Occult hepatitis B virus infection: a case of reactivation in a patient receiving immunosuppressive treatment for allogeneic bone marrow transplantation.

The presence of hepatitis B virus (HBV) genome in HBsAg-negative subjects is known as occult HBV infection1. This particular form of hepatitis, already recognised in the 1980s, has been confirmed and studied using molecular biology techniques. In fact, occult infection is usually associated with the presence of anti-HBc and anti-HBs, but given the relatively high percentage (approximately 20%) of subjects who are negative for all markers1, the introduction of a test to detect HBV DNA was fundamental. Occult infection is related in some cases to mutant viruses that are not detectable by the commonly used tests; it has also been observed that the reactivation of HBV related to variants of the viral genome often has an unfavourable clinical prognosis2,3. Much more frequently, however, an occult infection is associated with strong suppression of viral replication, which is responsible both for the negativity for HBsAg and the undetectable or very low levels of HBV DNA in the serum, although this latter can be found in liver tissue4,5. An occult infection can have a important impact in various different clinical settings, including transmission through blood transfusion or organ transplants6,7 and reactivation following immunosuppressive therapy. Indeed, it has been shown that the host's immune response, co-infections (e.g. with hepatitis C virus) and epigenetic factors all play significant roles in occult infection8. We present the case of a Georgian child negative for HbsAg who, after receiving an allogeneic bone marrow transplant and immunosuppressive therapy, was found to be positive for HBV. We then describe the investigations conducted in order to determine whether this was due to a new infection or reactivation of an occult infection.

[1]  R. Bruno,et al.  Prophylaxis and treatment of hepatitis B in immunocompromised patients. , 2007, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[2]  G. Raimondo,et al.  Occult hepatitis B virus infection. , 2007, Journal of hepatology.

[3]  T. Umemura,et al.  Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region , 2006, European journal of haematology.

[4]  W. Yeo,et al.  Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy , 2006, Hepatology.

[5]  J. Angel,et al.  Reactivation of hepatitis B infection following allogeneic bone marrow transplantation in a hepatitis B-immune patient: case report and review of the literature. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  W. Au,et al.  Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. , 2005, Journal of hepatology.

[7]  M. Asaka,et al.  Progressive Disappearance of Anti-Hepatitis B Surface Antigen Antibody and Reverse Seroconversion after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Previous Hepatitis B Virus Infection , 2005, Transplantation.

[8]  P. Colson,et al.  Fulminant hepatitis B associated with a specific insertion in the basal core promoter region of hepatitis B virus DNA after immunosuppressive treatment. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  Pietro Andreone,et al.  Clinical outcome of HBeAg‐negative chronic hepatitis B in relation to virological response to lamivudine , 2004, Hepatology.

[10]  F. Fabrizi,et al.  Lamivudine for the treatment of hepatitis B virus-related liver disease after renal transplantation: meta-analysis of clinical trials , 2004, Transplantation.

[11]  D. Fong,et al.  Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. , 2003, Gastroenterology.

[12]  M. Torbenson,et al.  Occult hepatitis B. , 2002, The Lancet. Infectious diseases.

[13]  M. Aljurf,et al.  Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease , 2002, Bone Marrow Transplantation.

[14]  T. Koike,et al.  [Reactivation of hepatitis B virus after autologous peripheral blood stem cell transplantation in patients with positive hepatitis B surface antibodies]. , 2000, [Rinsho ketsueki] The Japanese journal of clinical hematology.

[15]  P. Vereerstraeten,et al.  Reactivation of hepatitis B after transplantation in patients with pre-existing anti-hepatitis B surface antigen antibodies: report on three cases and review of the literature. , 1998, Transplantation.

[16]  C. Rieux,et al.  Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc. , 1998, Transplantation.

[17]  A. Mason,et al.  Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen , 1998, Hepatology.

[18]  H. Greinix,et al.  Hepatitis B virus clearance by transplantation of bone marrow from hepatitis B immunised donor , 1997, The Lancet.

[19]  H. Blum,et al.  Latent hepatitis B virus infection with full-length viral genome in a patient serologically immune to hepatitis B virus infection. , 2008, Liver.

[20]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.