Am J Blood Res 2012;2(1):18-28
Review Article
The association of Hepatitis B virus infection with B-cell Non-Hodgkin
lymphoma – a review
Fabrizio Marcucci, Enea Spada, Alfonso Mele, Carmelo Antonio Caserta, Alessandro Pulsoni
Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute (CNESPS), Istituto Superiore di Sanità (ISS), via
Giano della Bella 34, 00162 Rome, Italy; Hepatology Association of Calabria, Vico Cartisano primo, 89134 Reggio Calabria,
Italy; Department of Hematology, “La Sapienza” University, via Benevento 6, 00161 Rome, Italy.
Received October 15, 2011; accepted November 7, 2011; Epub December 15, 2011; Published January 15, 2011
Abstract: Epidemiological studies performed over the last decade have demonstrated a positive association between
persistent, hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma
(NHL), with HBV-infected patients having a 2-3-fold higher risk to develop NHL than non-infected patients. Moreover, there is
evidence that also occult HBV infection (HBsAg-negative, HBV DNA-positive) associates with NHL. An association with HBV
infection may exist also for other hematological malignancies, but available evidence is much less persuasive than for NHL.
In this review article we will discuss available results on the association between HBsAg-positive HBV infection and NHL, as
well as the significance of other serological markers of HBV infection in these subjects. We will also discuss the possible
etiopathogenic role of HBV, and propose a multifactorial model for lymphomagenesis. Experimental evidence for multifactorial
etiopathogenesis has been obtained in recent years for HBV-associated hepatocellular carcinoma (HCC), and we suggest
that a similar model may apply to HBV-associated lymphoma as well. Eventually, we will also address some unresolved
questions. Two of these are of particular relevance. First, do HBV-positive NHL patients show regression of their hematologic
malignancy upon antiviral therapy? A positive answer would represent a direct demonstration of the necessary etiological role
of the virus in the development of NHL, as has been shown previously for HCV-associated lymphomas. Second, if HBV plays
a necessary role in lymphomagenesis, then expansion of HBV vaccination is expected to reduce the number of incident NHL
cases, even though this effect might become evident only after a long time interval. Studies in those countries which have
introduced universal HBV vaccination about two decades ago, like Italy, may soon provide results on this important point.
(AJBR1110002).
Keywords: Hepatitis B virus, occult infection, anti-HBs antibodies, anti-HBe antibodies, anti-HBc antibodies, Non-Hodgkin
lymphoma, hematologic malignancies, antiviral therapy, multicausal etiology, vaccination
Full Text PDF
Address all correspondence to:
Dr. Fabrizio Marcucci
CNESPS, ISS, Via Giano della Bella 34
00162 Rome, Italy.
Phone: ++393477823945; Fax: ++390649904170
E-mail: fabmarcu@tin.it.
Review Article
The association of Hepatitis B virus infection with B-cell Non-Hodgkin
lymphoma – a review
Fabrizio Marcucci, Enea Spada, Alfonso Mele, Carmelo Antonio Caserta, Alessandro Pulsoni
Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute (CNESPS), Istituto Superiore di Sanità (ISS), via
Giano della Bella 34, 00162 Rome, Italy; Hepatology Association of Calabria, Vico Cartisano primo, 89134 Reggio Calabria,
Italy; Department of Hematology, “La Sapienza” University, via Benevento 6, 00161 Rome, Italy.
Received October 15, 2011; accepted November 7, 2011; Epub December 15, 2011; Published January 15, 2011
Abstract: Epidemiological studies performed over the last decade have demonstrated a positive association between
persistent, hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma
(NHL), with HBV-infected patients having a 2-3-fold higher risk to develop NHL than non-infected patients. Moreover, there is
evidence that also occult HBV infection (HBsAg-negative, HBV DNA-positive) associates with NHL. An association with HBV
infection may exist also for other hematological malignancies, but available evidence is much less persuasive than for NHL.
In this review article we will discuss available results on the association between HBsAg-positive HBV infection and NHL, as
well as the significance of other serological markers of HBV infection in these subjects. We will also discuss the possible
etiopathogenic role of HBV, and propose a multifactorial model for lymphomagenesis. Experimental evidence for multifactorial
etiopathogenesis has been obtained in recent years for HBV-associated hepatocellular carcinoma (HCC), and we suggest
that a similar model may apply to HBV-associated lymphoma as well. Eventually, we will also address some unresolved
questions. Two of these are of particular relevance. First, do HBV-positive NHL patients show regression of their hematologic
malignancy upon antiviral therapy? A positive answer would represent a direct demonstration of the necessary etiological role
of the virus in the development of NHL, as has been shown previously for HCV-associated lymphomas. Second, if HBV plays
a necessary role in lymphomagenesis, then expansion of HBV vaccination is expected to reduce the number of incident NHL
cases, even though this effect might become evident only after a long time interval. Studies in those countries which have
introduced universal HBV vaccination about two decades ago, like Italy, may soon provide results on this important point.
(AJBR1110002).
Keywords: Hepatitis B virus, occult infection, anti-HBs antibodies, anti-HBe antibodies, anti-HBc antibodies, Non-Hodgkin
lymphoma, hematologic malignancies, antiviral therapy, multicausal etiology, vaccination
Full Text PDF
Address all correspondence to:
Dr. Fabrizio Marcucci
CNESPS, ISS, Via Giano della Bella 34
00162 Rome, Italy.
Phone: ++393477823945; Fax: ++390649904170
E-mail: fabmarcu@tin.it.
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