Potential impact of long-term nucleoside therapy on the mortality and morbidity of active chronic hepatitis B.
The potential impact of long-term antiviral therapy on the burden of chronic hepatitis B has hardly been documented. The aim of this study was to estimate the effects of prolonged antiviral therapy and antiviral resistance on the mortality and morbidity of active chronic hepatitis B patients. A population cohort of chronic hepatitis B patients in the Netherlands was constructed and stratified according to 10-year age groups, prevalence of hepatitis B surface antigen, hepatitis B virus DNA level, alanine aminotransferase level, hepatitis B e antigen status, and presence of cirrhosis. A Markov model was created to mathematically simulate the cohort's progression through a finite series of health states. The analysis was performed on the basis of four scenarios: natural history, long-term therapy with a high-resistance profile drug without or with salvage, and therapy with a low-resistance profile drug. It has been estimated that there were 64,000 people (0.4%) suffering from chronic hepatitis B infection in the Netherlands in 2005, with 6521 (10%) of them having high viremia and elevated alanine aminotransferase levels. Within a 20-year period, 1725 (26%) of the 6521 patients in the active chronic hepatitis B cohort will die because of liver-related causes. Of the 5685 without cirrhosis at entry, 1671 (29%) will develop cirrhosis. Of those 836 with cirrhosis at entry, 619 (74%) will die within a 20-year period. If this active chronic hepatitis B cohort is fully detected and treated, mortality related to liver disease can be reduced by 80% if a low-resistance profile drug is chosen from the start. The effect is due to both the reduction in complications of cirrhosis and the prevention of the development of cirrhosis.


CONCLUSIONS
Long-term antiviral therapy with a strategy that minimizes or controls resistance will have a major preventive effect on liver-related mortality and morbidity.
Toy
Mehlika
M
Department of Public Health, University Medical Center Rotterdam, Rotterdam, The Netherlands. m.toy@erasmusmc.nl
Veldhuijzen
Irene K
IK
de Man
Robert A
RA
Richardus
Jan Hendrik
JH
Schalm
Solko W
SW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000187:drug effects; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology; D008107:Liver Diseases; D008390:Markov Chains; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use*; D012680:Sensitivity and Specificity
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D009705:Nucleosides