Kalyesubula R, Kagimu M, Opio K C, Kiguba R, Semitala C F, Schlech W F, Katabira E T
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Afr Health Sci. 2011 Mar;11(1):16-23.
Highly active antiretroviral therapy (HAART) has been associated with liver toxicity. The role of monitoring for liver toxicity has not been well studied in resource-limited settings (RLS).
To determine the background prevalence and incidence of liver injury and describe the associated signs and symptoms of acute hepatitis after initiating HAART; and to determine the role of liver enzyme tests in monitoring hepatotoxicity.
In this prospective study, in Mulago Hospital AIDS Clinics, we consecutively enrolled adult patients initiated on one of three first line HAART regimens [Stavudine (d4T)-Lamivudine (3TC) and nevirapine (NVP); Zidovudine (AZT)-3TC and Efavirenz (EFV) or d4T-3TC-EFV]. We monitored ALT (alanine aminotransferase) and clinical evidence of acute hepatitis at baseline, 2(nd), 6(th), 10(th) and 14(th) week of therapy.
Two hundred and forty HIV-positive HAART- naïve patients were enrolled in the study. The baseline prevalence of transaminitis was 1.7% with an incidence of 4.2% at 14 weeks. Grade 3-4 hepatotoxicity was documented in 1.3%. Jaundice was seen in grade 2-4 ALT elevations. Being on concurrent HAART and antituberculous drugs was associated with grade 2-4 toxicity compared to those who were only on HAART [OR; 16.0 (95% CI; 2.4-104.2)].
Incidence of severe hepatotoxicity within three months of first-line antiretroviral therapy was low, suggesting that routine measurement of transaminases may not be necessary in all patients initiating HAART in RLS. Routine measurement may be important in following patients on HAART and concurrent TB treatment as well as those with jaundice to avoid missing hepatotoxicity.
高效抗逆转录病毒疗法（HAART）与肝毒性有关。在资源有限的环境中（RLS），对肝毒性进行监测的作用尚未得到充分研究。
确定肝损伤的背景患病率和发病率，并描述开始HAART后急性肝炎的相关体征和症状；确定肝酶检测在监测肝毒性中的作用。
在这项前瞻性研究中，我们在穆拉戈医院艾滋病诊所连续招募了开始使用三种一线HAART方案之一的成年患者[司他夫定（d4T）-拉米夫定（3TC）和奈韦拉平（NVP）；齐多夫定（AZT）-3TC和依非韦伦（EFV）或d4T-3TC-EFV]。我们在治疗的基线、第2、6、10和14周监测丙氨酸氨基转移酶（ALT）和急性肝炎的临床证据。
240名未接受过HAART治疗的HIV阳性患者被纳入研究。基线时转氨酶升高的患病率为1.7%，14周时发病率为4.2%。记录到3-4级肝毒性的比例为1.3%。2-4级ALT升高时出现黄疸。与仅接受HAART治疗的患者相比，同时接受HAART和抗结核药物治疗与2-4级毒性相关[比值比；16.0（95%可信区间；2.4-104.2）]。
一线抗逆转录病毒治疗三个月内严重肝毒性的发生率较低，这表明在资源有限的环境中，并非所有开始HAART治疗的患者都需要常规检测转氨酶。对于接受HAART治疗同时合并结核病治疗的患者以及出现黄疸的患者，常规检测可能很重要，以避免漏诊肝毒性。
