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Human parvovirus B19 (B19) has been identified in the serum of hepatitis B virus (HBV) infected patients. However, the effect of B19-infection on the course of HBV-associated liver disease has not previously been investigated. We examined the prevalence of B19-DNA in HBV-infected Vietnamese patients and analysed the association between co-infection and the clinical outcome of HBV-infection.Serum samples from 399 HBV-infected patients and 64 healthy individuals were analysed for the presence of B19-DNA by PCR and DNA-sequencing.B19-DNA was detected in 99/463 (21.4%) individuals. The proportion of HBV-infected patients who were also co-infected with B19 was higher than the healthy controls (P0.001). B19-DNA was detected more frequently in patients with HBV-associated hepatocellular carcinoma compared to patients with acute and chronic HBV, HBV-associated liver cirrhosis and healthy subjects (P0.006). A positive correlation was also found between B19-DNA loads and both serum HBV-DNA loads and alanine aminotransferase (rho0.250 and P0.05).Our findings demonstrate that B19-infection is frequent in HBV-infected Vietnamese patients. Also, a significant correlation exists between HBV/B19 co-infection and a greater likelihood of progression to more severe hepatitis B-associated liver disease. Further studies are required to determine the role of B19-infection on HBV-associated pathogenesis.