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Zhang LL, Zhang F, Wang K, Song YH, Zhang Y, Zhou ZY, Dai WJ, Wang L, Chen H, Yin Q, Zhuge YZ, Zhang W. Validation of Drum Tower Severity Scoring (DTSS) System for Pyrrolizidine Alkaloid-Induced Hepatic Sinusoidal Obstruction Syndrome. J Dig Dis 2025. [PMID: 40329525 DOI: 10.1111/1751-2980.13347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 01/25/2025] [Accepted: 04/21/2025] [Indexed: 05/08/2025]
Abstract
OBJECTIVES The Drum Tower Severity Scoring (DTSS) system is a novel tool designed for assessing the outcome of anticoagulation therapy and disease severity in patients with pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). The aim of this study was to validate the predictive performance of the DTSS system in PA-HSOS patient outcome. METHODS We conducted a retrospective analysis of 111 PA-HSOS patients who received standard anticoagulation-transjugular intrahepatic portosystemic shunt (TIPS) stepwise therapy from six hospitals in China. Patients were categorized into two groups based on whether they responded to anticoagulation therapy. The predictive performance of the DTSS system was evaluated through the efficacy of anticoagulation therapy, the area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) analysis. RESULTS The response rates to anticoagulation therapy varied among patients with DTSS of different severity, being 94.12% for mild, 57.81% for moderate, and 13.33% for severe cases. The DTSS system demonstrated a robust predictive performance, with an AUROC of 0.864. The calibration curve indicated a close match between the predicted and observed effects of the DTSS system. Good calibration was confirmed by the Hosmer-Lemeshow test (p = 0.704), and both the DCA and CIC analysis indicated high clinical utility of the DTSS system. CONCLUSION The DTSS system is a practical tool that uses easily accessible data to predict the initial response to anticoagulation therapy in PA-HSOS patients, showing robust predictive performance and significant clinical benefit in guiding personalized management strategies.
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Affiliation(s)
- Li Li Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Department of Gastroenterology, Jiangnan University Medical Center, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu Province, China
| | - Feng Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Kai Wang
- Department of General Surgery, Xuzhou Medical University Affiliated Hospital, Xuzhou, Jiangsu Province, China
| | - Yu Hu Song
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ying Zhang
- Department of Infectious Disease, Nantong Third People's Hospital, Nantong, Jiangsu Province, China
| | - Zhen Yu Zhou
- Department of Gastroenterology, Yixing People's Hospital, Yixing, Jiangsu Province, China
| | - Wei Jie Dai
- Department of Gastroenterology, Huai'an First People's Hospital, Huai'an, Jiangsu Province, China
| | - Lei Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Huan Chen
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Qin Yin
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yu Zheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Wei Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
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Chen S, Ma Y, Ji M, Wang H, Chen Y, Li D, Jiang H, Song G, Xia J, Gao H. Phosphocreatine alleviates monocrotaline-induced liver injury dependent on PSRC1-regulated endoplasmic reticulum stress. Biochem Pharmacol 2025; 237:116915. [PMID: 40194605 DOI: 10.1016/j.bcp.2025.116915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 03/03/2025] [Accepted: 03/27/2025] [Indexed: 04/09/2025]
Abstract
Monocrotaline (MCT), a pyrrolizidine alkaloid (PA), is naturally found in certain plants and known for its hepatotoxic effects. In our prior research, we identified that phosphocreatine (PCr) mitigates PA-induced liver damage. However, the specific mechanism of PCr remains unknown. The objective of the present study was to elucidate the mechanism through which PCr shields against MCT-induced hepatic injury. In vitro assays demonstrated that PCr mitigated the MCT-induced ER stress and apoptosis. This alleviation was similarly observed with the use of the ER stress inhibitor 4-PBA, hinting at the role of ER stress in the protective mechanism of PCr against MCT-induced hepatic damage. In the MCT group, an upregulation of proline/serine-rich coiled-coil protein 1 (PSRC1) was evident, but this was notably downregulated following PCr treatment in vitro. The silencing of PSRC1 diminished the ER stress and apoptosis triggered by MCT, and the protective effect of PCr on liver injury remained evident. Overexpressing PSRC1 increased MCT-induced apoptosis and ER stress, and PCr still plays a protective role. In vivo experiments, we observed a notable attenuation of MCT-induced liver damage by PCr. Employing RNA sequencing and immunohistochemical staining techniques, we ascertained that endoplasmic reticulum (ER) stress, apoptosis and PSRC1 were significantly elevated in the liver samples treated with MCT. Notably, these alterations were counteracted by the presence of PCr. In conclusion, our findings suggest that PCr counteracts ER stress via modulation of PSRC1, which consequently confers protection against MCT-induced liver injury. Furthermore, this study offers potential therapeutic avenues for addressing hepatic damages attributable to MCT.
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Affiliation(s)
- Sinuo Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China; Liver Cancer Institute, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Yifan Ma
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Mingyan Ji
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Heming Wang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Yun Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Dongping Li
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Hongyue Jiang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Guangqi Song
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China
| | - Jinglin Xia
- Liver Cancer Institute, Zhongshan Hospital Fudan University, Shanghai 200032, China; Shanghai Institute of Liver Disease, Shanghai 200032, China.
| | - Hong Gao
- Department of Gastroenterology and Hepatology, Zhongshan Hospital Fudan University, Shanghai 200032, China; Shanghai Institute of Liver Disease, Shanghai 200032, China.
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Yu Z, Li W, Tian C, Cao Y, Zhang C. Drug-induced hepatic sinusoidal obstruction syndrome: current advances and future perspectives. Arch Toxicol 2025; 99:835-850. [PMID: 39718593 DOI: 10.1007/s00204-024-03950-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 12/17/2024] [Indexed: 12/25/2024]
Abstract
Hepatic sinusoidal obstruction syndrome (HSOS) has gained recognition as a rare form of drug-induced liver injury (DILI) in recent years. Although extensively studied in the context of hematopoietic stem cell transplantation (HSCT), the applicability of this knowledge to drug-induced HSOS remains limited due to distinct etiological factors. The primary causes of drug-induced HSOS include the ingestion of pyrrolizidine alkaloid (PA)-containing plants, as well as the use of chemotherapeutic agents and immunosuppressive drugs. The underlying pathogenesis is not yet fully understood. Noninvasive diagnostic imaging modalities such as ultrasonography, computed tomography, and magnetic resonance imaging play a valuable role in diagnosis. Further research is essential to develop standardized severity grading systems and optimize treatment strategies. This review summarizes the key etiologies, pathological mechanisms, clinical features, diagnostic approaches, severity assessment, and therapeutic options for drug-induced HSOS.
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Affiliation(s)
- Zaoqin Yu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Wei Li
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Cheng Tian
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Yan Cao
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
| | - Chengliang Zhang
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
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Chen J, Xu Y, Lin Y, Wang C. Hepatomegaly and ascites in a patient with UC. Gut 2024:gutjnl-2024-333587. [PMID: 39214671 DOI: 10.1136/gutjnl-2024-333587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024]
Affiliation(s)
- Jintong Chen
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, China
| | - Ye Xu
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, China
| | - Yanjun Lin
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, China
| | - Chengdang Wang
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
- Department of Gastroenterology, National Regional Medical Center, Fujian Medical University, Fuzhou, China
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Xiong A, Lu L, Jiang K, Wang X, Chen Y, Wang X, Zhang W, Zhuge Y, Huang W, Li L, Liao Q, Yang F, Liu P, Ding L, Wang Z, Yang L. Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Arch Toxicol 2024; 98:2557-2576. [PMID: 38703205 DOI: 10.1007/s00204-024-03762-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 04/10/2024] [Indexed: 05/06/2024]
Abstract
Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908-0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics.
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Affiliation(s)
- Aizhen Xiong
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China.
- Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai, 201210, China.
| | - Longhui Lu
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China
| | - Kaiyuan Jiang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China
| | - Xiaoning Wang
- E-Institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yan Chen
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China
| | - Xunjiang Wang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China
| | - Wei Zhang
- Department of Gastroenterology, The Drum Tower Hospital of Nanjing, Affiliated to Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, The Drum Tower Hospital of Nanjing, Affiliated to Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Wendong Huang
- Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, 91010, USA
| | - Lujin Li
- Center for Drug of Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China
| | - Qi Liao
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China
| | - Fan Yang
- Department of Obstetrics and Gynecology, and Shanghai Key Laboratory of Gynecologic Oncology Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Ping Liu
- E-Institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Lili Ding
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China.
- Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai, 201210, China.
| | - Zhengtao Wang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China.
- Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai, 201210, China.
| | - Li Yang
- The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China.
- Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai, 201210, China.
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Li R, Li L, Cai Z, Chen J, Zhang H, Zhao S, Tu J, Sun C, Jin Y, Zhang M, Zhang F, Zhang W, Yin Q, Xu H, Han H, Li T, Zhuge Y, Xiao J. Histological evaluation of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: Correlation with Drum Tower Severity Scoring. Dig Liver Dis 2024; 56:1220-1228. [PMID: 38151450 DOI: 10.1016/j.dld.2023.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 12/11/2023] [Accepted: 12/16/2023] [Indexed: 12/29/2023]
Abstract
BACKGROUND Hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids (PA-HSOS) is a complication of drug-induced liver damage. Few studies have examined the relationship between pathological changes and clinical circumstances in PA-HSOS. The Drum Tower Severity Scoring System (DTSS) was developed using prognostic indicators from clinical treatment outcomes. We hypothesized that the severity of pathological damage is consistent with DTSS. AIMS We aimed to improve our understanding and assessment of vascular liver injury disease histopathology by studying larger sample sizes of human histopathological samples. We also wanted to confirm the link between histopathological findings and DTSS. METHODS The study included 62 patients with PA-HSOS who underwent transjugular liver biopsy. Their hepatic pathological tissues were evaluated. Analyses of linear regression and Spearman's correlation were employed to examine the relationship between DTSS and pathological characteristics. RESULTS Clinical performance and the DTSS score were used to determine histopathological severity. The sinusoidal congestion area (SCA), central venous endothelial injury (CVEI), and fibrinoid exudation in congestion foci (FECF) were significant indicators. SCA was linearly related to the DTSS score. CONCLUSION Our findings show that hepatic pathological characteristics correlate with DTSS scores in PA-HSOS. SCA, CVEI, and FECF may be helpful for determining PA-HSOS severity.
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Affiliation(s)
- Ruiqi Li
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China; School of Medicine, Southeast University, Nanjing, China
| | - Lin Li
- Department of Pathology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Zihao Cai
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Jun Chen
- Department of Pathology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Han Zhang
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Si Zhao
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Jingjing Tu
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Chang Sun
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Yani Jin
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Ming Zhang
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Feng Zhang
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Wei Zhang
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Qin Yin
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Hui Xu
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Hao Han
- Department of Ultrasound, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Taishun Li
- Medical Statistical Analysis Center, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China; School of Medicine, Southeast University, Nanjing, China.
| | - Jiangqiang Xiao
- Department of Gastroenterology, Drum Tower Hospital, Affiliated Medical College of Nanjing University, Nanjing, China.
