土三七致肝小静脉闭塞病6例报道

肝小静脉闭塞病(hepaticveno-occlusive disease,HVOD),是某些原因导致非血栓性肝小静脉闭塞,以急性肝肿大、黄疸、腹水为主要表现,病死率高。由于该病在临床上较少见,本文报道我院2004年至2009年收治的6例中药土三七导致HVOD的病例并结合文献复习,旨在探讨HVOD的临床特点,为疾病预防和早期诊治提供依据,以期改善患者的预后。1资料与方法     

肝静脉闭塞病的临床和病理研究

目的通过对肝静脉闭塞病（HVOD）的临床和病理特点研究,提高对该病的认识.方法回顾性分析因骨髓移植和服用土三七所致12例HVOD的临床和病理特征.结果骨髓移植所致HVOD常表现为急性起病,且病情较重;而土三七所致HVOD除急性起病外,也可以表现为亚急性、慢性起病,且病情轻重不一,可能与土三七的剂量和疗程以及个体差异相关.抗凝疗法治疗急性和亚急性HVOD疗效优于慢性HVOD.两者所致HVOD的病理均表现为肝窦扩张、瘀血,肝索挤压、萎缩,肝细胞坏死,胆汁淤积,而肝小静脉缩窄甚至闭塞等典型表现并不常见,可能与经皮肝穿刺活检术有很大局限性有关.结论骨髓移植和应用土三七应警惕HVOD的发生,争取早期诊断和及时治疗.     

含吡咯烷生物碱的中草药与肝小静脉闭塞病

目的 总结分析含吡咯烷生物碱(PAs)的中草药导致肝小静脉闭塞病(HVOD)的临床特点,提高对HVOD的病因及诊治认识.方法 对1980年至2006年国内报道的中草药导致HVOD病例10例,以及北京协和医院诊断的中草药导致HVOD 3例进行综合分析,并进行国内外相关文献复习.结果 国内报道的中草药致HVOD病例以土三七为主,占84.6%(11/13).土三七用量150 g～1 800 g(平均约582 g),用药持续时间10余天至4个月(平均42.5天);千里光致病者1例,嗜食茶叶致病者1例.HVOD临床症状主要为腹部胀痛、腹水、肝大、黄疸,可有不同程度的肝功能受损,多有GGT及ALP升高;超声下可见门脉血流减慢以及CT下不均匀脂肪肝样表现为其影像学特点;通过组织学诊断(9/13)和临床诊断(4/13).保守治疗好转者2例,肝移植2例,死亡5例.结论 含有吡咯烷生物碱的中草药是导致HVOD的一个重要原因,临床上应慎用此类药物.影像学检查有一定的特点,早期临床诊断对改善预后非常重要.     

肝内静脉闭塞病的临床与病理诊断

目的通过分析肝内静脉闭塞病（HVOD）患者的临床和病理资料，旨在提高对该病的诊断水平。方法对5例HVOD患者的临床和病理资料进行回顾性分析，并结合文献总结HVOD的临床和病理学特点。结果该病临床表现为肝肿大、黄疸、腹水三大特征。组织学表现为肝小叶中央静脉及小叶下静脉内膜肿胀，管腔狭窄。中央静脉周围肝窦明显扩张、淤血伴有不同程度的肝细胞坏死，但网状纤维支架仍残留，部分区域中央静脉壁纤维化，整个病变过程不伴炎细胞浸润。结论HVOD发病与细胞毒性作用、免疫应答、凝血机制等多种因素异常有关，其晚期病死率高，应早期诊断。病理学检查是唯一的诊断标准。     

造血干细胞移植后肝静脉闭塞病的临床观察

目的 探讨造血干细胞移植（HSCT）后肝静脉闭塞病（HVOD）的临床特征、相关危险因素.方法 用回顾性分析方法对145例HSCT患者移植后HVOD的发病情况进行临床分析.结果 145例患者中,发生HVOD 8例,发生率为5.5%.对HVOD的相关危险因素分析发现,HSCT患者移植前乙型肝炎表面抗原（HbsAg）阳性或HBV-DNA阳性患者HVOD发生率显著增高,是HVOD发生的高危因素（P＜0.01）;PGE1脂质微球（Lipo-PGE1）预防HVOD的效果显著优于PGE1组（P＜0.05）,原因可能与本组病例PGE1预防剂量相对不足有关.结论 HVOD是HSCT常见并发症之一,移植前患者感染乙型肝炎病毒是其发生的高危因素;Lipo-PGE1对HVOD具有较好的预防效果.     

