Drug-induced liver injury and COVID-19:Use of artificial intelligence and the updated Roussel Uclaf Causality Assessment Method in clinical practice

BACKGROUND Liver injury is a relevant condition in coronavirus disease 2019(COVID-19)inpatients.Pathophysiology varies from direct infection by virus,systemic inflammation or drug-induced adverse reaction(DILI).DILI detection and monitoring is clinically relevant,as it may contribute to poor prognosis,prolonged hospitalization and increase indirect healthcare costs.Artificial Intelligence(AI)applied in data mining of electronic medical records combining abnormal liver tests,keyword searching tools,and risk factors analysis is a relevant opportunity for early DILI detection by automated algorithms.AIM To describe DILI cases in COVID-19 inpatients detected from data mining in electronic medical records(EMR)using AI and the updated Roussel Uclaf Causality Assessment Method(RUCAM).METHODS The study was conducted in March 2021 in a hospital in southern Brazil.The NoHarm©system uses AI to support decision making in clinical pharmacy.Hospital admissions were 100523 during this period,of which 478 met the inclusion criteria.From these,290 inpatients were excluded due to alternative causes of liver injury and/or due to not having COVID-19.We manually reviewed the EMR of 188 patients for DILI investigation.Absence of clinical information excluded most eligible patients.The DILI assessment causality was possible via the updated RUCAM in 17 patients.RESULTS Mean patient age was 53 years(SD±18.37;range 22-83),most were male(70%),and admitted to the non-intensive care unit sector(65%).Liver injury pattern was mainly mixed,mean time to normalization of liver markers was 10 d,and mean length of hospitalization was 20.5 d(SD±16;range 7-70).Almost all patients recovered from DILI and one patient died of multiple organ failure.There were 31 suspected drugs with the following RUCAM score:Possible(n=24),probable(n=5),and unlikely(n=2).DILI agents in our study were ivermectin,bicalutamide,linezolid,azithromycin,ceftriaxone,amoxicillin-clavulanate,tocilizumab,piperacillin-tazobactam,and albendazole.Lack of essential clinical information excluded most patients.Although rare,DILI is a relevant clinical condition in COVID-19 patients and may contribute to poor prognostics.CONCLUSION The incidence of DILI in COVID-19 inpatients is rare and the absence of relevant clinical information on EMR may underestimate DILI rates.Prospects involve creation and validation of alerts for risk factors in all DILI patients based on RUCAM assessment causality,alterations of liver biomarkers and AI and machine learning.

Atypical onset of bicalutamide-induced liver injury

Anti-androgen therapy is the leading treatment for advanced prostate cancer and is commonly used for neoadjuvant or adjuvant treatment. Bicalutamide is a non-steroidal anti-androgen, used during the initiation of androgen deprivation therapy along with a luteinizing hormone-releasing hormone agonist to reduce the symptoms of tumor-related flares in patients with advanced prostate cancer. As side effects, bicalutamide can cause fatigue, gynecomastia, and decreased libido through competitive androgen receptor blockade. Additionally, although not as common, drug-induced liver injury has also been reported. Herein, we report a case of hepatotoxicity secondary to bicalutamide use. Typically, bicalutamideinduced hepatotoxicity develops after a few days; however, in this case, hepatic injury occurred 5 mo after treatment initiation. Based on this rare case of delayed liver injury, we recommend careful monitoring of liver function throughout bicalutamide treatment for prostate cancer.

Anabolic androgenic steroid-induced liver injury:An update

Anabolic androgenic steroids(AASs)are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects.These properties make them therapeutically beneficial in medical conditions such as hypogonadism.However,they are commonly bought illegally and misused for their anabolic,skeletal muscle building,and performanceenhancing effects.Supraphysiologic and long-term use of AASs affects all organs,leading to cardiovascular,neurological,endocrine,gastrointestinal,renal,and hematologic disorders.Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse.Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis,peliosis hepatis,and hepatic benign and malignant tumors.It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors,upregulation of bile acid synthesis,and induction of hepatocyte hyperplasia.Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS.However,some long-term consequences are irreversible.AAS-induced liver injury should be taken in consideration in patients with liver disorders,especially with the increasing unintentional ingestion of supplements containing AAS.In this paper,we review the most current knowledge about AAS-associated adverse effects on the liver,and their clinical presentations,prevalence,and pathophysiological mechanisms.