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Zheng Q, Zhang H. Gynura segetum induces hepatic sinusoidal obstruction syndrome in a child: A case report. Medicine (Baltimore) 2024; 103:e37341. [PMID: 38489699 PMCID: PMC10939675 DOI: 10.1097/md.0000000000037341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 02/02/2024] [Indexed: 03/17/2024] Open
Abstract
RATIONALE Hepatic sinusoidal obstruction syndrome (HSOS), which includes hepatic stasis and portal hypertension, is a rare vascular disorder of the liver. It is often associated with hematopoietic stem cell transplantation. It is also possible to treat this disease using Chinese herbal medicines that contain pyrrolizidine alkaloids (PAs). This disease is extremely rare in children and poses a serious threat to their health. To our knowledge, this is the first case of HSOS in a child with PAs. PATIENT CONCERNS We report a 4-year-old boy suffering from abdominal pain, hepatomegaly, massive ascites, elevated liver enzyme level, and severe portal hypertension as a result of the consumption of Gynura segetum (also known as Tusanqi in Chinese, a traditional herbal medicine containing PAs). DIAGNOSES The child was finally diagnosed with PA-HSOS based on pathological diagnosis and imaging examination. INTERVENTION With active symptomatic and supportive care and sequential anticoagulation therapy, the abdominal distension and liver function improved in the patient. OUTCOMES The patient was eventually recovered. The levels of liver enzymes, hemoglobin, and bilirubin were normal, and the international normalized ratio fluctuated between 2.0 and 3.0 during 1-year follow-up after discharge. LESSONS This case report emphasizes the prevention of Chinese herb-induced liver injury in children and the importance of active long-term sequential anticoagulant therapy to reduce the progressive damage of PA-HSOS in the liver.
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Affiliation(s)
- Qian Zheng
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Haiyang Zhang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
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Lu F, Jia S, Lu H, Zhao H, Li Z, Zhuge Y, Romeiro FG, Mendez-Sanchez N, Qi X. Primary Budd-Chiari syndrome versus sinusoidal obstruction syndrome: a review. Curr Med Res Opin 2024; 40:303-313. [PMID: 38006404 DOI: 10.1080/03007995.2023.2288909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/09/2023] [Accepted: 11/24/2023] [Indexed: 11/27/2023]
Abstract
Budd-Chiari syndrome (BCS) and sinusoidal obstruction syndrome (SOS) are two major vascular disorders of the liver, of which both can cause portal hypertension related complications, but their locations of obstruction are different. BCS refers to the obstruction from the hepatic vein to the junction between the inferior vena cava and right atrium, which is the major etiology of post-sinusoidal portal hypertension; by comparison, SOS is characterized as the obstruction at the level of hepatic sinusoids and terminal venulae, which is a cause of sinusoidal portal hypertension. Both of them can cause hepatic congestion with life-threatening complications, especially acute liver failure and chronic portal hypertension, and share some similar features in terms of imaging and clinical presentations, but they have heterogeneous risk factors, management strategy, and prognosis. Herein, this paper reviews the current evidence and then summarizes the difference between primary BCS and SOS in terms of risk factors, clinical features, diagnosis, and treatment.
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Affiliation(s)
- Feifei Lu
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Siqi Jia
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, Shenyang, China
| | - Huiyuan Lu
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, Shenyang, China
| | - Haonan Zhao
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, Shenyang, China
| | - Zhe Li
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, Shenyang, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China
| | | | - Nahum Mendez-Sanchez
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
| | - Xingshun Qi
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, Shenyang, China
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Wang C, Wang Y, Zhao J, Yang C, Zhu X, Niu H, Sun J, Xiong B. Transjugular intrahepatic portosystemic shunt for the treatment of hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids: A multicenter retrospective study. Heliyon 2024; 10:e23455. [PMID: 38163189 PMCID: PMC10755310 DOI: 10.1016/j.heliyon.2023.e23455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 12/04/2023] [Accepted: 12/04/2023] [Indexed: 01/03/2024] Open
Abstract
Purpose To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on clinical outcomes and liver histology in patients with hepatic sinusoidal obstruction syndrome (HSOS) caused by pyrrolizidine alkaloids (PA), and compare these results with those of patients who received supportive treatment alone. Materials and methods From June 2015 to August 2022, 164 patients diagnosed with PA-HSOS in six tertiary care centers were retrospectively included in this study and divided into TIPS group (n = 69) and supportive treatment (ST) group (n = 95). The main endpoint was to determine whether TIPS placement could improve survival in PA-HSOS patients. The clinical symptoms associated with portal hypertension were also evaluated in this study. Additionally, a small TIPS-subgroup of 7 patients received liver biopsies before and after TIPS for histological analysis. Results The incidence of death was markedly lower in the TIPS group than in the ST group (log-rank p = 0.026). Multivariate Cox model revealed that group assignment (hazard ratio (HR) 5.146; 95 % confidence interval (CI) 1.587-16.687; p = 0.006), total bilirubin (HR 1.029; 95 % CI 1.020-1.038; p < 0.001), and INR (HR 13.291; 95 % CI 3.637-48.566; p < 0.001) were independent predictors for mortality. In addition, TIPS placement reduced the risk of complications associated with portal hypertension but did not increase the rate of overt hepatic encephalopathy (log-rank p = 0.731). Furthermore, six of 7 TIPS patients receiving liver biopsies improved after TIPS placement, and one patient developed fibrosis. Conclusions TIPS placement decreased the mortality and risk of complications associated with portal hypertension. Histological evaluation in a few patients showed a potential improvement by TIPS.
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Affiliation(s)
- Chaoyang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Yingliang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Jianbo Zhao
- Department of Vascular and Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510000, China
| | - Chongtu Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Xiaoli Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China
| | - Huanzhang Niu
- Department of Interventional Radiology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471000, China
| | - Junhui Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, 310000, China
| | - Bin Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, China
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Hountondji L, Pureur D, Chabannes M, Felix S, Thévenot T. Transjugular Intrahepatic Portosystemic Shunt is effective to treat portal hypertension due to sinusoidal obstructive syndrome. Clin Res Hepatol Gastroenterol 2023; 47:102201. [PMID: 37643693 DOI: 10.1016/j.clinre.2023.102201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 08/24/2023] [Accepted: 08/25/2023] [Indexed: 08/31/2023]
Abstract
Transjugular Intrahepatic Portosystemic Shunt (TIPS) is an established procedure for the complications of portal hypertension, such as variceal bleeding, refractory ascites and hepatic hydrothorax. We report an original case of a renal transplant patient successfully treated with TIPS for portal hypertension due to sinusoidal obstructive syndrome (SOS) induced by azathioprine (AZA). By reporting this case, we wish to draw the attention of healthcare professionals managing organ transplant patients, especially nephrologists, to the possible occurrence of liver toxicity due to AZA, and to emphasize the role of TIPS as an effective therapeutic option for portal hypertension-related complications.
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Affiliation(s)
- Lina Hountondji
- Service d'Hépatologie et de Soins Intensifs Digestifs, Centre Hospitalier Universitaire Jean Minjoz, 25030 Besançon cedex, France.
| | - Dimitri Pureur
- Service d'Hépatologie et de Soins Intensifs Digestifs, Centre Hospitalier Universitaire Jean Minjoz, 25030 Besançon cedex, France
| | - Melchior Chabannes
- Service de Néphrologie dialyse et transplantation, Centre Hospitalier Universitaire Jean Minjoz, 25000 Besançon, France
| | - Sophie Felix
- Service d'Anatomo-pathologie, Centre Hospitalier Universitaire Jean Minjoz, 25000 Besançon, France
| | - Thierry Thévenot
- Service d'Hépatologie et de Soins Intensifs Digestifs, Centre Hospitalier Universitaire Jean Minjoz, 25030 Besançon cedex, France
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11
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Huang T, Zhang X, Yan K, Lou D, He Y, Dai S, Zheng D, Chen P, Wu F, Gu L. Transjugular intrahepatic portosystemic shunt for pyrrolidine alkaloids-induced hepatic sinusoidal obstruction syndrome: a retrospective cohort study. Eur J Gastroenterol Hepatol 2023; 35:1004-1011. [PMID: 37395216 DOI: 10.1097/meg.0000000000002591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
BACKGROUND This study aimed to investigate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of patients with pyrrolidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). METHODS Patients diagnosed with PA-HSOS and treated in Ningbo No.2 Hospital between November 2017 and October 2022 were enlisted in this retrospective cohort study. RESULTS This cohort comprised a total of 22 patients with PA-HSOS, of which 12 patients received TIPS treatment and 10 patients experienced conservative treatment. The median follow-up duration was 10.5 months. Baseline characteristics existed with no significant difference between the two groups. No operation failures or any TIPS-associated intraoperative complications were observed after TIPS. In the TIPS group, the portal venous pressure was substantially decreased from 25.3 ± 6.3 mmHg to 14.4 ± 3.5 mmHg after TIPS ( P = 0.002). Compared with preoperative, the ascites after TIPS were significantly subsided ( P = 0.001) and there existed a considerable decrease in Child-Pugh score. At the end of follow-up, 5 patients died, involving 1 in the TIPS group and 4 in the conservative treatment group. The median survival time was 13 (3-28) months in the TIPS group and 6.5 (1-49) months in the conservative treatment group, respectively. The survival analysis demonstrated that the total survival time of TIPS group was longer than that of the conservative treatment group, no statistical significance was observed ( P = 0.08). CONCLUSION TIPS may be a secure and effective therapeutic strategy for PA-HSOS patients who do not respond to conservative treatment.
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Affiliation(s)
- Tongmin Huang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou
| | | | - Kun Yan
- Department of Radiology, Ningbo No. 2 Hospital, Ningbo
| | - Dandi Lou
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou
| | - Yujing He
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou
| | - Senjie Dai
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou
| | - Dingcheng Zheng
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
| | - Ping Chen
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
| | - Feng Wu
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
| | - Lihu Gu
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
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Du X, Liu Z, Yu H, Wang Y, Zou Z, Wei H, Liang J, Yang D, Liu Y, Zhang J, Pan CQ. Prognostic risk factors for patients with hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids. Medicine (Baltimore) 2023; 102:e34698. [PMID: 37565875 PMCID: PMC10419670 DOI: 10.1097/md.0000000000034698] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 07/20/2023] [Indexed: 08/12/2023] Open
Abstract
Pyrrolizidine alkaloids induced hepatic sinusoidal obstruction syndrome (PA-HSOS) often occurs after consuming herbs or a dietary supplement containing the plant Tu-San-Qi. Limited data exists to identify patients with fatal outcomes for early interventions. We aimed to analyze the predictors for 3-month survival. We retrospectively enrolled PA-HSOS patients in 5 hospitals and extracted data from the onset of PA-HSOS to 36 months. Outcome measurements were 3-month and 36-month survival rates, baseline prognostic predictors for survival, and the effects of anticoagulant therapy. Among 49 enrollees, the median age was 60 and 49% male. At the onset of PA-HSOS, patients with Child-Turcotte-Pugh (CTP) class of A, B, or C were 8.2% (4/49), 42.8% (21/49) and 49.0% (24/49), respectively. None of them received a transjugular intrahepatic portosystemic shunt or a liver transplant. The 3-month and 36-month survival rates were 86% and 76%, respectively. Compared to the CTP class A or B, class C at baseline independently predicted lower survival rates at both 3 and 36 months. However, anticoagulation therapy treatment within the first 3 months independently predicted significantly higher survival rates at both time points. CTP class C and anticoagulant therapy were the independent predictors for short-term and long-term survival. Anticoagulant therapy could decrease mortality rate of CTP class C patients. The greatest benefit of anticoagulant evaluated by 3-month survival rate was in patients with CTP class C compared with those without treatment (93% vs 40%, P = .009). There were no bleeding complications reported in patients treated with the anticoagulant.