肝静脉闭塞病的发病机制及治疗进展

肝静脉闭塞病(HVOD)是造血干细胞移植(HSCT)后最严重的并发症之一,其临床特征为体重迅速增加、腹水、疼痛性肝肿大及黄疸等,严重患者因多器官功能衰竭而死亡。典型的HVOD一般在移植后一个月内发生,既往报道发病率为10%- 40％,重症患者死亡率高达100%。新近回顾性分析表明,HVOD的发病率为6．6％,而移植后100 d内的死亡原因有24％源自HVOD。HVOD的发病机制目前尚未完全阐明,本文拟对HVOD发病机制和治疗进展做一综述。     

肝小静脉闭塞病28例临床分析

目的:探讨肝小静脉闭塞病(HVOD)的临床特点与诊治经验。方法:回顾性分析28例HVOD患者的病因、临床表现、实验室检查、彩超、CT、病理特征,治疗及转归。结果:28例HVOD多由服用土三七引起(20例,占71.4%),临床表现以腹胀、黄疸、肝肿大、腹水为其主要特征,超声造影检查显示肝实质持续不规则低灌注,呈"荒芜"症;CT增强扫描表现为全肝弥漫性密度不均匀改变,静脉期表现为特征性的"地图状"、斑片状强化和低密度区,肝静脉显示不清或未显示;病理提示中央静脉周围肝窦高度扩张淤血,肝细胞变性、坏死,中央静脉周围轻度纤维化,未见明确炎症。28例患者治疗后好转15例(53.6%),其余均因病情加重自动出院或死亡。结论:对有中药"土三七"服用史或长期服用中药泡酒者,出现腹胀、腹水、黄疸,要高度怀疑HVOD,影像学检查有助于诊断,病理学检查是诊断的金标准。HVOD病死率较高,早期诊断和及时治疗尤为重要。     

肝小静脉闭塞病的临床现状及研究进展

肝小静脉闭塞病(hepatic veno-occlusive disease,HVOD)是造血干细胞移植(hematopoietic stemcell transplantation,HSCT)的主要并发症之一.其发病机制主要是局部高凝状态,主要病理改变是终末肝小静脉的闭塞及肝细胞的坏死.HVOD的确诊依靠肝组织活检.明确并避免危险因素是降低HVOD的发病率及死亡率的主要措施,药物预防效果尚不确切并且多有不良反应.HVOD的治疗以去纤苷的效果最为肯定,其他药物的疗效仍需验证.本文就HVOD的临床现状及研究进展作一综述.     

肝脏影像学检查在土三七引起的肝小静脉闭塞性疾病中的诊断价值

目的探讨肝脏影像学改变在肝小静脉闭塞性疾病(HVOD)患者诊断中的价值。方法对45例HVOD患者临床表现、肝脏影像学检查及肝穿刺组织学变化进行分析。结果 45例患者肝脏超声检查有28例患者可见"斑片状"或"豹纹状"低回声区;CT检查均有"地图状"密度改变,肝脏MRI T1WI均呈大片状低信号,T2WI信号呈略高信号,增强后呈"地图状"不均匀强化。肝脏超声诊断HVOD符合率62.2%(28/45);肝脏CT、MRI诊断HVOD符合率100%,二者差异有统计学意义(χ2=15.06,P<0.05)。21例作肝组织穿刺确诊的HVOD患者,检查均显示肝脏有"地图状"的高、低密度改变。结论肝脏CT、MRI诊断HVOD较肝脏超声检查有更高敏感性和特异性。肝脏CT、MRI可替代肝穿刺组织学检查诊断HVOD。     

