何首乌致肝损害案例追溯分析与临床监控

目的：通过对何首乌致肝损害的案例回顾分析,制定临床监控路径。方法：案例分类统计和原因分析。结果：何首乌致肝损害可能与其有毒成分、患者肝酶缺陷或遗传基因有关,对何首乌的不良反应缺乏认识也是其一。结论：加强何首乌用药前后肝功能检测,可将损伤降至最低。     

口服何首乌致肝损害40例临床分析

目的分析何首乌致药物性肝损害的临床特点。方法对我科2004年5月-2008年5月期间共收治的40例口服何首乌致药物性肝损害的病例的临床资料进行回顾性分析。结果40例病例中男性16例,女性24例,平均发病年龄45.2岁;服药原因主要为治疗脱发、白发;服药后发病时间最早的1.3周,最晚的24周,平均9.4周;服药剂量大部分为常规剂量,仅2例为大剂量。临床分型：肝细胞损伤型为22例（占55%）,胆汁淤积型为8例（占20%）,混合型为10例（占25%）。临床表现主要为乏力、食欲减退、尿黄,其中有2例后期出现腹水,1例出现上消化道出血。肝功能损害以总胆红素、丙氨酸转氨酶明显升高为主。临床治愈38例,死亡2例。结论口服何首乌可引起肝功能损害,甚至诱发急性肝衰竭,对于有肝脏基础疾病及老年人应慎重使用。     

制何首乌致肝损害1例

病例:患者,男,28岁,因"纳差、厌油、尿黄"等症状入院。入院前3～4月曾服用中药饮片制何首乌(每天10片左右)治疗白发,近期由于劳累后自觉出现厌油、尿黄,逐渐出现上腹部饱胀,纳差,进食量减少,间断恶心、皮肤及巩膜黄染等症状。曾按"胃病"服用"吗丁啉、胃苏     

何首乌及其制剂相关肝损害国内文献回顾与分析

目的:调查何首乌及其制剂相关肝损害的临床特征和发生原因以提供预防措施。方法:检索中国期刊全文数据库、中国生物医学文摘数据库及维普中文科技期刊文献数据库,收集1996年至2009年国内文献报道的与何首乌及其制剂相关药物性肝损害病例,对患者的一般情况、用药情况、肝损害的临床表现、预后和转归进行调查分析。结果:何首乌及其制剂相关肝损害病例共35例,其中男20例,女15例,平均年龄(36.2±13.7)岁。单用何首乌中成药14例,单用何首乌饮片18例,两者兼用3例,在使用何首乌饮片的患者中用生首乌6例,制首乌2例,其余不详。35例患者中有18例再次给药后又发生肝损害,3例表现出家族性发病倾向。用药后肝损害发生时间:最短3～6d,最长>3个月,多数1～4周,临床主要表现为黄疸和肝功能异常。有肝功能检测记录的病例如下:31例患者ALT值为102～4584U/L,平均值为1153.1U/L;25例患者AST值为61.5～1937U/L,平均值为657.4U/L;29例患者TBil平均值为134.9μmol/L;23例患者DBil平均值为97.9μmol/L。症状较轻者停药后自愈,大部分患者经保肝治疗治愈,其中好转2例,治愈33例。结论:生首乌与制首乌及其制剂可引起肝损害。临床用药前应了解患者个人及家族用药史,严格剂量,用药时应监测患者肝功能。     

何首乌致肝损害和中性粒细胞缺乏

1例20岁女性为乌发自行服用何首乌粉15g/d。2周后,患者出现纳差及乏力;3周后出现尿色加深,肝功能检查示天冬氨酸转氨酶（AST）878 U/L,丙氨酸转氨酶（ALT）1121 U/L,总胆红素（TBil）100.8μmol/L,直接胆红素（DBil T）77.4μmol/L。服用何首乌粉第42天,实验室检查：AST472 U/L,ALT 755 U/L,TBil 102.9μmol/L,DBil 76.7μmol/L;白细胞计数3.2×10~9/L,中性粒细胞计数0.27×10~9/L。考虑药物引起肝损害和中性粒细胞缺乏可能性大。停用何首乌,给予保肝、退黄等综合治疗。治疗10 d后实验室检查：ALT 62 U/L,AST 73 U/L,DBil 20.5μmol/L,TBil 30.2μmol/L;白细胞计数6.2×10~9/L,中性粒细胞计数3.60×10~9/L。     