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Affiliation(s)
- Xiaofei Du
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Zhenli Liu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Haibin Yu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yu Wang
- Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Zhengsheng Zou
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Hongshan Wei
- Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jing Liang
- Tianjin Third Central Hospital, Tianjin, China
| | - Daokun Yang
- The First Affiliated Hospital of Xinxiang Medical University, Henan, China
| | - Yali Liu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jing Zhang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Calvin Q. Pan
- Division on Gastroenterology and Hepatology, NYU Langone Health, NYU Grossman School of Medicine, NY
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Xu XT, Wang BH, Wang Q, Guo YJ, Zhang YN, Chen XL, Fang YF, Wang K, Guo WH, Wen ZZ. Idiopathic hypereosinophilic syndrome with hepatic sinusoidal obstruction syndrome: A case report and literature review. World J Gastrointest Surg 2023; 15:1532-1541. [PMID: 37555104 PMCID: PMC10405125 DOI: 10.4240/wjgs.v15.i7.1532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/17/2023] [Accepted: 05/17/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Hypereosinophilic syndrome (HES) is classified as primary, secondary or idiopathic. Idiopathic HES (IHES) has a variable clinical presentation and may involve multiple organs causing severe damage. Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by damage to the endothelial cells of the hepatic sinusoids of the hepatic venules, with occlusion of the hepatic venules, and hepatocyte necrosis. We report a case of IHES with HSOS of uncertain etiology. CASE SUMMARY A 70-year-old male patient was admitted to our hospital with pruritus and a rash on the extremities for > 5 mo. He had previously undergone antiallergic treatment and herbal therapy in the local hospital, but the symptoms recurred. Relevant examinations were completed after admission. Bone marrow aspiration biopsy showed a significantly higher percentage of eosinophils (23%) with approximately normal morphology. Ultrasound-guided hepatic aspiration biopsy indicated HSOS. Contrast-enhanced computed tomography (CT) of the upper abdomen showed hepatic venule congestion with hydrothorax and ascites. The patient was initially diagnosed with IHES and hepatic venule occlusion. Prednisone, low molecular weight heparin and ursodeoxycholic acid were given for treatment, followed by discontinuation of low molecular weight heparin due to ecchymosis. Routine blood tests, biochemical tests, and imaging such as enhanced CT of the upper abdomen and pelvis were reviewed regularly. CONCLUSION Hypereosinophilia may play a facilitating role in the occurrence and development of HSOS.
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Affiliation(s)
- Xu-Tao Xu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Bing-Hong Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Qiang Wang
- Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Yang-Jie Guo
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Yu-Ning Zhang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Xiao-Li Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Yan-Fei Fang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Kan Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Wen-Hao Guo
- Department of Pathology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Zhen-Zhen Wen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
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Tan Y, Zheng S. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi - Case report and literature review. Open Med (Wars) 2023; 18:20230737. [PMID: 37333448 PMCID: PMC10276616 DOI: 10.1515/med-2023-0737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 05/05/2023] [Accepted: 05/25/2023] [Indexed: 06/20/2023] Open
Abstract
Tusanqi-induced hepatic sinusoidal obstruction syndrome (HSOS) is caused by exposure to pyrrolizidine alkaloids (PAs) and manifests as abdominal distension, liver pain, ascites, jaundice, and hepatomegaly. Pathologically, hepatic congestion and sinusoidal occlusion are observed in HSOS. We summarized the clinical characteristics of 124 patients with HSOS caused by Tusanqi in China between 1980 and 2019, along with those of 831 patients from seven English case series. The main clinical manifestations of PA-HSOS included abdominal pain, ascites, and jaundice. Common imaging features included characteristic heterogeneous density, slender hepatic veins, and other nonspecific changes. The acute stage is primarily manifested as hepatic sinus congestion and necrosis. Meanwhile, the persistence of hepatic sinus congestion and the onset of perisinusoidal fibrosis were observed during the repair stage. Finally, the persistence of hepatic sinusoidal fibrosis and resultant central hepatic vein occlusion were observed in the chronic stage. The new Nanjing standard for PA-HSOS incorporates the history of PA consumption and imaging features and eliminates weight gain and the serum total bilirubin value. Preliminary clinical validation of the Nanjing standard for PA-HSOS diagnosis revealed a sensitivity and specificity of 95.35 and 100%, respectively.
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Affiliation(s)
- Youwen Tan
- Department of Hepatology, Third Hospital of the Zhenjiang Affiliated Jiangsu University, No. 300, Daijiamen, Runzhou Distinct, Zhenjiang212003, China
| | - Sainan Zheng
- Department of Hepatology, Third Hospital of the Zhenjiang Affiliated Jiangsu University, No. 300, Daijiamen, Runzhou Distinct, Zhenjiang212003, China
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15
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Li S, Li Y, Zhou C, Li H, Chen C, Peng C, Wang T, Liu F, Xiao J, Shi L. Transjugular Intrahepatic Portosystemic Shunt Benefits for Hepatic Sinusoidal Obstruction Syndrome Associated with Consumption of Gynura Segetum: a Propensity Score-Matched Analysis. Cardiovasc Intervent Radiol 2023:10.1007/s00270-023-03451-9. [PMID: 37225971 DOI: 10.1007/s00270-023-03451-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 04/22/2023] [Indexed: 05/26/2023]
Abstract
PURPOSE Pyrrolidine alkaloids-related hepatic sinusoidal obstruction syndrome (PA-HSOS) is associated with a high mortality rate without standardized therapy. The efficacy of transjugular intrahepatic portosystemic shunts (TIPS) remains controversial. The study aimed to explore the risk factors influencing the clinical response in patients with PA-HSOS related to Gynura segetum (GS) to assess the disease prognosis at an early stage and to evaluate the efficacy of TIPS in these patients. METHODS This study retrospectively enrolled patients diagnosed with PA-HSOS between January 2014 and June 2021 with a clear history of exposure to GS. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors influencing the clinical response in patients with PA-HSOS. Propensity score matched (PSM) was performed to compensate for differences in baseline characteristics between patients with and without TIPS. The primary outcome was the clinical response defined as the disappearance of ascites with normal total bilirubin levels and/or a reduction of elevated transaminase levels < 50% within 2 weeks. RESULTS A total of 67 patients were identified in our cohort with a clinical response rate of 58.2%. Of these, thirteen patients were assigned to the TIPS group and 54 to the conservative treatment group. Logistic regression analysis revealed that TIPS treatment (P = 0.047), serum globulin levels (P = 0.043), and prothrombin time (P = 0.001) were independent factors influencing clinical response. After PSM, there was a higher long-term survival rate of patients (92.3% vs. 51.3%, P = 0.021) and a shorter hospital stay (P = 0.043), but a high trend in hospital costs (P = 0.070) in the TIPS group. The 6-month survival probability in patients undergoing TIPS therapy was more than ninefold higher than in patients without receiving that treatment [hazard ratio (95% CI) = 9.304 (4.250, 13.262), P < 0.05]. CONCLUSIONS TIPS therapy may be an effective treatment option for patients with GS-related PA-HSOS.
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Affiliation(s)
- Sai Li
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Yong Li
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Chunhui Zhou
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Haiping Li
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Changyong Chen
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Changli Peng
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Tianming Wang
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Fei Liu
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Juxiong Xiao
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China
| | - Liangrong Shi
- Interventional Radiology Center, Department of Radiology, Xiangya Hospital Central South University, Changsha, 410005, Hunan, China.
- Research Center for Geriatric Disorder, Xiangya Hospital Central South, Changsha, 410005, Hunan, China.
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16
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Mid- to long-term outcomes of initial transjugular intrahepatic portosystemic shunt versus anticoagulation for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Eur J Gastroenterol Hepatol 2023; 35:445-452. [PMID: 36719828 DOI: 10.1097/meg.0000000000002509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Anticoagulation therapy (AT) is often used as the initial treatment for pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS). However, transjugular intrahepatic portosystemic shunt (TIPS) is an alternative treatment. This study aimed to determine the mid- to long-term outcomes of TIPS versus AT as the initial treatment for PA-induced HSOS. METHODS We retrospectively analyzed the clinical data of 61 patients with PA-induced HSOS that were collected between November 2015 and July 2021. The patients were allocated to the TIPS group ( n = 20) or the AT group ( n = 41). These two groups were divided into subgroups according to the severity grading. The clinical data of the patients in both groups were analyzed. Cumulative survival rates were calculated and compared between the two groups and among the subgroups. RESULTS The clinical symptoms and signs improved or stabilized in 100% of the patients following TIPS and in 85% of the patients following AT at discharge ( P = 0.166). The mortality rate was 0.0% in the TIPS group and 34.1% in the AT group ( P = 0.005). The patients were followed up for 2-69 months (mean, 26.3 ± 20.5 months). In the mild- and moderate-grade subgroups, there was no difference in the cumulative survival rate between the TIPS and AT groups ( P = 0.589 and P = 0.364, respectively). In the severe and very severe-grade subgroups, the cumulative survival rate was higher in the TIPS group than in the AT group ( P = 0.018 and P = 0.025, respectively). CONCLUSION AT is a suitable initial treatment for mild or moderate PA-induced HSOS, whereas TIPS should be considered the appropriate initial treatment for severe or very severe PA-induced HSOS.
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17
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Tong Y, Zhang M, Qi Z, Wu W, Chen J, He F, Han H, Ding P, Wang G, Zhuge Y. Hepatic Venous Occlusion Type of Budd-Chiari Syndrome versus Pyrrolizidine Alkaloid-Induced Hepatic Sinusoidal Obstructive Syndrome: A Multi-Center Retrospective Study. J Pers Med 2023; 13:603. [PMID: 37108988 PMCID: PMC10143067 DOI: 10.3390/jpm13040603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/17/2023] [Accepted: 03/27/2023] [Indexed: 04/03/2023] Open
Abstract
(1) Background: Hepatic venous occlusion type of Budd-Chiari syndrome (BCS-HV) and pyrrolizidine alkaloid-induced hepatic sinusoidal obstructive syndrome (PA-HSOS), share similar clinical features, and imaging findings, leading to misdiagnoses; (2) Methods: We retrospectively analyzed 139 patients with BCS-HV and 257 with PA-HSOS admitted to six university-affiliated hospitals. We contrasted the two groups by clinical manifestations, laboratory tests, and imaging features for the most valuable distinguishing indicators.; (3) Results: The mean patient age in BCS-HV is younger than that in PA-HSOS (p < 0.05). In BCS-HV, the prevalence of hepatic vein collateral circulation of hepatic veins, enlarged caudate lobe of the liver, and early liver enhancement nodules were 73.90%, 47.70%, and 8.46%, respectively; none of the PA-HSOS patients exhibited these features (p < 0.05). DUS showed that 86.29% (107/124) of patients with BCS-HV showed occlusion of the hepatic vein, while CT or MRI showed that only 4.55%(5/110) patients had this manifestation (p < 0.001). Collateral circulation of hepatic veins was visible in 70.97% (88/124) of BCS-HV patients on DUS, while only 4.55% (5/110) were visible on CT or MRI (p < 0.001); (4) Conclusions: In addition to an established history of PA-containing plant exposure, local hepatic vein stenosis and the presence of collateral circulation of hepatic veins are the most important differential imaging features of these two diseases. However, these important imaging features may be missed by enhanced CT or MRI, leading to an incorrect diagnosis.
