初治肺结核并乙型肝炎病毒携带者抗结核治疗过程中出现肝损伤的影响因素及预后研究

doi:10.12114/j.issn.1007-9572.2021.00.566

摘要/Abstract

摘要： 背景　我国既是结核病高负担国家又是乙型肝炎（以下简称乙肝）大国，结核病合并乙肝很常见。从理论上来说，对于肺结核并乙型肝炎病毒（HBV）感染患者，抗HBV治疗或优化抗结核方案均可能减少肝损伤的发生。目的　探讨初治肺结核并HBV携带者抗结核治疗过程中出现肝损伤及肝损伤后死亡的影响因素。方法　收集江西省胸科医院、南丰县人民医院、都昌县第二人民医院、共青城市人民医院2015年6月至2019年6月收治的符合纳入标准的230例在抗结核治疗过程中出现肝损伤的初治肺结核并HBV携带者（记为肝损伤组），并根据性别、年龄、来源按1∶1匹配同期于四家医院完成抗结核治疗且未出现肝损伤的230例初治肺结核并HBV携带者作为对照（记为对照组）。回顾性收集所有患者的病历资料。分析初治肺结核并HBV携带者抗结核治疗过程中出现肝损伤的影响因素。依据患者预后情况将肝损伤组患者分为死亡亚组和好转亚组，分析初治肺结核并HBV携带者出现肝损伤后死亡的影响因素。结果　两组患者受教育水平、酗酒史、乙肝e抗原（HBeAg）、HBV-DNA水平、预防性抗HBV治疗情况、抗结核治疗方案、预防性护肝治疗情况比较，差异有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，预防性抗HBV治疗〔OR=1.88，95%CI（1.55，3.04）〕、抗结核治疗方案〔OR=5.16，95%CI（1.90，14.02）〕是初治肺结核并HBV携带者抗结核治疗过程中出现肝损伤的独立影响因素（P<0.05）。230例初治肺结核并HBV携带者中好转214例，死亡16例。两亚组患者合并感染情况、肝损伤发生时血清白蛋白水平、预防性抗HBV治疗情况、从出现消化道症状到停结核药物的间隔时间比较，差异有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，预防性抗HBV治疗〔OR=1.61，95%CI（1.13，2.28）〕、从出现消化道症状到停结核药物的间隔时间〔OR=3.07，95%CI（1.45，6.49）〕是初治肺结核并HBV携带者出现肝损伤后死亡的独立影响因素（P<0.05）。结论　预防性抗HBV治疗、抗结核治疗方案是肺结核并HBV携带者抗结核治疗过程中出现肝损伤的影响因素，而预防性抗HBV治疗、从出现消化道症状到停结核药物的间隔时间是初治肺结核并HBV携带者出现肝损伤后死亡的影响因素。

关键词: 乙型肝炎病毒；结核, 肺；化学性与药物性肝损伤；抗结核药；影响因素分析；预后

Abstract: Background　There are both high burden of tuberculosis and hepatitis B in China，and tuberculosis combined with hepatitis B is very common. Therefore，in principle，anti-HBV treatment or optimization of anti-tuberculosis programs should reduce the occurrence of liver injury for patients with tuberculosis and HBV infection. Objective　To explore the influencing factors of liver injury in patients with newly diagnosed pulmonary tuberculosis and hepatitis B co-infection during anti-tuberculosis treatment，and analyze the influencing factors of death in patients with liver injury. Methods　230 cases of patients admitted to Jiangxi Chest Hospital，Nanfeng County People's Hospital，Duchang County Second People's Hospital，and Gongqingcheng People's Hospital from June 2015 to June 2019 with newly diagnosed pulmonary tuberculosis and hepatitis B co-infection combined with liver injury during anti-tuberculosis treatment were collected（recorded as the liver injury group），and matched 1∶1 to 230 cases of newly diagonsed pulmonary tuberculosis patients with pulmonary tuberculosis and HBV infection who completed anti-tuberculosis treatment in four hospitals without liver injury according to gender，age and source（recorded as control group）. Medical records of all the enrolled patients were retrospectively collected and the influencing factors of liver injury during anti-tuberculosis treatment of patients with newly diagnosed pulmonary tuberculosis and hepatitis B co-infection were analyzed. According to the prognosis of the patients，the patients were divided into death subgroups and improvement subgroups，and the influencing factors of death after liver injury in patients with newly diagnosed pulmonary tuberculosis and hepatitis B co-infection during anti-tuberculosis treatment were analyzed. Results　There was a statistically significant difference in the level of education，history of alcohol abuse，hepatitis B e antigen（HBeAg），HBV-DNA level，whether rececived preventive anti-HBV treatment，anti-tuberculosis treatment plan，and whether rececived preventive liver protection treatment between the two groups（P<0.05）. The results of multivariate Logistic regression analysis showed that preventive anti-HBV treatment 〔OR=1.88，95%CI（1.55，3.04）〕 and anti-tuberculosis treatment rograms〔OR=5.16，95%CI（1.90，14.02）〕were influencing factors for patients with newly diagnosed pulmonary tuberculosis and hepatitis B co-infection during anti-tuberculosis treatment（P<0.05）. Among the 230 newly treated pulmonary tuberculosis patients with hepatitis B co-infection，214 improved and 16 died. There was a statistically significant difference between the two subgroups of patients with hepatitis B co-infection on serum albumin level at the time of liver injury，preventive anti-HBV treatment，and the interval from onset of gastrointestinal symptoms to stopping anti-tuberculosis treatment（P<0.05）. The results of multivariate logistic regression analysis showed that preventive anti-HBV treatment 〔OR=1.61，95%CI（1.13，2.28）〕，the interval from onset of gastrointestinal symptoms to stopping anti-tuberculosis treatment〔OR=3.07，95%CI（1.45，6.49）〕 were independent influencing factors of death after liver injury in patients with newly diagnosed pulmonary tuberculosis and hepatitis B co-infection（P<0.05）. Conclusion　Preventive anti-HBV treatment and anti-tuberculosis treatment programs are the factors affecting liver injury during anti-tuberculosis treatment for patients with pulmonary tuberculosis and HBV infection，while preventive anti-HBV treatment，the interval from onset of gastrointestinal symptoms to stopping anti-tuberculosis treatment are the influencing factors of death after liver injury in patients with pulmonary tuberculosis and HBV infection.

Key words: Hepatitis B virus；Tuberculosis, pulmonary；Chemical and drug induced liver injury；Antitubercular agents；Root cause analysis；Prognosis

李静虹,吴于青,廖永美,等. 初治肺结核并乙型肝炎病毒携带者抗结核治疗过程中出现肝损伤的影响因素及预后研究[J]. 中国全科医学, 2021, 24(30): 3837-3842. DOI: 10.12114/j.issn.1007-9572.2021.00.566.
LI Jinghong,WU Yuqing,LIAO Yongmei, et al. Study on the Influencing Factors and Prognosis of Liver Injury in Patients with Newly Diagnosed Pulmonary Tuberculosis and Hepatitis B Co-infection during Anti-tuberculosis Treatment　[J]. Chinese General Practice, 2021, 24(30): 3837-3842. DOI: 10.12114/j.issn.1007-9572.2021.00.566.

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