Hepatitis B virus core variants modify natural course of viral infection and hepatocellular carcinoma progression.
OBJECTIVE
We assessed the influence of genetic variants in the hepatitis B virus (HBV) core, which is a principal immunologic target, on the progression to hepatocellular carcinoma (HCC) in a cohort of 4841 male HBV carriers followed up for 16 years.


METHODS
First, baseline sera from 116 HCC cases and 154 controls nested within the cohort were used for sequencing of the HBV core gene to screen for variants with effects on HCC progression. By applying a high-throughput assay for detecting viral single nucleotide substitutions, we then used a longitudinal study (n = 1143) to examine whether 2 identified variants that lie in the region within or flanking epitopes affected the natural course of hepatitis B through investigating their relationships with time trends for viral load and clinical features.


RESULTS
In the nested case-control study, there were 6 core variants associated with decreased risk of HCC after accounting for viral genotype; 5 lie in the region within or flanking epitopes (P < .04). Each variant correlated with a 0.7- to 1-log decrease in viral load and hepatitis B virus e antigen negativity at baseline. The longitudinal study further showed that the appearance of 2 such variants (T1938C and T2045A) was preceded by long-term diminished viral load and decreased rate of liver abnormalities and was significantly less frequent in individuals with a prolonged immune clearance phase that associated with spectrum of liver disease than those in inactive carrier or reactivation phase.


CONCLUSIONS
HBV core variants affecting the kinetics of host-virus interplay may influence longitudinal viral load and HCC progression.
Sung
Feng-Yu
FY
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
Jung
Chun-Ming
CM
Wu
Chih-Feng
CF
Lin
Chih-Lin
CL
Liu
Chun-Jen
CJ
Liaw
Yun-Fan
YF
Tsai
Keh-Sung
KS
Yu
Ming-Whei
MW
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D018388:Codon, Terminator / Q000235:genetics; D015331:Cohort Studies; D014644:Genetic Variation / Q000235:genetics*; D006509:Hepatitis B / Q000473:pathology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load
D018388:Codon, Terminator; D014758:Viral Core Proteins