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Affiliation(s)
- Yaru Tong
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Ming Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Zexue Qi
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Wei Wu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Fuliang He
- Liver Disease Center, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, China
| | - Hao Han
- Department of Ultrasound, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Pengxu Ding
- Department of Intervention, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Guangchuan Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
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Xiang H, Liu C, Xiao Z, Du L, Wei N, Liu F, Song Y. Enoxaparin attenuates pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome by inhibiting oncostatin M expression. Liver Int 2023; 43:626-638. [PMID: 36354295 DOI: 10.1111/liv.15475] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 10/10/2022] [Accepted: 11/09/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND AND AIMS The definitive treatment for pyrrolizidine alkaloids (PAs)-induced hepatic sinusoidal obstruction syndrome (HSOS) is not available. The effectiveness of anticoagulation therapy remains controversial. The efficacy of low molecular weight heparin (LMWH) should be investigated in patients and animal models, and the underlying mechanism should be explored. METHODS The prognosis of patients with PAs-HSOS who received anticoagulation therapy was retrospectively analysed. The effect of enoxaparin on the liver injury was determined in animal models of monocrotaline (MCT)-induced HSOS was determined, and the underlying mechanism was investigated using a murine model. RESULTS The cumulative survival rate of patients with PAs-induced HSOS was 60.00% and 90.90% in the non-anticoagulation group and anticoagulation group. Enoxaparin attenuated liver injury effectively in a rat model of MCT-induced HSOS. Additionally, the improvement of severe liver injury was observed in MCT-treated mice after the administration of enoxaparin (40 mg/kg). The alleviation of liver injury was observed in mice with hepatocyte-specific deletion of oncostatin M (Osm△Hep ). In MCT-treated mice administrated with enoxaparin, no significant differences in liver injury were observed between Osm△Hep mice and Osmflox/flox mice. Additionally, adenovirus-mediated overexpression of Osm resulted in severe liver injury in MCT-induced mice after the administration of enoxaparin. CONCLUSIONS LMWH attenuated severe liver injury in patients with PAs-Induced HSOS and animal models of MCT-induced HSOS, which provides a rationale for the application of anticoagulation therapy.
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Affiliation(s)
- Hongyu Xiang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chang Liu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhuanglong Xiao
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Du
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ning Wei
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fang Liu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuhu Song
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Eckert E, Lepper H, Hintzsche H. Risk assessment of short-term intake of pyrrolizidine alkaloids in food: derivation of an acute reference dose. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2023; 40:588-596. [PMID: 36794362 DOI: 10.1080/19440049.2023.2178828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]
Abstract
Pyrrolizidine alkaloids (PA) are phytochemicals that are known to act as human hepatotoxins and are also considered to be genotoxic carcinogens. Several plant-derived foods are frequently contaminated with PA, like teas and herbal infusions, spices and herbs or certain food supplements. With respect to the chronic toxicity of PA, the carcinogenic potential of PA is generally regarded as the critical toxicological effect. The risk assessment of the short-term toxicity of PA, however, is internationally less consistent. The characteristic pathological syndrome of acute PA toxicity is hepatic veno-occlusive disease. High PA exposure levels may lead to liver failure and even death as documented by several case reports. In the present report, we suggest a risk assessment approach for the derivation of an acute reference dose (ARfD) for PA of 1 µg/kg body weight per day based on a sub-acute animal toxicity study in rats after oral PA administration. The derived ARfD value is further supported by several case reports describing acute human poisoning following accidental PA intake. The here derived ARfD value may be used for PA risk assessment in cases where the short-term toxicity of PA is of interest in addition to the assessment of the long-term risks.
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Affiliation(s)
- Elisabeth Eckert
- Department of Risk Assessment, Bavarian Health and Food Safety Authority, Erlangen, Germany.,Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Hans Lepper
- Department of Risk Assessment, Bavarian Health and Food Safety Authority, Erlangen, Germany
| | - Henning Hintzsche
- Department of Risk Assessment, Bavarian Health and Food Safety Authority, Erlangen, Germany.,Department of Food Safety, Institute of Food and Nutritional Sciences, University of Bonn, Bonn, Germany
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Xie YG, Xu C, Shi HB, Liu S, Yang W, Tian W, Zhou WZ. Transjugular intrahepatic portosystemic shunt for pyrrolidine-alkaloid-induced hepatic sinusoidal obstruction syndrome in a patient with situs inversus totalis and portal vein thrombus. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2023. [DOI: 10.18528/ijgii220055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Yu-Guan Xie
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chen Xu
- Department of Vascular Surgery, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, China
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Tian
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei-Zhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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21
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Lv Y, Fan D, Han G. Transjugular intrahepatic portosystemic shunt for portal hypertension: 30 years experience from China. Liver Int 2023; 43:18-33. [PMID: 35593016 DOI: 10.1111/liv.15313] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 04/05/2022] [Accepted: 05/15/2022] [Indexed: 01/04/2023]
Abstract
Liver diseases are a major cause of illness and death worldwide. In China, liver diseases, primarily viral hepatitis, affect approximately 300 million people, thus having a major impact on the global burden of liver diseases. Portal hypertension is the most severe complication of chronic liver diseases, including ascites, hepatic encephalopathy and bleeding from gastroesophageal varices. Transjugular intrahepatic portosystemic shunt (TIPS) represents a very effective treatment of these complications. Since its introduction 30 years ago in China, the use of TIPS has evolved and has played an increasingly important role in the management of the complications of portal hypertension. This review will focus on the history, current application and management of complications of TIPS in China.
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Affiliation(s)
- Yong Lv
- Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China.,Military Medical Innovation Center, Fourth Military Medical University, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, China
| | - Guohong Han
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, China
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22
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Cheng Y, Gu L, Yin X, Wang X, Xiao J, Wang Y, Zhang W, Wang L, Zou X, Zhang M, Zhuge Y, Zhang F. Agreement between Wedged Hepatic Venous Pressure and Portal Pressure in Hepatic Sinusoidal Obstruction Syndrome. J Pers Med 2022; 13:4. [PMID: 36675665 PMCID: PMC9865237 DOI: 10.3390/jpm13010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 12/09/2022] [Accepted: 12/18/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Wedge hepatic vein pressure (WHVP) accurately estimates the portal pressure (PP) in chronic sinusoidal portal hypertension patients. Whether this applies to patients with acute portal hypertension due to hepatic sinusoidal obstruction syndrome (HSOS) is unclear. Our aim was to assess the agreement between WHVP and PP in patients with HSOS by comparing them to decompensated cirrhosis patients. Methods: From December 2013 to December 2021, patients with pyrrolidine alkaloid-induced HSOS (PA-HSOS) receiving hepatic venous pressure gradient (HVPG) measurement and transjugular intrahepatic portosystem shunt (TIPS) were retrospectively collected and matched with those of patients with virus- or alcohol-related cirrhosis as a cirrhosis group. Pearson’s correlation (R), intraclass correlation coefficient (ICC), scatter plots, and the Bland−Altman method were performed for agreement evaluation. Results: A total of 64 patients were analyzed (30 PA-HSOS and 34 cirrhosis groups). The correlation between WHVP and PP was moderate in the PA-HSOS group (R: 0.58, p = 0.001; ICC: 0.68, p = 0.002) but good in the cirrhosis group (R: 0.81, p < 0.001; ICC: 0.90, p < 0.001). The percentage of patients with inconsistent WHVP and PP in the two groups was 13 (43.3%) and 15 (26.5%) (p = 0.156), respectively, and an overestimation of PP was more common in the PA-HSOS group (33.3% vs. 2.9%, p = 0.004). HVPG and portal pressure gradient (PPG) consistency was poor in both groups (R: 0.51 vs. 0.26; ICC: 0.65 vs. 0.41; p < 0.05). Conclusions: WHVP in patients with PA-HSOS did not estimate PP as accurately as in patients with virus- or alcohol-related cirrhosis, which was mainly due to PP overestimation.
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Affiliation(s)
- Yang Cheng
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing 210008, China
| | - Lihong Gu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Xiaochun Yin
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Xixuan Wang
- Department of Gastroenterology, Medical School of Southeast University Nanjing Drum Tower Hospital, Nanjing 210008, China
| | - Jiangqiang Xiao
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Yi Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Wei Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Lei Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Xiaoping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Ming Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing 210008, China
| | - Feng Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing 210008, China
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23
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Hepatic RNA adduction derived from metabolic activation of retrorsine in vitro and in vivo. Chem Biol Interact 2022; 365:110047. [DOI: 10.1016/j.cbi.2022.110047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 06/21/2022] [Accepted: 07/13/2022] [Indexed: 11/19/2022]
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Wang X, Zhang W, Zhang M, Zhang F, Xiao J, Yin Q, Han H, Li T, Lin G, Zhuge Y. Development of a Drum Tower Severity Scoring (DTSS) system for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Hepatol Int 2022; 16:669-679. [PMID: 35023026 PMCID: PMC9174127 DOI: 10.1007/s12072-021-10293-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 12/21/2021] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS There has been no reliable severity system based on the prognosis to guide therapeutic strategies for patients with pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS). We aimed to create a novel Drum Tower Severity Scoring (DTSS) system for these patients to guide therapy. METHODS 172 Patients with PA-HSOS who received supportive care and anticoagulation therapy in Nanjing Drum Tower Hospital from January 2008 to December 2020 were enrolled and analyzed retrospectively. These patients were randomized into a training or validation set in a 3:1 ratio. Next, we established and validated the newly developed DTSS system. RESULTS Analysis identified a predictive formula: logit (P) = 0.004 × aspartate aminotransferase (AST, U/L) + 0.019 × total bilirubin (TB, μmol/L) - 0.571 × fibrinogen (FIB, g/L) - 0.093 × peak portal vein velocity (PVV, cm/s) + 1.122. Next, we quantified the above variables to establish the DTSS system. For the training set, the area under the ROC curve (AUC) (n = 127) was 0.787 [95% confidence interval (CI) 0.706-0.868; p < 0.001]. With a lower cut-off value of 6.5, the sensitivity and negative predictive value for predicting no response to supportive care and anticoagulation therapy were 94.7% and 88.0%, respectively. When applying a high cut-off value of 10.5, the specificity was 92.9% and the positive predictive value was 78.3%. For the validation set, the system performed stable with an AUC of 0.808. CONCLUSIONS The DTSS system can predict the outcome of supportive care and anticoagulation in PA-HSOS patients with satisfactory accuracy by evaluating severity, and may have potential significance for guiding therapy.
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Affiliation(s)
- Xuan Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Wei Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Ming Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Feng Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Jiangqiang Xiao
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Qin Yin
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Hao Han
- Department of Ultrasound, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Taishun Li
- Medical Statistical Analysis Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
| | - Ge Lin
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008 Jiangsu China
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25
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Ma J, Zhang C, He Y, Chen X, Lin G. Fasting augments pyrrolizidine alkaloid-induced hepatotoxicity. Arch Toxicol 2022; 96:639-651. [PMID: 34792613 DOI: 10.1007/s00204-021-03193-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 11/04/2021] [Indexed: 12/16/2022]
Abstract
Pyrrolizidine alkaloids (PAs) are phytotoxins widely present in various natural products and foodstuffs. The present study aims to investigate the effects of fasting on PA-induced hepatotoxicity and the underlying biochemical mechanisms. The results of hepatotoxic study showed that 15-h overnight fasting significantly exacerbated the hepatotoxicity of retrorsine (RTS, a representative toxic PA) in fasted rats compared to fed rats, as indicated by remarkably elevated plasma ALT and bilirubin levels and obvious liver histological changes. Further toxicokinetic studies revealed that fasting significantly enhanced cytochromes P450 enzymes (CYPs)-mediated metabolic activation of RTS leading to increased formation of pyrrole-protein adducts and thus decreased the in vivo exposure and excretion of both parent RTS and its N-oxide metabolite. Metabolic studies demonstrated that fasting induced enzyme activities of CYP1A2, CYP2B6 and CYP2E1 that participated in catalyzing RTS to its reactive pyrrolic metabolites. Moreover, fasting also dramatically decreased hepatic glutathione (GSH) content, which restricted the detoxification of GSH by neutralizing the reactive pyrrolic metabolite of RTS, further contributing to the enhanced hepatotoxicity. The present findings may have an impact on future PA toxicity tests with different dietary styles and/or risk assessment of metabolite-mediated toxins by considering the profound effects of fasting.
