Relationship Between Gastric Localization of Hepatitis C Virus and Mucosa-associated Lymphoid Tissue in Helicobacter pylori Infection G. Cammarota, R. Cianci, R. L. Grillo, M. Martini, C. Di Campli, M. Pompili, G. Pignataro, L. Cuoco, A. De Lorenzo, G. Gasbarrini, F. Pandol & L. M. Larocca Department of Internal Medicine and Gastroenterology ; Institutes of Microbiology and of Pathology, Catholic University, Rome, Italy - Human Nutrition Unit, University of Rome Tor Vergata Cammarota G, Cianci R, Grillo RL, Martini M, Di Campli C, Pompili M, Pignataro G, Cuoco L, De Lorenzo A, Gasbarrini G, Pandolfi F, Larocca LM. Relationship between gastric localization of hepatitis C virus and mucosa-associate d lymphoid tissue in Helicobacter pylori infection. Scand J Gastroentero l 2002;37:1126 –1132. Background: Hepatitis C virus (HCV) has been localized in several extra-hepati c sites. Recent evidence suggests that the stomach can harbour HCV. We therefore evaluated the prevalence of gastric localizatio n of HCV and its possible relationshi p with the chronic inammatory response to Helicobacter pylori infection. Methods: Sixty patients with HCV infection (group A) and 60 subjects without HCV infection (control group), who underwent upper endoscopy for dyspeptic symptoms, were consecutivel y enrolled. Biopsy specimens of gastric mucosa obtained from each patient were assessed for H. pylori and chronic inammatory inltrates (classied as mild, moderate or marked). Furthermore, polymerase chain reaction (PCR) analyses were performed on the gastric biopsies to detect HCV and immunoglobuli n heavy-chai n (IgH) gene rearrangement s of mucosal B cells. Results: In group A, 24 of 36 patients with H. pylori infection and 6 of 24 without H. pylori hosted HCV in their stomach (P = 0.0017). In these subjects, the presence of both HCV in the gastric mucosa and H. pylori was signicantly associated with marked or moderate inammatory inltrates. Oligoclonal IgH gene rearrangement s were detected in three group A patients who harboure d both H. pylori and HCV in their stomach. In the control group, PCR analyses failed to nd HCV in the gastric mucosa, and polyclonal patterns were detected in all individuals . Conclusions: HCV is frequently localized in the stomach and is associated with the chronic lymphocytic inammatory response to H. pylori. H. pylori and HCV, when both present, may favour the selection of clonal B cells. Key words: Gastric HCV; hepatitis C virus; H. pylori ; MALT; MALT lymphoma; polymerase chain reaction G. Cammarota, Universita ` Cattolica del Sacro Cuore, Istituto di Medicina Interna e Geriatria, Largo A.Gemelli, 8 – 00168, Rome, Italy (fax. ‡39 063550 2775, e-mail. gcammarota@rm.unicatt.it ) G astric infection with Helicobacter pylori is currently considered a major cause of chronic gastritis, accompanied in many cases by the development of mucosa-associated lymphoid tissue (MALT) (1–3). The latter, which is absent in normal gastric mucosa, often has a follicular structure and may give rise to a distinct clinical- pathological group of low-grade B-cell lymphomas (4–6). The neoplastic transformation is thought to be caused, at least in part, by the interaction between the reactive lymphoid tissue and H. pylori (7–9). However, our understanding of the development of gastric lymphoproliferation is still incom- plete. In fact, most H. pylori-infected subjects do not develop gastric lymphomas, and gastric B-cell non-Hodgkin lympho- mas (NHL) have also been described in patients with no evidence of the infection, strongly suggesting that other factors (viral? dietary?) can trigger or contribute to the malignant transformation of gastric MALT (10–12). The occurrence of HCV infection and replication at extra- hepatic sites is a peculiar biologic feature of its variable clinical outcome (13). In addition to hepatocytes, HCV has been found in the epithelial cells of parotid glands (14), in the endothelial cells of patients with cryoglobulinaemic vasculitis (15, 16) and in peripheral blood mononuclear cells of patients with chronic HCV infection (17, 18). The virus’s peculiar tropism for immunologically privileged tissue helps to explain the persistence of the infection and the immunologic abnormalities associated with it, which include autoimmunity (e.g. Sjo ¨gren syndrome, immune-mediated peripheral neuro- pathy) (19) and lymphomagenesis (20, 21). In fact, HCV infection has been associated with B cell lymphoma (22–25) and with cryoglobulinaemia (which may have a type II monoclonal component) (16, 26–29). In patients with the latter condition, HCV RNA has been identied in both the sera and peripheral lymphocytes (30). Data indicate that the prevalence of HCV infection among patients with B-cell NHL ranges from 9% to 32% (22, 24, 31), values which are ORIGINAL ARTICLE Ó 2002 Taylor & Francis