Role of hepatitis B, C, and D viruses in dual and triple infection: Influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference

The interactions among hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) were studied by measuring HBV‐DNA and HCV‐RNA levels and by determining the influence of viral genotypes and mutations in HBV basal core promoter (BCP) and precore regions. We included 65 consecutive patients, 25 HBV/HCV, 18 HBV/HDV, and 22 HBV/HCV/HDV. Controls consisted of 55 patients with chronic HBV and 55 with chronic HCV infection. HBV‐DNA and HCV‐RNA levels were lower in coinfections than in single infections (P < .05). HBV/HCV coinfection was associated with lower HBV viremia (8.2 × 104 copies/mL) and lower HCV‐RNA levels (7 × 105 IU/mL), than the corresponding control group (P < .05), with more marked decrease in HBV replication (P < .05). Moreover, in HBV/HCV coinfection and in triple coinfection we observed an inverse relationship between HBV‐DNA and HCV‐RNA levels (P < .05). HBV/HDV coinfection was associated with lower HBV viremia (2.5 × 104 copies/mL) than that found in HBV infection (P < .05). Patients with triple coinfection showed lower HBV‐DNA and HCV‐RNA levels than control groups (P < .05). Prevalence of precore mutations was lower in HCV coinfections (P < .05). No significant association was observed between HCV‐RNA levels and HBV precore mutations, BCP mutations or HBV genotypes, or between HBV‐DNA levels and HCV genotypes (P < .05). In conclusion, HCV exhibited stronger inhibitory action in the reciprocal inhibition seen in HBV/HCV coinfection. HDV was the dominant virus in HBV/HDV coinfection and in triple coinfection, and had a greater unfavorable influence on HCV than on HBV replication. The reciprocal inhibition of viral replication seemed to be little influenced by the inherent genomic factors studied.