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Affiliation(s)
- Jiang Ma
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Chunyuan Zhang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yisheng He
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Xinmeng Chen
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ge Lin
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
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26
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Tu H, Li M, Chen Z, Zhao J, Wang H, Qian J, Wei C, Yang Y, Zhu Y, Zuo L. Plateletcrit for predicting prognosis in patients with hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloid. J Clin Lab Anal 2022; 36:e24240. [PMID: 35034375 PMCID: PMC8841175 DOI: 10.1002/jcla.24240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/30/2021] [Accepted: 12/31/2021] [Indexed: 11/20/2022] Open
Abstract
Background Platelet index was reported to be used as a potential prognostic marker in patients with liver fibrosis. We aimed to explore the association between plateletcrit (PCT) and severity of hepatic sinusoidal obstruction syndrome (HSOS). Methods Seventy consecutive patients who diagnosed as HSOS by CT and medical history during January 2017‐November 2021 were included. All patients were divided into two groups which confirmed as favorable prognosis and poor prognosis on the basis of Child‐Turcotte‐Pugh score system. The clinical manifestation and laboratory parameters of two groups were retrospectively selected. PCT was evaluated within two groups, and the diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve. Results The significant difference between the two groups not only in diarrhea, abdominal pain, abdominal distention, urine volume, and skin ecchymosis (p < 0.005), but also in WBC count, NE count, PLT count, TBIL, and D‐Dimer (p < 0.005) were found. The PCT level was significantly higher in HSOS patients with poor prognosis (0.169Â ± 0.060) than favorable prognosis patients (0.110Â ± 0.047). The area under the receiver operating characteristic curve of RDW in predicting poor prognosis was 0.781, with 67.70% sensitivity and 79.5%specificity. Conclusions The PCT level was correlated positively with the poor prognosis in HSOS patients. PCT can be a promising indicator for predicting prognosis in HSOS
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Affiliation(s)
- Hongfei Tu
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Miao Li
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Zhiyuan Chen
- School of Medicine &Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiamin Zhao
- School of Medicine &Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Huali Wang
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jingjing Qian
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Cheng Wei
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yang Yang
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yue Zhu
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Lingyun Zuo
- Department of Gastroenterology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
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Wu F, Yu J, Gan H, Zhang H, Tian D, Zheng D. Timing and efficacy of transjugular intrahepatic portosystemic shunt in patients with pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Sci Rep 2021; 11:21743. [PMID: 34741082 PMCID: PMC8571302 DOI: 10.1038/s41598-021-01201-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/25/2021] [Indexed: 11/09/2022] Open
Abstract
There is no specific treatment for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). It is not clear when transjugular intrahepatic portosystemic shunt (TIPS) should be implemented in PA-HSOS patients. This study aimed to evaluate the timing of TIPS using total bilirubin (TBIL) as a measure, and to investigate efficacy of TIPS. We retrospectively analyzed the medical records of 10 PA-HSOS patients, among whom 4 patients had received TIPS (TIPS group), and the remaining patients were assigned to the internal medicine group. In the TIPS group, the TBIL level before TIPS was 84.4 ± 45.2 µmol/L (> 3 mg/dL), and TBIL levels were increased to different degrees after TIPS. With the extension of time, serum TBIL levels gradually decreased, and no liver failure occurred. With regards to the short-term outcomes, 3 patients recovered, 1 developed chronic illness and 0 died in the TIPS group. Moreover, 0 patients recovered, 5 developed chronic illness and 1 died in the internal medicine group. The rank sum test of group design revealed significant differences in clinical outcomes (P = 0.02). It was suggested that when the internal medicine effect of PA-HSOS patients is poor, TIPS should be considered, which is no trestricted to the limit of 3 mg/dL TBIL. It was also found TIPS effectively promote the recovery of liver function and reduce the occurrence of chronicity.
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Affiliation(s)
- Fan Wu
- Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Jiang'an District, Wuhan, 430014, Hubei, China
| | - Jiao Yu
- Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Jiang'an District, Wuhan, 430014, Hubei, China
| | - Hongying Gan
- Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Jiang'an District, Wuhan, 430014, Hubei, China
| | - Heng Zhang
- Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Jiang'an District, Wuhan, 430014, Hubei, China
| | - Deying Tian
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Dan Zheng
- Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Jiang'an District, Wuhan, 430014, Hubei, China.
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Barcelos STA, Dall'Oglio VM, de Araújo A, Cerski CTS, Álvares-da-Silva MR. Sinusoidal obstruction syndrome secondary the intake of Senecio brasiliensis: A case report. Ann Hepatol 2021; 20:100138. [PMID: 31606353 DOI: 10.1016/j.aohep.2019.08.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 08/13/2019] [Accepted: 08/14/2019] [Indexed: 02/04/2023]
Abstract
Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease histologically characterized by edema, necrosis, detachment of endothelial cells in small sinusoidal hepatic and interlobular veins and intrahepatic congestion, which leads to portal hypertension and liver dysfunction. In the Western world, most HSOS cases are associated with myeloablative pretreatment in a hematopoietic stem cell transplantation setting. Here we report a case of a 54 years old female patient, otherwise healthy, with no history of alcoholic ingestion, who presented with jaundice and signs of portal hypertension, including ascites and bilateral pleural effusion. She had no history of liver disease and denied any other risk factor for liver injury, except Senecio brasiliensis ingestion as a tea, prescribed as a therapy for menopause. Acute viral hepatitis and thrombosis of the portal system were excluded in complementary investigation, as well as sepsis, metastatic malignancy and other liver diseases, setting a RUCAM score of 6. Computed tomography demonstrated a diffuse liver parenchymal heterogeneity (in mosaic) and an extensive portosystemic collateral venous circulation, in the absence of any noticeable venous obstruction. HSOS diagnosis was confirmed through a liver biopsy. During the following-up period, patient developed refractory pleural effusion, requiring hemodialysis. Right before starting anticoagulation, she presented with abdominal pain and distention, with findings compatible of mesenteric ischemia by computed tomography. A laparotomy was performed, showing an 80cm segment of small bowel ischemia, and resection was done. She died one day after as a result from a septic shock refractory to treatment. The presented case was related to oral intake of S. brasiliensis, a plant containing pyrrolidine alkaloids, which are one of the main causes of HSOS in the East, highlighting the risk of liver injury with herbs intake.
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Affiliation(s)
- Samantha Thifani Alrutz Barcelos
- Hepatology Division, Hospital de Clinicas de Porto Alegre, Brazil; Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
| | | | | | - Carlos Thadeu Schmidt Cerski
- Pathology Division, Hospital de Clinicas de Porto Alegre, Brazil; School of Medicine, Universidade Federal do Rio Grande do Sul, Brazil; Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Mário Reis Álvares-da-Silva
- Hepatology Division, Hospital de Clinicas de Porto Alegre, Brazil; School of Medicine, Universidade Federal do Rio Grande do Sul, Brazil; Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
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Metabolic Toxification of 1,2-Unsaturated Pyrrolizidine Alkaloids Causes Human Hepatic Sinusoidal Obstruction Syndrome: The Update. Int J Mol Sci 2021; 22:ijms221910419. [PMID: 34638760 PMCID: PMC8508847 DOI: 10.3390/ijms221910419] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/09/2021] [Accepted: 09/14/2021] [Indexed: 12/15/2022] Open
Abstract
Saturated and unsaturated pyrrolizidine alkaloids (PAs) are present in more than 6000 plant species growing in countries all over the world. They have a typical heterocyclic structure in common, but differ in their potential toxicity, depending on the presence or absence of a double bond between C1 and C2. Fortunately, most plants contain saturated PAs without this double bond and are therefore not toxic for consumption by humans or animals. In a minority of plants, however, PAs with this double bond between C1 and C2 exhibit strong hepatotoxic, genotoxic, cytotoxic, neurotoxic, and tumorigenic potentials. If consumed in error and in large emouns, plants with 1,2-unsaturated PAs induce metabolic breaking-off of the double bonds of the unsaturated PAs, generating PA radicals that may trigger severe liver injury through a process involving microsomal P450 (CYP), with preference of its isoforms CYP 2A6, CYP 3A4, and CYP 3A5. This toxifying CYP-dependent conversion occurs primarily in the endoplasmic reticulum of the hepatocytes equivalent to the microsomal fraction. Toxified PAs injure the protein membranes of hepatocytes, and after passing their plasma membranes, more so the liver sinusoidal endothelial cells (LSECs), leading to life-threatening hepatic sinusoidal obstruction syndrome (HSOS). This injury is easily diagnosed by blood pyrrolizidine protein adducts, which are perfect diagnostic biomarkers, supporting causality evaluation using the updated RUCAM (Roussel Uclaf Causality Assessment Method). HSOS is clinically characterized by weight gain due to fluid accumulation (ascites, pleural effusion, and edema), and may lead to acute liver failure, liver transplantation, or death. In conclusion, plant-derived PAs with a double bond between C1 and C2 are potentially hepatotoxic after metabolic removal of the double bond, and may cause PA-HSOS with a potential lethal outcome, even if PA consumption is stopped.
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Chen X, Ma J, He Y, Xue J, Song Z, Xu Q, Lin G. Characterization of liver injury induced by a pyrrolizidine alkaloid in rats. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 89:153595. [PMID: 34153877 DOI: 10.1016/j.phymed.2021.153595] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/27/2021] [Accepted: 05/08/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Pyrrolizidine alkaloids (PAs) are common phytotoxins. PA intoxication is reported to cause severe acute liver damage, typically known as hepatic sinusoidal obstruction syndrome (HSOS), but it remains obscure whether the acute liver damage may progress into chronic liver disease characterized by hepatic fibrosis. PURPOSE This study aims to characterize the biochemical markers of liver injury and histological features of regressive and progressive liver fibrosis, and to examine changes in hepatic gene expression that may underpin mechanisms of fibrogenesis in rats induced by retrorsine (RTS), a representative toxic PA. STUDY DESIGN/METHODS Rats were gavaged with RTS via two dosing regimens, i.e. a single dose of 40 mg/kg (Group 1) and two doses of 40 mg/kg and 20 mg/kg on day 0 and day 7 (Group 2), respectively. Rats receiving one (Group 3) or two (Group 4) doses of vehicle served as negative controls. The animals were followed for up to 16 weeks by serum biochemical analyses and histological examination, and gene expression assays of liver tissues. RESULTS Acute liver injury on day 2 manifested as HSOS, characterized by sinusoidal dilation, endothelial cell damage, and elevated serum alanine aminotransferase activity and bilirubin levels. In Group 1, mild liver fibrosis developed at sinusoids and perisinusoidal space surrounding the central veins at week 1 and 2, and thereafter, all liver injury resolved gradually. In Group 2, liver fibrosis progressed within the 16-week observation period. No apparent liver injury was observed in Groups 3 and 4. Compared with negative control groups, RTS induced myofibroblastic activation, TGF-β1 signaling, and changes in expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). These dynamic changes differed in Groups 1 and 2, corresponding with the regression and progression of liver fibrosis, respectively, in these groups. CONCLUSION This study has provided in-vivo proof of concept that "one hit" and "two hits" of RTS lead to acute resolving liver injury and chronic progressive liver fibrosis, respectively. These animal models may serve as powerful tools for studying RTS toxicology and related preventive and therapeutic strategies and as positive controls for studying other PA- and non-PA-induced liver injury.
