头孢曲松引起成年患者药物性肝脏损害分析

目的：分析成年患者应用头孢曲松过程中,发生肝脏损害（drug-induced liver injury, DILI）的危险因素。方法：回顾选取2015年1月至2016年12月于复旦大学附属中山医院使用头孢曲松注射液的成年患者384例。通过医院信息管理系统收集患者资料,包括基本信息、感染诊断、感染部位及其他合并症;观察指标主要包括用药前后肝功能指标以及合并用药情况。依据头孢曲松使用剂量分为低剂量（≤2 g/d）组和高剂量（＞2 g/d）组,比较两组患者DILI的发生率。将患者分为肝损害组和肝未损害组,分析两组头孢曲松应用情况。结果：高剂量组为66例（17.2%）,低剂量组为318例（82.8%）。384例患者中,12例（3.1%）在使用头孢曲松期间发生DILI,高剂量组发生率高于低剂量组（13.6% vs 0.9%;OR=16.58,95%CI 4.35~63.11,P<0.001）;384例患者中,44例（11.4%）发生轻度肝脏损害,高剂量组发生率高于低剂量组（25.8% vs 8.5%;OR=3.74,95%CI 1.90~7.37,P<0.001）。单因素分析结果显示,应用高剂量头孢曲松（＞2 g/d）是发生DILI的危险因素（OR=16.58,95%CI 4.36~63.11,P<0.001）。结论：应用高剂量头孢曲松(>2 g/d)的成人患者发生DILI的风险较大,是成人患者发生DILI的危险因素。     

异甘草酸镁治疗药物性肝损害的临床疗效探讨

目的探讨异甘草酸镁治疗药物性肝损害的临床疗效。方法选取24例药物性肝损害住院患者,随机分为治疗组12例和对照组12例,2组均以常规护肝治疗,治疗组在常规护肝基础上加用异甘草酸镁0.1 g+10%葡萄糖注射液250mL,静脉滴注1次/d,疗程1个月。观察2组治疗前后血清丙氨酸转氨酶(ALT)、谷草转氨酶(AST)、血清总胆红素(TBIL)、γ-谷氨酰转肽酶(GGT)和碱性磷酸酶(ALP)的变化情况,以及2组患者住院天数的差异。结果与对照组相比,异甘草酸镁治疗急性药物性肝损害能明显改善肝功能(P均<0.01),住院天数显著缩短(P<0.01)。结论异甘草酸镁治疗急性药物性肝损害的效果较好,值得临床推广使用。     

声辐射脉冲成像在评价急性药物性肝损伤中的应用价值

目的探讨声辐射脉冲成像(ARFI)评价急性药物性肝损伤应用价值。方法急性药物性肝损伤患者(急性肝损伤组)22例,体检健康者25例为对照组,超声检测其肝右叶及肝左叶的剪切波速度(SWV)值。急性肝损伤组分别于治疗前,治疗1、3、6个月后测定肝右叶SWV值和肝功能:谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TB)、直接胆红素(DB)水平。结果急性肝损伤组肝右叶、肝左叶SWV值均低于对照组(P<0.01)。急性肝损伤组治疗前、治疗1、3、6个月后肝右叶SWV值依次增加,ALT、AST、ALP、TB及DB依次减小,差异均有统计学意义(均P<0.05)。急性肝损伤组肝右叶SWV值与ALT、AST、ALP、TB呈负相关(r值分别为-0.402、-0.517、-0.611、-0.462,P<0.05)。结论 ARFI可以客观有效地评价急性肝损伤,同时对于治疗有一定的指导意义;患者治疗后SWV水平高于健康人群,可能与急性肝损害后肝脏慢性纤维化病变有关。     

急性药物性肝损伤64例临床分析

目的探讨64例急性药物性肝损伤（drug-induced liver injury,DILI）患者的临床特征。方法采用回顾性分析法对64例急性DILI住院患者的用药史、临床表现及治疗转归进行分析。结果多种药物均可引起急性DILI,以抗结核药物为主,占23.4%,其次为中药23.4%,抗菌药11.0%;临床类型为肝细胞型多见,占84.4%,胆汁淤积型占11.0%,混合型占4.7%;主要临床表现有纳差、乏力、黄疸、恶心、呕吐等;绝大多数患者治疗后预后较好,但重症患者仍可危及生命。结论多种药物均可引起急性DILI,以抗结核药和中药为主;急性DILI以肝细胞损伤型最为常见;大多患者预后良好,但重症患者仍可危及生命。     

