Abstract Background: Association between Helicobacter pylori (H. pylori) and chronic hepatitis C (CHC) still remains controversial. This work is concerned with assessing the potential role of H. pylori in the progression of hepatitis C virus (HCV)- related chronic liver disease. Results: A total of 449 individuals constituted this study (200 individuals were used to validate the assay while 249 individuals were used to assess the correlation between H. pylori infection and CHC). H. pylori antigen was quantifed in serum samples using ELISA. As a consequence, our fndings showed that H. pylori positivity was increased signifcantly (P = 0.021) with liver fbrosis progression as it was found in 44.45% of fbrotic patients and 71.88% of cirrhotic patients. We demonstrated that patients with F4 were accompanied by a signifcant (P < 0.05) increase in the concentration of H. pylori antigen displaying 16.52-fold and 1.34-fold increase in its level over F0 and F1-F3, respectively. Patients co-infected with H. pylori and HCV are 3.19 times (219%) more likely to experience cirrhosis than those who are mono-infected with HCV. This suggests that the risk for developing F4 was found to increase upon H. pylori coinfection when compared to CHC mono-infected patients. Conclusion: The elevated levels of H. pylori-antigen in HCV/H. pylori co-infection suggest increased susceptibility of co-infected patients for promoting hepatic fbrosis progression