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丙型肝炎病毒/人类免疫缺陷病毒合并感染个体联合治疗的肝脏组织学反应(HR):干扰素诱导的HR与持续病毒学应答(SVR)无关。

Hepatic histologic response (HR) to combination therapy among HCV/HIV-coinfected individuals: interferon induces HR independent of sustained virologic response (SVR).

作者信息

Wu Lynne, Kottilil Shyam, Lempicki Richard, Yang Jun, McLaughlin Mary, Hu Zonghui, Koratich Chad, Reitano Kristin N, Rehm Catherine A, Masur Henry, Wood Brad, Kleiner David E, Polis Michael A

机构信息

Laboratory of Immunoregulation, NIAID, NIH, DHHS, Bethesda, Maryland, USA.

出版信息

AIDS Res Hum Retroviruses. 2006 Nov;22(11):1091-8. doi: 10.1089/aid.2006.22.1091.

Abstract

Most HIV/HCV-coinfected patients fail to achieve a sustained virologic response (SVR) to peginterferon-ribavirin therapy. We examined the hepatic histologic response (HR), defined as an improvement in hepatic inflammation scores of two points or more, to combination therapy among HIV/HCV-coinfected subjects. An open label prospective trial treated 32 HIV/HCV-coinfected patients with peginterferon alpha-2b and ribavirin for 48 weeks. Liver biopsies, scored by a single pathologist using the Histology Activity Index (HAI, range 0-18) and Ishak fibrosis scores (range 0-6), were performed before and after treatment. Gene expression profiles of PBMCs were performed using Affymetrix U133A gene chips. A total of 87% of SVR subjects and 88% of nonresponders (NR) had an HR, but no significant change in the liver fibrosis scores was observed (p > 0.05). For genotype 1 patients, a baseline fibrosis score </=2 was related to a higher likelihood of SVR than those with a score >2 (p = 0.012). Combination therapy for HCV among HIV-coinfected subjects resulted in a modest SVR rate. Persons with mild liver disease had a better SVR rate, suggesting early treatment may be beneficial. Combination therapy resulted in an HR for most of the patients, however, further follow-up of these patients will determine the durability of such an HR.

摘要

大多数合并感染HIV/HCV的患者接受聚乙二醇干扰素-利巴韦林治疗后未能实现持续病毒学应答(SVR)。我们研究了合并感染HIV/HCV的受试者接受联合治疗后的肝脏组织学应答(HR),定义为肝脏炎症评分改善两分或更多。一项开放标签前瞻性试验对32例合并感染HIV/HCV的患者使用聚乙二醇干扰素α-2b和利巴韦林治疗48周。治疗前后均进行肝脏活检,由一名病理学家使用组织学活动指数(HAI,范围0 - 18)和Ishak纤维化评分(范围0 - 6)进行评分。使用Affymetrix U133A基因芯片对PBMCs进行基因表达谱分析。共有87%的SVR受试者和88%的无应答者(NR)有HR,但未观察到肝脏纤维化评分有显著变化(p>0.05)。对于基因1型患者,基线纤维化评分≤2的患者比评分>2的患者有更高的SVR可能性(p = 0.012)。合并感染HIV的受试者接受HCV联合治疗的SVR率中等。轻度肝病患者的SVR率更高,提示早期治疗可能有益。联合治疗使大多数患者有HR,然而,对这些患者的进一步随访将确定这种HR的持续性。

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