低剂量去纤苷治疗吡咯生物碱相关肝窦阻塞综合征1例报告

郭海清; 孙海青; 张晶; 仇丽霞

doi:10.12449/JCH260421

低剂量去纤苷治疗吡咯生物碱相关肝窦阻塞综合征1例报告

DOI: 10.12449/JCH260421

郭海清¹,
孙海青²,
张晶¹,
仇丽霞^1, , ,

1.
首都医科大学附属北京佑安医院肝病中心三科，北京 100069
2.
首都医科大学附属北京佑安医院临床检验中心，北京 100069

基金项目:

北京市属医院科研培育计划项目 (PX2023061);

首都医科大学附属北京佑安医院中青年人才孵育项目 (BJYAYY-YN2024-13)

伦理学声明： 本病例报道已获得患者本人知情同意。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：郭海清负责资料分析，撰写论文；孙海青参与收集数据；张晶参与修改论文；仇丽霞负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
仇丽霞， qiulixia@ccmu.edu.cn （ORCID： 0000-0001-9662-8705）

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出版历程
- 收稿日期: 2025-11-16
- 录用日期: 2025-12-19
- 出版日期: 2026-04-25

Low-dose defibrotide in the treatment of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome： A case report

1.
Third Department of Liver Disease Center，Beijing YouAn Hospital，Capital Medical University，Beijing 100069，China
2.
Clinical Laboratory Center，Beijing YouAn Hospital，Capital Medical University，Beijing 100069，China

Research funding:

Beijing Municipal Administration of Hospitals Incubating Program (PX2023061);

Young Investigator Grant in Beijing YouAn Hospital Affiliated to Capital Medical University (BJYAYY-YN2024-13)

More Information

Corresponding author: QIU Lixia， qiulixia@ccmu.edu.cn （ORCID： 0000-0001-9662-8705）

摘要

摘要: 本文报道1例60岁男性因服“土三七”致吡咯生物碱相关肝窦阻塞综合征。患者表现为腹水及肝功能异常，经影像学及肝活检确诊。因患者对低分子肝素过敏且支持治疗无效，予低剂量去纤苷挽救治疗。治疗后腹水迅速消退、肝功能恢复，复查肝活检显示肝窦淤血减轻、肝细胞再生。治疗期间出现自愈性结膜出血。本病例提示，对于标准抗凝禁忌或无效者，低剂量去纤苷或为有效且相对安全的替代治疗方案。
- 肝窦阻塞综合征 /
- 吡咯里西啶生物碱 /
- 去纤苷 /
- 治疗结果
Abstract: This article reports a case of a male patient， aged 60 years， who developed pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome （PA-HSOS） due to ingestion of Gynura segetum （Lour.） Merr. The patient presented with ascites and abnormal liver function， and a confirmed diagnosis was made based on radiological examination and liver biopsy. Since the patient was allergic to low-molecular-weight heparin and had no response to supportive therapy， low-dose defibrotide was administered as rescue treatment. After treatment， the patient achieved rapid regression of ascites and recovery of liver function， and liver biopsy reexamination showed alleviation of sinusoidal congestion and hepatocyte regeneration. Self-resolving conjunctival hemorrhage occurred during treatment. This case suggests that for patients with contraindications to standard anticoagulation therapy or those showing no response to such treatment， low-dose defibrotide may be used as an effective and relatively safe alternative treatment regimen.
- Hepatic Sinusoidal Obstruction Syndrome /
- Pyrrolizidine Alkaloid /
- Defibrotide /
- Treatment Outcome

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注： a，门脉期；b，延迟期。门脉期及延迟期肝实质内见斑片影，形成特征性的“地图样”改变。CT，计算机体层成像。

图 1 上腹部增强CT结果

Figure 1. Abdominal contrast-enhanced CT

下载: 全尺寸图片幻灯片

注： a、b，苏木精-伊红染色；c、d，马松染色。初次肝脏病理学显示（a、c），中央静脉周围肝窦明显扩张，淤血性肝细胞萎缩，部分肝细胞脱失，提示静脉回流障碍，符合HSOS。第2次肝脏病理学显示（b、d），Ⅲ带肝细胞再生性增生，窦细胞增生，局灶肝窦轻度扩张淤血；与初次肝穿刺比较，中央区肝窦淤血明显减轻，坏死区肝细胞大部分再生，符合急性HSOS修复期改变。HSOS，肝窦阻塞综合征。

