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Background: Epidemiological studies have demonstrated the relationship between Helicobacter pylori infection and gastric and extra-gastric diseases. Therefore, H. pylori infection might be a "systemic" disease., Aim: To investigate the relationship between H. pylori infection status and serum parameter levels responding to multi-organ functions., Methods: A total of 2,044 subjects were selected, including 1,249 males and 795 females with ages ranging from 16 to 86 years. Relevant parameters including blood lipids, complete blood count, tumor markers, indexes of stomach, kidney, liver, thyroid, and immune system function, H.pylori IgG antibody levels, and (14)C-UBT were collected., Results: Serum pepsinogen (PG)I, PGII, and gastrin (G)17 levels were decreased in chronic long-term, past, and acute short-term infection patients compared with uninfected controls. However, the serum PGI/II ratio increased gradually. Serum white blood cell levels gradually decreased in past, chronic long-term, and acute short-term infection patients compared with uninfected controls. The same trend was also observed for CD4(+) T cell levels. In addition, LDL levels were higher in chronic long-term infection, HDL levels were lower in past infection, and ALP and CEA levels were higher in acute short-term infection compared with the uninfected group., Conclusions: Helicobacter pylori infection correlated with increased PGI, PGII, G17, WBC, and CD4(+) T cell levels, and decreased PGI/II ratio. In chronic long-term or past infection, H. pylori infection was associated with higher LDL or lower HDL levels. In acute short-term infection, H. pylori infection correlated with higher ALP and CEA levels. H. pylori infection correlated with serum parameter levels responding to multi-organ functions.