High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation

Lau, George; Leung, Y.-Y. R.; Fong, Daniel Yee Tak; Au, Wing‐Yan; Kwong, Yok–Lam; Lie, Albert K. W.; Hou, Ji-lin; Wen, Yumei; Nanj, Amin; Liang, Raymond

doi:10.1182/blood.v99.7.2324

Cited by 212 publications

(150 citation statements)

References 67 publications

(81 reference statements)

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“…ml À1 , the present study has revealed that detectable HBV DNA load prior to chemotherapy was a significant predictive factor for viral reactivation. Although a recent study has demonstrated that a detectable HBV DNA may predict HBV reactivation in HBsAg-positive individuals (Lau et al, 2002), the finding, which was based on a small heterogeneous group of patients who underwent autologous hematopoietic cell transplantation, could not be generalised and applied to the majority of cancer patients who require conventional cytotoxic chemotherapy without transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical features such as young age, male sex, the diagnosis of lymphoma and the use of anthracyclines and/or steroids as part of the anticancer therapy have been suggested (Lok et al, 1991;Yeo et al, 2000a), while virological factors such as HBeAg positivity (Yeo et al, 2000a, b) and, more recently, the pre-chemotherapy HBV viral load (Lau et al, 2002) have also been associated.…”

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confidence: 99%

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Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy

et al. 2004

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For cancer patients with chronic hepatitis B virus (HBV) infection, who receive cytotoxic chemotherapy, HBV reactivation is a welldescribed complication, which may result in varying degrees of liver damage. Several clinical features and the pre-chemotherapy HBV viral load have been suggested to be associated with an increased risk of developing the condition: (1) to assess the clinical and virological factors in a comprehensive manner and thereby identify those that are associated with the development of HBV reactivation; (2) to develop a predictive model to quantify the risk of HBV reactivation. In all, 138 consecutive cancer patients who were HBV carriers and undergoing chemotherapy were studied, of which 128 patients had sera available for real-time PCR HBV DNA measurement. They were followed up throughout their course of chemotherapy and the HBV reactivation rate was determined. The clinical and virological features between those who did and did not develop viral reactivation were compared. These included age, sex, baseline liver function tests, HBeAg status and viral load (HBV DNA) prior to the chemotherapy, and the use of specific cytotoxic agents. In all, 36 (26%) developed HBV reactivation. Multivariate analysis revealed pre-chemotherapy HBV DNA level, the use of steroids and a diagnosis of lymphoma or breast cancer to be significant factors. Based on real-time HBV DNA PCR assay, detectable baseline HBV DNA prior to the administration of cytotoxic chemotherapy, the use of steroids and a diagnosis of lymphoma or breast cancer are predictive factors for the development of HBV reactivation. A predictive model was developed from the current data, based on a logistic regression method.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy

et al. 2004

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“…Since then, this important observation was further confirmed in other studies [8,15,16], with the rate of HBV reactivation ranging from 19% to 48%. Among them, one-quarter to half would be complicated, with severe hepatitis, hepatic failure, and even death [1][2][3][4][5][6][17][18][19][20].…”

Section: How Important Is the Problem?mentioning

confidence: 99%

“…However, owing to the wide variation of the sensitivity and linearity of the different assay, the reported incidence varies. For example, the earlier branched DNA hybridization assay (Quantiplex HBV DNA assay; Chiron, Berkeley, CA) has a detection limit of 0.7 9 10 6 copies/ml [20], whereas recent real-time polymerase chain reaction assays have a lower detection limit down to 11 copies/ml [75]. Second, the patient should have serological evidence of chronic HBV infection.…”

Section: Pathogenesis and Diagnosis Of Hbv Reactivationmentioning

confidence: 99%

“…As hepatitis due to HBV reactivation is preceded by enhanced HBV viral replication [1][2][3][4][5], a high prechemotherapy HBV viral load has been consistently found to be the most important risk factor for postchemotherapy HBV reactivation, by multivariate analysis (Table 1). In our center, by studying 137 consecutive autologous BMT patients, we first described that pre-BMT HBV DNA level[10 5 copies/ ml (by Digene Hybrid Capture II assay) was the only significant risk factor [20] associated with post-BMT HBV reactivation. Subsequently, in breast cancer patients receiving standard cytotoxic chemotherapy, a high HBV viral load prior to the administration of cytotoxic chemotherapy was also identified as the most significant predictive factor for the development of HBV reactivation.…”

Section: Risk Factors Involved In Hbv Reactivationmentioning

confidence: 99%

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Hepatitis B reactivation after chemotherapy: two decades of clinical research

Lau

2008

Hepatol Int

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102

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Hepatitis due to hepatitis B virus reactivation after cytotoxic or immunosuppressive therapy is a serious cause of liver-related morbidity and mortality. With the characterization of the underlying pathogenesis, much progress in the management of this important clinical problem has been made in the past 2 decades. By year 2008, it is mandatory to screen for hepatitis B surface antigen status before initiating intensive chemotherapy or immunosuppressive therapy. All those who are hepatitis B surface antigen positive should be started on preemptive nucleos(t)ide analogues. However, there remains important issues, such as the type and duration of nucleos(t)ide analogue therapy, which need to be understood. As not all hepatitis B surface antigen-positive patients will suffer from HBV reactivation, it is therefore useful to identify risk factors related to HBV reactivation so that patients will not be treated unnecessarily with nucleos(t)ide analogues. To date, a high baseline level of viral replication, as reflected by high serum HBV DNA level, positive serum hepatitis B e antigen, and a high intrahepatic covalently closed circular DNA level, is the most important predictor for HBV reactivation. Recently, there has been an increased awareness of reactivation of occult hepatitis B virus, especially in hepatitis B virus endemic area, such as the Asia-Pacific region. Careful epidemiological study will be needed to clarify the impact of occult hepatitis B infection in patients treated with cytotoxic or immunosuppressive therapy. How important is the problem?Over the past 20 years of clinical practice at Queen Mary Hospital, we have seen a lot of progress in the management of hepatitis due to HBV reactivation in hepatitis B surface antigen carriers [1][2][3][4][5]. In the past, we saw patients who died of fulminant hepatic failure after being administered a few courses of cytotoxic therapy to treat their life-threatening lymphoma [6][7][8][9] and breast cancer [10][11][12] if they were also hepatitis B surface antigen positive. At that time, the literature report of this important clinical issue was scanty. The first report in the field was published by Wand et al. [13] who studied the effects of antitumor chemotherapeutic agents on hepatitis antigen (HBAg) and antibody (HBAb) in 25 patients with myeloproliferative and in 60 patients with lymphoproliferative disorders. This elegant study was performed at the time when only antigen and antibody associated with viral hepatitis could be semiquantified [14]. In those patients who had HBAg at the time of initiation of chemotherapy, bone marrow suppression by chemotherapeutic agents was associated with a marked increase in HBAg titer, which was then followed by hepatocellular damage, as manifested by an elevation in serum transaminase enzymes [13]. Since then, this important observation was further confirmed in other studies [8,15,16], with the rate of HBV reactivation ranging from 19% to 48%. Among them, one-quarter to half would be complicated, with severe hepatitis...

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Gastrointestinal and Hepatic Complications

Strasser¹,

McDonald²

2003

Thomas' Hematopoietic Cell Transplantation

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High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation

Cited by 212 publications

References 67 publications

Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy

Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Gastrointestinal and Hepatic Complications

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