图 2 去纤苷治疗前后肝脏病理学变化（×200）

Figure 2. Pathological comparison of liver biopsy before and after use of defibrotide （×200）

下载: 全尺寸图片幻灯片

表 1 去纤苷治疗前后肝功能及其他指标的变化

Table 1. Changes in liver function and other clinical indicators before and after defibrotide treatment

检查时间	ALT（U/L）	AST（U/L）	TBil（μmol/L）	TBA（μmol/L）	GGT（U/L）	Alb（g/L）	PLT（×10⁹/L）	PT（s）	INR
2024/1/12	24.1	40.2	46.9	46.9	239.3	43.5	106	10.0	1.13
2024/1/26	30.2	35.1	26.9	40.0	117.3	40.1	109	9.9	1.13
2024/2/10	16.2	23.4	10.2	7.3	98.1	36.1	143	9.5	1.08
2024/2/18	16.3	23.3	10.2	5.0	128.1	37.3	143	8.8	1.00
2024/2/29	21.3	27.3	8.9	4.9	76.2	36.6	144	9.8	1.12
注：ALT，丙氨酸氨基转移酶；AST，天门冬氨酸氨基转移酶；TBil，总胆红素；TBA，总胆汁酸；GGT，γ-谷氨酰转移酶；Alb，白蛋白；PLT，血小板计数；PT，凝血酶原时间；INR，国际标准化比值。

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参考文献(25)

