We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients trea...We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 ±1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n = 209) and 1 untreated (n = 195). Virological or biochemical remission rate at 48 mon-ths under lamivudine was 34%or 36%, respectively, whereas adefovir was administered in 79 patients with virological-biochemical breakthroughs or no response. Of the lamivudine-treated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event-free survival was 93%. The major event-free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event-free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96%or 98%vs. 88%or 90%, respectively). In conclusion, in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered.展开更多
目的研究HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者核苷(酸)类似物[(nucleos(t)ide analogs,NA]序贯干扰素治疗疗效的影响因素。方法NA治疗的HBeAg阳性CHB向PEG-IFNα-2a转换(序贯治疗),二者联合应用3个月后单独应用PEG-IFN...目的研究HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者核苷(酸)类似物[(nucleos(t)ide analogs,NA]序贯干扰素治疗疗效的影响因素。方法NA治疗的HBeAg阳性CHB向PEG-IFNα-2a转换(序贯治疗),二者联合应用3个月后单独应用PEG-IFNα-2a治疗,PEG-IFNα-2a 180μg每周1次皮下注射。监测序贯治疗前(基线)及序贯治疗的第12、24、36、48、及72周的HBsAg、HBeAg和HBV DNA含量。结果共有56例HBeAg阳性的CHB患者入组,其中5例(8.9%)获得HBsAg消失/血清学转换,获得组基线HBsAg含量显著低于非获得组(2.750 lg IU/ml vs 3.699 lg IU/ml,t=0.955,P=0.000);序贯治疗的第12、24、36、48周两组HBsAg下降幅度差异均有统计学意义(0.913 vs 0.149,2.847 vs 0.189,4.378 vs 0.248,4.587 vs 0.274,lg IU/ml)(t=-2.950、P=0.040;t=-8.732、P=0.009;t=-8.483、P=0.001;t=-8.214,P=0.003)。11例(19.6%)获得HBeAg消失/血清学转换,获得组基线HBeAg含量低于非获得患者(1.217 lgS/CO vs 1.884 lgS/CO,t=2.061,P=0.044);序贯治疗第24、36、48周两组HBsAg、HBeAg下降幅度差异均有统计学意义(1.330 vs 0.205,2.084 vs 0.258,1.972 vs 0.284,lg IU/ml;1.168 vs 0.455,1.363 vs 0.461,1.177 vs 0.447,lgS/CO)(t=2.238、p=0.049,t=2.619、P=0.025,t=2.278、P=0.048;t=2.273、P=0.043,t=3.415、P=0.001,t=2.271、P=0.049)。结论基线HBsAg、HBeAg以及其早期滴度下降均可预测HBeAg阳性的CHB患者应用核苷(酸)类似物序贯干扰素治疗的HBs(e)Ag消失/血清学转换率。展开更多
文摘We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 ±1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n = 209) and 1 untreated (n = 195). Virological or biochemical remission rate at 48 mon-ths under lamivudine was 34%or 36%, respectively, whereas adefovir was administered in 79 patients with virological-biochemical breakthroughs or no response. Of the lamivudine-treated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event-free survival was 93%. The major event-free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event-free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96%or 98%vs. 88%or 90%, respectively). In conclusion, in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered.
文摘目的研究HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者核苷(酸)类似物[(nucleos(t)ide analogs,NA]序贯干扰素治疗疗效的影响因素。方法NA治疗的HBeAg阳性CHB向PEG-IFNα-2a转换(序贯治疗),二者联合应用3个月后单独应用PEG-IFNα-2a治疗,PEG-IFNα-2a 180μg每周1次皮下注射。监测序贯治疗前(基线)及序贯治疗的第12、24、36、48、及72周的HBsAg、HBeAg和HBV DNA含量。结果共有56例HBeAg阳性的CHB患者入组,其中5例(8.9%)获得HBsAg消失/血清学转换,获得组基线HBsAg含量显著低于非获得组(2.750 lg IU/ml vs 3.699 lg IU/ml,t=0.955,P=0.000);序贯治疗的第12、24、36、48周两组HBsAg下降幅度差异均有统计学意义(0.913 vs 0.149,2.847 vs 0.189,4.378 vs 0.248,4.587 vs 0.274,lg IU/ml)(t=-2.950、P=0.040;t=-8.732、P=0.009;t=-8.483、P=0.001;t=-8.214,P=0.003)。11例(19.6%)获得HBeAg消失/血清学转换,获得组基线HBeAg含量低于非获得患者(1.217 lgS/CO vs 1.884 lgS/CO,t=2.061,P=0.044);序贯治疗第24、36、48周两组HBsAg、HBeAg下降幅度差异均有统计学意义(1.330 vs 0.205,2.084 vs 0.258,1.972 vs 0.284,lg IU/ml;1.168 vs 0.455,1.363 vs 0.461,1.177 vs 0.447,lgS/CO)(t=2.238、p=0.049,t=2.619、P=0.025,t=2.278、P=0.048;t=2.273、P=0.043,t=3.415、P=0.001,t=2.271、P=0.049)。结论基线HBsAg、HBeAg以及其早期滴度下降均可预测HBeAg阳性的CHB患者应用核苷(酸)类似物序贯干扰素治疗的HBs(e)Ag消失/血清学转换率。
