Reactivation of precore mutant hepatitis B virus leading to fulminant hepatic failure following cytotoxic treatment

Yoshiba, Makoto; Sekiyama, Kazuhiko; Sugata, Fumio; Okamoto, Hiroaki; Yamamoto, Keijiro; Yotsumoto, Shigeru

doi:10.1007/bf01296569

Cited by 72 publications

(36 citation statements)

References 31 publications

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“…Among 19 published complete HBV sequences, only 3 (16%) had MO (17)(18)(19)21). Of 13 studies on pre-core HBV mutations, only 3 (23%) reported the presence of MO in a small proportion of the clones sequenced (1,3,4,(7)(8)(9)(24)(25)(26)(27)(28)(29)(30)(31). The single patient with coexistent M9 and M10 further illustrates the importance of base pairing in this stem-loop structure.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal.

Lok

Akarca

Greene

1994

Proc. Natl. Acad. Sci. U.S.A.

362

280

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Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal ABSTRACTWe conducted a large-scale survey to determine the frequency and clinical significance of mutations in the pre-core region of hepatitis B virus (HBV). Sera from 263 patients with chronic HBV infection were analyzed by direct sequencing of PCR-amplif ed HBV DNA. Four major missense/nonsense mutations (M) were found: (Ml)

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Section: Discussionmentioning

confidence: 99%

Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal.

Lok

Akarca

Greene

1994

Proc. Natl. Acad. Sci. U.S.A.

362

280

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“…However, HBsAg-positive patients could suffer from reactivation even if they remain HBeAg negative. Sequence analysis of the HBV isolated from these patients had demonstrated the presence of point mutation in the precore region that inhibited the synthesis of HBeAg [59,[72][73][74]. Therefore, it would be more reliable to demonstrate the presence of HBV reactivation by showing an increase of serum HBV DNA by quantitation.…”

Section: Pathogenesis and Diagnosis Of Hbv Reactivationmentioning

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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“…6 Hepatic complications related to HBV infection after hematopoietic cell transplantation are mainly related to exacerbation of HBV. [12][13][14][15][16] Before the availability of nucleoside analogue therapy for HBV infection, various agents such as interferon, 16 prostaglandin E 2 , 14 corticosteroids, 15,[17][18] and cyclosporine 16 were used to treat hepatitis due to exacerbation of HBV after immunosuppression, with largely disappointing results. With the recent introduction of effective antiviral therapy to HBV (anti-HBV) such as lamivudine 19,20 and famciclovir, [21][22][23] new treatment options are available for these patients.…”

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confidence: 99%

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

et al. 2002

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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 ...

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Reactivation of precore mutant hepatitis B virus leading to fulminant hepatic failure following cytotoxic treatment

Cited by 72 publications

References 31 publications

Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal.

Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal.

Hepatitis B reactivation after chemotherapy: two decades of clinical research

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

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