核苷类似物治疗慢性乙肝的现状与未来(精)课件.pptVIP

HBeAg阳性CHB治疗目的 在HBeAg阳性CHB的疗效判断中，推荐可行目标是HBeAg血清转换，1 因为血清转换最终与疾病缓解和提高生存率相关。次要目标为减少HBV DNA和ALT复常。 长期的治疗目标是预防、终止、减轻肝坏死、发展成肝硬化和/或肝癌，从而延长患者的生存期。 慢性HBV感染的最终治疗目标是实现HBsAg血清转化，因为这代表一个与急性感染患者实现有效控制HBV感染的相同的状态。它表示免疫系统已成功地战胜了感染。 1. Lok, McMahon. Hepatology 2004 (AASLD Guidelines) HBeAg血清转换后的转归 HBeAg血清转换与HBsAg消失及血清转化（治疗的最终目标）、病情缓解、HCC防止和延长生存期密切相关。 Hoofnagle. Ann Intern Med 1981; Fattovich. Hepatology 1986; Di Bisceglie. Gastroenterology 1987; Niederau. N Engl J Med 1996; Chu. Gastroenterology 2002; van Zonneveld. Hepatology 2004 取得HBeAg血清转换后的临床结局 长期随访研究已显示出抗HBV治疗与延长患者生存期之间的关系。在常规IFN? 治疗的HBeAg阳性患者中，HBeAg清除与临床转归改善、总的生存改善和无并发症生存延长相关，因而显示出常规IFN? 对HBeAg阳性CHB的长期好处。 Niederau et al. N Eng J Med 1996 The response rates achieved with PEGASYS (with or without LAM) were significantly higher than with LAM monotherapy HBeAg阴性CHB的流行状况 HBsAg阳性患者中， HBeAg 阴性CHB的流行因地区不同，并且主要由感染的基因型决定。 在地中海地区高达90% 在亚太地区约为30–55% 在北欧约为30–50% 在美国高达40% HBeAg 阴性CHB的流行在全球范围内不断增加2。 1. Hadziyannis, Vassilopoulos. Hepatology 2001; 2. Funk et al. J Viral Hepat 2002. However, immune tolerance is relative and reversible So, the immune response can be more active later in life, When patients enter into immune clearance phase There are 2 key features during this phase Spon HBeAg seroconversion – which occurs at an annual rate of 5-15% per year depending on the ALT level and immune response Predictors of HBeAg seroconversion include ALT, age, gender and recent studies suggest a role for HBV genotype 2) Hepatitis flares, the flares may be mild and patients are asymptomatic, or severe and associated with increase bilirubin and in extreme cases hepatic decompensation and death It has been said that these flares may be beneficial as they represent immune clearance of infected hepatocytes, Indeed HBeAg seroconversion is frequently preceded by ALT flares, but only a small percent of flares result in HBeAg seroconversion So many flares represent failed attempts at immune clearance These flares are more common in men