中药土三七致肝小静脉闭塞病的文献分析

[目的]探讨中药土三七导致肝小静脉闭塞病(HVOD)的临床特点,提高对HVOD的病因及诊断、治疗的认识。[方法]通过检索2001~2011年国内医药学期刊中关于土三七导致HVOD的文献,对报道的166例患者进行综合统计分析。[结果]土三七导致HVOD可能与吡咯烷生物碱相关,其发病与患者服药时间长短以及服药总量等有关,主要表现可有腹胀、腹痛、恶心呕吐、乏力、食欲减退、黄疸、肝肿大和腹腔积液等,实验室可见肝功能相关指标异常,影像学检查及肝活检病理检查对诊断有重要意义。[结论]含有吡咯烷生物碱的土三七是导致HVOD的一个重要原因,临床上应慎用或避免大量使用该类药物。并且应该对患者进行安全意识教育,规范药物使用方法和剂量,指导临床合理使用。     

Recombinant tissue plasminogen activator for treatment of hepatic veno-occlusive disease following bone marrow transplantation in children: effectiveness and a scoring system for initiating treatment

Hepatic veno-occlusive disease (HVOD) following bone marrow transplantation is potentially fatal. Criteria for diagnosis and starting treatment are mainly based on adult studies. Recombinant tissue plasminogen activator (rtPA) has been used with variable success. rtPA and heparin were given to 12 children (nine with immunodeficiency, two malignancy, one thalassaemia) with moderate to severe HVOD. Of the 12, 10 responded with a fall in bilirubin concentration; eight survived with complete resolution of HVOD. Four of the five patients with associated multiorgan failure (MOF) died despite rtPA treatment. One child suffered significant, and one minor, bleeding during rtPA treatment. A scoring system for quantifying the severity of HVOD in children is proposed, incorporating the criteria used to diagnose HVOD, risk factors for its development and also parameters reflective of the patient's general condition. This will facilitate early diagnosis and management of those cases which, if not treated promptly, are likely to deteriorate with an adverse outcome. Our experience suggests rtPA and heparin are an effective treatment for HVOD in children, with relatively little toxicity provided therapy is started before MOF develops.     

中草药致肝小静脉闭塞病11例临床分析

目的评估各种常规临床检测方法对中草药所致肝小静脉闭塞病（HVOD）的诊断价值,并探寻评价疾病转归及预后的方法。方法采用回顾性研究方法,分析我院近3年间服用中草药所致11例HVOD的临床表现、生化指标和影像学特点。结果所有患者均有明确用药史,7例患者服用土三七,2例患者服用雷公藤,2例患者服用不明中草药,CT对HVOD的诊断有重要意义,死亡4例患者均为重型患者。结论我国肝小静脉闭塞病的诊断应重视患者用药史,HVOD患者的疾病分型对病情评估有重要意义。     

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation

Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR=3.7, 95% CI 1.2-12.1) and increased progressively with C282Y allelic dose (RR=1.7, 95% CI 0.4-6.8 in heterozygotes; RR=8.6, 95% CI 1.5-48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.     

Association of hepatic veno-occlusive disease with interstitial pneumonitis in bone marrow transplant recipients

Hepatic veno-occlusive disease (HVOD) and interstitial pneumonitis (IP) are both widely regarded as toxicities of intensive cytoreductive therapy, but their association has not been previously examined. Risk factors for IP were evaluated in 154 patients given intensive cytoreductive therapy followed by allogeneic bone marrow transplantation during a 2 1/2 year period. IP occurred in 68 patients; HVOD occurred in 39. The actuarial incidence of IP in patients with VOD was 71% and 45% in those without VOD (p = 0.0002). In multivariate analysis, the diagnosis of hematologic malignancy (p less than 0.001), the occurrence of HVOD (p less than 0.01), and pretransplant CMV seropositivity (p less than 0.02) were significantly associated with IP. The individual relative risks for IP of presence to absence of these factors was 4.5 for the diagnosis of hematologic malignancy, 2.1 for HVOD, and 1.9 for CMV seropositivity. Pulmonary veno-occlusive disease (PVOD), a previously rare observation, was noted at autopsy in 1/5 (20%) patients with HVOD alone, 6/20 (30%) patients with IP alone, and 10/14 (71%) of patients with both HVOD and IP. The association of HVOD and IP is supportive of the concept that toxic effects of cytotoxic therapy have a major role in pathogenesis of HVOD and IP.     