老年人急性药物性肝损伤的病因及临床特点分析

目的探讨老年人急性药物性肝损伤的病因和临床特点。方法回顾性分析2005年10月至2011年5月首都医科大学附属北京地坛医院收治的102例老年急性药物性肝损伤住院患者的病历资料,并与150例中青年急性药物性肝损伤患者进行比较。结果按照国际医学科学组织理事会(CIOMS)分型标准以及RUCAM评分量表,老年组确诊95例,中青年组135例。老年组原发疾病前三位为骨关节疾病(26.3%)、心脑血管疾病(17.9%)、皮肤疾病(12.6%);而中青年组排名前三位的分别是皮肤疾病(20.7%)、使用抗生素及抗真菌药物(13.3%)、结核病(10.4%)。两组患者服用中药比例分别为52.6%、50.4%。老年组主要临床表现包括乏力(67.4%)、纳差(88.1%)、恶心/呕吐(42.15%)、黄疸(77.9%),与中青年组相比无显著性差异。两组均以肝细胞损伤型为主,但老年组胆汁淤积型发生率较中青年组更高(P<0.05)。结论老年患者急性药物性肝损伤的原发疾病谱与中青年不同,胆汁淤积型发生率较中青年更高。     

药物性肝病218例病因及临床分析

目的：探讨药物性肝病的常见诱发药物、临床表现、分型及预后．方法：对符合诊断标准的218例药物性肝病的临床资料进行回顾性分析、结果：诱发药物性肝病的药物中，中草药占46例（21％），抗结核病药占45例（21％），解热镇痛药占22例（10％），抗菌药占17例（8％），化学治疗药占27例（12％），其它占62例（28％），临床表现为急性药物性肝病198例（91％），其中急性肝炎型45例，胆汁淤积型111例。混合型42例；慢性药物性肝病20例（9％），治愈168例（77％），好转28例（13％），无变化5例（2％），恶化8例（4％），死亡9例（4％）．结论：药物性肝病常见的诱发药物为中草药、抗结核病药、化学治疗药及解热镇痛药等，主要为急性病程，预后良好。     

Biomarkers of drug-induced liver injury: progress and utility in research,medicine, and regulation

Introduction: The difficulty of understanding and diagnosing drug-induced liver injury (DILI) has led to proliferation of serum and genetic biomarkers. Many applications of these biomarkers have been proposed, including investigation of mechanisms, prediction of DILI during early trials or before initiation of therapy in patients, and diagnosis of DILI during therapy.

Areas covered: We review the definition and categories of DILI, describe recent developments in DILI biomarker development, and provide guidance for future directions in DILI biomarker research.

Expert commentary: There are major obstacles to DILI biomarker development and implementation, including the low prevalence of idiosyncratic DILI (IDILI), weak associations of IDILI with genetic variants, and lack of specificity of many biomarkers for the liver. Certain serum biomarkers, like miR-122, may have clinical utility in early-presenting patients with either intrinsic or idiosyncratic DILI in the future, while others likely will not find use. Future research should focus on implementation of biomarkers to predict later injury and outcome in early presenters with intrinsic DILI, and on development of biomarkers of adaptation and repair in the liver that can be used to determine if a liver test abnormality is likely to be clinically significant in IDILI.     

The reliability of prehospital clinical evaluation for potential spinal injury is not affected by the mechanism of injury

Introduction. Traditional EMS teaching identifies mechanism of injury as an important predictor of spinal injury. Clinical criteria to select patients for immobilization are being studied in Michigan and have been implemented in Maine. Maine requires automatic immobilization of patients with “a positive mechanism” clearly capable of producing spinal injury. Objective. To determine whether mechanism of injury affects the ability of clinical criteria to identify patients with spinal injury. Methods. In this multicenter prospective cohort study, EMS personnel completed a check-off data sheet for prehospital spine-immobilized patients. Data included mechanism of injury and yes/no determinations of the clinical criteria: altered mental status, neurologic deficit, evidence of intoxication, spinal pain or tenderness, and suspected extremity fracture. Hospital outcome data included confirmation of spinal injury and treatment required. Mechanisms of injury were tabulated and rates of spinal injury for each mechanism were calculated. The patients were divided into three different high-risk and low-risk groups. Results. Data were collected for 6,500 patients. There were 209 (3.2%) patients with spinal injuries identified. There were 1,058 patients with 100 (9.4%) injuries in the first high-risk mechanism group, and 5,423 patients with 109 (2%) injuries in the first low-risk group. Criteria identified 97 of 100 (97%) injuries in the high-risk group and 102 of 109 (94%) in the low-risk group. Two additional data divisions yielded identical results. Conclusion. Mechanism of injury does not affect the ability of clinical criteria to predict spinal injury in this population.     

