Farci P, Mandas A, Coiana A, Lai M E, Desmet V, Van Eyken P, Gibo Y, Caruso L, Scaccabarozzi S, Criscuolo D
Istituto di Medicina Interna, University of Cagliari, Italy.
N Engl J Med. 1994 Jan 13;330(2):88-94. doi: 10.1056/NEJM199401133300202.
Chronic hepatitis D is a severe and rapidly progressive liver disease for which no therapy has been proved effective. To evaluate the efficacy of treatment with interferon, we studied 42 patients with chronic hepatitis D who were randomly assigned to receive either 9 million or 3 million units of recombinant interferon alfa-2a (three times a week for 48 weeks) or no treatment.
By the end of the treatment period, serum alanine aminotransferase values had become normal in 10 of 14 patients receiving 9 million units (71 percent), as compared with 4 of 14 treated with 3 million units (29 percent, P = 0.029) and 1 of 13 untreated controls (8 percent, P = 0.001). Seven patients treated with the higher dose of interferon (50 percent) had a complete response (normal levels of alanine aminotransferase and no detectable serum hepatitis delta virus [HDV] RNA), as compared with three of those who received the lower dose (21 percent, P = 0.118), and none of the controls (P = 0.004). Treatment with 9 million units of interferon was associated with a marked improvement in the histologic findings (reduced periportal necrosis and portal and lobular inflammation), whereas in the untreated controls there was considerable histologic deterioration. In 5 of the 10 patients treated with 9 million units of interferon whose alanine aminotransferase values became normal, the biochemical responses persisted for up to 4 years (mean, 39 months), but the effects of treatment on viral replication were not sustained. In contrast, none of those who received 3 million units and none of the untreated controls had a sustained biochemical or virologic response.
In about half the patients with chronic hepatitis D treated with high doses of interferon alfa-2a (9 million units three times a week for 48 weeks), the serum alanine aminotransferase level becomes normal, HDV RNA becomes undetectable in serum, and there is histologic improvement. However, a relapse is common after treatment has been stopped.
慢性丁型肝炎是一种严重且进展迅速的肝脏疾病，尚无已被证实有效的治疗方法。为评估干扰素治疗的疗效，我们研究了42例慢性丁型肝炎患者，这些患者被随机分配接受900万单位或300万单位的重组干扰素α-2a（每周三次，共48周）治疗或不接受治疗。
在治疗期结束时，接受900万单位治疗的14例患者中有10例（71%）血清丙氨酸氨基转移酶值恢复正常，相比之下，接受300万单位治疗的14例患者中有4例（29%，P = 0.029），未接受治疗的13例对照中有1例（8%，P = 0.001）。接受高剂量干扰素治疗的7例患者（50%）有完全应答（丙氨酸氨基转移酶水平正常且血清中检测不到丁型肝炎病毒[HDV]RNA），相比之下，接受低剂量治疗的患者中有3例（21%，P = 0.118），而对照组中无一例（P = 0.004）。900万单位干扰素治疗与组织学表现的显著改善相关（门周坏死、门脉和小叶炎症减轻），而未接受治疗的对照组则有明显的组织学恶化。在接受900万单位干扰素治疗且丙氨酸氨基转移酶值恢复正常的10例患者中，有5例的生化应答持续长达4年（平均39个月），但治疗对病毒复制的影响未持续。相比之下，接受300万单位治疗的患者和未接受治疗的对照组均无持续的生化或病毒学应答。
在大约一半接受高剂量干扰素α-2a（每周三次，每次900万单位，共48周）治疗的慢性丁型肝炎患者中，血清丙氨酸氨基转移酶水平恢复正常，血清中检测不到HDV RNA，且有组织学改善。然而，停药后复发很常见。
