Virological analysis, genotypes and mutational patterns of the HBV precore/core gene in HBV/HCV-related hepatocellular carcinoma.
We investigated the replicative profile of hepatitis B (HBV) and hepatitis C (HCV) viruses and the mutational pattern of the HBV precore/core (pre-C/C) domain in hepatocellular carcinoma (HCC). Thirty-eight consecutive patients with HCC were included in the study - 18 of them with HBV/HCV co-infection and 20 with HBV single infection. Twenty-three additional patients with co-infection, without HCC were recruited as the control group. Replication activity was evaluated by detecting and quantitating both HBV and HCV genomes. The HBV pre-C/C region, encompassing the pregenome encapsidation signal involved in viral replication, was analysed by direct sequencing. HBV viraemia levels were significantly lower (P = 0.04) in patients with co-infection in comparison with single-infected HCC, whereas two different HBV viraemia profiles were detected in co-infection with or without circulating HCV. HBV genotype D was prevalent in the three groups and HCV genotype 1b was found to be the infecting strain in all patients. Lower variability in the pre-C/C region was found in co-infection in comparison with HBV single infection (P = 0.0004). A synonymous T1936C mutation was found in all co-infected HCC cases not related to the presence or absence of circulating HCV, and a hypermutated pre-C strain, characterized by the same mutational pattern, was identified in three HCC cases. The mutational pattern of the pre-C/C region was closely related to HBV replication efficiency, and specific HBV mutations selectively associated with HCV co-infection could be linked with accelerated HBV/HCV-related disease progression.
De Mitri
M S
MS
Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, Bologna, Italy. sdemitri@med.unibo.it
Cassini
R
R
Morsica
G
G
Bagaglio
S
S
Andreone
P
P
Loggi
E
E
Muratori
P
P
Bernardi
M
M
D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D002648:Child; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D014758:Viral Core Proteins / Q000235:genetics; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication
D014758:Viral Core Proteins