Review
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World J Hematol. May 6, 2014; 3(2): 29-43
Published online May 6, 2014. doi: 10.5315/wjh.v3.i2.29
Anti-CD20 monoclonal antibodies and associated viral hepatitis in hematological diseases
Shih-Hung Yang, Chiun Hsu, Ann-Lii Cheng, Sung-Hsin Kuo
Shih-Hung Yang, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan
Shih-Hung Yang, Chiun Hsu, Ann-Lii Cheng, Sung-Hsin Kuo, Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan
Shih-Hung Yang, Chiun Hsu, Ann-Lii Cheng, Sung-Hsin Kuo, Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
Chiun Hsu, Ann-Lii Cheng, Sung-Hsin Kuo, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
Ann-Lii Cheng, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
Author contributions: All authors contributed equally to the work.
Author contributions: Yang SH conducted the literature review and drafted the article; Hsu C and Cheng AL wrote the manuscript; Kuo SH revised the content and approved the final version for publication.
Supported by Research grants NSC 101-2321-B-002-032 and NSC 101-2314-B-002-157-MY3 from the National Science Council, Taiwan; NHRI-EX102-10239BI, and NHRI-EX102-10239BI from the National Health Research Institutes, Taiwan; and DOH100-TD-B-111-001 from the Department of Health, Taiwan
Correspondence to: Sung-Hsin Kuo, MD, PhD, Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. shkuo101@ntu.edu.tw
Telephone: +886-2-23123456 Fax: +886-2-23123456
Received: November 13, 2013
Revised: January 27, 2014
Accepted: March 17, 2014
Published online: May 6, 2014
Processing time: 188 Days and 15.7 Hours
Abstract

Over the past decade, the administration of anti-CD20 monoclonal antibodies such as rituximab has demonstrated various degrees of effectiveness and has improved patients’ outcomes during the treatment of autoimmune hematological disorders and hematological malignancies. However, the depletion of B-cells, the distribution of T-cell populations, and the reconstruction of host immunity resulting from the use of anti-CD20 monoclonal antibodies potentially lead to severe viral infections, such as hepatitis B virus (HBV), hepatitis C virus (HCV), parvovirus B19, and herpes viruses, in patients who are undergoing immune therapy or immunochemotherapy. Of these infections, HBV- and HCV-related hepatitis are a great concern in endemic areas because of the high morbidity and mortality rates in untreated patients. As a result, prophylaxis against HBV infection is becoming a standard of care in these areas. Parvovirus B19, a widespread pathogen that causes red blood cell aplasia in immunocompromised hosts, also causes hepatitis in healthy individuals. Recently, its association with hepatitis was recognized in a patient treated with rituximab. In addition, adenovirus, varicella-zoster virus, hepatitis E virus, and rituximab itself have been linked to the occurrence of hepatitis during or after rituximab treatments. The epidemiologies and pathogeneses of these etiologies remain unknown. Because of the increasing use of anti-CD20 monoclonal antibodies for the treatment of hematological malignancies or autoimmune hematological disorders, it is imperative that physicians understand and balance the risks of hepatotropic virus-associated hepatitis against the benefits of using anti-CD20 monoclonal antibodies.

Keywords: CD20; Monoclonal antibody; Hepatitis; Hepatitis B virus; Hepatitis C virus

Core tip: Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies and autoimmune disorders. These agents produce prolonged B-cell depletion and significant immune suppression. In this review, we summarized the clinical use of anti-CD20 monoclonal antibodies and the reports of acute or chronic hepatitis associated with the use of these agents. Most of these hepatitis cases had viral etiologies. We discuss the mechanisms of the hepatitis caused by these drugs. These infections not only interrupted the immunotherapy but are also associated with high mortality and morbidity. This review may prompt physicians to monitor patients’ liver function more closely and to provide adequate prophylaxis while using these agents.