慢性乙型肝炎干扰素治疗后长期随访复发与再治疗后复发研究

目的观察和分析慢性乙型病毒性肝炎（CHB）经重组α干扰素（rIFN-α）治疗取得联合应答后,在长期随访过程中的复发情况,及再次rIFN-α治疗后的复发情况。方法523例经肝穿刺活检证实的CHB患者,给予rIFN-α1b治疗,每次500万u,每周3次,疗程6～37个月（中位数10个月）,治疗中每1～3个月检测肝功能、HBVDNA、乙肝炎e抗原（HBeAg）。治疗后随访至少12个月,随访时每3～6个月检查肝功能、HBVDNA、HBeAg,随访中的复发病例,予以第2次rIFN-α治疗。结果523例患者HBeAg（＋）403例,HBeAg（-）120例。初次rIFN—α治疗结束后,HBeAg（＋）组近期应答225例（55．8％）,HBeAg（-）组77例（64．2％）,差异无统计学意义（Χ^2=2．633,P=0．105）。302例近期应答者,经随访（39±22）个月,复发119例（39．4％）,其中HBeAg（＋）组76／225例（33．8％）、HBeAg（-）组43／77例（55．8％）,差异有统计学意义（Χ^2=19．335,P=0.000）。按随访每12个月为一时间段,分1～12个月、13～24个月、25～36个月、37～48个月、49～60个月和≥61个月6个时间段,各时间段复发的发生率差异有统计学意义（Χ^2=73．518,df=5,P=0．000）,累计复发率差异亦有统计学意义（Χ^2=32．167,df=5,P=0．000）。各时间段复发发生的HBeAg阳性比差异无统计学意义,Χ^2=2．518,df=4,P=0．641,累计复发的HBeAg阳性比差异亦无统计学意义,）（Χ^2=0．370,df=5,P=0．996。57例复发者HBeAg（＋）组25例,（-）组32例]接受第2次rIFN-α治疗,治疗结束时全部取得联合应答,但HBeAg（＋）组13例,（-）组7例第2次复发,差异有统计学意义（Χ^2=5．592,P=0．018）。结论CHB患者经初次rIFN-α治疗后,HBeAg阴性组与HBeAg阳性组的近期应答率相同,而HBeAg阴性组的复发率高于HBeAg阳性组。复发者第2次rIFN-α治疗结束时可全部取得联合应答,而第2次复发HBeAg阴性组低于HBeAg阳性组。

Study of the relapse of patients with chronic hepatitis B undergoing first and repeated recombinant interferon-alpha therapy during long-term follow up

OBJECTIVE: To investigate the relapse of patients with chronic hepatitis B (CHB) undergoing first and repeated recombinant interferon-alpha (rIFN-alpha) therapy during long-term follow up. METHOD: Five hundred and twenty three patients with chronic hepatitis B including 403 hepatitis B e-antigen (HBeAg) positive patients and 120 HBeAg negative ones were treated with 5MU recombinant interferon-alpha 1b (rIFN-alpha1b) subcutaneously thrice weekly for 6 - 25 (median 10) months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically and serum HBV DNA level was detected by fluoresecent-quantitative PCR, HBeAg with enzyme immuoassay every 1 - 3 month during therapy and every 3 - 6 month during the follow up period. Some of the individuals who relapsed during the follow-up period were treated with interferon-alpha repeatedly. RESULTS: Ratios of early response to interferon-alpha were similar in HBeAg positive patients (55.8%, 225/403), and HBeAg negative patients (64.2%, 77/120) at the end of naive treatment (chi(2) = 2.633, P = 0.105). 39.4% (119/302) of early responders relapsed during 39 +/- 22-month follow up, and relapse rates in HBeAg negative group (55.8%, 43/77) were higher than those in HBeAg positive group (33.8%, 76/225) at the end of follow up (chi(2) = 19.335, P = 0.000). Divided the follow-up period into six fragments as 1 - 12 months, 13 - 24 months, 25 - 36 months, 37 - 48 months, 48 - 60 months and > or = 61 months, we found that the differences of relapse incidence were significant (chi(2) = 73.518, df = 5, P = 0.000), and accumulative relapse rates were significant too (chi(2) = 32.167, df = 5, P = 0.000) in all follow-up periods. Constituent ratios of HBeAg in relapsed patients of every follow-up period were similar. 57 relapsed individuals (25 in HBeAg positive group and 32 in HBeAg negative group) were retreated with interferon-alpha, and complete response were achieved in all cases at the end of repeated therapy. The relapse rates in HBeAg positive group (52.0%, 13/25) were higher than in HBeAg negative group (21.9%, 7/32) during the follow-up period after the end of retreatment (chi(2) = 5.592, P = 0.018). CONCLUSION: Rates of early response to interferon-alpha therapy were similar in HBeAg positive and HBeAg negative patients at the end of nave treatment, and relapse rates in HBeAg negative group were higher than in HBeAg positive group during long term follow-up. Combined response was achieved in all relapse cases received repeated interferon-alpha therapy at the end of retreatment. The relapse rates in HBeAg positive group were higher than in HBeAg negative group during the follow-up period after repeated therapy.