Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximab

Miyagawa, Masami; Minami, Masahito; Fujii, Kimio; Sendo, Rei; Mori, Kumiko; Shimizu, Daisuke; Nakajima, Tomoaki; Yasui, Kohichiroh; Itoh, Yoshito; Okanoue, Takeshi; Yoshikawa, Toshikazu

doi:10.1002/jmv.21311

Cited by 20 publications

(10 citation statements)

References 61 publications

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“…Similar reports exist with combined rituximab chemotherapy, suggesting that adding steroids or fludarabine to rituximab may result in a high frequency of drug resistance [49] . We believe that the relationship of immunosuppression and HBV genomic mutations requires further study because it remains undetermined whether long-term preventive lamivudine treatment combined with strong immunosuppression treatment is possible.…”

Section: Risk Factors For Hbv Reactivationsupporting

confidence: 68%

Hepatitis B virus reactivation with a rituximab-containing regimen

Tsutsumi

Yamamoto

et al. 2015

WJH

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Rituximab is recognized as a useful drug for the treatment of B-cell non-Hodgkin's lymphoma and its use has been extended to such diseases as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, chronic rheumatoid arthritis and AN-CA-associated vasculitides. One serious complication associated with its use is the reactivation of hepatitis B virus and the search for methods to prevent this occurrence has resulted in the rapid accumulation of knowledge. In this review, we discuss case analyses from our department and other groups and outline the current knowledge on the topic and the remaining issues.© 2013 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Rituximab; Hepatitis B virus; Reactivation; Chemotherapy; Lamivudine; Non-Hodgkin's lymphoma Core tip: The deleterious effects of hepatitis B virus (HBV) reactivation in rituximab-containing chemotherapy regimens have been reported and the effect of lamivudine treatment in the prevention of HBV reactivation is also well documented. Once reactivated, HBV may lead to death due to hepatitis. In this review, we discuss the factors of preventive lamivudine treatment (especially in the course of HBV antibody), including to whom and for how long the drug should be given, based on case studies and reports that span rituximab's debut in 2002 on the Japanese market to June 2013.

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Section: Risk Factors For Hbv Reactivationsupporting

confidence: 68%

Hepatitis B virus reactivation with a rituximab-containing regimen

Tsutsumi

Yamamoto

et al. 2015

WJH

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“…The patient had been anti-HBc-and anti-HBs-positive before therapy and had obviously harbored the occult variant in the liver. A similar case with heavily mutated HBsAg was published recently by Miyagawa et al [28] .…”

Section: Reactivation Of Obi Under Immunosuppressionmentioning

confidence: 64%

“…It can be fatal, however, after immune reconstitution. To make things worse, it is often caused by escape mutants [26][27][28] . Table 2 lists 9 cases which we have analyzed [W.H.G., unpubl.].…”

Section: Reactivation Of Obi Under Immunosuppressionmentioning

confidence: 99%

Occult Hepatitis B Virus Infection: Detection and Significance

Gerlich

Bremer²,

Saniewski³

et al. 2010

Dig Dis

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The Taormina Consensus Conference defined ‘occult hepatitis B virus (HBV) infection’ (OBI) as the ‘presence of HBV DNA in the liver of individuals testing HBsAg-negative with currently available assays’. Most occult is the so-called ‘window period’ after exposure before HBV DNA appears in the blood. We identified two blood donors whose donations tested HBsAg- and HBV DNA-negative, but transmitted HBV. Both subsequently developed HBsAg and acute hepatitis. However, such cases are not considered as true OBI. A true transient OBI remains HBsAg-negative during the entire course. One case of acute OBI showed a peak viremia of 15,000 IU/ml HBV DNA and sub-borderline HBsAg, suggesting a ratio of virions to subviral particles of 1:10, whereas ‘normal’ cases show at peak viremia a ratio of 1:3,000. Blood donors with OBI may transmit HBV. We studied 5 blood donors with OBI and 55 of their recipients. In 22 recipients, transmission was probable, but they remained healthy. However, in 3 recipients, who were immunosuppressed at the time of transfusion, fatal fulminant hepatitis B developed. The majority of anti-HBc-positive healthy individuals have HBV DNA in the liver which may start replication under severe immunosuppression. Nine such cases are described here. OBI or reactivated HBV infections often lead to selection of HBsAg escape mutations as we could show in 11 of 14 cases. Infection of vaccinated individuals favors development of OBI as we observed in 6 blood donors. HB vaccination may solve the problem of overt HBV infection but may favor OBI.

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“…However, almost all previously reported cases of HBV reactivation after rituximab therapy have had negative anti-HBs at the time of the HBV flares [1,20], with the exception of one case report [21]. In that case, Miyagawa et al reported that one patient with persistent antiHBs had hepatitis caused by a mutated HBV strain that did not produce HBsAg [21]. In our study, no patient with initial antiHBs titers greater than 100 mIU/mL lost anti-HBs, suggesting low risk of HBV reactivation after rituximab therapy.…”

Section: Discussionmentioning

confidence: 92%

Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy

Pei

Wang

et al. 2012

Ann Hematol

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Hepatitis B virus (HBV) reactivation is a well-known complication after rituximab therapy in patients with B cell lymphoma. Traditionally, hepatitis B surface antibody (anti-HBs) is a protective antibody, but the effect of rituximab on these antibodies has not been well studied. In 29 B cell lymphoma patients who were positive for anti-HBs before rituximab therapy, anti-HBs serologies before and after rituximab therapy were compared. Anti-HBs titers after rituximab treatment were significantly lower (P < 0.001) than those before treatment. None of the ten cases with pre-treatment anti-HBs titers above 100 mIU/mL became negative for anti-HBs after rituximab therapy. In contrast, 8 of the 19 patients with pre-treatment anti-HBs titers below 100 mIU/mL lost their anti-HBs (P = 0.027). Of these, one patient developed HBsAg seroreversion and HBV reactivation after rituximab therapy. Regarding patients with loss of anti-HBs or not, there was no significant difference in pre- and post-treatment immunoglobulin G levels between both groups. The rate of anti-HBs loss increased with advanced lymphoma stage and international prognostic index (P = 0.002 and <0.001, respectively). Multiple logistic regression analysis showed that pre-treatment anti-HBs titer is the only independent factor influencing the loss of anti-HBs (per one log mIU/mL, odds ratio, 0.003; 95% confidence interval, 0.000-0.302; P = 0.014). In conclusion, we found that anti-HBs titers decreased significantly (P < 0.001) after rituximab treatment. B cell lymphoma patients with low pre-treatment anti-HBs titers (<100 mIU/mL) were more likely to lose anti-HBs antibodies and were at risk of HBV reactivation after rituximab immunochemotherapy.

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Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximab

Cited by 20 publications

References 61 publications

Hepatitis B virus reactivation with a rituximab-containing regimen

Hepatitis B virus reactivation with a rituximab-containing regimen

Occult Hepatitis B Virus Infection: Detection and Significance

Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy

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