Anna S.F. Lok, MD; John W. Ward, MD; Robert P. Perrillo, MD; Brian J. McMahon, MD; T. Jake Liang, MD
Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the CDC.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2603.
Requests for Single Reprints: Anna S.F. Lok, MD, Division of Gastroenterology and Hepatology, University of Michigan Health System, 3110G Taubman Center, SPC 5368, 1500 East Medical Center Drive, Ann Arbor, MI 48109; e-mail, mailto:email@example.com.
Current Author Addresses: Dr. Lok: Division of Gastroenterology and Hepatology, University of Michigan Health System, 3110G Taubman Center, SPC 5368, 1500 East Medical Center Drive, Ann Arbor, MI 48109.
Dr. Ward: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Mailstop G-37, 1600 Clifton Road, Atlanta, GA 30333.
Dr. Perrillo: Baylor University Medical Center, Sammons Center Building, 3410 Worth Street, Dallas, TX 75246.
Dr. McMahon: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, 4315 Diplomacy Drive, Anchorage, AK 99508.
Dr. Liang: American Association for the Study of Liver Diseases, 1001 North Fairfax Street, Suite 400, Alexandria, VA 22314.
Author Contributions: Conception and design: A.S.F. Lok, J.W. Ward, R.P. Perrillo, B.J. McMahon, T.J. Liang.
Analysis and interpretation of the data: A.S.F. Lok, J.W. Ward, R.P. Perrillo, B.J. McMahon, T.J. Liang.
Drafting of the article: A.S.F. Lok, J.W. Ward, R.P. Perrillo.
Critical revision of the article for important intellectual content: A.S.F. Lok, J.W. Ward, R.P. Perrillo, B.J. McMahon, T.J. Liang.
Final approval of the article: A.S.F. Lok, J.W. Ward, R.P. Perrillo, B.J. McMahon, T.J. Liang.
Provision of study materials or patients: R.P. Perrillo.
Administrative, technical, or logistic support: A.S.F. Lok.
Collection and assembly of data: A.S.F. Lok, R.P. Perrillo, T.J. Liang.
Lok A., Ward J., Perrillo R., McMahon B., Liang T.; Reactivation of Hepatitis B During Immunosuppressive Therapy: Potentially Fatal Yet Preventable. Ann Intern Med. 2012;156:743-745. doi: 10.7326/0003-4819-156-10-201205150-00013
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Published: Ann Intern Med. 2012;156(10):743-745.
Reactivation of hepatitis B virus (HBV) replication, an abrupt increase or reappearance of serum HBV DNA in a patient with chronic or past HBV infection, is a known complication of immunosuppressive therapy. This condition can lead to hepatocellular injury, elevated alanine aminotransferase levels, symptoms of acute hepatitis, liver failure, and even death (1). Many physicians who regularly prescribe immunosuppressive therapy unfortunately do not recognize this potentially fatal condition.
Hepatitis B virus reactivation has been best studied in patients receiving chemotherapy for hematologic cancer, but it has also been reported during treatment of solid tumors (2). In addition, reactivation can occur in patients receiving antirejection treatment, long-term corticosteroid therapy, and tumor necrosis factor-α inhibitors (3, 4). Most cases of HBV reactivation occur in patients who are hepatitis B surface antigen (HBsAg)–positive, but it has also been reported in patients who are HBsAg-negative/hepatitis B core antibody (anti-HBc)–positive, particularly when rituximab is used (5).
Eric M.Yoshida, MD MHSc FRCP(C), FACP, Nawal Al Nahdi MD, FRCP(C)
From the Division of Gastroenterology* ,University of British Columbia, and the Vancouver General Ho
June 5, 2012
Preventing Reactivation of Hepatitis B during Immunosuppressive Therapy: Framing the Question in the Context of What a Reasonable Patient Would Want
To the Editor,
We applaud the recent paper by Lok and colleagues (1) in the Ideas and Opinions section of the Annals that provides a concise review of reactivation of hepatitis B (HBV) in the context of immunosuppressive medications, both oncologic chemotherapy and non-oncologic immunosuppression (eg. DMARDs in rheumatology). Although from a hepatology/gastroenterology perspective, HBV screening of all patients who will undergo immunosuppressive therapy with the view to starting prophylaxis with antiviral agents would seem rational and intuitive, as Lok et al observe, the idea received qualified support from the medical oncology community (2) and from practicing rheumatologists (3).
