Correspondence
Correction
Hepatitis B Virus Infection
N Engl J Med 2009; 360:304-306January 15, 2009
- Article
To the Editor:
In his review article on drug therapy for hepatitis B virus (HBV) infection, Dienstag (Oct. 2 issue)1 does not mention the use of prophylactic antiviral drugs in patients treated with chemotherapy, stem-cell transplantation, or immunosuppressive agents. Reactivation of hepatitis B (including death2) has been described in patients who were anti–hepatitis B core–positive and hepatitis B surface antigen (HBsAg)–negative.3 Several guidelines and discussions4,5 on this topic have been published, recommending lamivudine as prophylaxis. This is an important issue that should have been included in the review article because there is an increasing population of patients who are at risk for this threatening complication.
5 ReferencesJuan Miguel Bergua, M.D.
Carmen Cabrera, M.D.
Helena Bañas, M.D.
Hospital San Pedro de Alcántara, 10003 Cáceres, Spain
jmbergua@terra.es 1
Dienstag JL . Hepatitis B virus infection. N Engl J Med 2008;359:1486-1500
Full Text | Web of Science | Medline2
Gwak GY ,Koh KC ,Kim HY . Fatal hepatic failure associated with hepatitis B virus reactivation in a hepatitis B surface antigen-negative patient with rheumatoid arthritis receiving low dose methotrexate. Clin Exp Rheumatol 2007;25:888-889
Web of Science | Medline3
Targhetta C ,Cabras MG ,Mamusa AM ,Mascia G ,Angelucci E . Hepatitis B virus-related liver disease in isolated anti-hepatitis B-core positive lymphoma patients receiving chemo- or chemo-immune therapy. Haematologica 2008;93:951-952
CrossRef | Web of Science | Medline4
Loomba R ,Rowley A ,Wesley R , et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008;148:519-528
Web of Science | Medline5
Lalazar G ,Rund D ,Shouval D . Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007;136:699-712[Erratum, Br J Haematol 2007;137:81.]
CrossRef | Web of Science | Medline
To the Editor:
We believe it would be relevant to stress that nucleotide and nucleoside analogues can prevent HBV reactivation in patients undergoing immunosuppression who have either inactive disease (HBsAg-positive, hepatitis B e antigen [HBeAg]–negative, anti-HBe–positive, normal aminotransferase levels, HBV DNA of <20,000 IU per milliliter, and anti–hepatitis B core IgM–negative) or occult disease (HBsAg-negative, with markers of previous HBV contact [i.e., isolated hepatitis B core antigen]).1 HBV reactivation is a known and feared complication in patients who are undergoing immunosuppressive regimens that favor viral replication and, consequently, widespread hepatocyte infection. After immunocompetence is regained, immunomediated hepatic damage develops, leading to acute hepatitis or hepatic failure.2 Reactivation has also been described in patients receiving immunosuppressive agents such as glucocorticoids, azathioprine, and infliximab in various clinical settings (gastroenterology, dermatology, oncology, and rheumatology).1 Preemptive treatment with nucleotide and nucleoside analogues effectively reduces the risk of HBV reactivation in hematology patients,3 even if protocols and the issue of treating occult carriers are still debated.4 The search for inactive or occult HBV infection should be mandatory in all patients undergoing immunosuppression, since effective prophylaxis is now available.
4 ReferencesMassimo Marignani, M.D.
M. Christina Cox, M.D.
Gianfranco Delle Fave, M.D.
University La Sapienza, 00189 Rome, Italy
mmarignani@hotmail.com 1
Marzano A ,Angelucci E ,Andreone P , et al. Prophylaxis and treatment of hepatitis B in immunocompromised patients. Dig Liver Dis 2007;39:397-408
CrossRef | Medline2
Perrillo RP . Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 2001;120:1009-1022
CrossRef | Web of Science | Medline3
Loomba R ,Rowley A ,Wesley R , et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008;148:519-528
Web of Science | Medline4
Cox MC, Marignani M, Veggia B, et al. Is management with lamivudine always the appropriate choice for HBV patients with onco-hematologic diseases? Ann Hematol 2008 September 20 (Epub ahead of print).
