Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich, Switzerland.
Clin Infect Dis. 2010 Feb 15;50(4):502-11. doi: 10.1086/649922.
BACKGROUND: Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose. METHODS: We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at 2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used. RESULTS: A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/microL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI 30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels. CONCLUSIONS: Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.
背景：人类免疫缺陷病毒（HIV）感染患者的慢性肝病主要由肝炎病毒合并感染引起。其他导致慢性丙氨酸氨基转移酶（ALT）升高的原因则更难诊断。
方法：我们研究了瑞士 HIV 队列研究中无乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染的参与者在 2002 年至 2008 年期间连续两次半年度就诊时出现 ALT 水平持续升高（大于正常值上限 2 次）的发生率和危险因素。采用泊松回归分析。
结果：共有 2365 名参与者随访了 9972 人年（中位年龄 38 岁；男性 66%；中位 CD4+细胞计数 426/μL；接受抗逆转录病毒治疗[ART]者 56%）。共有 385 名参与者（16%）出现慢性 ALT 水平升高，发生率为每 100 人年 3.9 例（95%置信区间[CI]为 3.5-4.3 例/100 人年）。多变量分析显示，慢性 ALT 水平升高与 HIV RNA 水平＞100,000 拷贝/ml（发病率比[IRR]为 2.23；95%CI 为 1.45-3.43）、体重指数（BMI）升高（定义为体重以千克为单位除以身高以米为单位的平方）（BMI 为 25-29.9 与 IRR 为 1.56[95%CI 为 1.24-1.96]；BMI 为 30 与 IRR 为 1.70[95%CI 为 1.16-2.51]）、重度饮酒（1.83[1.19-2.80]）、暴露于司他夫定（每暴露 1 年的 IRR 为 1.12[95%CI 为 1.07-1.17]）和齐多夫定（每暴露 1 年的 IRR 为 1.04[95%CI 为 1.00-1.08]）相关。与联合 ART、核苷逆转录酶抑制剂和未强化蛋白酶抑制剂的累积暴露相关的关联在调整司他夫定的暴露后不再具有统计学意义。黑种人呈负相关（IRR 为 0.52[95%CI 为 0.33-0.82]）。治疗结果和死亡率在 ALT 水平升高组和无 ALT 水平升高组之间没有差异。
结论：在无肝炎病毒合并感染的患者中，慢性 ALT 水平升高的发生率为每 100 人年 3.9 例，与高 HIV RNA 水平、BMI 升高、重度饮酒以及司他夫定和齐多夫定暴露时间延长有关。需要进行长期随访以评估 ALT 水平的慢性升高是否会导致发病率或死亡率增加。
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