Lamivudine treatment for reverse seroconversion of hepatitis B 4 years after allogeneic bone marrow transplantation

Hashino, S; Nozawa, Atsushi; Izumiyama, Koh; Yonezumi, Masakatu; Chiba, Kazuhiro; Kondo, Takeshi; Suzuki, Shinya; Hige, Shuhei; Asaka, Masahiro

doi:10.1038/sj.bmt.1703387

Cited by 21 publications

(14 citation statements)

References 8 publications

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“…In the present study, only one of three patients with reverse seroconversion had biochemical signs of liver damage. In contrast, the vast majority of reported patients with reverse seroconversion after allo-HSCT were identified only because they developed clinical hepatitis (Table 2); (iii) changes in immunosuppressive therapy strategies, for example, the use of mycophenolate mofetil as given to the majority of our patients, could influence risk of HBV reactivation; (iv) HBV reactivation has been reported as late as 2 years after complete clearance of anti-HBs, anti-HBc and anti-HBe 15 or 51 months after HSCT and 40 months after cessation of immunosuppressive therapy, 20 suggesting that HBV reactivation was due not only to immunosuppression but also to reconstitution with donor-derived naive immunity against HBV. Therefore, the risk of reactivation of latent HBV could increase in long-term allo-HSCT survivors and would be underestimated in studies with a short follow-up.…”

Section: Discussionmentioning

confidence: 99%

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

Knöll

Boehm

Hahn

et al. 2004

Bone Marrow Transplant

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Summary:Hepatitis B virus (HBV) reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is well known in HBsAg-positive carriers but has only occasionally been reported in patients with resolved HBV infection. We investigated six allo-HSCT recipients with pretransplant anti-HBs and anti-HBc antibodies for serologic markers of HBV infection and for the presence of HBV-DNA in serum. Reverse seroconversion, that is, reappearance of HBsAg after a gradual loss of anti-HBs, but no severe liver damage was observed in three patients at 14, 22 and 12 months after HSCT, respectively. There was an increase in HBV-DNA concentration prior to reverse seroconversion. One patient was repeatedly HBV-DNA positive (10 2 -10 3 copies/ml) without reverse seroconversion. Sequencing of the HBsAg and precore region derived from the four HBV-DNA-positive patients showed no relevant mutations. In conclusion, this study demonstrated a high risk (50%) of reverse seroconversion in allo-HSCT recipients with resolved HBV infection. A highly sensitive HBV-DNA assay (TaqMan-PCR) allowed early identification of the individual patients at risk. Reactivation of HBV is a well-known complication in patients with chronic hepatitis B virus (HBV) infection undergoing immunosuppressive or cytotoxic therapy. HBsAg-positive recipients of haematopoietic stem cell transplantation (HSCT) have a higher incidence of clinical hepatitis associated with HBV reactivation, most often during immunological recovery. 1 The proposed mechanism is an increase in viral replication in the liver during the period of immunosuppression, followed by an immune mediated destruction of infected hepatocytes after cessation of immunosuppressive therapy. The risk of fatal HBV liver disease among patients who are persistently HBsAg positive after HSCT is approximately 12%. 2 HBV reactivation has also been observed in HBsAgnegative HSCT recipients with antibodies against HBs and HBc antigens (anti-HBs and anti-HBc, respectively), that is, in patients with resolved HBV infection. Therefore, the presence of these antibodies does not necessarily reflect viral clearance. In individuals with resolved infection, HBV has been shown to persist in a 'latent' state in the liver and in peripheral blood mononuclear cells. 3,4 However, there are no data about the percentage of patients who keep a transcriptionally active HBV genome for years or decades after complete clinical and serological recovery from acute hepatitis. In these patients, immunosuppression and loss of recipient B and T cell repertoire during allo-HSCT may lead to viral reactivation with reappearance of HBsAg after a gradual loss of anti-HBs; this has been termed 'reverse seroconversion'. To further characterize the risk of HBV reactivation in allo-HSCT recipients with resolved HBV infection, we investigated consecutive serum samples from six anti-HBs and anti-HBc-positive patients after allo-HSCT for the presence of HBV-DNA and for serologic markers of HBV infection. Methods and patients PatientsFrom 1...

