Hepatitis B Virus Reactivation in a Patient With Chronic GVHD After Allogeneic Peripheral Blood Stem Cell Transplantation

Sakamaki, Hisashi; Sato, Yoriko; Mori, Shinichiro; Ohashi, Kazuteru; Tanikawa, S; Akiyama, Hideki; Sasaki, Tsuneo; Hiruma, Kiyoshi

doi:10.1007/bf02982072

Cited by 22 publications

(22 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21 HBV-associated liver disease after allo-HSCT is often temporary and not serious, but fatal liver damage has been reported in some cases. 16,18 In the three patients with reverse seroconversion reported herein, there was mild hepatitis in only one patient, followed by spontaneous clearance of HBsAg. The other two patients had no biochemical signs of liver damage but became chronic carriers with high-level HBV viraemia.…”

Section: Discussionmentioning

confidence: 84%

“…During early follow-up, they had low-level viraemia and there was a 2 log increase in HBV-DNA concentration starting 2-4 months prior to reverse seroconversion. Similarly, Sakamaki et al 18 reported one patient who was HBV-DNA positive by real-time PCR with 89 copies/ml serum (branched DNA assay negative) about 10 months after allo-HSCT. After an additional 12 months he developed fatal liver damage with reverse seroconversion and HBV-DNA concentrations of 2 Â 10 6 copies/ml.…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

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

Knöll

Boehm

Hahn

et al. 2004

Bone Marrow Transplant

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 87%

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

Knöll

Boehm

Hahn

et al. 2004

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…[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

View full text Add to dashboard Cite

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 ...

show abstract

“…It was reported that two types of PBSCT, i.e., autologous PBSCT (auto-PBSCT) and allo-PBSCT, induce post-transplantation de novo hepatitis B. [14][15][16][17][18][19] Because immunosuppressive therapy is performed over a long period to suppress chronic GVHD particularly after allo-PBSCT, the transplantation potentially induces de novo hepatitis B at a higher incidence than auto-PBSCT and even after a long post-transplantation period. [14][15][16] Large-scale studies on de novo hepatitis B have been conducted recently and typical drugs that could induce HBV reactivation have been identified.…”

Section: Discussionmentioning

confidence: 99%

“…[14][15][16][17][18][19] Because immunosuppressive therapy is performed over a long period to suppress chronic GVHD particularly after allo-PBSCT, the transplantation potentially induces de novo hepatitis B at a higher incidence than auto-PBSCT and even after a long post-transplantation period. [14][15][16] Large-scale studies on de novo hepatitis B have been conducted recently and typical drugs that could induce HBV reactivation have been identified. [13,20,21] In general, the immunosuppressants were categorized into low-, moderate-, or high-risk groups based on estimates of reactivation using available evidence.…”

Section: Discussionmentioning

confidence: 99%

Development of de novo hepatitis B in patient during follow-up of liver-graft-versus-host disease associated with allogeneic peripheral blood stem cell transplantation

Michikawa

Ikeda

Okuse

et al. 2015

CRIM

View full text Add to dashboard Cite

A 66-year-old female patient with acute myeloid leukemia underwent remission-induction therapy and allogeneic peripheral stem cell transplantation. The patient was found to have a resolved hepatitis B virus (HBV) infection, as shown by her positivity for the hepatitis B surface (HBs) antibody and hepatitis B core antibody and negativity for the HBs antigen and HBV-DNA. Administration of an immunosuppressant was started after transplantation for the prevention of graft-versus-host disease (GVHD), and hepatic impairment developed four months after transplantation. No changes were observed in serum HBV-related marker levels, and a liver biopsy revealed GVHD. The course of hepatic impairment was followed up with the diagnosis of liver GVHD, without determining the level of HBV-related markers. Hepatic impairment recurred 13 months after transplantation. Determination of the HBV-related markers showed that the patient was positive for the HBs antigen and HBV-DNA. The patient was diagnosed as having de novo hepatitis B, and the hepatitis improved after the start of anti-viral therapy. In administering immunosuppressive therapy and chemotherapy for patients with a resolved HBV infection, it is important to test for viral markers regularly by paying constant attention to the possible onset of de novo hepatitis B, despite the existing hepatic disease.

show abstract

Hepatitis B Virus Reactivation in a Patient With Chronic GVHD After Allogeneic Peripheral Blood Stem Cell Transplantation

Cited by 22 publications

References 14 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

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

Development of de novo hepatitis B in patient during follow-up of liver-graft-versus-host disease associated with allogeneic peripheral blood stem cell transplantation

Contact Info

Product

Resources

About