Detection of HCV RNA in gastric mucosa—associated lymphoid tissue by in situ hybridization: evidence of a new extrahepatic localization of HCV with increased risk of gastric malt lymphoma

OBJECTIVES: Mucosa-associated lymphoid tissue (MALT) is absent in the normal gastric mucosa but it can develop in several conditions, such as Helicobacter pylori infection. A certain correlation between hepatitis C virus (HCV) infection and low grade MALT lymphomas has recently been reported. The aim of this study was to investigate the presence of HCV RNA in acquired gastric MALT of HCV-infected patients using the in situ hybridization technique. METHODS: Twenty-five patients (16 male and nine female, average age = 56.6 yr [range = 33–75]) affected by chronic HCV hepatitis and with gastric MALT were studied. Giemsa stain and the rapid urease test were also used to evaluate the presence of H. pylori. A polymerase chain reaction product corresponding to the complete 5′ noncoding region of the HCV genome was cloned directly in the pCR 1000 vector on gastric biopsies with acquired MALT. RESULTS: Twenty patients showed grade 2 gastric MALT and five showed grade 3, and H. pylori’s presence was detected in 18 of 25 patients (72%). Using in situ hybridization, we detected HCV RNA in gastric acquired MALT of seven of 25 patients (28%): five showed grade 2 gastric MALT (two of these were H. pylori negative and the other three were positive), whereas two patients showed grade 3 gastric MALT (without H. pylori infection). CONCLUSIONS: This study shows that HCV not only may colonize gastric MALT but also may permit the development of a grade of acquired MALT, which may represent the first step toward a MALT lymphoma. However, further studies are needed to demonstrate the antigenic role of HCV in the progression of acquired MALT into MALT lymphoma.