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Affiliation(s)
- Xinmeng Chen
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Jiang Ma
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yisheng He
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Junyi Xue
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Zijing Song
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Qihe Xu
- Renal Sciences and Integrative Chinese Medicine Laboratory, Department of Inflammation Biology, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
| | - Ge Lin
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
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Tu-San-Qi (Gynura japonica): the culprit behind pyrrolizidine alkaloid-induced liver injury in China. Acta Pharmacol Sin 2021; 42:1212-1222. [PMID: 33154553 PMCID: PMC8285480 DOI: 10.1038/s41401-020-00553-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/05/2020] [Indexed: 02/07/2023]
Abstract
Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu-San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu-San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.
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He Y, Zhang W, Ma J, Xia Q, Song Z, Zhu L, Zhang C, Liu J, Ye Y, Fu PP, Zhuge Y, Lin G. Blood Pyrrole–DNA Adducts Define the Early Tumorigenic Risk in Patients with Pyrrolizidine Alkaloid-Induced Liver Injury. ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS 2021; 8:551-557. [DOI: 10.1021/acs.estlett.1c00359] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2024]
Affiliation(s)
- Yisheng He
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR 999077, China
| | - Wei Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University School of Medicine, Nanjing 210008, China
| | - Jiang Ma
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR 999077, China
| | - Qingsu Xia
- National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States
| | - Zijing Song
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR 999077, China
| | - Lin Zhu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR 999077, China
| | - Chunyuan Zhang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR 999077, China
| | - Jia Liu
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, China Academy of Sciences, Shanghai 201203, China
| | - Yang Ye
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, China Academy of Sciences, Shanghai 201203, China
| | - Peter P. Fu
- National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University School of Medicine, Nanjing 210008, China
| | - Ge Lin
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR 999077, China
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Zhang W, Liu L, Zhang M, Zhang F, Peng C, Zhang B, Chen J, Li L, He J, Xiao J, Feng Y, Wang X, Xiong A, Yang L, Zou X, Yu Y, Zhuge Y. Validation of the Nanjing Criteria for Diagnosing Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstruction Syndrome. J Clin Transl Hepatol 2021; 9:345-352. [PMID: 34221920 PMCID: PMC8237138 DOI: 10.14218/jcth.2020.00124] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/31/2021] [Accepted: 03/08/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury to sinusoidal endothelial cells in the liver. The intake of pyrrolizidine alkaloids (PAs) in some Chinese herbal remedies/plants remains the major etiology for HSOS in China. Recently, new diagnostic criteria for PA-induced HSOS (i.e. PA-HSOS) have been developed; however, the efficacy has not been clinically validated. This study aimed to assess the performance of the Nanjing criteria for PA-HSOS. METHODS Data obtained from consecutive patients in multiple hospitals, which included 86 PA-HSOS patients and 327 patients with other liver diseases, were retrospectively analyzed. Then, the diagnostic performance of the Nanjing criteria and simplified Nanjing criteria were evaluated and validated. The study is registered in www.chictr.org.cn (ID: ChiCTR1900020784). RESULTS The Nanjing criteria have a sensitivity and specificity of 95.35% and 100%, respectively, while the simplified Nanjing criteria have a sensitivity and specificity of 96.51% and 96.33%, respectively, for the diagnosis of PA-HSOS. Notably, a proportion of patients with Budd-Chiari syndrome (11/49) was misdiagnosed as PA-HSOS on the basis of the simplified Nanjing criteria, and this was mainly due to the overlapping features in the enhanced computed tomography/magnetic resonance imaging examinations. Furthermore, most of these patients (10/11) had occlusion or thrombosis of the hepatic vein, and communicating vessels in the liver were found in 8/11 patients, which were absent in PA-HSOS patients. CONCLUSIONS The Nanjing criteria and simplified Nanjing criteria exhibit excellent performance in diagnosing PA-HSOS. Thus, both could be valuable diagnostic tools in clinical practice.
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Affiliation(s)
- Wei Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Lu Liu
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Department of Gastroenterology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ming Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Feng Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Chunyan Peng
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Bin Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jun Chen
- Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Lin Li
- Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jian He
- Department of Imaging, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jiangqiang Xiao
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Yanhong Feng
- Department of Hepatology, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xunjiang Wang
- The Ministry of Education Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Aizhen Xiong
- The Ministry of Education Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Li Yang
- The Ministry of Education Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoping Zou
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Yuecheng Yu
- Liver Diseases Center of PLA and Department of Infectious Diseases, General Hospital of Eastern Theater Command, and Bayi Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
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Xiao J, Tu J, Zhang H, Zhang F, Zhang W, Xu H, Yin Q, Yang J, Han H, Wang Y, Zhang B, Peng C, Zou X, Zhang M, Zhuge Y. Risk factors of poor prognosis in patients with pyrrolidine alkaloid-induced hepatic sinusoidal obstruction syndrome after transjugular intrahepatic portosystemic shunt. Hepatol Int 2021; 15:720-729. [PMID: 33507485 DOI: 10.1007/s12072-020-10126-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 12/19/2020] [Indexed: 11/09/2022]
Abstract
AIMS Transjugular intrahepatic portosystemic shunt (TIPS) is an effective method in treating patients with severe hepatic sinusoidal obstruction syndrome induced by pyrrolidine alkaloids (PA-HSOS). However, some patients still have poor postoperative prognosis. So, we aim to evaluate the predictors associated with poor outcomes in PA-HSOS patients receiving TIPS. METHODS Patients who were diagnosed as PA-HSOS and received TIPS in our hospital between January 2013 and April 2019 were reviewed retrospectively. Baseline information and clinical data were collected. The hazard ratios (HRs) of factors associated with poor prognosis were analyzed by Cox proportional hazard analysis. The Kaplan-Meier method was used to analyze and compare the cumulative incidence of the poor results and survival rate of patients. RESULTS During a median of 19.25-month follow-up, death occurred in 17 patients. We found that prothrombin time at baseline with an adjusted HR 1.110 (95% confidence interval 1.014-1.216, p = 0.024) and serum total bilirubin of 9 mg/dl 5 days after TIPS with an adjusted HR 1.114 (95% confidence interval 1.042-1.190, p = 0.001) were independent risk factors for death. The 1-year and 5-year survival rate were 86.2% and 82.1%, respectively. The 1-year survival rate in patients with prothrombin time > 17.85 s at baseline and serum total bilirubin > 9 mg/dl at 5 days after TIPS was significantly lower than that of patients below the corresponding threshold, respectively. CONCLUSIONS Prolonged prothrombin time at baseline and increased serum total bilirubin levels 5 days after TIPS are independent risk factors for predicting death after TIPS treatment in PA-HSOS patients.
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Affiliation(s)
- Jiangqiang Xiao
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Jingjing Tu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Han Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, China
| | - Feng Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Wei Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Hui Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Qin Yin
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Jian Yang
- Department of Ultrasound, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Hao Han
- Department of Ultrasound, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Yi Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Bin Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Chunyan Peng
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Xiaoping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Ming Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321#, Zhongshan Road, Nanjing, 210008, Jiangsu, China.
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He Y, Zhu L, Ma J, Lin G. Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids. Arch Toxicol 2021; 95:1917-1942. [PMID: 34003343 DOI: 10.1007/s00204-021-03060-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023]
Abstract
Pyrrolizidine alkaloids (PAs) and PA N-oxides are common phytotoxins produced by over 6000 plant species. Humans are frequently exposed to PAs via ingestion of PA-containing herbal products or PA-contaminated foods. PAs require metabolic activation to form pyrrole-protein adducts and pyrrole-DNA adducts which lead to cytotoxicity and genotoxicity. Individual PAs differ in their metabolic activation patterns, which may cause significant difference in toxic potency of different PAs. This review discusses the current knowledge and recent advances of metabolic pathways of different PAs, especially the metabolic activation and metabolism-mediated cytotoxicity and genotoxicity, and the risk evaluation methods of PA exposure. In addition, this review provides perspectives of precision toxicity assessment strategies and biomarker development for the risk control and translational investigations of human intoxication by PAs.
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Affiliation(s)
- Yisheng He
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Lin Zhu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Jiang Ma
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Ge Lin
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.
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Cen P, Ding J, Jin J. Hepatic sinusoidal obstruction syndrome caused by the ingestion of Gynura segetum in a patient with alcoholic cirrhosis: a case report. J Int Med Res 2021; 49:300060520980649. [PMID: 33845617 PMCID: PMC8047090 DOI: 10.1177/0300060520980649] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Hepatic sinusoidal obstruction syndrome (HSOS) is a rare hepatic vascular disorder characterized by intrahepatic congestion, liver injury, and post-sinusoidal portal hypertension, and it is frequently associated with hematopoietic stem cell transplantation. In this study, we observed a case of HSOS associated with the ingestion of Gynura segetum, a pyrrolizidine alkaloid (PA)-containing Chinese herb, in a patient with alcoholic cirrhosis. The patient was a 43-year-old man with chief complaints of physical asthenia and a loss of appetite for more than a month. The diagnosis of HSOS combined with alcoholic cirrhosis was confirmed via the histopathological examination of liver tissues. With proper supportive and symptomatic care and anticoagulation therapy using low-molecular-weight heparin, the patient’s condition was stabilized. Because of its nonspecific symptoms in the early stage and a lack of information about PA consumption, PA-induced HSOS (PA-HSOS) has been long neglected, especially in patients with underlying liver diseases. Early identification and intervention are critical for optimizing outcomes. Further efforts are needed to supervise the use of PA-containing herbal medicines and identify accurate biomarkers for PA-HSOS.