环丙沙星致肝损害32例文献分析

目的探讨环丙沙星致肝损害的规律与特点,为临床医生合理用药提供参考。方法检索国内外有关医药数据库,下载病例报告原文进行统计与分析。结果环丙沙星致肝损害病例报告32例,其中男性22例,40岁以上的中老年人23例。肝损害的主要临床表现为黄疸、恶心、腹痛、转氨酶升高,以肝细胞型为主,胆汁淤积型次之,混合型少见。中老年、男性、药物过敏史、原患肝病、合并肝毒性药物、再次用药、剂量过大、疗程过长等属高危人群和危险因素。经停药、采取相应治疗措施,大部分可恢复正常,但也可进展为慢性化、肝衰竭,严重者死亡。已有至少3例死亡报告。结论环丙沙星的肝损害严重不良反应应引起临床医务人员的高度重视。     

持续小剂量口服何首乌致肝损害一例

1 病例资料男,28岁.主因乏力、食欲缺乏、厌油腻、黄疸,伴尿黄3个月就诊.3个月前因脱发严重,用何首乌每日8 g水煎代茶饮,服用3 d后,出现胃胀、乏力、食欲缺乏,未引起重视,之后减至每日4 g,继续服用2月余,3个月后乏力加重,食欲缺乏,厌油腻,黄疸,伴尿黄,遂来我院就诊.查血丙氨酸转氨酶1965 U/L,天冬氨酸转氨酶1182 U/L,γ-谷氨酰转肽酶181 U/L,总胆红素194.1 μmol/L,直接胆红素 135.9 μmol/L,甲、乙、丙、丁、戊型肝炎病毒的血清学标志物均为阴性.     

抗结核药致肝损害1949例文献分析

目的探讨抗结核药致肝损害的临床特点和危险因素,为临床合理用药提供参考。方法以抗结核药、肝损害、肝损伤等词为检索词,检索中国知网CHKD期刊全文数据库和万方医学数据库,收集抗结核药致肝损害的文献进行统计分析。结果共收集到抗结核药致肝损害患者1 949例,其中男性1 209例(62.03%),女性740例(37.97%);年龄14~89岁。原发疾病均为结核病,伴有乙肝病毒或丙肝病毒感染者305例(15.65%),伴有酗酒者202例(10.36%)。发病时间为用药后7~60d。临床表现以消化系统症状、乏力、皮疹、发热为主。实验室检查以肝功能指标异常为主。停药并给予保肝及对症治疗后,1 770例(90.82%)治愈;170例(8.72%)好转;9例(0.46%)死亡。结论抗结核药所致肝损害发生率为10.58%,发生率较高,但除重度肝损害外大多愈后良好。抗结核治疗时,少年及老年人是高危人群,肝炎病毒感染及酗酒是危险因素,必须加强肝功能检测,早发现、早治疗,以便有利于肝功能恢复正常。     

