初始应用拉米夫定和阿德福韦酯联合抗病毒治疗乙型肝炎肝硬化失代偿期临床研究

目的 探讨拉米夫定(LAM)和阿德福韦酯(ADV)初始联合抗病毒治疗乙型肝炎肝硬化失代偿期的治疗效果和安全性.方法 选取2013年3月至2015年3月在我院进行治疗的乙型肝炎肝硬化失代偿期患者40例,其中22例确诊后立即接受拉米夫定联合阿德福韦酯治疗者为初始组,18例病毒变异出现耐药后应用拉米夫定联合阿德福韦酯治疗者为抗药组,观察两组患者的治疗效果以及用药安全性.结果 ①治疗48周后,初始组转阴率和发生血清转换率明显高于抗药组(82%vs 56%,64%vs 22%),差异有统计学意义(P<0.05);②两组患者治疗后的肝功能指标谷丙转氨酶(ALT)初始组(45.6±10.5)U/L vs(117.8±18.7)U/L,抗药组(98.7±25.7)U/L vs(267.5±38.6)U/L]、HBV-DNA水平初始组(6.22±0.89)log拷贝/mL vs(3.08±1.01)log拷贝/mL,抗药组(6.38±0.89)log拷贝/mL vs(3.75±1.03)log拷贝/mL]、Child-Pugh评分初始组(11.0±1.1)分vs(7.1±1.2)分,抗药组(10.8±1.2)分vs(8.2±1.2)分]较治疗前明显改善,差异有统计学意义(P<0.05);初始组肝功能指标ALT治疗前(117.8±18.7)U/L vs(267.5±38.6)U/L]及治疗后(45.6±10.5)U/L vs(98.7±25.7)U/L]均明显优于抗药组,差异有统计学意义(P<0.05).初始组肾功能指标BUN(5.84±1.23)mmol/L vs(5.06±1.24)mmol/L vs(4.94±1.21)mmol/L]和Cr(99.5±18.5)μmol/L vs(84.6±14.6)μmol/L vs(79.8±11.5)μmol/L]在治疗24、48周较治疗前明显改善,差异有统计学意义(P<0.05),抗药组治疗后肾功能较治疗前改善差异无统计学意义(P>0.05);③两组患者治疗后不良反应发生率(18.2%vs 33.3%)差异无统计学意义(P<0.05).结论 拉米夫定初始联合阿德福韦酯抗病毒治疗乙型肝炎肝硬化失代偿期患者的临床疗效优于病毒出现变异后再进行联合治疗.

Clinical study of initial application of lamivudine combined with adefovir dipivoxil for antiviral treatment of hepatitis B in decompensated liver cirrhosis

Objective To investigate the therapeutic effect and safety of initial application of lamivudine (LAM) combined with adefovir dipivoxil (ADV) antiviral for antiviral treatment of hepatitis B in decompensated liver cirrhosis. Methods Forty patients of hepatitis B in decompensated liver cirrhosis treated in our hospital from Mar. 2013 to Mar. 2015 were enrolled in the study. Twenty-two of the patients were treated by LAM combined with ADV imme-diately after diagnosis (initial group), and 18 patients accepted treatment of LAM combined with ADV after the emergence of viral variants (drug resistant group). The therapeutic effect and safety of the two groups were observed. Results ①For-ty-eight weeks after treatment, the clearance rate and serum conversion rate the initial group were significantly higher than those of drug resistant group (82%vs 56%, 64%vs 22%), with statistically significant difference (P<0.05).②The two groups showed significant improvement 48 h after treatment in ALT (45.6 ± 10.5) U/L vs (117.8 ± 18.7 U/L) in initial group, (98.7±25.7) U/L vs (267.5±38.6) U/L in drug resistant group], HBV-DNA level (6.22±0.89) log copies/mL vs (3.08 ± 1.01) log copies/mL in initial group, (6.38 ± 0.89) log copies/mL vs (3.75 ± 1.03) log copies/mL in drug resistant group], Child-Pugh score (11.0±1.1) vs (7.1±1.2) in initial group, (10.8±1.2) vs (8.2±1.2) in drug resistant group], com-pared with before treatment, and the differences were statistically significant (P<0.05). The ALT in initial group was sig-nificantly better than that in drug resistant group both before treatment (117.8±18.7) U/L vs (267.5±38.6) U/L] and after treatment (45.6 ± 10.5) U/L vs (98.7 ± 25.7) U/L], and the differences were statistically significant (P<0.05). The renal function indexes BUN (5.84±1.23) mmol/L vs (5.06±1.24) mmol/L vs (4.94±1.21) mmol/L] and Cr (99.5±18.5)μmol/L vs (84.6 ± 14.6)μmol/L vs (79.8 ± 11.5)μmol/L] in initial group were significantly improved 24 and 48 weeks after treat-ment, compared with before treatment (P<0.05), but they showed no statistically significant difference before and after treatment in drug resistant group (P>0.05).③There were no significant difference in the incidence of adverse reactions between the two groups after treatment (18.2%vs 33.3%, P>0.05). Conclusion In antiviral treatment of hepatitis B in decompensated liver cirrhosis, application of lamivudine combined with adefovir dipivoxil at initial stage results in bet-ter efficacy than application after the emergence of viral variants.