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Affiliation(s)
- Panpan Cen
- Department of Infectious Diseases, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Jiexia Ding
- Department of Infectious Diseases, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Jie Jin
- Department of Infectious Diseases, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
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Yang X, Lei P, Song Y, Fei Z, Ai Y, Shang H, Bai T, Ye J, Li X. Quantitative CT assessment by histogram and volume ratio in pyrrolizidines alkaloids-induced hepatic sinusoidal obstruction syndrome. Eur J Radiol 2021; 138:109632. [PMID: 33711570 DOI: 10.1016/j.ejrad.2021.109632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 02/22/2021] [Accepted: 03/02/2021] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To quantitatively assess hypoattenuation volume ratio and hepatic parenchymal hypoattenuation on contrast enhanced computed tomography (CECT) in patients with pyrrolizidines alkaloids (PAs)-induced hepatic sinusoidal obstruction syndrome (HSOS), and evaluate the correlations of the CT-based quantitative values with clinical factors. METHODS Thirty-five patients with PAs-induced HSOS who underwent CECT were retrospectively enrolled. The ratio of hypoattenuation volume to total liver volume, and changes in damaged area-to-normal liver density ratio (ΔDR) derived from histogram on portal venous phase were quantitatively measured. Heterogeneous hypoattenuation (CT score) scored by hypoattenuation volume ratio and ΔDR were calculated. The correlation between imaging findings and clinical factors was analyzed using Pearson correlation test. RESULTS Liver function tests were abnormal in most patients, the mean Hounsfield unit (HU) of damaged area (58.68 ± 17.3) was significantly lower (P < 0.001) than the corresponding normal liver (82.27 ± 23.97). Heterogeneous hypoattenuation were mild in 13 patients (37 %), moderate in 16 patients (46 %), and severe in 6 patients (17 %). ΔDR derived from histogram was positively correlated (weakly to moderately) with total bilirubin (r = 0.341, P = 0.045), direct bilirubin (r = 0.385, P = 0.022), and alkaline phosphatase (r = 0.491, P = 0.003), while such correlation was not observed in hypoattenuation volume ratio. The severity of heterogeneous hypoattenuation scored by hypoattenuation volume ratio and ΔDR was positively correlated (weakly) with prothrombin time (r = 0.357, P = 0.035), international normalized ratio (r = 0.363, P = 0.032), alkaline phosphatase (r = 0.359, P = 0.034), and model for end-stage liver disease (MELD) score (r = 0.347, P = 0.041). CONCLUSION Heterogeneous hypoattenuation scored by volume ratio and ΔDR on CECT provides a non-invasive approach in evaluating the severity of PAs-induced HSOS.
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Affiliation(s)
- Xiaoqian Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ping Lei
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yuhu Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhenyu Fei
- Siemens Shanghai Medical Equipment Ltd., Shanghai, 201318, China
| | - Yan Ai
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Haitao Shang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Bai
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jin Ye
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Xin Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Magaz M, García-Pagán JC. Risk factors of poor prognosis in patients with pyrrolidine alkaloids induced hepatic sinusoidal obstruction syndrome after transjugular intrahepatic portosystemic shunt : Transjugular intrahepatic portosystemic shunt in patients with sinusoidal obstruction syndrome, etiology matters. Hepatol Int 2021; 15:568-570. [PMID: 33733320 DOI: 10.1007/s12072-021-10166-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 02/22/2021] [Indexed: 11/28/2022]
Affiliation(s)
- Marta Magaz
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital ClínicInstitut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.,CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas Y Digestivas), Barcelona, Spain.,Health Care Provider of the European Reference Network On Rare Liver Disorders (ERN-Liver), Paris, France
| | - Juan Carlos García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital ClínicInstitut de Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, 08036, Barcelona, Spain. .,CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas Y Digestivas), Barcelona, Spain. .,Health Care Provider of the European Reference Network On Rare Liver Disorders (ERN-Liver), Paris, France.
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Zhang W, Peng C, Zhang S, Huang S, Shen S, Xu G, Zhang F, Xiao J, Zhang M, Zhuge Y, Wang L, Zou X, Lv Y. EUS-guided portal pressure gradient measurement in patients with acute or subacute portal hypertension. Gastrointest Endosc 2021; 93:565-572. [PMID: 32615178 DOI: 10.1016/j.gie.2020.06.065] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 06/21/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS EUS-guided portal pressure gradient (EUS-PPG) measurement is a novel method to evaluate portal hypertension severity. In this study, we determined the consistency between EUS-PPG and hepatic venous pressure gradient (HVPG) measurements in patients with acute or subacute portal hypertension. METHODS Twelve patients were prospectively enrolled. EUS-PPG measurements were performed using a 22-gauge FNA needle and a central venous pressure measurement monitor. The HVPG measurements were performed using the transjugular approach. If an HVPG measurement was not attainable and the patient underwent transjugular intrahepatic portosystemic shunt (TIPS) treatment, a PPG was recorded as a reference standard during the procedure. We assessed the feasibility and safety of EUS-PPG and calculated the correlation between the 2 measurements. RESULTS EUS-PPG measurements were successful in 11 patients (91.7%). Subsequent HVPG measurements failed in 2 patients with Budd-Chiari syndrome (hepatic vein occlusion subtype), 1 of whom underwent TIPS treatment to obtain transjugular PPG data. A small shunt was found during 1 HVPG measurement that introduced inaccuracy. Nine patients were included in the statistical analysis. Mean EUS-PPG and HVPG/PPG (transjugular) were 18.07 ± 4.32 mm Hg and 18.82 ± 3.43 mm Hg, respectively. Pearson's correlation coefficient between the 2 methods was .923 (P < .001). CONCLUSIONS EUS-PPG measurement using a 22-gauge FNA needle was a safe and accurate method to evaluate portal hypertension and has the potential to supplement the measurement of HVPG in liver diseases. (Clinical trial registration number: ChiCTR1800017317.).
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Affiliation(s)
- Wei Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Chunyan Peng
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Song Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Shuling Huang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Shanshan Shen
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Guifang Xu
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Feng Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jiangqiang Xiao
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Ming Zhang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Lei Wang
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoping Zou
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Ying Lv
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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Zhang L, Li Q, Makamure J, Zhao D, Liu Z, Zheng C, Liang B. Transjugular intrahepatic portosystemic shunt for hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum. BMC Gastroenterol 2021; 21:26. [PMID: 33423668 PMCID: PMC7798314 DOI: 10.1186/s12876-021-01599-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 01/01/2021] [Indexed: 12/03/2022] Open
Abstract
Background To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic sinusoidal obstruction syndrome (HSOS) associated with consumption of Gynura segetum (GS). Methods We retrospectively reviewed 9 consecutive patients with GS-related HSOS who were refractory to supportive treatment and underwent TIPS at our institution between January 2014 and September 2019. The patients were evaluated for safety and efficacy, including TIPS complications and changes in portosystemic pressure gradient (PPG), ascites, total bilirubin, liver size and portal vein diameter. Results TIPS procedures were performed successfully in the 9 patients, and no technically-related complications due to the TIPS procedure were recorded. The PPG was improved by TIPS in all patients (mean PPG before TIPS, 30.4 ± 5.2 vs. 13.0 ± 4.1 mm Hg post-TIPS, P = 0.008). One patient who was lost to follow-up, whereas the remaining 8 patients survived with a median follow-up period of 12 months (range 5–39 months). Although the total bilirubin was significantly increased 5–7 days after TIPS compared with that before the procedure (3.57 ± 1.58 vs. 4.82 ± 2.06 mg/dl, P = 0.017), it returned to baseline levels at 1-month follow-up (3.53 ± 2.72 vs. 4.82 ± 2.06 mg/dl, P = 0.401). The patients experienced complete resolution or noticeable reduction of ascites (P < 0.001), significant reduction of liver size (16.7 ± 2.2 vs. 13.7 ± 1.7 cm, P = 0.018), and significant enlargement of the portal trunk (10.7 ± 2.5 vs. 13.4 ± 2.4 mm, P = 0.017) after TIPS compared to the pre-TIPS state. Conclusion TIPS may offer a potentially useful treatment for the GS-related HSOS.
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Affiliation(s)
- Lijie Zhang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China
| | - Qing Li
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China
| | - Joyman Makamure
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China
| | - Dan Zhao
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China
| | - Ziyi Liu
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China
| | - Bin Liang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China.
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Shang H, Bai T, Zhu S, Yang X, Liu C, Xu D, Zhuge Y, Song Y, Hou X. Prognostic factors for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: a multicenter study in China. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:11. [PMID: 33553304 PMCID: PMC7859749 DOI: 10.21037/atm-20-731] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 09/29/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND In China, one of the major causes of hepatic sinusoidal obstruction syndrome (HSOS) is the intake of herbals containing pyrrolizidine alkaloid (PA). However, prognostic factors for PA-induced HSOS are poorly understood. The aim of this study was to identify the independent prognostic factors for PA-induced HSOS using a multi-center study. METHODS A total of 117 PA-induced HSOS patients were enrolled for data collection in three university hospitals from November 2003 to September 2018. Univariate and multivariate Cox proportional hazards analysis were used to determine prognostic factors for PA-induced HSOS. RESULTS The median age of the PA-induced HSOS patients was 61 years (range, 21-88 years), and 64% of them were male. The survival rates at 1, 3, and 36 months were 89.71%, 72.60%, and 69.19%, respectively. Significant differences in prothrombin time (PT), international normalized ratio, total bilirubin, severity grading [new criteria for severity grading of hematopoietic stem cell transplantation (HSCT)-related HSOS in adults] were found between patients who survived and those who died. Univariate and multivariate survival analysis using Cox's regression model demonstrated low serum albumin (<35 g/L), elevated serum urea (>8.2 mmol/L) and severe or very severe HSOS (European Society for Blood and Marrow Transplantation 2016 criteria) were independent prognostic factors of survival. CONCLUSIONS Serum albumin, serum urea, and severity grading were independent prognostic factors for patients with PA-induced HSOS, and can contribute to identifying potentially high-risk patients for early effective intervention. TRIAL REGISTRATION ChiCTR-DRD-17010709 (www.chictr.org.cn).
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Affiliation(s)
- Haitao Shang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Bai
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shenghua Zhu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoqian Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chang Liu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dong Xu
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Yuhu Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Zhu TY, Zhou GH, Chen XH, Teng XD, Sun JH. Hepatic veno-occlusive disease may be a rare characteristic of hepatic involvement in systemic amyloidosis: case report and literature review. J Int Med Res 2020; 48:300060520904857. [PMID: 32090649 PMCID: PMC7110914 DOI: 10.1177/0300060520904857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Systemic amyloidosis is a rare disease and patients with hepatic amyloidosis often present with hepatomegaly. Hepatomegaly can also be a feature of hepatic veno-occlusive disease (HVOD). We report here a case of systemic amyloidosis in a patient who was suspected of having HVOD. On the basis of computed tomography findings in the abdomen, HVOD was initially suspected in a 63-year-old man with the chief complaint of upper abdominal pain, ascites, and weight loss. Multiple patchy purpura and nerve symptoms were identified and these were due to amyloidosis. An increase in proteinuria and immunoglobulin κ light-chain levels, and thickening of the ventricular wall supported the diagnosis of systemic light-chain amyloidosis involving the liver, heart, kidney, skin, and nerves. This diagnosis was confirmed by histological examination of a bone marrow core biopsy with Congo red dye. Sequential treatment of bortezomib and dexamethasone led to good results in the patient. Findings of this rare case indicate that HVOD can be diagnosed without a definite history of hematopoietic stem cell transplantation or pyrrolizidine alkaloid ingestion, but more evidence is required to make an accurate diagnosis. Importantly, we speculate that HVOD is a rare characteristic of liver involvement in systemic amyloidosis.