何首乌联合多种感冒药致重症肝损害一例

患者女,43岁,于2010年12月10日以"急性黄疸型肝炎"收住我院消化科.患者于入院前1个月因感冒间断服用感冒胶囊、维C银翘片、白加黑感冒片、重感片、康泰克、大青叶片等药物后,于入院前10 d出现全身乏力、纳差、恶心,偶有呕吐,伴巩膜黄染、尿色加深,未予以重视,此后上述症状逐渐加重,于入院前3d出现全身皮肤黄染,伴皮肤瘙痒,尿液呈浓茶样,全身乏力明显加重,不思饮食,遂来我院就诊.患者入院后药师在与其交流时了解到患者因白发、脱发,从网上查到"生发灵"(成分为黑芝麻、核桃仁、何首乌),研磨成粉冲服2个月余,8 ～ 10 g/d,感冒期间未停用,全身不适症状加重,来医院就诊后停用.患者平素体健,否认肝炎病史及饮酒史,否认高血压、糖尿病等慢性病史,否认重大外伤史、输血史,发病前未服用其他药物,否认酗酒史.入院体格检查:T 36.5℃,P 76次/min,R 19次/min,BP 115/65 mm Hg(1 mm Hg=0.133 kPa),全身皮肤黏膜黄染,未见肝掌、蜘蛛痣,心肺检查未见明显异常,腹平软,未见腹壁静脉曲张,全腹无压痛及反跳痛,脾肋下未触及,莫菲氏征阴性,肝剑突下5 cm,肋下3 cm触及,质软,边缘锐,无压痛,腹水征阴性,肠鸣音3次/min.肝功能示:总胆红素(TBil)249 μmol/L,直接胆红素(DBil) 135.3 μmol/L,间接胆红素(IBil) 113.7 μmol/L,ALT 1330 U/L,AST 1019.2 U/L,γ-谷氨酰转氨酶(γ-GTP)357 U/L,尿常规示:尿胆原3.3μmol/L,胆红素阳性(++),潜血(+++).凝血功能示:凝血酶原时间(PT) 14.2 s,APTT 39 s.甲、乙、丙、戊型肝炎标示物均为阴性,自身免疫性抗体均为阴性.腹部CT示:肝大,肝内密度减低,脾轻度增大.     

从何首乌致肝损害分析中药不良反应发生原因及预防措施

目的：通过何首乌致肝损害的原因分析中药不良反应发生原因及预防措施。方法探讨中药饮片何首乌及其制剂所导致肝损害的原因,分析引起中药不良反应发生的原因及提出有效预防措施。结果滥用、误用、长期盲目用药等是引起中药不良反应的关键所在。结论任何药物都是双刃剑,须大力普及中药知识,提高合理用药的认识和观念,杜绝盲目用药。     

Assessing potential liver injury induced by Polygonum multiflorum using potential biomarkers via targeted sphingolipidomics

ContextPolygonum multiflorum Thunb. (Polygonaceae) (PM) can cause potential liver injury which is typical in traditional Chinese medicines (TCMs)-induced hepatotoxicity. The mechanism involved are unclear and there are no sensitive evaluation indicators.ObjectiveTo assess PM-induced liver injury, identify sensitive assessment indicators, and screen for new biomarkers using sphingolipidomics.Materials and methodsMale Sprague–Dawley (SD) rats were randomly divided into four groups (control, model with low-, middle- and high-dose groups, n = 6 each). Rats in the three model groups were given different doses of PM (i.g., low/middle/high dose, 2.7/8.1/16.2 g/kg) for four months. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and liver were quantitatively analyzed. Fixed liver tissue sections were stained with haematoxylin and eosin and examined under a light microscope. The targeted sphingolipidomic analysis of plasma was performed using high-performance liquid chromatography tandem mass spectrometry.ResultsThe maximal tolerable dose (MTD) of PM administered intragastrically to mice was 51 g/kg. Sphingolipid profiling of normal and PM-induced liver injury SD rats revealed three potential biomarkers: ceramide (Cer) (d18:1/24:1), dihydroceramide (d18:1/18:0)-1-phosphate (dhCer (d18:1/18:0)-1P) and Cer (d18:1/26:1), at 867.3–1349, 383.4–1527, and 540.5–658.7 ng/mL, respectively. A criterion for the ratio of Cer (d18:1/24:1) and Cer (d18:1/26:1) was suggested and verified, with a normal range of 1.343–2.368 (with 95% confidence interval) in plasma.ConclusionsThree potential biomarkers and one criterion for potential liver injury caused by PM that may be more sensitive than ALT and AST were found.     