To the Editor:
In his report on the worldwide prevalence of HBV infection, Dienstag places Italy among countries with a medium endemic level (defined as a prevalence of HBsAg of >2%). Actually, the epidemiology of HBV infection has changed markedly in Italy during the past three decades. In the early 1980s, Italy was a country with a medium endemic level, with an HBsAg prevalence of 3.4%. The prevalence dropped to 1.6% in 1990.1 Currently, Italy is at a very low endemic level, with an HBsAg prevalence of less than 1%, as clearly stated by some surveys, which were performed from 1994 through 2008 (Table 1Table 1
Prevalence of Hepatitis B Surface Antigen (HBsAg) in Italy, According to Recent Surveys.).2,3 At the same time, a decrease in the prevalence of HBeAg and hepatitis delta positivity was observed among HBV carriers.Since 1991, HBV vaccination has been mandatory in Italy for all newborns and adolescents, and coverage of 94% has been reached. According to the National Surveillance System, the incidence of acute HBV infection per 100,000 inhabitants declined from 5.1 in 1991 to 1.3 in 2005.4
4 ReferencesLaura Milazzo, M.D.
Spinello Antinori, M.D.
University of Milan, 20157 Milan, Italy
laura.milazzo@unimi. it 1
D'Amelio R ,Matricardi PM ,Biselli R , et al. Changing epidemiology of hepatitis B in Italy: public health implications. Am J Epidemiol 1992;135:1012-1018
Web of Science | Medline2
Da Villa G ,Romano L ,Sepe A , et al. Impact of hepatitis B vaccination in highly endemic area of south Italy and long-term duration of anti-HBs antibody in two cohorts of vaccinated individuals. Vaccine 2007;25:3133-3136
CrossRef | Web of Science | Medline3
Fabris P ,Baldo V ,Baldovin T , et al. Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population. J Clin Gastroenterol 2008;42:527-532
CrossRef | Web of Science | Medline4
Mele A ,Tosti ME ,Mariano A , et al. Acute hepatitis B 14 years after the implementation of universal vaccination in Italy: areas of improvement and emerging challenges. Clin Infect Dis 2008;46:868-875
CrossRef | Web of Science | Medline
Author/Editor Response
Bergua et al. and Marignani et al. point out the importance of beginning antiviral therapy preemptively in patients with HBV infection (whether active, inactive, or even recovered) who undergo immunosuppressive chemotherapy, without which HBV reactivation can result in substantial morbidity and mortality. My brief review of antiviral therapy for HBV infection had space constraints, which prevented me from addressing the topic of patients with therapeutic immunosuppression, as well as other special populations (e.g., children, pregnant women, organ-allograft recipients, and patients with renal failure or extrahepatic disease). For a thorough overview of antiviral therapy in these specific populations in general and in immunosuppressed patients in particular, readers should consult comprehensive practice guidelines issued by national organizations,1,2 as well as the October 2008 proceedings of the National Institutes of Health Consensus Development Conference on Management of Hepatitis B.3
I thank Milazzo and Antinori for pointing out the declining prevalence of HBV infection in Italy, a pattern evolving in other countries with either a low or moderate prevalence during the contemporary era of HBV vaccination. My intent in showing the world map of HBV prevalence was to emphasize the difference in clinical expression of HBV infection on the basis of the time in life when the infection is acquired. This factor, in turn, is a reflection of the prevalence of the infection in the general population, with a high prevalence in countries in which there is primarily perinatal infection and a low prevalence in countries in which there is primarily adult infection. I was not able to update the current world map on a country-by-country basis and relied instead on data in the public domain derived from the Centers for Disease Control and Prevention (CDC).4 On September 19, 2008, 2 weeks before the publication of my article in the Journal, the CDC published an updated world map showing the prevalence of HBV infection, in which Italy was categorized as a low-prevalence country.5 A corrected version of the world map in my article, which also corrects other areas in western and northern Europe, is available at NEJM.org.
5 ReferencesJules L. Dienstag, M.D.
Massachusetts General Hospital, Boston, MA 02114
jdienstag@partners.org 1
Lok AS ,McMahon BJ . Chronic hepatitis B. Hepatology 2007;45:507-539[Erratum, Hepatology 2007;45:1347.]
CrossRef | Web of Science | Medline2
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2008 October 29 (Epub ahead of print).
3
NIH Consensus Development Conference: management of hepatitis B. (Accessed December 22, 2008, at http://consensus.nih.gov/2008/2008HepatitisBCDC120main.htm.)
4
Mast EE ,Margolis HS ,Fiore AE , et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). 1. Immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54:RR-16:1-31[Erratum, MMWR Morb Mortal Wkly Rep 2006;55:158-9, 2007;56:1267.]
Medline5
Weinbaum CM ,Williams I ,Mast EE , et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008;57:1-20
Medline