Overexpression of p27^(KIP1)induced cell cycle arrest in G_1 phase and subsequent apoptosis in HCC-9204 cell line

AIM We have previously reported that inducibleover-expression of Bak may prolong cell cycle inG1 phase and lead to apoptosis in HCC-9204 cells.This study is to investigate whether p27KIP1playsan important role in this process.METHODS In order to elucidate the exactfunction of p27KIP1in this process,a zinc induciblep27KIP1stable transfectant and transient p27KIP1-GFP fusion transfectant were constructed.Theeffects of inducible,p27KIP1on cell growth,cellcycle arrest and apoptosis were examined in themock,control pMD vector,and pMD-KIP1transfected HCC-9204 cells.RESULTS This p27KIP1-GFP transfectant maytransiently express the fusion gene.The cellgrowth was reduced by 35% at 48 h of p27KIP1induction with zinc treatment as determined bytrypan blue exclusion assay.These differencesremained the same after 72 h of p27KIP1expression,p27KIP1caused cell cycle arrest after24 h of induction,with 40% increase in G1population.Prolonged p27KIP1expression in thiscell line induced apoptotic cell death reflected byTUNEL assay.Fourty-eight h and 72 h of p27KIP1expression showed a characteristic DNA ladder onagarose gel electrophoresis. CONCLUSION Bak may induce cell cycle arrest inG1 phase through upregulating expression ofp27KIP1and subsequently lead to apoptosis inHCC-9204 cells.The p27KIP1-GFP fusion proteincan be transiently expressed in HCC-9204 cells.The inducible p27KIP1-expressing cell line providesa model to assess p27KIP1function.

Changes of integrin expression in rat hepatocarcinogenesis induced by 3′-Me-DAB

AIM To investigate the expression of integrinsin rats liver during 3’-Me-DAB inducedhepatocarcinogenesis and to find out therelationship between integrins and liver cancermetastasis.METHODS The expressions of integrins α1,α2,α3 and α5 and epidermal keratin（EK）wereobserved by immunohistochemical PAP method.RESULTS In the normal liver tissues,hepatocytes express integrins α1 and α5 and inthe bile duct epithlium,EK.In liver cirrhosis,hepatocytes highly express integrins α1,α2,α3and α5 and in hyperplastic bile duct epithelium,integrins α1,α5 and EK.Expression of integrinsα1,α2,α3 and α5 were obviously decreased in thepreneoplastic nodules and primary carcinomabut expressions of integrins α1 and α5 inmetastasis in the lung and diaphragma werehigher than those in primary carcinoma.CONCLUSION Integrins α1 and α5 may play amajor role in chemically inducedhepatocarcinogenesis and metastasis in rats.

Expression of Hypoxia-inducible Factor-1α in Liver Tumors after Transcatheter Arterial Embolization in an Animal Model

To examine the effect of transcatheter arterial embolization （TAE） of liver tumors on hypoxia-inducible factor-1α （HIF-1α） expression in the residual viable tumor, a total of 30 New Zealand White rabbits implanted with VX2 liver tumor were divided into 2 groups. TAE-treated group animals （n=15） were subjected to TAE with 150–250 μm polyvinyl alcohol particles. Control group animals （n=15） underwent sham embolization with distilled water. Six hours, 3 days or 7 days after TAE, the animals were sacrificed, and samples of tumor and adjacent normal liver tissue were harvested. Expression of HIF-1α protein was examined immunohistochemically. Real-time PCR was performed to examine the HIF-1α mRNA levels. Our results showed that HIF-1α protein was expressed in the VX2 tumors but not in the adjacent normal liver tissue. The HIF-1α-positive tumor cells were located predominantly at the periphery of necrotic tumor regions. The mean levels of HIF-1α protein were significantly higher in TAE-treated tumors than those in control tumors （P=0.002）. Among the three sacrificing time points, the difference in increase in HIF-1α protein was significant between the two groups at the sacrificing time point of 6 h and 3 days after TAE （P=0.020, P=0.031, respectively）, whereas no significant increase was noted 7 days after TAE （P=0.502）. In contrast, although HIF-1α mRNA was expressed in TAE-treated and control VX2 tumors, there existed no significant difference in the HIF-1α mRNA level between the two groups （P=0.372）. It is concluded that TAE of liver tumors increases the expression of HIF-1α at protein level in the residual viable tumor, which could be attributed to hypoxia generated by the procedure.

Immune-mediated liver injury following COVID-19 vaccination

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

药物性肝损伤患者预后影响因素分析及列线图模型的建立

目的探讨药物性肝损伤(DILI)患者临床转归的影响因素,构建列线图模型并进行内部验证。方法回顾性分析哈尔滨工业大学附属黑龙江省医院2017年1月—2022年12月收治的188例DILI患者的一般资料和实验室数据,根据患者临床转归分为结局良好组(n=146)和不良结局组(n=42)。正态分布计量资料两组间比较采用成组t检验;非正态分布计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ^(2)检验。通过单因素和多因素Logistic回归分析筛选DILI患者临床转归相关的独立影响因素。R Studio 4.1.2软件构建列线图模型,通过校准曲线、受试者工作特征曲线(ROC曲线)和决策曲线分析(DCA)对模型进行内部验证。结果单因素Logistic回归分析结果显示,肝活检诊断DILI、PLT、ChE、Alb、PTA、IgM和IgG与DILI患者不良结局相关(P值均<0.05)。多因素Logistic回归分析结果显示,肝活检诊断DILI(OR=0.072,95%CI:0.022~0.213,P<0.001)、临床分型(OR=0.463,95%CI:0.213~0.926,P=0.039)、ALT(OR=0.999,95%CI:0.998~1.000,P=0.025)、PTA(OR=0.973,95%CI:0.952~0.993,P=0.011)和Ig M(OR=1.456,95%CI:1.082~2.021,P=0.015)是DILI患者临床转归的独立影响因素。构建列线图,经验证校准曲线接近参考曲线,ROC曲线下面积为0.829,决策曲线分析显示该模型具有良好的临床净收益。结论构建的列线图模型对评估DILI患者的临床转归具有较好的临床校准度、鉴别能力和应用价值。

不同评估量表在药物性肝损伤中的诊断价值分析

目的采用RUCAM评估量表、Maria&Victorino评估量表、RECAM评估量表3种因果关系评估量表分别对药物性肝损伤(DILI)确诊病例进行评分,比较3种量表之间的诊断准确性差异,探讨其对于DILI诊断的临床意义。方法纳入2011年1月—2022年12月于北京大学第一医院住院、肝组织学活检病理结果支持DILI及有明确用药史的98例DILI确诊患者。采集研究对象的临床资料,并用上述因果关系评估量表评分,应用χ^(2)检验分析因果关系评估量表的诊断准确性,应用加权kappa系数(κw系数)分析因果关系评估量表的一致性。结果在纳入的所有DILI患者中,RECAM评估量表的准确性最高,与RUCAM评估量表比较差异有统计学意义(χ^(2)=5.667,P=0.017)。RUCAM评估量表和RECAM评估量表的诊断一致性中等(κw=0.469),而RECAM评估量表和Maria&Victorino评估量表的诊断一致性较差(κw=0.156)。在急性DILI患者中,RECAM量表、RUCAM量表、Maria&Victorino量表的不符合诊断率分别为3.7%、11.1%、42.6%;在肝细胞型DILI患者中,RECAM量表、RUCAM量表、Maria&Victorino量表的不符合诊断率分别为8.9%、21.4%、62.5%;在胆汁淤积型和混合型DILI患者中,RECAM量表、RUCAM量表、Maria&Victorino量表的不符合诊断率分别为10.0%、22.5%、47.5%。结论在急性DILI中使用RECAM评估量表和RUCAM评估量表能提高诊断率;在肝细胞型DILI和临床表现包含胆汁淤积的DILI(胆汁淤积型DILI和混合型DILI)中使用RECAM评估量表和RUCAM评估量表能提高诊断率;根据不同的病程及临床分型选择诊断准确性较高的因果关系评估量表有助于进一步提高临床诊断率。

药物诱导的自身免疫样肝炎的研究进展

药物诱导的自身免疫样肝炎(DI-ALH)是药物性肝损伤的一种特殊临床表型,与自身免疫性肝炎有相似的临床特征和实验室检查,多数时候通过肝组织活检也无法直接区分,因此正确鉴别DI-ALH与自身免疫性肝炎是临床实践中的重难点。本文总结了DI-ALH的发病机制、临床特点、诊治、预后的研究进展,为临床医生提供此类疾病的诊治思路。

小窝蛋白1在肝脏疾病中的调控作用

小窝蛋白(CAV)1是质膜上小窝的结构蛋白,是肝脏功能的重要调节因子。CAV1可通过多种分子通路调节肝脏脂质沉积、脂质和葡萄糖代谢、线粒体功能和肝细胞增殖等。因此,CAV1在肝脂肪变性和肝细胞增殖等代谢调节过程中维持肝脏生理方面起着至关重要的作用。此外,CAV1还参与调节不同类型肝损伤、肝炎、肝硬化等疾病的发生发展过程。本文就CAV1在肝脏及相关疾病中的作用及调控肝巨噬细胞的机制进行综述,为靶向CAV1治疗肝脏相关疾病提供理论依据。

中成药致药物性肝损伤159例回顾性分析

目的探讨中成药致药物性肝损伤(DILI)的发生原因、发生特征,以期规范中成药的使用,减少中成药相关不良反应。方法回顾性分析2015年1月至2022年12月苏州市中西医结合医院中成药致DILI病人159例,记录病人的基本情况(性别、年龄)、原发疾病、用药史、临床特征、实验室检查结果等。结果中成药致DILI的发生与病人年龄分布和有无基础疾病有关,而与性别无关;涉及的中成药总共有16种,主要用于治疗妇科及乳腺疾病、皮肤病、骨科疾病、心脑血管疾病以及肾脏疾病。使用骨康胶囊引发的药物性肝损病人有31例,占比19.50%;其次是仙灵骨葆胶囊,占比11.95%;占比排名第三的是接骨七厘片/丸(18例,11.32%);骨科疾病的病人服用相关中成药的时间较长。159例确诊病人涵盖了药物性肝损伤的三种分型,包括肝细胞损伤型(76例,47.80%)、混合型(51例,32.08%)、胆汁淤积型(32例,20.13%),肝细胞损伤型病人占比最高。其中,半数以上为轻度肝损伤(81例,50.94%)。结论在中医药理论指导下,严格遵循中医辨证施治的治疗原则,科学、规范应用中药,是提高用药安全性、减少中成药所致药物性肝损伤的重要措施。

新型冠状病毒感染抗病毒药物引起肝损伤的发生机制

药物性肝损伤是药物使用过程中因药物本身和/或其代谢产物,或由于特殊体质对药物的超敏感性或耐受性降低所导致。在近三年抗击新型冠状病毒感染(COVID-19)的诊治过程中,抗病毒药物起到了非常重要的作用,但国内外关于抗COVID-19药物引起肝损伤的报道较多,且其导致肝损伤的发生机制尚未明确。本文对COVID-19抗病毒药物的种类及其引起肝损伤机制的相关研究进展作一综述,旨在促进抗病毒药物的合理使用。

细胞角蛋白检测对儿童ALL药物性肝损伤预测价值

目的探究血清细胞角蛋白18-M30(CK18-M30)和18-M65(CK18-M65)对儿童急性淋巴细胞白血病(ALL)治疗后发生药物性肝损伤(DILI)的预测价值。方法2019年3月—2022年2月,新乡医学院第一附属医院收治ALL病儿66例,依据DILI分为观察组49例(发生)和对照组17例(未发生),观察组依据DILI病情分为轻度、中度和重度亚组。收集病儿相关临床资料,检测血清CK18-M30和CK18-M65活力。分析发生DILI的影响因素及血清CK18-M30和CK18-M65表达对并发DILI的预测价值。结果观察组血清CK18-M30和CK18-M65活力高于对照组(t=14.230、12.735,P<0.05)。DILI病情越严重,血清CK18-M30和CK18-M65活力越高(F=20.122、5.551,P<0.05)。ALL疾病危险程度、感染、输血、血清CK18-M30和CK18-M65活力等均为ALL病儿发生DILI的危险因素(OR=1.869~2.866,95%CI=(1.205~1.799)~(2.773~4.257),P<0.05),保肝药应用则为发生DILI的保护因素(OR=0.522,95%CI=0.395~0.670,P<0.05)。血清CK18-M30和CK18-M65预测ALL病儿发生DILI的受试者工作特征曲线下面积(AUC)分别为0.739和0.699,两者联合预测效能更高。结论ALL病儿血清CK18-M30和CK18-M65活力可作为发生DILI的预测指标。

何首乌致肝损伤的信号通路及其作用机制

何首乌是一种临床常用的补益类中草药,相关肝损伤事件近年来被频繁报道,其安全性问题逐渐引起国内外关注。本文梳理近年来何首乌致药物性肝损伤信号通路及作用机制的研究进展,基于信号通路角度,为临床正确合理应用何首乌提供新思路。现有研究证据表明,何首乌参与调控多条信号通路,通过破坏线粒体功能、加重胆汁酸淤积、诱发免疫应激、氧化应激、内质网应激等多种途径导致肝细胞死亡,多靶点、多途径、多层次诱导药物性肝损伤的发生发展。

Effect of Boschniakia rossica on expression of GSTP,p53 and p21^(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats

AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21rasproteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21rasproteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H2O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21rasproteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH2Cl2 and H2O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H2O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH2CI2 and H2O extracts from BR exerted anti-inflammatory effect in rats and mice.

Protective action of glutamine in rats with severe acute liver failure

BACKGROUND Severe acute liver failure(SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function.Thioacetamide(TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2(Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress.AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκBmediated inflammation in rats with TAA-induced IHAG.METHODS Male Wistar rats(n = 28) were divided into four groups: control,control+glutamine, TAA, and TAA + glutamine. Two TAA doses(400 mg/kg)were administered intraperitoneally, 8 h apart. Glutamine(25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances(TBARS), catalase(CAT), glutathione peroxidase(GPx), glutathione S-transferase(GST), glutathione(GSH), Nrf2, Kelch-like ECH-associated protein 1(Keap1),NADPH quinone oxidoreductase1(NQO1), superoxide dismutase(SOD)] and inflammatory process.RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatoryinfiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS(P < 0.001), GSH(P < 0.01), IL-1β, IL6, and TNFα levels(P <0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP(P <0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group(P<0.01, P <0.01, and P <0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2(P < 0.05), NQO1, and SOD(P < 0.01), as well as levels of IL-10(P <0.001), while decreasing expression of Keap1, TLR4, NFκB(P < 0.001), COX-2 and iNOS,(P < 0.01), and reducing NO_2 and NO_3 levels(P < 0.05).CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway,thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation.

总胆红素反弹率与总胆红素清除率在人工肝治疗重症药物性肝损伤预后评估中的作用

目的评估总胆红素反弹率(TBRR)、总胆红素清除率(TBCR)及治疗1周后总胆红素清除率(ΔTBCR)在人工肝治疗重症药物性肝损伤短期预后评估中的作用。方法回顾性分析2013年9月—2021年12月在天津市第三中心医院住院并行人工肝治疗的重症药物性肝损伤患者203例,收集患者的一般资料、生化指标及临床分型,根据患者出院时病情转归分为好转组和未愈组,并计算MELD评分、TBRR、TBCR及ΔTBCR。正态分布的计量资料,两组间比较采用独立样本t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U检验;计数资料两组间比较采用χ^(2)检验。绘制受试者工作特征曲线(ROC曲线)用来评估各个评价指标对患者预后的预测价值。Kaplan-Meier法用来描述不同评价指标下患者住院时间的差异。结果好转组患者的年龄(t=-2.762)、WBC(Z=-3.184)、TBil(t=-2.809)、CBil(t=-2.739)、INR(Z=-2.357)、MELD评分(t=-3.090)、TBRR(t=-4.749)低于未愈组,而Alb(t=2.198)、PTA(t=2.018)、TBCR(t=2.166)、ΔTBCR(t=9.549)则高于未愈组(P值均<0.05)。MELD评分、TBRR、TBCR及ΔTBCR的ROC曲线下面积分别为0.656、0.727、0.611和0.879,ΔTBCR在预测价值上优于TBRR(Z=3.169,P=0.0015)。TBRR、ΔTBCR最佳临界值为22.5%(敏感度94.6%,特异度45.2%)、27.4%(敏感度77.7%,特异度86.5%)。而对于不同的临床病理分型,ΔTBCR均显示出良好的预测价值,特别是对混合型DILI患者进行人工肝治疗的疗效评价具有极高的敏感度(91.4%)和特异度(100.0%)。结论TBRR、ΔTBCR对人工肝治疗重症药物性肝损伤患者短期预后评估中作用优于MELD评分,其中ΔTBCR评分的预测价值更高。

陕西省2009—2019年药物性肝损伤患者的临床特征分析

目的探讨药物性肝损伤(DILI)患者的临床特点。方法回顾性收集陕西省内20家医院2009—2019年收治的以RUCAM量表为诊断标准的1376例药物性肝损伤患者的临床资料,分析性别、年龄、基础疾病、可疑肝损伤药物、临床表现、实验室检查、治疗经过及预后。计量资料2组间比较采用成组t检验或Wilcoxon秩和检验;计数资料组间比较采用χ^(2)检验;多分类有序资料比较采用Kruskal-Wallis H秩和检验。结果1376例患者中男577例(41.93%),女799例(58.07%),男女比为0.72∶1;各年龄段中40~60岁年龄段高发,占比44.77%;各年龄组中男女性别分布差异有统计学意义(χ^(2)=20.784,P=0.008),三种临床分型中,男女发病占比差异无统计学意义(χ^(2)=1.409,P=0.494),各年龄组中临床分型分布差异有统计学意义(χ^(2)=47.025,P<0.001)。引起肝损伤的药物中,居前三位的依次为:中药(41.13%)、抗结核药(11.70%)、解热镇痛药(7.27%)。临床分型以肝细胞损伤型为主,占比65.77%(905例);住院时间平均15.31天,以1~4周居多,占比91.86%;痊愈45例(3.27%),好转1322例(96.08%),整体预后较好。不同临床分型的预后不同,差异具有统计学意义(H=59.300,P=0.011),进一步比较显示,肝细胞损伤型和混合型预后好于胆汁淤积型(P<0.05),肝细胞损伤性和混合型预后差异无统计学意义(P>0.05)。结论DILI在女性及中老年的占比较高,中药是引起DILI的首位原因,不同临床分型的预后不同,整体预后较好。

4例不同类型胆管损伤型药物性肝损伤的临床病理特点分析

目的 对比观察不同类型胆管损伤型药物性肝损伤(DILI)患者的临床、生化、病理、病程及预后特点。方法 选取石家庄市第五医院2015年3月-2020年10月经肝穿刺组织病理明确诊断为胆管损伤型DILI 4例患者。收集患者的临床资料、历次实验室检查、影像学检查及预后情况,并对肝脏病理形态进行半定量评分,对比分析4例患者各指标之间的差异。结果 胆管损伤型DILI女性患者多见,多数预后较好。胆管损伤的部位、级别、范围及再生修复不同,其相应的临床症状、肝生化指标及预后亦不同。结论 肝穿刺组织病理仍然是胆管损伤型DILI明确诊断、了解病变损伤情况及判断预后的金标准。