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 x 10(4) copies/mL) and lower HCV-RNA levels (7 x 10(5) 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 x 10(4) 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.
Jardi
R
R
Department of Biochemistry, Hospital Universitario Vall d'Hebron, Barcelona, Spain. rjardi@hg.vhebron.es
Rodriguez
F
F
Buti
M
M
Costa
X
X
Cotrina
M
M
Galimany
R
R
Esteban
R
R
Guardia
J
J
D000328:Adult; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006509:Hepatitis B / Q000150:complications*; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications*; D003699:Hepatitis D / Q000150:complications*; D003698:Hepatitis Delta Virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D014779:Virus Replication
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D012367:RNA, Viral