Sarin Shiv Kumar, Kumar Manoj, Kumar Rakesh, Kazim Syed Naqui, Guptan Rajkumar Chander, Sakhuja Puja, Sharma Barjesh Chander
Department of Gastroenterology, G.B. Pant Hospital, Affiliated to the University of Delhi, India.
Am J Gastroenterol. 2005 Nov;100(11):2463-71. doi: 10.1111/j.1572-0241.2005.00247.x.
Monotherapy with interferon (IFN) or lamivudine is effective in a limited proportion of chronic hepatitis B (CHB) patients. A sequential combination may have better therapeutic effects by sustained viral suppression combined with immunomodulation.
To compare the efficacy of sequential lamivudine and IFN therapy versus lamivudine monotherapy in HBeAg positive CHB patients.
Seventy-five treatment naïve HBeAg positive patients with histologically proven CHB and alanine aminotransferase (ALT) >1.5 x ULN received lamivudine 100 mg per day for 52 wks with IFN 5 MIU per day added for 16 wks after the first 8 wks (group A, n = 38; age 30 +/- 12 yr; M:F = 35:3) or lamivudine 100 mg per day for 52 wks (group B, n = 37; age 30 +/- 16 yr; M:F = 31:6). Biochemical and virologic responses were assessed at weeks 52 and 76 and analysis was done on intention-to-treat. Serial samples were studied for the emergence of lamivudine-resistant YM552I/VDD mutations by direct sequencing.
At week 52, HBeAg loss occurred in 15 (39.5%) in group A and 14 (37.8%) in group B (p= 1.00). HBeAg loss, anti-HBe appearance, and undetectable DNA levels were seen in 26.3% and 13.5% (p= 0.249), respectively. Nine of 10 (90%) patients in group A and 1 of 5 (20%) in group B maintained the response through week 76 (p= 0.017). At week 76, 5 additional patients in group A and 3 in group B further achieved the primary end point and the overall HBeAg loss was observed in 44.7% and 18.9% (p= 0.025) and HBeAg loss, anti-HBe appearance, and undetectable hepatitis B virus (HBV) DNA levels in 36.8% and 10.8% in group A and group B, respectively (p= 0.026). At week 76, undetectable HBV DNA was seen in 39.5% and 16.2% in groups A and B, respectively (p= 0.039). Normal ALT was seen in 47.7% and 40.5% at week 52 (p= 0.489) and ALT was normal in 39.5% and 13.5% at week 76 (p= 0.018) in groups A and B, respectively. YM552I/VDD-resistant mutants emerged in 6 of 38 (15.5%) patients in group A, and 3 of 37 (8.1%) in group B (p= ns). The rate of histological improvement was comparable in the two groups.
Our results demonstrate that sequential therapy is superior to lamivudine monotherapy in achieving sustained seroconversion, ALT normalization, and HBV DNA loss. Compared to 80% with sequential therapy, only 20% Indian patients with CHB did not relapse after stopping lamivudine monotherapy.
单用干扰素（IFN）或拉米夫定对有限比例的慢性乙型肝炎（CHB）患者有效。序贯联合治疗通过持续的病毒抑制和免疫调节可能具有更好的治疗效果。
比较拉米夫定与干扰素序贯治疗和拉米夫定单药治疗对HBeAg阳性CHB患者的疗效。
75例未经治疗的HBeAg阳性、经组织学证实为CHB且丙氨酸氨基转移酶（ALT）>1.5倍正常上限（ULN）的患者，接受每天100mg拉米夫定治疗52周，其中38例（A组，年龄30±12岁；男：女=35：3）在前8周后加用每天5MIU干扰素治疗16周，37例（B组，年龄30±16岁；男：女=31：6）接受每天100mg拉米夫定治疗52周。在第52周和第76周评估生化和病毒学反应，并对意向性治疗进行分析。通过直接测序研究系列样本中拉米夫定耐药YM552I/VDD突变的出现情况。
在第52周时，A组15例（39.5%）出现HBeAg消失，B组14例（37.8%）出现HBeAg消失（p=1.00）。A组和B组HBeAg消失、抗-HBe出现及DNA水平不可测的比例分别为26.3%和13.5%（p=0.249）。A组10例患者中的9例（90%）和B组5例患者中的1例（20%）在第76周时仍维持应答（p=0.017）。在第76周时，A组又有5例患者、B组又有3例患者达到主要终点，总体HBeAg消失率分别为44.7%和18.9%（p=0.025），A组和B组HBeAg消失、抗-HBe出现及乙肝病毒（HBV）DNA水平不可测的比例分别为36.8%和10.8%（p=0.026）。在第76周时，A组和B组HBV DNA不可测的比例分别为39.5%和16.2%（p=0.039）。在第52周时，A组和B组ALT正常的比例分别为47.7%和40.5%（p=0.489），在第76周时，A组和B组ALT正常的比例分别为39.5%和13.5%（p=0.018）。A组38例患者中有6例（15.5%）、B组37例患者中有3例（8.1%）出现YM552I/VDD耐药突变（p=无统计学意义）。两组组织学改善率相当。
我们的结果表明，序贯治疗在实现持续血清学转换、ALT正常化和HBV DNA消失方面优于拉米夫定单药治疗。与序贯治疗80%的患者相比，仅20%的印度CHB患者在停用拉米夫定单药治疗后未复发。
