Gastric mucosa as an additional extrahepatic localization of hepatitis C virus: Viral detection in gastric low-grade lymphoma associated with autoimmune disease and in chronic gastritis

Abstract

Hepatitis C virus (HCV) has been localized in several tissues besides the liver. 1 The definition of the possible extrahepatic localizations of the virus may be relevant to better address the issue of some of the extrahepatic manifestations of chronic HCV infection. As regards the gastric microenvironment, gastric lymphoma has been reported in patients with HCV infection, 2-6 and a relationship was noticed between HCV infection and B-cell clonal expansion in chronic gastritis lesions in Sjö gren' s syndrome (SS). 7 At present, local infection by Helicobacter pylori (HP) in the gastric mucosa is considered a crucial step for the development of chronic gastritis and gastric low-grade B-cell non-Hodgkin' s lymphoma (NHL) of mucosa-associated lymphoid tissue (MALT). [8][9][10] However, important issues regarding the pathobiology of HP-related gastric lymphoproliferation are still ill-defined, such as the definition of additional pathogenetic events implicated in the malignant transformation (nearly all the HP-infected individuals do not develop a gastric lymphoma), the possible lack of regression of HPassociated gastric lymphoproliferation after HP eradication, [8][9][10][11] and the evidence of gastric low-grade B-cell NHLs, which appear HP-negative ab initio. 8,9,12,13 Autoimmunity may contribute to gastric chronic inflammation and lymphoproliferation. 11,[14][15][16][17][18][19] In particular, studies on SS-related chronic gastritis and gastric low-grade B-cell NHL showed intragastric B-cell clonal expansion also in the absence of HP infection. 11,18,19 Furthermore, recent clinical and experimental results have linked the HCV to SS-like manifestations and acquisition of MALT. 2,[20][21][22] We herein report the gastric mucosa as a possible extrahepatic localization of HCV. Viral antigens and RNA were detected within a HP-positive low-grade B-cell NHL lesion, in an HCV-infected patient with clinical and pathological findings consistent with SS. This gastric low-grade B-cell NHL did not regress, despite successful HP eradication. Molecular analyses of the immunoglobulin heavy chain (IgH) genes used by the neoplastic clone indicated an antigen-driven

Salivary gland B cell lymphoproliferative disorders in Sjögren's syndrome present a restricted use of antigen receptor gene segments similar to those used by hepatitis C virus-associated non-Hodgkins's lymphomas

“…Current knowledge derived from epidemiological data [22][23][24][25][26][27][28][29][30], regression of HCV-LPD after HCV eradication [30], in situ studies of the presence of HCV (RNA and structural proteins) in stromal cells surrounded by the lymphoproliferative processes [11,26,31] and structural homology of the antigen-binding sites of the IgR expressed by HCV-NHL with antibodies specific for the E2 protein of HCV [12,24] strongly suggest that a protein of HCV, alone or in association with the Fc part of the immunoglobulin [32,33], may express the antigenic epitope(s) involved in HCV-LPD.…”

Oligoclonal non-neoplastic B cell expansion is the key feature of type II mixed cryoglobulinemia: Clinical and molecular findings do not support a bone marrow pathologic diagnosis of indolent B cell lymphoma

“…Whether a putative anti-HCV (cross-)reactivity may be implicated in selected cases (ref. 40 and see patient 3 in group 1) also warrants further investigation.…”

Extrahepatic disorders of HCV infection: A distinct entity of B-cell neoplasia?

“…RT-PCR, in situ hybridization, and immunochemistry studies have demonstrated that HCV colocalizes with low grade B-cell NHL tissue. In contrast, HCV-positive cells were primarily located along the edges of low grade B-cell NHL tissue and were only rarely observed to be interspersed within it (23)(24)(25). Additionally, neoplastic tissue biopsies from two HCV-positive patients with high grade B-cell NHL were found to be HCV-negative (26).…”