抗结核治疗的乙肝病毒患者的抗病毒治疗：一个被遗忘的问题。,Clinical Infectious Diseases

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抗结核治疗的乙肝病毒患者的抗病毒治疗：一个被遗忘的问题。
Clinical Infectious Diseases ( IF 8.2 ) Pub Date : 2019-12-17 , DOI: 10.1093/cid/ciz1199
Lucio Boglione ₁ , Filippo Lipani ₂ , Anna Maria Lucchini ₂ , Elena Salvador ₁ , Ilaria De Benedetto ₁ , Tommaso Lupia ₁ , Giovanni Di Perri ₁

Affiliation

致编辑—我们感兴趣地阅读了Lui等人的文章[1]，该文针对抗乙肝病毒（HBV）的抗病毒治疗在同时接受结核病治疗的患者中的作用。在本研究中，使用基线乙型肝炎“ s”抗原（HBsAG）定量分析，包括了活动性或非活动性慢性乙型肝炎（CHB）之间，特别是活动性或非活动性携带者之间，没有任何区别[2]。这方面可能与治疗选择有关，因为CHB无效或携带者无效的患者不符合抗病毒治疗的条件。在未接受抗病毒治疗的患者组中，我们观察到HBV-DNA的中位数较低（3.76 log IU / mL），丙氨酸转氨酶（ALT）为正常值（26 U / L），假设在这一人群中非活性携带者可能普遍存在活动性CHB患者。然而，在治疗组中，据报道平均为2.18 log IU / mL HBV-DNA：这一发现难以解释，因为抗病毒治疗是使用更有效的类似物恩替卡韦或替诺福韦进行的，尽管未描述抗病毒治疗的持续时间。如美国胸科学会/疾病控制与预防中心/美国传染病学会药物敏感性结核病临床实践指南中所述，主要在晚期肝病，肝移植或丙型肝炎病毒感染中观察到肝毒性增加[3]。 ]。尽管药物性肝炎是一线结核治疗最常见的副作用，但如果ALT水平低于上限的5倍，毒性可被认为是轻度的，通常应在监测肝功能的情况下继续治疗。在研究人群中，住院期间接受抗病毒治疗的患者（131 U / L）和未经治疗的患者（127 U / L）之间的ALT水平无差异。但是，尚无关于HBV-DNA或定量HBsAg水平的数据可用于区分由病毒引起的耀斑和由于结核病治疗而引起的肝毒性。由于接受抗病毒治疗的HBeAg阳性患者人数众多，因此还应考虑存在与抗HBeAg血清转化有关的免疫性耀斑。此外，两组中肝硬化患者的存在可能有助于了解HBV在转氨酶耀斑中的真正作用。在Chen等人的研究中[4]，P<.001）且HBV-DNA活性水平以上的患者不要。在Zhu等人的研究中[5]，还报道了HBV-DNA的水平与肝毒性无关，而白蛋白的水平与肝功能损害的严重程度显着相关。这些发现似乎证实了肝硬化在肝耀斑发展中的重要作用。我们还报告了在治疗受活动性CHB和结核病影响的患者方面的经验，无论抗病毒治疗如何，仅在肝硬化患者中观察到中度或重度毒性[6]。最后，在纳入标准中，使用了结核的一般诊断，但是未报告肺外结核的发生率，特别是有肝脏累及的播散性结核。

"点击查看英文标题和摘要"

Antiviral Therapy in Patients With Hepatitis B Virus Treated for Tuberculosis: A Forgotten Issue.

To The Editor—We read with interest the article by Lui et al [1] about the role of antiviral therapy against hepatitis B virus (HBV) in patients receiving a concomitant treatment for tuberculosis. In this study, patients with HBV infection were included without any distinction between active or inactive chronic hepatitis B (CHB), in particular between active or inactive carriers using the baseline hepatitis B “s” antigen (HBsAG) quantification [2]. This aspect may be relevant in the choice of treatment, because patients with inactive CHB or inactive carriers are not eligible for antiviral treatment. In the group of patients without antiviral treatment we observe a low median HBV-DNA (3.76 log IU/mL) with normal values of alanine transaminase (ALT) (26 U/L), assuming that in this population inactive carriers are probably prevalent over patients with active CHB. In the treated group, however, a mean of 2.18 log IU/mL HBV-DNA was reported: this finding is difficult to explain since antiviral treatment was given with the more potent analogues entecavir or tenofovir, although the duration of antiviral therapy was not described. As reported in the American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines for drug-susceptible tuberculosis, an increased hepatotoxicity was mainly observed in advanced liver disease, liver transplant, or hepatitis C virus infection [3]. Despite drug-induced hepatitis being the most common side-effect of first-line tuberculosis therapy, if the ALT level is less than 5 times the upper limit, the toxicity can be considered mild and generally the treatment should be continued with monitoring of liver function. In the study population no differences in ALT levels were reported between patients receiving the antiviral therapy (131 U/L) and those without treatment (127 U/L) at the time of hospitalization. However no data on HBV-DNA or quantitative HBsAg levels are available to distinguish between a virus-induced flare and hepatotoxicity due to tuberculosis treatment. Due to a high number of patients who are HBeAg positive in antiviral treatment, the presence of an immunological flare related to anti-HBeAg seroconversion should also be considered. Furthermore, the presence of cirrhotic patients in the 2 groups can be useful to understand the real role of HBV in the transaminase flare. In the study by Chen et al [4], HBV coinfection was associated with poor outcome in patients with tuberculosis, but the risk of liver toxicity was observed only in cirrhotic subjects (odds ratio, 9.648; 95% confidence interval, 2.39–38.87; P < .001) and not in patients with HBV-DNA above the level of activity. In the study by Zhu et al [5] it was also reported that the levels of HBV-DNA were not related to liver toxicity, whereas the albumin levels were significantly related to severity of liver impairment. These findings seem to confirm the essential role of cirrhosis in the development of hepatic flare. We also reported our experience in the treatment of patients affected by active CHB and tuberculosis, in which moderate or severe toxicity was observed only in cirrhotic patients, regardless of antiviral treatment [6]. Finally, in the inclusion criteria, a generic diagnosis of tuberculosis was used, but the rate of extrapulmonary tuberculosis—in particular, the disseminated tuberculosis with hepatic involvement—was not reported: this could be an important confounding factor in the hepatotoxicity investigation.

更新日期：2019-12-17

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