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Affiliation(s)
- Tong-Yin Zhu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.,Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
| | - Guan-Hui Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.,Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
| | - Xin-Hua Chen
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.,Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
| | - Xiao-Dong Teng
- Division of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun-Hui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.,Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
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Jiang M, Wang L, Du X, Hao M, Gao P. Low molecular weight heparin in the treatment of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome: five case reports. J Int Med Res 2020; 48:300060520961916. [PMID: 32993424 PMCID: PMC7536489 DOI: 10.1177/0300060520961916] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of
pyrrolizidine alkaloids (PAs). The disease has a high mortality rate, a poor
prognosis and limited treatment options. Managing pyrrolizidine alkaloid-induced
hepatic sinusoidal obstruction syndrome (PA-HSOS) is a significant challenge for
hepatologists. This case report describes five patients with PA-HSOS that were
treated with low molecular weight heparin (LMWH) between 2014 and 2019. All five
patients had a history of taking PA-containing herbal preparations before the
onset of the disease. They all met the Nanjing diagnostic criteria and were
diagnosed with PA-HSOS. Symptomatic treatment was administered to all five
patients. In addition to symptomatic treatment, all five patients were treated
with LMWH for approximately 8–21 days. After treatment, their ascites
disappeared, symptoms improved and the hepatic venous blood flow had improved
compared with before treatment. There was no obvious discomfort during the 6
months of follow-up. LMWH may play a useful role in the early treatment of
PA-HSOS. Therefore, for patients in the early stages of PA-HSOS, in addition to
symptomatic treatment, early anticoagulant intervention can be attempted to
improve patient prognosis under close monitoring of coagulation.
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Affiliation(s)
- Minjie Jiang
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Luyuan Wang
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Xiaodong Du
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Miaomiao Hao
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Pujun Gao
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China
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Peng C, Zhang X, Zhang F, Liu L, Shao Y, Xiang X, Zhang W, Xiao J, Wang Y, Zhang B, Yin Q, Song Y, Mo Z, Zou X, Zhang M, Zhuge Y. Clinical efficacy and safety of anticoagulation therapy for Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: a retrospective multicenter cohort study. Eur J Gastroenterol Hepatol 2020; 32:1168-1178. [PMID: 31834055 DOI: 10.1097/meg.0000000000001630] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
AIM Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome(PA-HSOS) has been reported to have high mortality. We evaluated the efficacy and safety of anticoagulation therapy for the patients with PA-HSOS. METHODS We collected clinical data on 249 PA-HSOS patients from January 2012 to December 2017 at four tertiary care hospitals. Among them, 151 patients received anticoagulation therapy, and 98 patients received supportive treatment. The outcomes were analyzed using the Fine and Gray competing risk analysis method and Cox regression model. RESULTS The cumulative complete response rate was higher in the anticoagulation group than in the supportive group (60.9 vs 36.7%; P < 0.0001). The cumulative mortality was 12.6% in the anticoagulation group compared with 43.9% in the supportive group (P < 0.0001). In subgroup analysis, for mild, moderate, severe, and very severe groups, the adjusted hazard ratios [95% confidence interval (CI)] for complete response rates were 7.05 (3.00-16.59), 5.26 (2.31-12.42), 2.59 (0.85-7.87), and 2.05 (0.61-6.92), respectively; and the adjusted hazard ratios (95% CI) for mortalities were 0.02 (0.01-0.09), 0.04 (0.01-0.14), 0.19 (0.01-3.98), and 0.07 (0.02-1.27), respectively (P < 0.0001). There was no significant difference between both groups in the incidence of bleeding events (P = 0.674). CONCLUSIONS Anticoagulation therapy improves clinical remission and the survival in selected patients with mild or moderate PA-HSOS. Anticoagulation therapy has a similar safety profile to supportive therapy.
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Affiliation(s)
- Chunyan Peng
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Xiaofeng Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Feng Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Longgen Liu
- Department of Hepatology, Changzhou Third People's Hospital, Changzhou
| | - Youlin Shao
- Department of Hepatology, Changzhou Third People's Hospital, Changzhou
| | - Xiaoxing Xiang
- Department of Gastroenterology, the Northern Jiangsu People's Hospital, Yangzhou
| | - Wei Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Jiangqiang Xiao
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Yi Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Bin Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Qin Yin
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Yuhu Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Zhe Mo
- Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Xiaoping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Ming Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
| | - Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing
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Lu Y, Wong KY, Tan C, Ma J, Feng B, Lin G. Establishment of a novel CYP3A4-transduced human hepatic sinusoidal endothelial cell model and its application in screening hepatotoxicity of pyrrolizidine alkaloids. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART C, TOXICOLOGY AND CARCINOGENESIS 2020; 38:169-185. [PMID: 32469285 DOI: 10.1080/26896583.2020.1769409] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Pyrrolizidine alkaloids (PAs) are extensively distributed in plants and are known to damage hepatic sinusoidal endothelial cells (HSECs) via metabolic activation mediated by hepatic cytochrome P450 enzymes (CYPs), particularly the CYP3A4 isozyme. Different PAs have distinct toxic potencies and their toxic effects on HSECs are difficult to be determined in cultured cells, because HSECs lack the key CYP3A4 isozyme for metabolic activation. This study aims to establish a novel, convenient and reliable CYP3A4-expressing HSEC model using human HSECs transduced with lentivirus carrying CYP3A4-ires-eGFP, for evaluating the hepatotoxicity of different PAs on their target HSECs. The developed CYP3A4-expressing HSEC (HSEC-CYP3A4) model was verified by the expression of GFP and CYP3A4 and by the ability to metabolize nifedipine, a classic CYP3A4 substrate. Treated with retrorsine, a representative toxic PA, HSEC-CYP3A4 cells showed significantly reduced cell viability, depletion of GSH, and increased formation of pyrrole-protein adducts. Furthermore, this newly developed cell model successfully discriminated the cytotoxic potency of different PAs evidenced by their IC40 values. In conclusion, the established HSEC-CYP3A4 cell model can be used as a rapid screening platform for assessing the relative potencies of individual PAs on their target HSECs and for investigating the mechanisms underlying PA-induced hepatic sinusoidal damage.
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Affiliation(s)
- Yao Lu
- School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR
| | - Ka Yan Wong
- School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR
| | - Chunlai Tan
- School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR
| | - Jiang Ma
- School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR
| | - Bo Feng
- School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR
| | - Ge Lin
- School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR
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Xu J, Wang W, Yang X, Xiong A, Yang L, Wang Z. Pyrrolizidine alkaloids: An update on their metabolism and hepatotoxicity mechanism. LIVER RESEARCH 2019. [DOI: 10.1016/j.livres.2019.11.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
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EASL Clinical Practice Guideline: Occupational liver diseases. J Hepatol 2019; 71:1022-1037. [PMID: 31540728 DOI: 10.1016/j.jhep.2019.08.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 08/12/2019] [Indexed: 12/15/2022]
Abstract
A variety of chemicals have been linked to occupational liver diseases, including several solvents and mixtures thereof, pesticides, and metals. Workplace exposures have been associated with virtually the entire spectrum of acute and chronic liver diseases. However, their prevalence is inadequately quantified and their epidemiology limited. Occupational liver diseases may result from high accidental or from prolonged lower level exposures. Whereas the former is uncommon and easily recognised, the latter are relatively more frequent but often overlooked because they may display normal values of conventional markers, have an insidious onset and be asymptomatic or be obfuscated and confounded by concurrent conditions. In addition, specific tests of toxicity are not available, histopathology may not be revealing and the assessment of internal dose of chemicals is usually not decisive. Given these circumstances, the diagnosis of these liver disorders is challenging, one of exclusion and often requires an interdisciplinary approach. These recommendations offer a classification of the type of liver injuries associated with occupational exposures - based in part on the criteria for drug-induced liver injury - a grading of their severity, and the diagnostic and preventive criteria for chemically induced occupational liver disease.
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Yang XQ, Ye J, Li X, Li Q, Song YH. Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis, treatment, and outcomes. World J Gastroenterol 2019; 25:3753-3763. [PMID: 31391770 PMCID: PMC6676551 DOI: 10.3748/wjg.v25.i28.3753] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 06/05/2019] [Accepted: 06/25/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.
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Affiliation(s)
- Xiao-Qian Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Jin Ye
- Division of Gastroenterology, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xin Li
- Department of Radiology, Union Hospital, Tongji Medical college, Huazhong University of Science and technology, Wuhan 430022, Hubei Province, China
| | - Qian Li
- Department of Radiology, Union Hospital, Tongji Medical college, Huazhong University of Science and technology, Wuhan 430022, Hubei Province, China
| | - Yu-Hu Song
- Division of Gastroenterology, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Zhuge Y, Liu Y, Xie W, Zou X, Xu J, Wang J. Expert consensus on the clinical management of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. J Gastroenterol Hepatol 2019; 34:634-642. [PMID: 30669184 DOI: 10.1111/jgh.14612] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 12/28/2018] [Accepted: 01/17/2019] [Indexed: 02/06/2023]
Abstract
Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease presenting with abdominal distension, pain in the hepatic region, ascites, jaundice, and hepatomegaly. In China, this disease is often associated with the oral intake of plants that contain pyrrolidine alkaloids. The existing guidelines are limited to HSOS associated with hematopoietic stem cell transplantation in Western countries. The Hepatobiliary Diseases Committee of the Chinese Society of Gastroenterology convened an expert consensus conference on the diagnosis and treatment of PA-HSOS to evaluate current research in China and abroad. The "Nanjing criteria" developed by the committee to diagnose PA-HSOS include a confirmed history of PA-containing plant use and (i) abdominal distention and/or pain in the hepatic region, hepatomegaly, and ascites; (ii) elevation of serum total bilirubin or abnormal laboratory liver tests; (iii) evidence on enhanced computed tomography or magnetic resonance imaging; or (iv) pathological evidence that rules out other known causes of liver injury. Supportive symptomatic treatment, anticoagulant therapy, and placement of a transjugular intrahepatic portosystemic shunt for patients who do not respond to medical treatment are effective for the treatment of PA-HSOS. The benefits of glucocorticoids and prostaglandin E1 in PA-HSOS are not clear.
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Affiliation(s)
- Yuzheng Zhuge
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated to Nanjing University Medical School, Nanjing, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
| | - Weifen Xie
- Department of Gastroenterology, Changzheng Hospital of the Second Military Medical University, Shanghai, China
| | - Xiaoping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated to Nanjing University Medical School, Nanjing, China
| | - Jianming Xu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui University, Anhui, China
| | - Jiyao Wang
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China
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Quantitative Analysis of CT Images in Patients with Pyrrolizidine Alkaloid-Induced Sinusoidal Obstruction Syndrome. Sci Rep 2019; 9:2179. [PMID: 30778132 PMCID: PMC6379399 DOI: 10.1038/s41598-019-38669-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 01/04/2019] [Indexed: 12/28/2022] Open
Abstract
This study evaluated hepatic lesion volumes on contrast-enhanced computed tomography (CT) images in patients with pyrrolizidine alkaloid-induced sinusoidal obstruction syndrome (PA-SOS) and the association of lesion volume with the clinical severity and prognosis of the disease. Twenty-five patients with PA-SOS were included in this study, and all patients were subjected to a complete CT imaging series. The imaging results were quantitatively analyzed by a threshold-based region growing algorithm. The liver volumes and hepatic lesion volumes of the patients were estimated. Based on clinical presentations, PA-SOS was classified into three categories: mild, moderate and severe. The associations of hepatic lesion volumes with liver function test parameters and the clinical severity and prognosis of the disease were analyzed. Based on estimations using the threshold-based region growing algorithm, hepatic lesion volumes in patients with mild PA-SOS were significantly lower than those in patients with moderate and severe PA-SOS (P < 0.05). The ratio of hepatic lesion volume to liver volume (Ratio) varied based on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum total bilirubine levels; clinical severity; and disease prognosis, and the differences were statistically significant (P < 0.05). In conclusion, the threshold-based region growing algorithm can be employed to quantitatively analyze enhanced CT images of PA-SOS patients. And the ratio of hepatic lesion volume to liver volume in patients with PA-SOS is associated with a more serious clinical course and a poorer outcome.
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