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Section: Discussionmentioning

confidence: 99%

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

Knöll

Boehm

Hahn

et al. 2004

Bone Marrow Transplant

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“…Overall, a sizable proportion of patients with HBsAg seroreversion linked to immunosuppression, ultimately developed fulminant hepatitis or hepatic decompensation or progressive chronic hepatitis B. [13][14][15][16][17][18][23][24][25][26][28][29][30][31][32][33][34][35] In our study, no patient with HBV reactivation experienced acute liver failure, but two had acute icteric hepatitis B and all become HBeAg-positive chronic carriers. Though recommended, anti-HBV treatment of these patients is challenged by the high viral load, the immunosuppression status, the presence of comorbidities and the high risk of drug resistance in the long term.…”

Section: Yes Nomentioning

confidence: 99%

Risk of hepatitis B surface antigen seroreversion after allogeneic hematopoietic SCT

Viganò

Vener

Lampertico

et al. 2010

Bone Marrow Transplant

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Allogeneic hematopoietic SCT (HSCT) increases the risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) carriers but the incidence, risk factors and course of HBV reactivation after HSCT in HBsAg-negative/anti-hepatitis B core antigen (antiHBc)-positive recipients are not well known. A total of 50 HBsAg-negative/anti-HBc-positive HSCT recipients with onco-hematological diseases, underwent sequential clinical and laboratory examinations, including serum HBsAg, during follow-up. Serum HBV DNA collected at HSCT was retrospectively amplified by a sensitive PCR assay. During 17 months of follow-up, six (12%) patients had seroreverted to HBsAg, 7-32 months after HSCT, with 1-and 5-year cumulative rates of 13 and 22%. HBsAg seroreversion was associated with serum HBeAg higher than 8 log 10 copies per ml HBV DNA and a 1.5 to 36 fold increase of serum alanine aminotransferase leading to HBeAg-positive chronic hepatitis B in all patients. Patients with chronic onco-hematological disease and long-lasting immunosuppression following HSCT had a higher risk of HBsAg seroreversion independently of serum HBV DNA levels at HSCT. HBsAg-negative/antiHBc-positive HSCT recipients with chronic onco-hematological disease carry a significant risk of HBsAg seroreversion and HBeAg-positive chronic hepatitis B, independently of serum levels of HBV DNA at transplantation.

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“…[39][40][41][42][43][44][45][46][47][48][49][50] Based on reported series, 47,[51][52][53][54] the frequency of seroreversion ranges between 14% and 50% (Table 1A). The wide range reported could be explained by risk estimation based on small series, missed cases of seroreversion due to absence of symptoms, and variable duration of posttransplant follow-up.…”

Section: Reactivation Inmentioning

confidence: 99%

Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy

2006

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It is estimated conservatively that more than one third of the world's population has been infected with the hepatitis B virus (HBV) and that there are 350 million people with chronic infection, 75% of whom live in Southeast Asia and the Western Pacific regions. [1][2][3] Reactivation of HBV infection is now a well-recognized complication in infected patients who undergo cytotoxic chemotherapy for cancer. The condition ranges from asymptomatic self-limiting anicteric hepatitis to severe, potentially fatal progressive decompensated hepatitis. With the increasing use of potent cytotoxic chemotherapy, reactivation of hepatitis B in endemic regions is becoming a common clinical problem. This adversely affects advances made in various forms of cancer therapy. In this review, we consider the diagnosis, prevention, and management of HBV reactivation in association with chemotherapy and hematopoietic stem cell transplantation, particularly in light of the availability of effective prophylactic antiviral therapy.Reactivation of HBV was first described by Wands et al., 4 who in 1975 reported the condition in 20 patients with lympho-and myeloproliferative disorders. Most of the cases reported since were similar in patients with hematological malignancies-in particular, lymphomas. [4][5][6][7][8][9][10][11][12][13][14][15][16] The skewed observations may be due to the fact that these patients are often subjected to intense myelosuppressive treatment regimens, the malignancies per se are often associated with an immunocompromised state, and the patients have been consistently reported to have a higher rate of hepatitis B surface antigen (HBsAg) seropositivity than the normal population. 9,[17][18][19] Over the past decade, HBV reactivation has been increasingly observed in patients with solid tumors. [18][19][20][21][22] In patients with hepatocellular carcinoma (85% of whom have chronic HBV infection in Southern China 3,23 ), hepatitis following systemic chemotherapy has been reported in 60% 20,24 ; this is mostly attributed to HBV reactivation, which has a 30% mortality rate. 20 In other cancer subpopulations, the incidence of HBV reactivation ranges between 25% and 40%. 10,15,18,21,25 In the setting of hematopoietic stem cell transplantation (HSCT) for various hematological and oncological conditions, HBV reactivation has been reported in over 50% of patients. [26][27][28] This is related to the intense chemotherapy with or without total body irradiation, and the coexistence of acute graft-versus-host disease. 28 Although the frequency of viral reactivation among HBsAg-positive patients with cancer would be expected to be the same irrespective of geographical area, the prevalence of HBV infection varies between different populations from 10% to 25% in endemic areas to less than 1% in others. 3,10,29 As a result, there would be proportional difference in the incidence of viral reactivation in a given population. Definitions and DiagnosisIn early reports, the diagnosis of HBV reactivation was based on HBsAg and hepatitis B ...

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Lamivudine treatment for reverse seroconversion of hepatitis B 4 years after allogeneic bone marrow transplantation

Cited by 21 publications

References 8 publications

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

Risk of hepatitis B surface antigen seroreversion after allogeneic hematopoietic SCT

Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy

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