MiR-122 and other microRNAs as potential circulating biomarkers of drug-induced liver injury

Introduction: Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits preclinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers.

Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI. Furthermore, the use of miRNAs as potential markers of progression of DILI and specific zonated damage within the liver is discussed.

Expert commentary: MiRNAs offer more sensitive and specific markers over the current biomarkers for DILI. Combinations of different miRNAs may be able to relay the location of DILI and the progression of disease. More studies using different hepatotoxins apart from acetaminophen will ultimately strengthen the case for the clinical introduction of miRNAs as biomarkers of DILI.     

Exploring the efficacy and safety of polyene phosphatidylcholine for treatment of drug-induced liver injury using the Roussel Uclaf causality assessment method: a propensity score matching comparison

Objective In China, polyene phosphatidylcholine (PPC) is widely used to treat alanine aminotransferase (ALT) elevation associated with various liver diseases. Here, we assessed the efficacy and safety of PPC in treating drug-induced liver injury (DILI).Methods Data from a multicenter retrospective cohort study (DILI-R) were analyzed to compare PPC and magnesium isoglycyrrhizinate (MgIG) for treatment of DILI. We used the Roussel Uclaf causality assessment method (RUCAM) to evaluate patients with DILI. Patients with RUCAM scores ≥6 were included in the study, while those with RUCAM scores <6 were further evaluated by a panel of hepatologists. The primary outcome was the proportion of patients with ALT normalization at discharge. Propensity score matching was used to identify 183 matched pairs of patients (366 patients in total) from 25,927 patients with DILI.Results Among the DILI patients, 64 of 183 (34.97%) achieved normal ALT levels after treatment in both the PPC and the MgIG groups.Conclusion There were no significant differences in safety biomarkers including serum creatinine, blood urea nitrogen, white blood cells, platelets, hemoglobin, and albumin between patients treated with PPC or MgIG. The safety and efficacy of these two agents for treatment of DILI were comparable.     

稳定同位素iTRAQ标记联合液相色谱-串联质谱法定量分析药物性肝损伤患者血清氨基酸的变化

目的探索药物性肝损伤(DILI)患者治疗的不同阶段血清氨基酸水平的变化差异,探讨其临床意义及可用于DILI早期诊断及疗效评价的氨基酸类生物标志物。方法收集21例健康志愿者(健康组)及24例DILI患者不同阶段(初诊、治疗、转归)的血清标本,采用稳定同位素iTRAQ标记方法联合液相色谱串联质谱技术检测血清氨基酸进行定量并分析其差异。结果在血清中共定量氨基酸28种,与健康组比较,DILI患者共有14种氨基酸浓度在诊疗不同阶段发生显著性改变;其中异亮氨酸、亮氨酸、苯丙氨酸及丝氨酸的浓度在初诊时显著升高,随治疗进程降低,逐渐接近于正常水平。结论 4种氨基酸中,苯丙氨酸与DILI的相关性更高,可能为DILI早期诊断及治疗效果评价的潜在生物标志物。     

异甘草酸镁治疗抗结核药物性肝损伤疗效

目的 探讨异甘草酸镁(MgIG)治疗对抗结核药物引起肝损伤患者的疗效及细胞因子(IFN-γ, IL-10, TNF-α)的影响。方法 选取2016年2月至2019年12月昆明医科大学第六附属医院感染科就诊的符合抗结核药物性肝损伤诊断标准的轻度肝细胞损伤型患者,随机分为观察组使用MgIG治疗(n=25)和对照组使用多烯磷脂酰胆碱治疗(n=25)。比较两组患者治疗前后肝功能(ALT, AST, TBIL)和细胞因子水平(IFN-γ, IL-10, TNF-α)变化。结果 观察组患者治疗总有效率显著高于对照组患者(100% vs 76.0%, P<0.01)。两组患者IFN-γ、IL-10、TNF-α均较治疗前降低(P均<0.05);观察组IFN-γ, IL-10, TNF-α均低于对照组(P均<0.05)。Pearson相关分析显示,两组治疗前、治疗后的所有细胞因子水平与ALT呈正相关关系。结论 在轻度的抗结核药物性肝损伤中,MgIG快速改善肝功能可能与其降低炎症细胞因子相关。     

Assessment of the accuracy of the CALCULATE scale for pressure injury in critically ill patients

