Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study

Lau, George; Liang, Raymond; Chiu, E. K. W.; Lee, C. K.; Lam, Sum

doi:10.1038/sj.bmt.1700744

Cited by 128 publications

(72 citation statements)

References 4 publications

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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%

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Lau

2008

Hepatol Int

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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Section: How Important Is the Problem?mentioning

confidence: 99%

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Lau

2008

Hepatol Int

102

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“…15 In HBV carriers, the incidence of significant viral reactivation ranges from 15% for autologous BMT to 85% for allogeneic BMT between HBV positive donor-recipient pairs. 4 This incidence is reduced by pre-emptive viral suppression with HBV DNA monitoring. 12 However, with acquired resistance to purine analogues, the eventual incidence of cirrhosis and HCC may still be high.…”

Section: Discussionmentioning

confidence: 99%

“…Among all marrow recipients, 23 autologous and 60 allogeneic cases were HBV carriers. 4 Their median age was 35 years (range 5-56 years), and they included 56 men and 27 women. The protocol for myeloablation and HBV chemoprophylaxis were according to the study protocol during the time periods.…”

Section: Methodsmentioning

confidence: 99%

Aggressive hepatocellular carcinoma complicating pregnancy after autologous bone marrow transplantation for non-Hodgkin's lymphoma

Lie

Liang

et al. 2002

Bone Marrow Transplant

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Summary:In the Asia-Pacific region, autologous and allogeneic bone marrow transplantation (BMT) in patients infected with the hepatitis B virus (HBV) may be complicated by fatal hepatic failure due to viral reactivation. Survivors may suffer from accelerated hepatitis and cirrhosis. We report the first case of hepatocellular carcinoma (HCC) after autologous BMT for mediastinal B cell lymphoma. The tumor developed rampantly during a planned pregnancy 5 years after BMT. Less than 40 cases of HCC complicating pregnancy have been reported, and outcome is invariably poor. Immunosuppression and HBV reactivation after autologous BMT, as well as immune tolerance and hormonal changes associated with pregnancy may contribute to the rapid tumor growth. Biochemical and radiological surveillance for HCC should be strengthened in HBV carriers after BMT, especially in patients with the histology of chronic liver disease, or biochemical/ virological evidence of increased HBV activity. Bone Marrow Transplantation (2002) 29, 177-179. DOI: 10.1038/sj/bmt/1703339 Keywords: autologous bone marrow transplanation; hepatitis B virus; hepatocellular carcinoma; pregnancyThe incidence of secondary malignancy is increased after bone marrow transplantation (BMT). The commonest secondary malignancy after autologous BMT is therapy-related myelodysplasia (t-MDS). 1 After allogeneic BMT, the incidence of post-transplantation lymphoma (PTLD) is also increased. 2,3 The incidence of other common solid malignancies, including lung and breast carcinoma, increase with longer follow-up of survivors. 2 Hepatocellular carcinoma (HCC) is the second commonest malignancy in the Southern Chinese (10% population hepatitis B virus (HBV) carriers). We report the first case of aggressive HCC after autologous BMT. Materials and methodsBetween 1991 and 2000, 159 and 525 consecutive autologous and allogeneic BMTs were performed at the Queen Mary Hospital. Among all marrow recipients, 23 autologous and 60 allogeneic cases were HBV carriers. 4 Their median age was 35 years (range 5-56 years), and they included 56 men and 27 women. The protocol for myeloablation and HBV chemoprophylaxis were according to the study protocol during the time periods. 5 HBV carriers were monitored by serial hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe), liver biochemistry, half-yearly alpha-fetoprotein (AFP) and ultrasound (USG), and quantitative serum circulating HBV DNA (Digene Capture II) assays, at 1-6 monthly interval. 6 The median overall survival of 83 HBV cases was 23 months, with an actuarial median follow-up of 115 months. There were 32 deaths, 10 due to conditioning toxicity and liver failure (Ͻday 100), 13 due to relapse, and eight due to graft-versus-host disease (GVHD). One patient died of aggressive HCC, during a rare planned pregnancy after autologous BMT. Among the other 647 BMT recipients, no other cases of a solid tumor developing after BMT have been detected to date. Case history and resultsA 29-year-old w...

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“…37 Reverse seroconversion is common, with patients with anti-HBc without HBsAg redeveloping HBsAg and HBVDNA after bone marrow transplantation. [38][39][40] The frequency of seroreversion ranges between 14 and 50%. 36 Immune suppression for non-malignant diseases like autoimmune disorders in patients who have HBsAg or anti-HBc in serum can also result in reappearance of HBV replication.…”

Section: Risk Factors Of Hepatitis B Virus Reactivationmentioning

confidence: 99%

Acute Exacerbation of Chronic Hepatitis B: The Dilemma of Differentiation from Acute Viral Hepatitis B

Puri

2013

Journal of Clinical and Experimental Hepatology

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Exacerbations of chronic hepatitis B are common in endemic countries. Acute exacerbation of chronic hepatitis B virus (CHB-AE) causing derangement of liver functions may be seen in a flare of HBV in immune clearance phase or as a reactivation of HBV in patients with inactive or resolved HBV infection. While reactivation of HBV is usually seen in HBsAg positive patients, it is being increasingly recognized in patients with apparently resolved HBV infection who do not have HBsAg in serum but have IgG antibody to core antigen (anti-HBc) in the serum, especially so in patients on chemotherapy, immunosuppressive therapy or undergoing hematopoietic stem cell transplantation. In an icteric patient who is HBsAg positive, it may be difficult to differentiate CHB-AE from acute viral hepatitis B (AVH-B). Both may have similar clinical presentation and even IgM anti-HBc, the traditional diagnostic marker of AVH-B, may also appear at the time of exacerbation of CHB. The differentiation between CHB-AE and AVH-B is important not only for prognostication but also because management strategies are different. Most cases of AVH-B will resolve on their own, HBsAg clearance is achieved spontaneously in 90-95% of adults and treatment is rarely indicated except in the few with severe/fulminant disease. In contrast, in CHB-AE, the onset of jaundice may lead to decompensation of liver disease and treatment is warranted. The mechanisms of acute exacerbation and the differentiating features between AVH-B and CHB-AE are reviewed. ( J CLIN EXP HEPATOL 2013;3:301-312)

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Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study

Cited by 128 publications

References 4 publications

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Aggressive hepatocellular carcinoma complicating pregnancy after autologous bone marrow transplantation for non-Hodgkin's lymphoma

Acute Exacerbation of Chronic Hepatitis B: The Dilemma of Differentiation from Acute Viral Hepatitis B

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