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. Conclusion: Long‐term antiviral therapy with a strategy that minimizes or controls resistance will have a major preventive effect on liver‐related mortality and morbidity. (H EPATOLOGY 2009.)