In Vancouver, our experience of fatal reactivation HBV post- chemotherapy, of which we published two of the more unusual cases, one in a HBV surface antigen negative but core antibody positive patient (4), and the second in the setting of lamivudine resistance (5) resulted in a change in the policy of the British Columbia Cancer Agency, an agency of the Provincial Health Services Authority of the Ministry of Health. The official policy towards HBV is that all patients with a hematologic malignancy undergo screening and targeted screening be undertaken for solid cancer patients who are at risk. HBV antiviral prophylaxis must be provided to all HBV carriers as well as patients who are only HBV core antibody seropositive. Last year, we performed an emergency transplant in an Asian patient in his early 60s who developed acute fulminant liver failure due to HBV reactivation post-DMARD therapy. We feel that our experience, which we would like to avoid in the future, qualifies us to make some comments. From Lok and colleagues' paper, it appears that some may argue that the evidence for screening and prophylaxis do not meet the rigors of the highest standard of evidence based medicine. We offer the opinion that since screening for HBV is easily performed and that the antiviral agents available for prophylaxis are efficacious and without significant adverse effects, a reasonable patient, knowing that reactivation can be fatal, would want prophylaxis. At the very least, the patient should be allowed to make an informed decision. Although we agree that further medical research is needed in this area, and in most areas of medicine, this is from an academic viewpoint. From the clinical viewpoint, however, what is in the best interests of the patient, must take precedence over academic debate. We note that society does not allow automobile drivers to get away with not wearing their seatbelts (even in the era of safer cars with airbags). Similarly, why would society allow patients undergoing immunosuppressive medications not to be screened for HBV and given prophylaxis if positive? A death (or liver transplant) that can be prevented is unacceptable, no matter how rare an occurrence some may consider it to be.
1. Lok ASF, Ward JW, Perillo R, McMahon BJ, Liang JT. Reactivation of hepatitis B during immunosuppresive therapy: potentially fatal yet preventable. Ann Intern Med 2012; 156: 743-45. [PMID 22586011] 2. Artz AS, Sommerfield MR, Feld JJ, Giusti AF, Kramer BS, Sabichi AL et al. American Society of Clinical Oncology provisional clinical opinion: chronic ehpatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. J Clin Oncol 2010; 28: 3199-202 [PMID: 20516452]
3. Stine JG, Khokhar OS, Charalambopoulos J, Shanmugam VK, Lewis JH. Rheumatologists' awareness of and screening practices for hepatitis B virus infection prior to initiating immunomodulatory therapy. Arthritis Care Res (Hoboken) 2010; 62: 704-11. [PMID 20461789]
4. Law JK, Ho JK, Hoskins PJ, Erb SR, Steinbrecher UP, Yoshida EM. Fatal reactivation of hepatitis B post-chemotherapy for lymphoma in a hepatitis B surface antigen-negative hepatitis B core antibody-positive patient: potential implications for future prophylaxis recommendations. Leuk Lymphoma 2005; 46: 1085-89. [PMID 16019563].
5. Law JK, Ali JA, Harrigan PR, Sherlock CH, Savage KJ, Yoshida EM. Fatal postlymphoma chemotherapy hepatitis B reactivation secondary to the emergence of a YMDD mutant strain with hepatitis B resistance in a non- cirrhotic patient. Am J Hematol 2006; 81: 969-72. [PMID 16937392]
In the area of hepatitis B, Dr. Yoshida has received honoraria for lectures sponsored by Gilead Sciences Inc and Cangene Inc. He has also been an investigator in clinical research studies sponsored by Gilead Sciences and Cangene Inc. Dr. Al Nahdi has no conflicts to declare.
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Gastroenterology/Hepatology, Hematology/Oncology, Infectious Disease, Viral Hepatitis, Liver Disease.
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