to seven months after the end of chemotherapy with rituximab (Dai et al, 2004; Pelizzari et al, 2004). Dai et al, (2004) noted that delayed HBV reactivation could occur in lymphoma patients receiving R+CHOP after withdrawal of preemptive lamivudine. They noted that more protracted lamivudine therapy may be an alternative to close monitoring following chemotherapy, and further studies were needed to define optimal duration of lamivudine therapy (Dai et al, 2004). Pelizzari et al (2004) noted that among HBV carriers treated with chemotherapy for haematologic malignancies, the emergence of HBV YMMD mutant occurred in 3.1% of prophylactic lamivudine courses and was of little clinical relevance. Treatment duration is mentioned for its association with the resistance of lamivudine (Lok AS et al, 2001; Lok ASF et al, 2001). This caution should also be bewared.

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