Hepatitis C virus and its genotypes and Helicobacter pylori in pediatric non-Hodgkin's lymphoma: could there be a possible etiologic role?
BACKGROUND
It has been recently hypothe-sized that Helicobacter pylori (H. pylori) and Hepatitis C virus (HCV) might be involved in the pathogenesis of malignant non-Hodgkin's lymphoma (NHL). However, most of the studies were carried out on adult patients. On the basis of this observation, we sought to determine the prevalence of these infections in pediatric NHL patients at National Cancer Institute (NCI) and whether there is any clinical or histopathologic picture linked to the presence of these infectious agents.


PATIENTS AND METHODS
The study was performed on 119 pediatric NHL patients, either as new or relapse cases, at the hematology out patient clinic of NCI from January 2002 to July 2003. Thirty apparently healthy children were studied as the control. We searched for H. pylori IgG antibodies using an enzyme immuno-assay (EIA) procedure. HCV was investigated by EIA to detect its antibodies, reverse transcriptase polymerase chain reaction (RT-PCR) for the presence of its RNA and viral sequencing for the determination of the viral genotype.


RESULTS
Antibodies for H. pylori were detected in 51/119 (43.2%) and in none of the control group, p<or= 0.001, whereas HCV antibodies were found in 21/119 (17.6%) of the NHL patients and in one of the controls (3.3%), p<or= 0.001. HCV RNA was detected in 18/21 (85.7%) anti-HCV positive patients analyzed, but was negative in the anti-HCV positive control. Viral genotype most frequently encountered was genotype 4; a mixed genotype of 1+4 was detected in four patients and only one patient showed genotype 1. No specific histological subtype, extra-nodal presentation, nor stage of disease was related to H. pylori or HCV positivity. Older age was significantly related to H. pylori positive NHL patients. A positive correlation between the presence of H. pylori antibodies and a complaint of vomiting and diarrhea was observed in our patients, p<or= 0.001.


CONCLUSIONS
We report a high prevalence of HCV and H. pylori infections in paediatric NHL patients at NCI. Concerning the hypothesis of their pathogenetic role in lymphomagenesis, it is still unclear whether these agents have a direct role in malignant transformation in pediatric lymphoma because a typical NHL clinico-histological feature associated with HCV and H. pylori is lacking.