[1]	WANG CY, WANG YL, ZHAO JB, et al. Transjugular intrahepatic portosystemic shunt for the treatment of hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids: A multicenter retrospective study[J]. Heliyon, 2023, 10( 1): e23455. DOI: 10.1016/j.heliyon.2023.e23455.
[2]	NASSEREDDINE S, ALSUBAIT S, TABBARA I. Sinusoidal obstruction syndrome(veno-occlusive disease) following hematopoietic stem cell transplant: Insights and therapeutic advances[J]. Anticancer Res, 2018, 38( 5): 2597- 2605. DOI: 10.21873/anticanres.12501.
[3]	DIGNAN FL, WYNN RF, HADZIC N, et al. BCSH/BSBMT guideline: Diagnosis and management of veno-occlusive disease(sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation[J]. Br J Haematol, 2013, 163( 4): 444- 457. DOI: 10.1111/bjh.12558.
[4]	CORBACIOGLU S, CARRERAS E, MOHTY M, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: Final results from the international compassionate-use program[J]. Biol Blood Marrow Transplant, 2016, 22( 10): 1874- 1882. DOI: 10.1016/j.bbmt.2016.07.001.
[5]	KERNAN NA, GRUPP S, SMITH AR, et al. Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome[J]. Br J Haematol, 2018, 181( 6): 816- 827. DOI: 10.1111/bjh.15267.
[6]	DANAN G, TESCHKE R. RUCAM in drug and herb induced liver injury: The update[J]. Int J Mol Sci, 2015, 17( 1): 14. DOI: 10.3390/ijms17010014.
[7]	SHEN T, LIU YX, SHANG J, et al. Incidence and etiology of drug-induced liver injury in mainland China[J]. Gastroenterology, 2019, 156( 8): 2230- 2241. e 11. DOI: 10.1053/j.gastro.2019.02.002.
[8]	NEUMAN MG, COHEN L, OPRIS M, et al. Hepatotoxicity of pyrrolizidine alkaloids[J]. J Pharm Pharm Sci, 2015, 18( 4): 825- 843. DOI: 10.18433/j3bg7j.
[9]	ROEDER E. Medicinal plants in Europe containing pyrrolizidine alkaloids[J]. Pharmazie, 1995, 50( 2): 83- 98.
[10]	ROEDER E, WIEDENFELD H, EDGAR JA. Pyrrolizidine alkaloids in medicinal plants from North America[J]. Pharmazie, 2015, 70( 6): 357- 367.
[11]	ROEDER E. Medicinal plants in China containing pyrrolizidine alkaloids[J]. Pharmazie, 2000, 55( 10): 711- 726.
[12]	Cooperative Group for Hepatic and Gall Diseases, Chinese Society of Gastroenterology, Chinese Medical Association. Expert consensus on diagnosis and treatment of pyrrolizidine alkaloids-related sinusoidal obstruction syndrome(2017, Nanjing)[J]. J Clin Hepatol, 2017, 33( 9): 1627- 1637. DOI: 10.3969/j.issn.1001-5256.2017.09.003. 中华医学会消化病学分会肝胆疾病协作组. 吡咯生物碱相关肝窦阻塞综合征诊断和治疗专家共识意见(2017年,南京)[J]. 临床肝胆病杂志, 2017, 33( 9): 1627- 1637. DOI: 10.3969/j.issn.1001-5256.2017.09.003.
[13]	LI RQ, LI L, CAI ZH, et al. Histological evaluation of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: Correlation with Drum Tower Severity Scoring[J]. Dig Liver Dis, 2024, 56( 7): 1220- 1228. DOI: 10.1016/j.dld.2023.12.008.
[14]	WANG JY, GAO H. Tusanqi and hepatic sinusoidal obstruction syndrome[J]. J Dig Dis, 2014, 15( 3): 105- 107. DOI: 10.1111/1751-2980.12112.
[15]	PENG CY, ZHANG XF, ZHANG F, et al. Clinical efficacy and safety of anticoagulation therapy for pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: A retrospective multicenter cohort study[J]. Eur J Gastroenterol Hepatol, 2020, 32( 9): 1168- 1178. DOI: 10.1097/MEG.0000000000001630.
[16]	YANG XQ, YE J, LI X, et al. Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis, treatment, and outcomes[J]. World J Gastroenterol, 2019, 25( 28): 3753- 3763. DOI: 10.3748/wjg.v25.i28.3753.
[17]	JIANG MJ, WANG LY, DU XD, et al. Low molecular weight heparin in the treatment of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: Five case reports[J]. J Int Med Res, 2020, 48( 9): 0300060520961916. DOI: 10.1177/0300060520961916.
[18]	SONG Y, FAN YH. Clinical features of hepatic veno-occlusive disease induced by Gynura root: Analysis of 102 cases[J]. J Clin Hepatol, 2011, 27( 5): 496- 499. DOI: 10.3969/j.issn.1001-5256.2011.05.014. 宋宇, 樊艳华. 土三七所致肝小静脉闭塞病102例临床分析[J]. 临床肝胆病杂志, 2011, 27( 5): 496- 499. DOI: 10.3969/j.issn.1001-5256.2011.05.014.
[19]	ZHU WL, CHEN SH, CHEN WX, et al. Clinical analysis of 50 cases of hepatic veno-occlusive disease[J]. Chin J Dig, 2012, 32( 9): 620- 624. DOI: 10.3760/cma.j.issn.0254-1432.2012.09.013. 朱晚林, 陈韶华, 陈卫星, 等. 肝小静脉闭塞病50例临床分析[J]. 中华消化杂志, 2012, 32( 9): 620- 624. DOI: 10.3760/cma.j.issn.0254-1432.2012.09.013.
[20]	LI S, LI Y, ZHOU CH, et al. Transjugular intrahepatic portosystemic shunt benefits for hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum: A propensity score-matched analysis[J]. Cardiovasc Intervent Radiol, 2023, 46( 7): 931- 942. DOI: 10.1007/s00270-023-03451-9.
[21]	RICHARDSON PG, TRIPLETT BM, HO VT, et al. Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome[J]. Expert Rev Clin Pharmacol, 2018, 11( 2): 113- 124. DOI: 10.1080/17512433.2018.1421943.
[22]	KERNAN NA, RICHARDSON PG, SMITH AR, et al. Defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome following nontransplant-associated chemotherapy: Final results from a post hoc analysis of data from an expanded-access program[J]. Pediatr Blood Cancer, 2018, 65( 10): e27269. DOI: 10.1002/pbc.27269.
[23]	LIU ZL, LIANG S, WEI XH, et al. Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome[J]. BMC Gastroenterol, 2022, 22( 1): 525. DOI: 10.1186/s12876-022-02523-3.
[24]	BAGAL B, CHANDRASEKHARAN A, CHOUGLE A, et al. Low, fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation[J]. Hematol Oncol Stem Cell Ther, 2018, 11( 1): 47- 51. DOI: 10.1016/j.hemonc.2017.02.005.
[25]	ZHUGE YZ, LIU YL, XIE WF, et al. Expert consensus on the clinical management of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome[J]. J Gastroenterol Hepatol, 2019, 34( 4): 634- 642. DOI: 10.1111/jgh.14612.