Hepatitis B viral load and risk for liver cirrhosis and hepatocellular carcinoma in The Gambia, West Africa.
The main objectives of this study were to define the occurrence and levels of hepatitis B virus (HBV) DNA in asymptomatic HBV carriers, cirrhosis patients and hepatocellular carcinoma (HCC) cases from The Gambia, and to evaluate the risk for cirrhosis or HCC associated with HBV viremia. We used sensitive real-time quantitative PCR assays to measure HBV DNA in samples from a case-control study consisting of 60 asymptomatic HBV carriers, 53 cirrhotic patients and 129 HCC cases. Logistic regression was used to estimate the risks of cirrhosis and HCC associated with HBV-DNA levels and HBV e antigenemia (HBeAg) detection (a surrogate marker for viral replication). Detectable HBV viremia and HBeAg positivity were both significantly associated with cirrhosis (increasing risk by fourfold and 11-fold respectively) and with HCC (increasing risk by sixfold and threefold respectively). HBV-DNA levels were significantly higher in both HCC cases and cirrhotic patients compared to asymptomatic carriers (P < 0.01 for both). High-level HBV DNA (>10,000 copies/mL) was strongly associated with both HCC and cirrhosis (17- and 39-fold increased risk). Lower level HBV viremia (200-10,000 copies/mL) conferred a significant risk of HCC, although the association with cirrhosis was not significant. In conclusion, we find that high HBV-DNA levels are strongly associated with the serious sequelae of HBV infection, independent of HBeAg status. While risk for cirrhosis and for HCC notably increases at HBV-DNA levels >or=10,000 copies/mL, low-level viremia was also associated with significant risk for HCC.
Mendy
M E
ME
Viral Diseases Programe, Medical Research Council, Banjul, The Gambia. mmendy@mrc.gm
Welzel
T
T
Lesi
O A
OA
Hainaut
P
P
Hall
A J
AJ
Kuniholm
M H
MH
McConkey
S
S
Goedert
J J
JJ
Kaye
S
S
Rowland-Jones
S
S
Whittle
H
H
Kirk
G D
GD
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000821:virology*; D002353:Carrier State / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005714:Gambia / Q000453:epidemiology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019562:Viral Load
D004279:DNA, Viral; D006513:Hepatitis B e Antigens