长期应用核苷（酸）类似物治疗慢性乙型肝炎患者的远期预后很少阐述。因此我们将121例e抗体阳性的病人纳入此项前瞻性监测研究，进行>36个月的核苷（酸）类似物治疗。对病毒清除、附加治疗以及安全性进行评估。随访过程中如发展至失代偿期肝硬化及肝细胞癌为观察的终点。基线有74例（61%）为慢性肝炎患者，剩余为肝硬化患者。103例病毒载量>38 000 IU/mL 。入组患者中79例为首次接受核苷（酸）类似物治疗。给予拉米夫定单药治疗或其它核苷（酸）类似物治疗。6个月治疗后，88例(73%)实现了病毒清除。52例因为病毒学突破或反应欠佳而更改了治疗时间。平均随访6 ± 3 年，大多数病人都实现了病毒清除。 74例慢性肝炎患者有10例(13.5%) 发展为肝硬化，1例发展为肝细胞癌。47例代偿期肝硬化患者中有14例(30%) 发展为肝细胞癌，5例（11%）发展为失代偿期肝硬化。5年和10年无不良事件生存率：慢性肝炎患者 89.3% (95% CI, 81.7 −96.9) 和 75.6% (95% CI, 61.5 −89.7) ；肝硬化患者70.2% (95% CI, 56.3 −84.1) 和 40.4% (95% CI, 16.9 −63.9)。长期有效的口服核苷（酸）类似物可以通过减少肝硬化及并发症的发生率来影响慢性乙肝病毒感染的自然史。但不能保证可以阻止肝硬化向肝细胞癌发展。
吉林大学第一医院肝病科 陈倩 摘译
本文首次发表于[J Viral Hepat,2013,20(7):502-9]
Long-term outcome of hepatitis B virus-related Chronic Hepatitis under protracted nucleos(t)ide analogues.
Abstract
Long-term outcome of patients with chronic hepatitis B virus (HBV) infection under continuous nucleos(t)ide analogues (NUCs) has been poorly elucidated. We enrolled 121 anti-HBe-positive patients into a prospective surveillance programme while on (>36 months) NUCs therapy. HBV-DNA clearance, add-on therapy and safety were evaluated. Development of cirrhosis, events of liver decompensation and hepatocellular carcinoma (HCC) during the follow-up were the main endpoints, as the complication-free survival. At baseline, 74 patients (61%) had chronic hepatitis, the remainders a cirrhotic liver. HBV-DNA levels >38 000 IU/mL were discovered in 103 patients. At enrolment, 79 patients were naïve to NUCs treatment. Lamivudine monotherapy (n = 70) or a different NUC (n = 51) was administered. At month 6 of therapy, HBV-DNA clearance was documented in 88 patients (73%). Treatment schedule was modified in 52 patients due to breakthrough or suboptimal response. During a mean follow-up of 6 ± 3 years, viral clearance was achieved in the majority of patients. Ten of 74 patients (13.5%) with chronic hepatitis progressed to cirrhosis, 1 patient developed a HCC. In the 47 patients with cirrhosis at presentation, HCC occurred in 14 (30%) and liver decompensation in 5 (11%). The 5 and 10-year event-free survivals were, respectively, 89.3% (95% CI, 81.7 -96.9) and 75.6% (95% CI, 61.5 -89.7) for patients with chronic hepatitis, and 70.2% (95% CI, 56.3 -84.1) and 40.4% (95% CI, 16.9 -63.9) for those with cirrhosis. Protracted, effective treatment with oral NUCs affects the natural history of chronicHBV infection by reducing the incidence of cirrhosis and risk of complications, but does not guarantee against the development of HCC in cirrhosis at presentation.