Gynura root induces hepatic veno-occlusive disease： A case report and review of the literature

Gynura root has been used extensively in Chinese folk medicine and plays a role in promoting microcirculation and relieving pain.However,its hepatic toxicity should not be neglected.Recently,we admitted a 62-year old female who developed hepatic veno-occlusive disease(HVOD)after ingestion of Gynura root.Only a few articles on HVOD induced by Gynura root have been reported in the literature.It is suspected that pyrrolizidine alkaloids in Gynura root might be responsible for HVOD.In this paper,we report a case of HVOD and review the literature.     

Risk factors for hepatic veno-occlusive disease after high-dose busulfan-containing regimens followed by autologous bone marrow transplantation: a study in 136 children.

Risk factors for hepatic veno-occlusive disease (HVOD) were analysed in a population of 136 autografted children who received high-dose busulfan (BU) as part of a conditioning regimen. HVOD was diagnosed according to McDonald's clinical criteria. The incidence of HVOD was particularly high in this series (22%) compared with series with other conditioning regimens but the outcome was favorable in 26 patients (87%). Four deaths occurred (13%), one of which was HVOD related. The clinical presentation of HVOD was similar to that described in previous reports. Although statistical analysis failed to demonstrate any factors predictive of outcome, it did identify risk factors for the occurrence of HVOD: these were (1) a total dose of BU exceeding the standard 16 mg/kg dose; (2) the use of three as opposed to two alkylating agents; (3) the sequence of BU administration when given in the conditioning regimen containing three alkylating agents; and (4) concomitant ketoconazole therapy.     

Successful treatment with danhong injection for hepatic veno-occlusive disease

Hepatic veno-occlusive disease (HVOD) is a clinical syndrome characterized as hepatomegaly, ascites, jaundice and elevation of hepatic enzymes as an outcome from fibrous obliteration of small centrilobular hepatic venules. It is recognized as a rare but life-threatening complication of organ transplantation, tumor eradication chemotherapy and is associated with haematopoietic stem cell transplantation (SCT). Recent researches report that ingestion of plants which contain pyrrolizidine alkaloids (PAs) is associated with the onset of HVOD with unclear pathogenesis. Nowadays, there is no effective therapeutic strategy for HVOD besides supportive care using diuretics or albumin. In our case, a 42-year-old woman administered a concoction of Chinese traditional medicine supposed to contain PAs, was found to develop HVOD confirmed by liver biopsy. A therapeutic strategy was developed using Danhong injection, accompanied with supportive care, and obtained a favorable response manifesting as regression of symptoms and decline of hepatic enzymes. Danhong injection, a Chinese medical product exerting a milder anticoagulation and antithrombotic effect, is beneficial to HVOD probably by promoting microcirculation, ameliorating liver function and inhibiting hepatic fibrosis.     

内皮损伤相关因子在小鼠肝小静脉闭塞病模型中的表达

随着中草药的广泛应用,近年我国因误服含吡咯烷类生物碱（PAs）的中草药致肝小静脉闭塞病（HVOD）的报道逐渐增多.目的：探讨内皮细胞损伤及其相关因子在HVOD发病中的作用.方法：分别以土三七灌胃30 d和野百合碱灌胃7 d诱导小鼠HVOD模型.动物处死后行血清肝功能指标榆测和全血细胞计数;肝组织切片HE染色、Masson三色染色,行组织学评分;RT-PCR检测肝组织内皮损伤相关因子内皮素-1（ET-1）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）以及纤溶酶原激活物抑制剂-1（PAI-1）的表达.结果：土三七组和野百合碱组成模率分别为80.0%和92.0%.两模型组小鼠体质量、肝指数、血清肝功能指标和全血细胞计数的变化以及肝组织学改变符合人类HVOD的临床和病理特征,肝组织ET-1、TNF-α、IL-1β和PAI-1 mRNA表达较正常对照组显著增高（P〈0.05）,其中土三七组PAI-1 mRNA表达显著高于野百合碱组（P〈0.05）.结论：土三七和野百合碱均可成功诱导小鼠HVOD模型,模型小鼠肝组织内皮损伤相关因子表达显著增高,提示内皮细胞损伤后内皮损伤相关因子的释放参与了HVOD的发生过程.