Idris Berlian I, Brosa Max, Richardus Jan H, Esteban Rafael, Schalm Solko W, Buti Maria
Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Eur J Gastroenterol Hepatol. 2008 Apr;20(4):320-6. doi: 10.1097/MEG.0b013e3282f340c8.
Chronic hepatitis B virus (HBV) infection can lead to fatal complications and death. Only a relatively small proportion of patients actually receive medication, and the majority requires long-term antiviral therapy that can result in the emergence of resistant strains of HBV. The study aimed to estimate the future burden of chronic hepatitis B in Spain over the next 20 years, the impact of current lamivudine treatment and the emergence of drug-resistant HBV.
We constructed a hypothetical cohort of people with active chronic HBV infection in Spain in 2005, and 'followed' the cohort for 20 years. The cohort was stratified with respect to factors that affect prognosis (i.e. hepatitis B e-antigen and histology-defined status). To estimate the burden, Markov mathematical simulation was performed based on three scenarios: natural history, treatment with antiviral drug (lamivudine) and treatment with a hypothetical drug with identical profiles to lamivudine but to which there is no resistance.
We estimated that in 2005 there were around 111,000 individuals suffering from active chronic HBV infection. If the cohort is not treated, by the year 2025 there will be about 60,000 events of morbidity and 40,000 cases of liver-related deaths, with 1.84 billion euro expected to be consumed in providing care for the cohort. Treating 35% of the cohort with lamivudine will reduce the morbidity and mortality by 19 and 15%, respectively; whereas the hypothetical drug will reduce the morbidity and mortality by 27 and 24%. The cumulative cost savings resulting from the use of lamivudine and the hypothetical drug, respectively, are 160 and 300 million euro. Antiviral resistance accounts for a reduction of about one-third in the potential benefit of treatment, and almost a half of the potential cost saving.
Chronic hepatitis B will pose a great burden in the future if the individuals with active disease are left untreated. Effective antiviral therapy and treatment coverage have substantial impact in reducing the future burden; however, antiviral resistance decreases treatment benefit considerably.
慢性乙型肝炎病毒(HBV)感染可导致致命并发症和死亡。实际上只有相对较小比例的患者接受药物治疗,且大多数患者需要长期抗病毒治疗,这可能导致HBV耐药菌株的出现。该研究旨在估计未来20年西班牙慢性乙型肝炎的负担、当前拉米夫定治疗的影响以及HBV耐药性的出现。
我们构建了一个2005年西班牙活动性慢性HBV感染患者的假设队列,并对该队列进行了20年的“随访”。该队列根据影响预后的因素(即乙肝e抗原和组织学定义的状态)进行分层。为了估计负担,基于三种情况进行了马尔可夫数学模拟:自然史、抗病毒药物(拉米夫定)治疗以及使用与拉米夫定特征相同但无耐药性的假设药物治疗。
我们估计2005年约有111,000人患有活动性慢性HBV感染。如果该队列不接受治疗,到2025年将有约60,000例发病事件和40,000例肝脏相关死亡病例,预计为该队列提供护理将花费18.4亿欧元。用拉米夫定治疗该队列的35%将分别降低发病率和死亡率19%和15%;而假设药物将分别降低发病率和死亡率27%和24%。使用拉米夫定和假设药物分别带来的累计成本节省为分别为1.6亿欧元和3亿欧元。抗病毒耐药性导致治疗潜在益处减少约三分之一,几乎使潜在成本节省减半。
如果不治疗活动性疾病患者,慢性乙型肝炎在未来将带来巨大负担。有效的抗病毒治疗和治疗覆盖率对减轻未来负担有重大影响;然而,抗病毒耐药性会显著降低治疗益处。