Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease

Seth, Pankaj; Alrajhi, Abdulrahman A.; Kagevi, I; Chaudhary, Mohammad A.; Colcol, E; Sahovic, Entezam; Aljurf, Mahmoud; Gyger, M

doi:10.1038/sj.bmt.1703614

Cited by 85 publications

(77 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 In the present study, four patients had extensive cGVHD, and three of them showed reverse seroconversion. Only one patient with extensive cGVHD showed no evidence of viral reactivation (ID 6): she was the only recipient of stem cells from a vaccinated donor, but also the patient with the shortest follow-up (15 months).…”

Section: Discussionmentioning

confidence: 93%

“…8,9 This difference could be explained by a variety of reasons: (i) In our study -as in others -the risk had to be estimated from a small number of available allo-HSCT patients with pretransplant anti-HBs and anti-HBc antibodies; (ii) detection of HBV reactivation might be missed in the absence of clinical symptoms. In the present study, only one of three patients with reverse seroconversion had biochemical signs of liver damage.…”

Section: Discussionmentioning

confidence: 99%

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: 93%

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

View full text Add to dashboard Cite

show abstract

“…21 The rituximab ϩ steroid-containing chemotherapy has recently been demonstrated to be a risk factor for HBV reactivation in HBsAgnegative patients, 5,6 HBV reactivation is a well-known complication after allogeneic hematopoietic stem cell transplantation (HSCT) because of the long-term use of immunosuppressive drugs and the gradual immune reconstitution after HSCT. 22,23 Additional host risk factors for HBV reactivation have been reported as male sex, 6 diagnosis of lymphoma, 3 absence of anti-HBs at baseline, 6,24 and decrease of anti-HBs titers after immunosuppressive therapy. 25 The risk classification for HBV reactivation according to serum HBV markers and the intensity of immunosuppressive therapy can be determined based on the current evidence ( Figure 1).…”

Section: Risk Of Hbv Reactivation After Immunosuppressive Therapymentioning

confidence: 99%

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

Kusumoto

Tobinai

2014

Hematology

View full text Add to dashboard Cite

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication after anti-B-cell therapy. It can develop not only in patients seropositive for hepatitis B surface antigen (HBsAg), but also in those with resolved HBV infection who are seronegative for HBsAg but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs). The risk of HBV reactivation depends on the balance between replication of the virus and the immune response of the host. Anti-CD20 monoclonal antibody-rituximab in combination with steroid-containing chemotherapy (R-CHOP: rituximab ϩ cyclophosphamide ϩ hydroxydaunorubicin ϩ vincristine ϩ prednisone/prednisolone)-is an important risk factor for HBV reactivation in HBsAg-negative patients. More obviously, HBsAg-positive patients are considered to be at very high risk for HBV reactivation and, in the rituximab era, 59%-80% of these patients develop HBV reactivation after R-CHOP-like chemotherapy. Patients with resolved HBV infection should also be considered at high risk of HBV reactivation, the incidence of which is reported to be 9%-24% in such lymphoma patients. All patients should be screened to identify risk groups for HBV reactivation before initiating anti-B-cell therapy by measuring serum HBV markers including HBsAg, anti-HBc and anti-HBs. To prevent the development of hepatitis due to HBV reactivation after anti-B-cell therapy, antiviral prophylaxis is recommended for HBsAg-positive patients and/or patients in whom HBV DNA is detectable at baseline, whereas regular monitoring of HBV DNA-guided preemptive antiviral therapy is a reasonable and useful approach for patients with resolved HBV infection. Learning Objectives• To become familiar with the risk of HBV reactivation in patients who receive anti-B-cell therapy • To manage such high-risk patients successfully using antiviral prophylaxis or by HBV DNA-monitoring-guided preemptive antiviral therapy

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

Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease

Abstract: Summary:We conducted a retrospective study with the aim of identifying risk factors and clinical characteristics associated with HBV reactivation and clinical flare after allogeneic stem cell transplantation (aSCT). We

Cited by 85 publications

References 47 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

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

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

Contact Info

Product

Resources

About