Toy Mehlika, Veldhuijzen Irene K, de Man Robert A, Richardus Jan Hendrik, Schalm Solko W
Department of Public Health, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Hepatology. 2009 Sep;50(3):743-51. doi: 10.1002/hep.23061.
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.
Long-term antiviral therapy with a strategy that minimizes or controls resistance will have a major preventive effect on liver-related mortality and morbidity.
长期抗病毒治疗对慢性乙型肝炎负担的潜在影响鲜有文献记载。本研究旨在评估延长抗病毒治疗及抗病毒耐药性对慢性乙型肝炎活动期患者死亡率和发病率的影响。构建了荷兰慢性乙型肝炎患者的群体队列,并根据10岁年龄组、乙肝表面抗原流行率、乙肝病毒DNA水平、丙氨酸转氨酶水平、乙肝e抗原状态和肝硬化情况进行分层。创建了一个马尔可夫模型,以数学方式模拟该队列在一系列有限健康状态下的进展。基于四种情景进行分析:自然史、使用高耐药性药物进行长期治疗(有无挽救治疗)以及使用低耐药性药物进行治疗。据估计,2005年荷兰有64000人(0.4%)患有慢性乙型肝炎感染,其中6521人(10%)病毒血症高且丙氨酸转氨酶水平升高。在20年期间,慢性乙型肝炎活动期队列中的6521名患者中有1725人(26%)将因肝脏相关原因死亡。入组时无肝硬化的5685名患者中,1671人(29%)将发展为肝硬化。入组时患有肝硬化的836名患者中,619人(74%)将在20年内死亡。如果对这个慢性乙型肝炎活动期队列进行全面检测和治疗,从一开始就选择低耐药性药物,与肝病相关的死亡率可降低80%。这种效果归因于肝硬化并发症的减少以及肝硬化发展的预防。
采用使耐药性最小化或得到控制的策略进行长期抗病毒治疗,将对与肝脏相关的死亡率和发病率产生重大预防作用。