IntroductionPressure injury is damage to the skin and underlying soft tissue that occurs in response to intense and/or prolonged skin pressure. The Braden scale is the most used in health services to assess pressure injury. However, this scale was not specifically developed for critically ill patients. The Critical Care Pressure Ulcer Assessment Tool Made Easy (CALCULATE) scale was developed for patients in intensive care units.ObjectiveThe objective of this study was to compare the accuracy of the CALCULATE scale with that of Braden in predicting the risk of pressure injury in critically ill patients.MethodsThis was a prospective cohort study, involving patients who did not have pressure injury on admission to the intensive care unit of a tertiary hospital in the city of Porto Alegre, Brazil. Data collection took place between January and July 2020 using the Braden and CALCULATE scales, in addition to clinical and sociodemographic variables. Patients were followed up until discharge from the intensive care unit or death.ResultsFifty-one patients were included in the study. Of these, 29 (56.9%) developed pressure injury. To predict pressure injury onset, the areas under the receiver operator characteristic curve of the Braden scale on the first day and the lowest score during the first 3 days were 0.71 (0.56–0.86) and 0.70 (0.53–0.87), respectively. The areas under the receiver operator characteristic curve of the CALCULATE scale on the first day and the highest score during the first 3 days were 0.91 (0.82–0.99) and 0.92 (0.85–1.00), respectively. In the logistic regression analysis, the CALCULATE scale on the first day remained an independent predictor of pressure injury onset after controlling for age and length of stay in the intensive care unit.ConclusionWe found that the CALCULATE scale may be more accurate than the Braden scale as a tool to assess the risk of developing pressure injury in critically ill patients.     

异甘草酸镁与复方甘草酸单胺治疗血液肿瘤化疗后药物性肝损害的疗效比较

目的比较异甘草酸镁与复方甘草酸单胺治疗血液肿瘤化疗后药物性肝损害的临床疗效与不良反应。方法选取48例血液肿瘤化疗后药物性肝损害患者,随机分为2组,各24例。异甘草酸镁组予异甘草酸镁注射液150 mg,复方甘草酸单胺组予复方甘草酸单胺注射液60 mL,2组试剂均加入5%葡萄糖注射液250 mL静滴,每日1次,疗程均为2周。观察治疗后临床症状、体征、肝功能改善情况及不良反应。结果 2组治疗后临床症状、体征及肝功能指标较治疗前均有明显改善,改善率无显著性差异(P>0.05),但在复常天数上有显著性差异(P<0.05)。异甘草酸镁组显效率明显高于复方甘草酸单胺组(P<0.05)。异甘草酸镁组未出现明显不良反应;复方甘草酸单胺组发生颜面部水肿4例,血压升高1例。结论异甘草酸镁治疗血液肿瘤化疗后药物性肝损害的疗效优于复方甘草酸单胺,且副作用显著低于复方甘草酸单胺。     

甘草酸二胺联合谷胱甘肽治疗抗结核药物性肝损伤

目的观察甘草酸二胺联合谷胱甘肽治疗抗结核药物性肝损伤的疗效。方法将63例抗结核药物性肝损伤患者随机分为治疗组和对照组。治疗组给予甘草酸二胺注射液联合谷胱甘肽注射液治疗,对照组给予维生素C和门冬氨酸钾镁注射液治疗,疗程均为2周。观察和对比两组治疗前后的临床症状和体征、肝功能等变化情况。结果治疗组总有效率为96．9％,对照组总有效率为74．2％,治疗组疗效明显高于对照组（P〈0．01）。治疗组在治疗后丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、血清总胆红素（TBIL）较治疗前明显改善（P〈0．01）,且三者的下降优于对照组（P〈0．05）。结论甘草酸二胺联合谷胱甘肽对抗结核药物性肝损伤疗效明确,能够抗炎症反应,改善肝脏微循环,保护肝细胞受损,是临床治疗抗结核药物性肝损伤的有效方法之一。     

肺结核患者121例抗结核药物引起肝损害的临床分析

目的探讨应用抗结核药物所致药物性肝损害的临床特点、预防和治疗措施。方法我院1152例结核患者中,抗结核药物治疗后出现121例药物性肝损害,分析肝损害出现的年龄、初复治情况、乙肝病毒感染关系以及治疗方法。结果接受抗结核治疗的患者中,≥60岁的老龄、复治及乙肝病毒表面抗原（HBsAg）（＋）患者出现肝损害的发生率较〈60岁、初治及HBsAg（-）患者高,差异具有统计学意义（P〈0．001）。给予保肝、降酶等治疗后,肝功能恢复效果好。结论对高龄、复治及乙肝病毒感染肺结核患者,是抗结核药物致肝损害的高危人群,应密切观察肝功能情况．．旱发明．、旱预防、早治疗肝桶窖．以利干顺利旁威抗结核化疗疗程．