Risk and predictors of mortality associated with chronic hepatitis B infection.
OBJECTIVE
The study objective was to determine the risk of all-cause and cause-specific mortality as well as to examine the predictors of mortality in chronic hepatitis B infection.


METHODS
We performed a prospective cohort study of 23,820 persons (age, 30-65 y) recruited between 1991 and 1992 and followed up through 2004 from 7 townships in Taiwan. The main outcomes were all-cause and liver-related mortality rates. Mortality analyses used time-to-events methods, and survival curves were derived by the Kaplan-Meier method. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios.


RESULTS
There were 1814 deaths during a mean follow-up period of 12.5 years (282,323.7 person-years of follow-up evaluation). Persons positive for hepatitis B surface antigen (HBsAg) had significantly (P < .01) higher adjusted hazard ratios for all causes of mortality (1.7; 95% confidence interval [CI], 1.5-1.9), liver cancer mortality (22.4; 95% CI, 15.2-32.9), and chronic liver disease and cirrhosis mortality (5.4; 95% CI, 3.5-8.4). When compared with HBsAg-negative persons, hepatitis B virus (HBV)-infected persons with HBV DNA levels less than 10(4) had a high risk of hepatocellular carcinoma mortality (4.4; 95% CI, 2.4-8.2). In HBsAg-positive persons, the mortality rate increased with cohort entry serum HBV DNA level. Liver cancer mortality ranged from 72.8 per 100,000 person-years for subjects with HBV DNA levels less than 300 copies/mL to 815.6 per 100,000 person-years for those with HBV DNA levels of 1 million copies/mL or greater. Chronic liver disease and cirrhosis deaths ranged from 9.1 to 267.4 per 100,000 person-years.


CONCLUSIONS
Chronic HBV infection is associated with significant preventable excess mortality risk. This mortality risk is correlated strongly with the level of viral replication among other factors.
Global Epidemiology and Outcomes Research, Pharmaceutical Research Institute, Bristol-Myers Squibb Company Wallington, Connecticut, USA.
Uchenna H
UH
Iloeje
Hwai-I
HI
Yang
Chin-Lan
CL
Jen
Jun
J
Su
Li-Yu
LY
Wang
San-Lin
SL
You
Chien-Jen
CJ
Chen
D000328:Adult; D000368:Aged; D002423:Cause of Death / Q000639:trends*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000401:mortality* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013624:Taiwan / Q000453:epidemiology
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens