Baseline
HBV Viral Load and Excess Mortality Associated with Chronic HBV Infection
The
amount of viral replication has a varying relationship with disease status. High
HIV viral load is associated with disease progression and immunological decline,
for example, while hepatitis C virus (HCV) viral load appears to have minimal
impact on liver disease progression.
As
reported at the recent 57th Annual Meeting of the American Association for the
Study of Liver Diseases (AASLD) in Boston, researchers conducted an analysis to
assess the relationship between hepatitis B virus (HBV) DNA levels and mortality
in patients with chronic hepatitis B.
The
analysis looked at 23,820 participants in the REVEAL-HBV study, a prospective
population-based cohort. Follow-up data for the mortality analyses were collected
from January 1991 through December 2004. Mortality was ascertained via data linkage
to the Taiwanese National Death Certification Registry. Mortality rates due to
all causes, liver cancer, chronic liver disease and cirrhosis, and other causes
were calculated, and survival was analyzed according to HBV surface antigen (HBsAg)
status and HBV DNA level.
Results
Over 12.5 years of follow-up (298,866 total person-years), there were 1564 deaths
(8%) among HBsAg negative subjects and 460 deaths (11%) among HBsAg positive patients:
Resulting mortality rates were 632 and 895 per 100,000 person-years, respectively.
- all
cause mortality: relative risk (RR) 1.6 (95% CI 1.4-1.8); - liver cancer:
RR 10.3 (95% CI 7.7-13.9); - chronic liver disease and cirrhosis: RR 4.4 (95%
CI 3.0-6.6).
The overall risk of mortality was higher among individuals with higher HBV DNA
levels.
This difference was especially pronounced for deaths due to liver cancer or chronic
liver disease and cirrhosis)
Further results from the HBsAg positive subgroup are shown in the table below.
(N
=3653) Predictors of Mortality in HBsAg Positive and anti-HCV Negative
Subjects
Adjusted
hazard ratio (95% CI)
All causes
(N=388)
Liver cancer
(N=119)
Chronic liver
disease and cirrhosis (N=40)
Others* (N=229)
HBeAg-
Referent
Referent
Referent
Referent
HBeAg+
1.9(1.3-2.6)†
3.3(1.9-5.6)†
2.2(0.8-5.5)
1.0 (0.6-1.8)
ALT, U/L
<45
Referent
Referent
Referent
Referent
≥45
1.4(1.0-1.9)
1.3(0.8-2.0)
2.3(1.1-5.0)‡
1.3(0.8-2.2)
Cirrhosis
No
Referent
Referent
Referent
Referent
Yes
3.7(2.6-5.4)†
8.9(5.5-14.4)†
6.7(2.8-16.1)†
0.7(0.3-1.9)
HBV DNA,
c/mL
<300(Undetectable)
Referent
Referent
Referent
Referent
300-9999
0.9(0.7-1.3)
0.7(0.3-1.9)
5.3(0.7-43.5)
0.9(0.6-1.3)
10000-99999
1.0(0.7-1.4)
2.1(0.9-5.0)
7.6(0.9-63.1)
0.8(0.5-1.2)
100000-999999
2.0(1.4-2.9)†
6.9(3.1-15.4)†
11.1(1.3-94.4)‡
1.2(0.8-1.9)
≥1
million
2.1(1.4-3.1)†
5.7(2.4-13.6)†
15.6(1.8-134.7)‡
1.3(0.8-2.3)
*Causes other
than liver cancer, chronic liver disease and cirrhosis. Also adjusted for age,
gender, smoking and alcohol. †P<0.001; ‡P<0.05
Conclusion
"Persons
with chronic hepatitis B have a significantly higher risk of mortality compared
to uninfected persons," the researchers concluded. "This excess mortality
is directly related to liver mortality, which is predictable based upon the HBV
viral load. Sustained suppression of viral replication should reduce this excess
mortality."
Bristol-Myers
Squibb Pharmaceutical Research Institute, Wallingford, CT; Genomics Research Center,
Academia Sinica, Taipei, Taiwan; National Taiwan University, Taipei, Taiwan.
11/10/06
Reference U
H Iloeje, H Yang, J Su, and others. Baseline HBV Viral Load and Excess Mortality
Associated with Chronic Hepatitis B Infection: The REVEAL-HBV Study. 57th AASLD.
October 27-31, 2006. Boston, MA. Abstract 949.
Over 12.5 years of follow-up (298,866 total person-years), there were 1564 deaths
(8%) among HBsAg negative subjects and 460 deaths (11%) among HBsAg positive patients:
