Propylthiouracyl-induced severe liver toxicity:An indication for alanine aminotransferase monitoring?

Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.

Antiretroviral Therpay Induced Liver Toxicity among Immunecompromised HIV Patients at Chu Brazzaville

Introduction: Human immunodeficiency virus (HIV) infection is a public health problem of concern. Anti-retroviral therapy (ART) is associated with multiple side effects. This study aimed at identifying the different hepatic manifestations of antiretroviral therapy and the responsible molecules. Patients and Methods: This was an eight months period prospective descriptive study, from January 1st to August 31st, 2015, conducted in the Department of Gastroenterology and Internal Medicine at the Brazzaville University Teaching Hospital. Study participants were treatment-na?ve HIV patients who were initiated on ART treatment during the study period. Patients with liver disease, liver cytolysis prior to initiation of therapy, and those with alternative therapy that may cause hepatotoxicity were excluded. The sample size was 110 patients. Results: The age was ranging from 25 to 70 years with a mean age of 47.5 ± 7.5 years. During the six months of follow-up, the alarming hepatic signs were observed in 26.36% of cases (n = 29) in the 3rd month of treatment. There was no observed alarming sign in the 6th month of follow-up. The cytolytic pattern was observed in 54.55% of cases (n = 60) in the 3rd month. The cholestatic pattern was observed in 6.36% of cases (n = 7) in the 3rd month. Triple therapy combination of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most used in 57.27% (n = 63) with a statistically significant p value to the occurrence of cytolytic pattern (p Conclusion: Drug induced liver toxicity occurs in a significant number of patients starting ART. The prevalence of hepatic events was high at the third month of treatment and the triple therapy of Zidovudine, Lamivudine and Nevirapine (AZT + 3TC + NVP) was the most incriminated.

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory,anti-fibrotic,and antioxidant properties in rats

Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture.Moreover,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured.Results:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde levels.Immunohistochemical results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract.Moreover,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and COX-2.Conclusions:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.

Anxiety and depression propensities in patients with acute toxic liver injury

AIM:To investigate anxiety and depression propensities in patients with toxic liver injury.METHODS:The subjects were divided into three groups:a healthy control group(Group 1,n=125),an acute non-toxic liver injury group(Group 2,n=124),and a group with acute toxic liver injury group caused by noncommercial herbal preparations(Group 3,n=126).These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale(HADS),Beck Anxiety Inventory(BAI),Beck Depression Inventory(BDI),and the hypochondriasis scale.RESULTS:The HADS anxiety subscale was 4.9±2.7,5.0±3.0 and 5.6±3.4,in Groups 1,2,and 3,respectively.The HADS depression subscale in Group 3 showed the most significant score(5.2±3.2,6.4±3.4 and 7.2±3.4in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).The BAI and BDI in Group 3showed the most significant score(7.0±6.3 and 6.9±6.9,9.5±8.6 and 8.8±7.3,10.7±7.2 and 11.6±8.5in Groups 1,2,and 3,respectively)(BAI:P<0.01 vs Group 1,P<0.05 vs Group 2)(BDI:P<0.01 vs Group1 and 2).Group 3 showed a significantly higher hypochondriasis score(8.2±6.0,11.6±7.5 and 13.1±6.5in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).CONCLUSION:Psychological factors that present vulnerability to the temptation to use alternative medicines,such as herbs and plant preparations,are important for understanding toxic liver injury.

Massive hepatic necrosis with toxic liver syndrome following portal vein ligation

Right portal vein ligation (PVL) is a safe and widespread procedure to induce controlateral liver hypertrophy for the treatment of bilobar colorectal liver metastases. We report a case of a 60-year-old man treated by both right PVL and ligation of the glissonian branches of segment 4 for colorectal liver metastases surrounding the right and median hepatic veins. After surgery, the patient developed massive hepatic necrosis with secondary pulmonary and renal insufficiency requiring transfer to the intensive care unit. This so-called toxic liver syndrome finally regressed after hemofiltration and positive oxygen therapy. Diagnosis of acute congestion of the ligated lobe was suspected. The mechanism suspected was an increase in arterial inflow secondary to portal vein ligation concomitant with a decrease in venous outflow due to liver metastases encircling the right and median hepatic vein. This is the first documented case of toxic liver syndrome in a non-cirrhotic patient with favorable issue, and a rare complication of PVL.

Influences of Chloropazine, Nimodipine and Their Combination on the Toxic Effects of Cadmium in Liver and Kidney of Mice

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

Lesser celandine(pilewort) induced acute toxic liver injury: The first case report worldwide

Lesser celandine, also known as Ranunculus ficaria, is a herbaceous perennial plant that commonly utilizes piles and is taken either internally or used externally.The causality assessment of several reports provided evidence for the existence of Greater Celandine hepatotoxicity. However, there hasn't been any case report published thus far, about lesser celandine induced liver injury. Here, we present a case of 36-year-old woman admitted to the hospital with acute hepatitis and jaundice on her sclera with no history of drug abuse or alcohol consumption. However, the patient had a recent history of lesser celandine extract consumption for hemorrhoids, for about 10 d, prior to the admission. Viral hepatitis, autoimmune hepatitis, and drug induced toxic hepatitis were ruled out by further imaging studies and laboratory analysis. Using the Council for International Organizations of Medical Sciences scale, the type of liver injury was assumed as hepatocellular and was scored as 7 which shows probable causality. Immediate discontinuation of lesser celandine extract resulted in rapid decrease of the elevated enzymes. Herbs have been reported to cause liver injury and therefore should be suspected in the case of acute hepatitis with an unknown etiology. This case is important to be the first to explain hepatotoxicity caused by lesser celandine. Physicians should consider lesser celandine as a causative agent for hepatotoxicity.

Assessment of Nephro-, Hepato-, and Sex-Dependent Toxicity of Carmoisine Exposure in Albino Rats

Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves treatment for 30, 60, and 90 days. Each phase consists of 40 rats, divided into treatment and control groups. The treated groups were orally administered with 4.0 mg/kg of carmoisine daily for the periods of 30, 60, and 90 days. Methodology: At the end of the treatment, the rats were allowed to fast for 18 hours followed by the collection of 5 ml of whole blood specimens by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose only). Plasma obtained was analyzed for glucose (GLU), AST, ALT, ALP, creatinine (CRT), and urea. Hepatic and Renal tissues collected were fixed in 10% formol saline and later examined histologically using H&E stain. Statistical data analysis was done using GraphPad Prism version 9.02. Results: Glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, Creatinine, AST, ALT and ALP showed significantly higher values after 60 and 90 days of treatment (except creatinine in male rats and ALP in female rats after 60 and 90 days respectively). Hepatic distortions, vacuolation, compression of central vein were seen in the liver section while distortion of proximal and distal tubules, and inflammation of the glomerulus were observed in the renal tissue of the treated rats. Conclusion: The administration of camoisine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, and kidneys. However, after 60 and 90 days, mild hepatocellular, and renal derangements were seen. No sex-dependent toxicity was observed.

基于“有故无殒”理论的京大戟肝肾毒性研究

目的:研究京大戟对正常大鼠和佐剂性关节炎(AA)大鼠肝肾毒性的差异。方法:SD大鼠随机分为正常组、正常给药低、中、高剂量组,AA模型组、AA模型给药低、中、高剂量组,阳性组。连续灌胃4周,考察其对大鼠一般状态、血液生化指标血肌酐(CREP)、尿素氮(UREAL)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和脏器指数及体质量的影响,并通过病理切片观察大鼠肝肾组织的损伤情况。结果:与正常组相比,模型组行动明显减少,喜蜷缩,但体质量无明显变化。正常给药各组大鼠毛发无光泽,皮肤呈现黑棕色,蜷缩少动,大便不成型,体质量增长缓慢。模型给药各组大鼠大便不成型状况有所缓解,体质量无明显变化。肝肾功能方面,与正常组相比,模型组和阳性组AST、ALT、UREA、CREP含量,差异无统计学意义(P>0.05)。正常给药组在给予不同剂量的京大戟灌胃后,各剂量组AST、ALT指标明显升高(P<0.05),高、中剂量组UREAL指标明显升高(P<0.05)。而模型给药组中,仅高剂量组AST、CREP指标明显升高(P<0.05)。且肝肾脏切片显示,正常给药组肝脏肝细胞有轻度空泡变性,胞质疏松淡染;而肾脏系膜细胞和系膜基质轻微变多,其中少量肾小管管腔可见嗜酸性物质。京大戟对正常状态下大鼠的毒性大于AA模型状态下的毒性。结论:由此可以推断出,京大戟用于AA模型大鼠时主要体现的是治疗作用,而对正常大鼠主要体现的是毒性作用。在“有故无殒”理论指导下正确的辨证论治运用中药是临床安全用药的前提。

京大戟醋制前后对正常大鼠毒性的研究

目的比较京大戟醋制前后对正常大鼠肝、胃、肠、肾毒性的差异。方法采用雄性SD大鼠56只,随机分为7组:空白组、京大戟低、中、高剂量组和醋京大戟低、中、高剂量组。给药组大鼠分别灌胃0.253 g/kg、0.506 g/kg、1.012 g/kg京大戟、醋京大戟粉末,空白组灌胃等量的0.5%羧甲基纤维素钠,连续7天。考察给药后各组大鼠各脏器的组织病理形态学变化,测定血清中的肝肾功能指标及血清和组织中的氧化损伤指标。结果与空白组比较,各给药组大鼠肝、胃、肠病理切片可见不同程度的组织损伤,京大戟各剂量组的大鼠血清中谷丙转氨酶(alanine aminotransferase,ALT)与谷草转氨酶(aspartate transaminase,AST)活性显著升高(P<0.01,P<0.05),肌酐(creatinine,CRE)与尿素氮(blood urea nitrogen,BUN)活性略有升高;血清和肝、胃、肠组织中的超氧化歧化酶(superoxide dismutase,SOD)和谷胱甘肽(glutathione,GSH)含量明显降低,丙二醛(malondialdehyde,MDA)含量显著升高(P<0.01,P<0.05)。与京大戟组比较,醋京大戟组的大鼠肝、胃、肠组织损伤较轻,血清中AST、ALT活性显著降低;血清和肝、胃、肠组织中的MDA含量明显降低,SOD和GSH含量明显升高(P>0.05),但两组间无显著性差异。结论京大戟对正常大鼠肝、胃、肠毒性明显,对肾无明显损伤,醋制后毒性均下降,其毒性作用与氧化损伤相关。

何首乌化学成分、药理作用及肝毒性的研究进展

从化学成分、药理作用及肝毒性3个方面综述何首乌的研究进展。何首乌含有二苯乙烯苷类、蒽醌类、磷脂类、黄酮类等多种化学成分,具有延缓衰老、抗癌、抗疲劳、抗炎镇痛、保护心血管等药理作用。目前,何首乌引起肝毒性的化学成分探讨主要集中于3类,即蒽醌类、二苯乙烯苷类及鞣质类。加大何首乌肝毒性成分、肝毒性机制研究的力度,加强中药安全用药知识宣教,规范其炮制及使用,可以在一定程度上降低何首乌肝毒性。

2C-B的亚慢性毒性研究

研究4-溴-2,5-二甲氧基苯乙胺(4-bromo-2,5-dimethoxyphenethylamine,2C-B)的亚慢性毒性.通过对大鼠进行长期连续染毒,以体重变化、脏器系数、病理学检查及肝肾生化酶水平的影响探讨2C-B对机体造成损伤的情况.综合各指标结果分析长期服用2C-B会对心脏、肝脏、肺脏、肾脏、大脑产生损害,上述器官可能是2C-B毒性的靶器官.

何首乌肝损伤机制及减毒方法研究进展

何首乌Polygonum multiforum Thunb.是临床常用滋补中药,同时作为一种保健中药在药膳和食膳中广泛应用,但是近年来由于不时出现何首乌及其制品致肝损伤的报道,引起了研究者的警觉及关注。本文通过整理分析关于何首乌致肝损伤的国内外临床相关报道,从何首乌致肝毒性的物质基础二苯乙烯苷类、蒽醌类化合物和没食子酸等成分及其潜在肝毒性机制(包括代谢酶改变、氧化应激、炎症反应、线粒体损伤、肝细胞异常凋亡等方面)进行归纳总结,探讨炮制减毒和配伍减毒两种减毒方法对何首乌肝毒性的影响和机制。

苍耳子不同炮制品对小鼠肝脏肾脏毒性的“量-时-毒”关系研究

目的比较苍耳子不同炮制品的“量-时-毒”关系,为其毒性反应规律及炮制减毒机制提供依据。方法取240只小鼠随机分为正常组和苍耳子生品、清炒、砂炒组低中高剂量组,除正常组外,各低、中、高剂量组分别按照1.3、6.5、13.0 g·kg^(-1)剂量,分别灌胃给药1、7和14 d,Elisa法检测各组动物的血清ALT、AST、BUN、CR值,计算各组肝、肾脏器指数,并观察连续给药1、7、14 d后的肝、肾组织病理变化。结果与正常组相比,苍耳子生品组显著升高小鼠血清中ALT、AST、BUN、CR的含量(P<0.05,P<0.01),肝、肾组织病理可见明显损伤;与苍耳子生品组比较,清炒组和砂炒组显著降低小鼠血清中ALT、AST、BUN、CR的含量(P<0.05,P<0.01),减轻肝、肾组织病理损伤程度,且肝、肾脏指数和病理形态学的改变具有时间和剂量的依赖性。结论苍耳子生品对正常动物具有一定的肝、肾毒性,并呈现一定的“量-时-毒”关系;苍耳子不同炮制品均可减轻体内肝、肾毒性,且砂炒组较清炒组减毒效果更为明显。

清火消痈汤治疗心肝火旺及热毒内蕴型肺痈临床观察

目的研究清火消痈汤治疗心肝火旺及热毒内蕴型肺痈的临床价值。方法以2021年1月—2021年12月为研究周期,抽取研究对象72例,采用随机数字表法分为研究组、对照组,各36例;对照组予西药治疗,研究组予清火消痈汤治疗,对比两组呼吸功能指标和中医证候积分。结果治疗后,研究组二氧化碳分压(PaCO_(2))水平为(41.42±3.75)mm Hg(1 mm Hg≈0.133 kPa),低于对照组的(47.59±5.88)mm Hg(P<0.05);氧分压(PaO_(2))水平为(82.99±6.75)mm Hg,高于对照组的(73.26±2.48)mm Hg(P<0.05)。治疗后,研究组主证积分为(2.44±0.68)分、次证积分为(0.65±0.11)分、总积分为(3.12±0.64)分,均低于对照组的(5.29±1.05)分、(1.89±0.62)分、(7.28±1.75)分(P<0.05)。结论清火消痈汤治疗肺痈效果显著。

草乌致大鼠肝肾亚急性毒性的代谢组学研究

目的基于代谢组学技术分析和探讨草乌致大鼠肝肾亚急性毒性的生物标志物和可能的作用机制。方法以草乌为示例药物,以大鼠为研究对象,除正常组外,给药组灌胃相应溶液,连续给予28 d。通过代谢组学技术对采集的大鼠血清、肝、肾样本进行检测,用主成分分析结合偏最小二乘判别分析筛选肝肾亚急性毒性敏感标志物及代谢通路。结果代谢组学分析显示,与正常组比较,草乌组血清、肝、肾样本中分别鉴定得到34、23和30个差异代谢物,主要富集于ABC转运蛋白、精氨酸和脯氨酸代谢、癌症的中心碳代谢、烟酸和烟酰胺代谢等通路。结论初步认为草乌通过影响ABC转运蛋白、精氨酸和脯氨酸代谢、癌症的中心碳代谢等对肝肾造成损伤,亚精胺、羟脯氨酸、葡萄糖、L-亮氨酸和尿素可作为潜在的肝肾毒性敏感生物标志物。

Pseudocirrhosis in a pancreatic cancer patient with liver metastases: A case report of complete resolution of pseudocirrhosis with an early recognition and management

We report a case of pseudocirrhosis arising in the setting of regression of liver metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and nearly complete resolution of hepatic metastases in computed tomography (CT) scan. Shortly after, she developed increasing bilateral ankle edema and ascites, associated with dyspnea, progressive weight gain, and declining performance status. Gemcitabine and oxaliplatin were discontinued as other causes of her symptoms such as congestive heart disease or venous thrombosis were ruled out. CT scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable pancreatic mass. However, it also revealed a lobular hepatic contour, segmental atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was managed with aggressive diuresis and albumin infusions which eventually resulted in a resolution of the above- mentioned symptoms as well as complete resolution of pseudocirrhotic appearance of the liver and ascites in CT scan. This case demonstrates that pancreatic cancer patients can develop pseudocirrhosis. Clinicians and radiologist should be well aware of this entity asearly recognition and management can lead to a near complete recovery of liver function and much improved quality of life as illustrated in this case.

慢加急性肝衰竭“毒浊致病”学说的科学内涵及其代表方解毒化瘀Ⅱ方的临床应用

慢加急性肝衰竭“毒浊致病”学说是毛德文教授团队在急性肝衰竭“毒邪致病”学说基础上提炼而来。本文详细介绍慢加急性肝衰竭“毒浊致病”学说的形成、科学内涵及其对中医临床实践的指导意义,充分阐述慢加急性肝衰竭“毒浊致病”学说的科学性及其代表方解毒化瘀Ⅱ方治疗慢加急性肝衰竭的可行性及确切疗效。

中草药相关肝损伤的研究进展与挑战

中草药相关肝损伤发生众多,对中药临床安全用药与产业健康发展等有重要影响,近年来中草药肝损伤研究受到广泛重视并取得显著进展,我国与国际学术组织均制订并更新了相关临床诊疗指南。本文比较分析了近期有关中草药相关肝损伤诊疗指南的特点,继而从毒性机制、临床诊断与病情评估、风险因素与临床防治等方面简述主要进展,提出部分尚未满足的需求、需要重视的研究难点与可能的防治措施。

Herbal and dietary supplement induced liver injury:Highlights from the recent literature

Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.