接受不同抗逆转录病毒药物治疗的HIV-HCV合并感染患者的肝纤维化进展及聚乙二醇化干扰素/利巴韦林治疗的影响。

Liver fibrosis progression in HIV-HCV-coinfected patients treated with distinct antiretroviral drugs and impact of pegylated interferon/ribavirin therapy.

作者信息

Fernández-Montero José V, Barreiro Pablo, Vispo Eugenia, Labarga Pablo, Sánchez-Parra Clara, de Mendoza Carmen, Treviño Ana, Soriano Vicente

机构信息

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.

出版信息

Antivir Ther. 2014;19(3):287-92. doi: 10.3851/IMP2703. Epub 2013 Nov 5.

DOI:10.3851/IMP2703

PMID:24192598

Abstract

BACKGROUND

Advanced liver fibrosis frequently develops in patients with chronic hepatitis C coinfected with HIV. Non-invasive techniques for staging liver fibrosis, such as transient elastometry, may allow both periodic monitoring and examination of large patient populations.

METHODS

A programme of liver fibrosis assessment using transient elastometry has been ongoing at our institution since 2004. All HIV-HCV-coinfected patients having ≥2 examinations separated by >18 months were included. Liver fibrosis progression (LFP) was defined as an increase in liver stiffness from <9.5 kPa (Metavir F0-F2) to >9.5 kPa (Metavir F3-F4), or an increase >30% in patients with baseline Metavir F3-F4.

RESULTS

A total of 545 HIV-HCV-coinfected patients were analysed (mean age 41 years, 71% male, 81% intravenous drug users, mean body mass index 23.3 kg/m(2), 4.2% hepatitis B surface antigen-positive, 8.4% alcohol abuse, mean CD4(+) T-cell count 519 cells/μl). At baseline, 527 patients were on antiretroviral therapy, with the most frequent third drug being atazanavir (19.7%), efavirenz (15.9%), lopinavir (13.1%) or nevirapine (7.2%). A total of 99 (18%) patients experienced LFP during a mean (sd) follow-up of 70.9 (15.7) months. Use of protease inhibitors (OR 4.93, 95% CI 1.73, 14.0; P=0.03) and male gender (OR 5.12, 95% CI 1.37, 19.1; P=0.01) were associated with LFP. By contrast, the achievement of HCV clearance following pegylated interferon/ribavirin (PEG-IFN/RBV) therapy (OR 0.27, 95% CI 0.1, 0.79; P=0.02) was protective. Lopinavir exposure was significantly associated with LFP (OR 1.02, 95% CI 1.0, 1.04; P=0.03), whereas nevirapine was protective (OR 0.94, 95% CI 0.9, 0.99; P=0.02).

CONCLUSIONS

The use of protease inhibitors, mainly lopinavir, is associated with increased LFP in HIV-HCV-coinfected patients. By contrast, nevirapine therapy and, particularly, HCV clearance with PEG-IFN/RBV significantly reduce LFP.

摘要

背景

慢性丙型肝炎合并人类免疫缺陷病毒（HIV）感染的患者常出现晚期肝纤维化。诸如瞬时弹性成像等肝纤维化分期的非侵入性技术，可对大量患者群体进行定期监测和检查。

方法

自2004年起，我们机构一直在开展一项使用瞬时弹性成像进行肝纤维化评估的项目。纳入所有HIV-HCV合并感染且进行过≥2次检查且间隔>18个月的患者。肝纤维化进展（LFP）定义为肝硬度从<9.5 kPa（梅塔维分级F0-F2）增加至>9.5 kPa（梅塔维分级F3-F4），或基线梅塔维分级为F3-F4的患者增加>30%。

结果

共分析了545例HIV-HCV合并感染患者（平均年龄41岁，71%为男性，81%为静脉吸毒者，平均体重指数23.3 kg/m²，4.2%乙肝表面抗原阳性，8.4%有酒精滥用，平均CD4⁺T细胞计数519个/μl）。基线时，527例患者接受抗逆转录病毒治疗，最常用的第三种药物是阿扎那韦（19.7%）﹑依非韦伦（15.9%）﹑洛匹那韦（13.1%）或奈韦拉平（7.2%）。在平均（标准差）70.9（15.7）个月的随访期间，共有99例（18%）患者出现LFP。使用蛋白酶抑制剂（比值比[OR]4.93，95%置信区间[CI]1.73，14.0；P=0.03）和男性（OR 5.12，95%CI 1.37，19.