Clinical analysis of liver injury caused by Chinese patent medicines containing Polygonum multiflorum

In the present study, we discussed the drug-induced liver injury caused by Chinese patent medicines containing Polygonum multiflorum to provide a reference for clinical rational drug use of Polygonum multiflorum and its preparations. One case of long-term taking Jingwu capsule and Huolisu oral liquid, which led to the drug-induced liver injury, was reported. The other case took Runzaozhiyang capsule for a long time, which also led to drug-induced liver injury. Jingwu capsule, Huolisu oral liquid, and Runzaozhiyang capsule all contained Polygonum multiflorum, which could result in liver injury when used long-term. Moreover, we explored the clinical features and toxicity of liver damage induced by Polygonum multiflorum. Liver damage in serum transaminase was significantly increased, and the increasing rate of ALT was more than that of AST. Jaundice appeared obviously. The liver damage mechanisms included drug metabolism, immune response, physical fitness, and many other reasons. Corresponding suggestions on rational use of Polygonum multiflorum and its preparations were presented. The dosage and period should be regulated. The index of liver function should be monitored during the medication periods. Collectively, patients with a history of liver disease or a history of allergies should pay more attention when using the above-mentioned drugs.     

Hepatoprotection of emodin and Polygonum multiflorum against CCl4-induced liver injury

Context: Polygonum multiflorum is known as a medicinal plant. It has been used as a folk medicine which showed antioxidative property.

Objective: Protective effects of the water extracts (w/v:1/10) from fresh P. multiflorum (WEP) on carbon tetrachloride (CCl₄)-induced liver damage in rats were investigated.

Materials and methods: CCl₄ was used for inducing liver damage of SD rats, and WEP and emodin were fed for eight consecutive weeks.

Results: We found that emodin levels in fresh WEP was higher than that in ripening WEP. Rats were administered WEP and emodin, the main active compound, for 56 consecutive days. WEP significantly lowered the serum levels of hepatic enzyme markers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and reduced the generation of malonaldehyde. Treatment with WEP recovered glutathione S-transferase and catalase activity in rats as compared to treatment with CCl₄ alone. In addition, serum tumor necrosis factor-α, an inflammatory marker, was found to decrease in rats treated with WEP. In histopathological evaluation, fatty degeneration and necrosis were found to be significantly decreased in the CCl₄ plus WEP treatment group.

Discussion and conclusion: WEP may be effective in attenuating liver damage by reducing lipid peroxidation as well as by positively modulating inflammation.     

The hepatotoxicity of Polygonum multiflorum: The emerging role of the immune-mediated liver injury

Herbal and dietary supplements(HDS)-induced liver injury has been a great concern all over the world.Polygonum multiflorum Thunb.,a well-known Chinese herbal medicine,is recently drawn increasing attention because of its hepatotoxicity.According to the clinical and experimental studies,P.multiflorum-induced liver injury(PM-DILI)is considered to be immune-mediated idiosyncratic liver injury,but the role of immune response and the underlying mechanisms are not completely elucidated.Previous studies focused on the direct toxicity of PM-DILI by using animal models with intrinsic drug-induced liver injury(DILI).However,most epidemiological and clinical evidence demonstrate that PM-DILI is immune-mediated idiosyncratic liver injury.The aim of this review is to assess current epidemiological,clinical and experimental evidence about the possible role of innate and adaptive immunity in the idiosyncratic hepatotoxicity of P.multiflorum.The potential effects of factors associated with immune tolerance,including immune checkpoint molecules and regulatory immune cells on the individual’s susceptibility to PM-DILI are also discussed.We conclude by giving our hypothesis of possible immune mechanisms of PM-DILI and providing suggestions for future studies on valuable biomarkers identification and proper immune models establishment.     

