Trigo C, do Brasil P E A A, Costa M J M, de Castro L
Pharmacogenetics Research Laboratory, Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
Intensive Care Clinical Research Laboratory, Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
J Viral Hepat. 2016 Dec;23(12):1027-1035. doi: 10.1111/jvh.12583. Epub 2016 Sep 13.
Occult hepatitis B virus infection (OBI) is characterized by the absence of HBsAg and persistence of the virus genome (HBV-DNA) in liver tissue and/or blood. OBI has been reported in several clinical contexts. However, the clinical significance of OBI in tuberculosis (TB) treatment is unknown. We investigated the OBI prevalence and its impact on the risk of drug-induced liver injury (DILI) during TB treatment. This was a prospective cohort study with one hundred patients who were treated for TB from 2008 to 2015. Laboratory, clinical and demographic data of TB patients were extracted from medical records. Based on HBV-DNA testing of serum samples, an OBI prevalence of 12% was established; almost half of these patients had both anti-HBc and anti-HBs serological markers. Low CD4 cell counts have been shown to be a risk factor for OBI among TB patients co-infected with HIV (P=.036). High DILI incidence was observed in this study. A multivariable Cox proportional hazard model was conducted and identified OBI (HR 2.98, 95% CI 1.30-6.86) as the strongest predictor for DILI when adjusted to CD4 cell count (HR 0.38, 95% CI 0.17-0.90), ALT before TB treatment (HR 1.37, 95% CI 0.81-2.32) and TB extrapulmonary clinical form (HR 2.91, 95% CI 1.75-7.21). The main aim of this study was to highlight DILI as a clinical outcome during treatment of TB patients with OBI. Therefore, HBV-DNA testing should be considered routinely in monitoring DILI, and also in other clinical implications associated with OBI, reduce morbidity and mortality.
隐匿性乙型肝炎病毒感染(OBI)的特征是肝组织和/或血液中不存在乙肝表面抗原(HBsAg)但病毒基因组(HBV-DNA)持续存在。OBI已在多种临床情况下被报道。然而,OBI在结核病(TB)治疗中的临床意义尚不清楚。我们调查了OBI的患病率及其对结核病治疗期间药物性肝损伤(DILI)风险的影响。这是一项前瞻性队列研究,研究对象为2008年至2015年期间接受结核病治疗的100名患者。结核病患者的实验室、临床和人口统计学数据从病历中提取。基于血清样本的HBV-DNA检测,确定OBI患病率为12%;这些患者中近一半同时具有抗-HBc和抗-HBs血清学标志物。在合并感染HIV的结核病患者中,低CD4细胞计数已被证明是发生OBI的一个危险因素(P = 0.036)。本研究中观察到较高的DILI发生率。进行了多变量Cox比例风险模型分析,在对CD4细胞计数(风险比[HR] 0.38,95%置信区间[CI] 0.17 - 0.90)、结核病治疗前丙氨酸氨基转移酶(ALT)水平(HR 1.37,95% CI 0.81 - 2.32)和肺外结核临床类型(HR 2.91,95% CI 1.75 - 7.21)进行校正后,确定OBI(HR 2.98,95% CI 1.30 - 6.86)是DILI的最强预测因素。本研究的主要目的是强调DILI是OBI结核病患者治疗期间的一种临床结局。因此, 在监测DILI以及与OBI相关的其他临床情况时,应常规考虑进行HBV-DNA检测,以降低发病率和死亡率。