HIV感染者中非肝硬化门静脉高压症与抗逆转录病毒治疗使用去羟肌苷的关联：一项巢式病例对照研究。

Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study.

作者信息

Kovari Helen, Ledergerber Bruno, Peter Ulrich, Flepp Markus, Jost Josef, Schmid Patrick, Calmy Alexandra, Mueller Nicolas J, Muellhaupt Beat, Weber Rainer

机构信息

Divisions of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich CH-8091, Switzerland.

出版信息

Clin Infect Dis. 2009 Aug 15;49(4):626-35. doi: 10.1086/603559.

DOI:10.1086/603559

PMID:19589079

Abstract

BACKGROUND

Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine.

METHODS

We performed a nested case-control study including 15 patients with NCPH and 75 matched control subjects of the Swiss HIV Cohort Study to investigate risk factors for the development of NCPH. Matching criteria were similar duration of HIV infection, absence of viral hepatitis, and follow-up to at least the date of NCPH diagnosis in the respective case.

RESULTS

All 15 case patients had endoscopically documented esophageal varices and absence of liver cirrhosis on biopsies; 4 died because of hepatic complications. At NCPH diagnosis, case patients and control subjects were similar concerning sex; race; Centers for Disease Control and Prevention stage; HIV-RNA level; CD4 cell count nadir; and lipids and lipodystrophy. Differences were found in age (conditional logistic regression odds ratio [OR] for 10 years older, 2.9; 95% confidence interval [CI], 1.4-6.1); homosexuality (OR, 4.5; 95% CI, 1.2-17); current CD4 cell count <200 cells/microL (OR, 34.3; 95% CI, 4.3-277); diabetes mellitus (OR, 8.8; 95% CI, 1.6-49); alanine aminotransferase level higher than normal (OR, 13.0; 95% CI, 2.7-63); alkaline phosphatase higher than normal (OR, 18.3; 95% CI, 4.0-85); and platelets lower than normal (OR, 20.5; 95% CI, 2.4-178). Cumulative exposure to antiretroviral therapy (OR per year, 1.3; 95% CI, 1.0-1.6), nucleoside reverse-transcriptase inhibitor (OR, 1.3; 95% CI, 1.1-1.7), didanosine (OR, 3.4; 95% CI, 1.5-8.1), ritonavir (OR, 1.4; 95% CI, 1.0-1.9), and nelfinavir (OR, 1.4; 95% CI, 1.0-1.9) were longer in case patients. Exposure to nonnucleoside reverse-transcriptase inhibitor and other protease inhibitors were not different between groups. In bivariable models, only the association of NCPH with didanosine exposure was robust; other covariables were not independent risk factors.

CONCLUSIONS

We found a strong association between prolonged exposure to didanosine and the development of NCPH.

摘要

背景

非肝硬化性门静脉高压症（NCPH）是一种新发现的、病因不明的、危及生命的肝脏疾病，见于感染人类免疫缺陷病毒（HIV）的人群。推测的发病机制包括长期接受抗逆转录病毒治疗，尤其是去羟肌苷。

方法

我们进行了一项巢式病例对照研究，纳入了瑞士HIV队列研究中的15例NCPH患者和75例匹配的对照对象，以调查NCPH发生的危险因素。匹配标准为HIV感染持续时间相似、无病毒性肝炎，且至少随访至各病例的NCPH诊断日期。

结果

所有15例病例患者经内镜检查均证实有食管静脉曲张，活检显示无肝硬化；4例因肝脏并发症死亡。在NCPH诊断时，病例患者和对照对象在性别、种族、疾病控制和预防中心分期、HIV-RNA水平、CD4细胞计数最低点以及血脂和脂肪代谢障碍方面相似。在年龄方面存在差异（每大10岁的条件逻辑回归比值比[OR]为2.9；95%置信区间[CI]为1.4 - 6.1）；同性恋（OR为4.5；95% CI为1.2 - 17）；当前CD4细胞计数<200个/微升（OR为34.3；95% CI为4.3 - 277）；糖尿病（OR为8.8；95% CI为1.6 - 49）；丙氨酸氨基转移酶水平高于正常（OR为13.0；95% CI为2.7 - 63）；碱性磷酸酶高于正常（OR为18.3；95% CI为4.0 - 85）；血小板低于正常（OR为20.5；95% CI为2.4 - 178）。病例患者接受抗逆转录病毒治疗（每年OR为1.3；95% CI为1.0 - 1.6）、核苷类逆转录酶抑制剂（OR为1.3；95% CI为1.1 - 1.7）、去羟肌苷（OR为3.4；95% CI为1.5 - 8.1）、利托那韦（OR为1.4；95% CI为1.0 - 1.9）和奈非那韦（OR为1.4；95% CI为1.0 - 1.9）的累积暴露时间更长。两组之间接受非核苷类逆转录酶抑制剂和其他蛋白酶抑制剂的暴露情况无差异。在双变量模型中，只有NCPH与去羟肌苷暴露之间的关联较为显著；其他协变量不是独立的危险因素。