Neuroprotective effects of Polygonum multiflorum on nigrostriatal dopaminergic degeneration induced by paraquat and maneb in mice

The neuroprotective effects of Polygonum multiflorum extract (PME) and its two fractions, ethanol-soluble PME (PME-I) and -insoluble PME (PME-II), on the degeneration of nigrostriatal dopaminergic neurons induced by a combination of paraquat and maneb (PQMB) were investigated in male C57BL/6 mice. The mice were treated twice a week for 6 weeks with intraperitoneal injections of PQMB. This combination caused a reduction of spontaneous locomotor activity, motor incoordination, and declines of dopamine level in the striatum and tyrosine hydroxylase-positive neurons in the substantia nigra. Administration of PME and PME-I once daily for 47 days during 6 weeks of PQMB treatment and last 8 days after PQMB significantly attenuated the impairment of behavioral performance and the decrease in striatal dopamine level and substantia nigral tyrosine hydroxylase-positive neurons in the PQMB-treated animals, whereas the administration of PME-II had no effect on these behavioral, neurochemical and histological indices. The present findings suggest that PME has a beneficial influence on parkinsonism induced by PQMB and that the effects of PME are attributable to some substance(s) included in the ethanol-soluble fraction of PME (PME-I).     

何首乌中鞣质对大鼠肝脏生化指标的影响

目的：研究何首乌中提取出的鞣质对大鼠肝脏生化指标的影响。方法：每天按不同剂量（分别相当于成人每日30g/60kg体质量临床用量的25、50、100倍）ig大鼠1次,连续给药90d,恢复期15d。分别于第60、90、105天采取动物血液进行生化指标的检测。结果：给药组与对照组相比,给药60d时大鼠血清中ALT大剂量组显著升高（P〈0.01）,中剂量组升高（P〈0.05）;ALP中、小剂量组有所降低（P〈0.05）;TG大剂量组升高（P〈0.05）;GGT大、小剂量组升高（P〈0.05）;TBIL大、中、小剂量组均显著性降低（P〈0.01）。给药90d后大剂量组大鼠血清ALT、GGT均升高（P〈0.05）。恢复15d后各项指标与对照组均无显著差异。结论：何首乌中提取的鞣质长期ig大剂量对大鼠肝脏有损害,中剂量短期内对肝脏有所损害,小剂量无明显肝损害,但其对肝脏的损害在停药后均可以恢复。     

何首乌致药物性肝炎2例

病例1：患者,女,52岁,为增强免疫力自服制首乌、核桃、黑芝麻混合物（制首乌250g、黑芝麻200g、核桃150g）,每次15gqd,服用约20d后全身皮肤、巩膜黄染加重,小便颜色进行性加深,全身乏力、恶心、食欲减退,肝功能示TBIL116μmol·L^-1、ALT1105U·L^-、AST1110u·L^-,诊断为药物性肝炎。即刻停药,予保肝、利胆、降酶治疗,24d后,患者肝功能恢复正常。病例2：患者,女,61岁,因血脂偏高而自服山楂、荷叶、生首乌混合物（每次量为各5g泡水饮用）,间断共服用生首乌约500g,6个月后,患者眼黄,小便颜色加深,呈浓茶色,伴低热、乏力、纳差、腹胀,于外院查肝肾功能示TBIL123．0gmol·L^-、DBIL105．0gmol·L^-、AKP284．0U·L^-、γ-GT330U·L^-,诊断为药物性肝炎。即刻停药,予保肝、退黄、降酶等对症治疗,40d后,患者肝功能恢复正常。     

高效液相色谱法测定何首乌和夜交藤中蒽醌类成分的含量

建立了何首乌中的主要有效成分大黄素、大黄素甲醚、大黄酚及大黄酸等蒽醌类的反相高效液相色谱法。以ＴＳＤ－ｇｅｌ８０Ｔｓ为固定相，甲醇－水－磷酸（７２０：２８０：１）为流动相。样品用７０％甲醇提取浓缩后用氯仿萃取，分离出游离型和结合型蒽醌的定量用试液。本法精确、可靠。用此方法测定了不同产地的９种何首乌和４种夜交藤样品。