Anticoagulant therapy and transjugular intrahepatic portosystemic shunt for pyrrolizidine alkaloid related hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

Hepatic sinusoidal obstruction syndrome (HSOS) is a vascular liver disease characterized by varying degrees of liver injury and portal hypertension. HSOS in China is mostly associated with the intake of pyrrolizidine alkaloids. The step-up approach with anticoagulant therapy and transjugular intrahepatic portosystemic shunt (TIPS) as the core treatment methods is the therapy currently recommended for this disease. Subcutaneous injection of low-molecular-weight heparin is the first choice for anticoagulant therapy, and oral warfarin can be used in combination or sequentially to enhance anticoagulation. Patients with no response to anticoagulant therapy can switch to TIPS. The Drum Tower Severity Score (DTSS) system can be used during treatment to evaluate the severity of the disease, in order to identify high-risk patients earlier and switch to TIPS in time, thereby improving the prognosis of patients.

Research advances in the pathogenesis of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

Pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) is a type of hepatic sinusoidal obstruction syndrome mainly caused by the intake of Chinese herbal medicine or food containing pyrrolizidine alkaloids. This article reviews the recent research advances in the mechanism of action of pyrrolizidine alkaloids and their metabolites in disease development and progression from the aspects of drug factors, host factors, and influencing factors. It is pointed out that PA-HSOS has complex pathogenesis and various influencing factors, and some patients tend to have a poor prognosis; its pathogenesis remains unclear and needs further in-depth studies.

Gynura segetum induces hepatic sinusoidal obstruction syndrome in mice by impairing autophagy

ABSTRACT Purpose: To investigate the underlying mechanism of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum by measuring autophagy in mouse models. Methods: The model group was administered G. segetum (30 g/kg/d) by gavage, while the normal control group was administered an equal volume of saline daily for five weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic histopathological examinations, and Masson staining were performed to evaluate liver injury. Liver intercellular adhesion molecule-1 (ICAM-1) and P-selectin were evaluated by immunohistochemistry. Hepatocellular apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Protein expression levels of autophagy markers were measured using Western blot analysis. Results: Gynura segetum was found to significantly induce liver injury compared with control mice, as evidenced by the increase of serum transaminases, a decrease in triglyceride levels, and histopathological changes in mice. Gynura segetum remarkably induced hepatocellular apoptosis and upregulated the expressions of ICAM-1 and P-selectin and also downregulated the protein expression levels of LC3, Atg12 and cytoplasmic polyadenylation element binding protein. Conclusions: Our results suggested that G. segetum induced liver injury with HSOS, and it was partly due to its ability to impair the autophagy pathway.

Causes of death after transjugular intrahepatic portosystemic shunt in patients with hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

ObjectiveTo investigate the clinical features and causes of death after transjugular intrahepatic portosystemic shunt (TIPS) in patients with hepatic sinus obstruction syndrome (HSOS), as well as the prevention and treatment measures to further improve the survival rate of such patients. MethodsA retrospective analysis was performed for 293 patients with HSOS who were admitted to Nanjing Drum Tower Hospital from January 2013 to December 2019, among whom 20 patients died after TIPS. General information, laboratory examination, and clinical treatment regimen were analyzed, and clinical indices and complications were compared at different stages of the disease. The paired t-test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups. ResultsThe mean survival time was 15.15±4.21 weeks for the 20 patients who died, among whom there were 15 male patients and 5 female patients, with a mean age of 67.60±7.01 years; there were 17 patients (85%) aged ≥60 years, and more than 90% of the patients had abdominal distention and oliguria. Among the 20 patients who died, 9 (45%) had chronic underlying diseases, and 5 (25%) had more than two underlying diseases. Portal venous pressure decreased from 21.67±5.15 mm Hg before surgery to 8.17±4.98 mm Hg after surgery (t=10.318,P＜0.05). The levels of total bilirubin, direct bilirubin, and D-dimer were significantly higher than the normal values before surgery, and there were significant increases in these levels on day 5 after surgery (Z=3.823,3.823,2.756, all P＜0.05); the hemoglobin level, platelet count, and creatinine level tended to decrease on day 5 after surgery (t=4.979,t=2.147,Z=-3.125, all P＜005). Three patients had hepatic encephalopathy before surgery, while 10 patients (50%) had hepatic encephalopathy after surgery. Causes of death included acute liver failure, infectious shock, and multiple organ failure syndrome (MODS). ConclusionThe possible risk factors for death after TIPS in HSOS patients include underlying diseases, high bilirubin, and complications such as hepatic encephalopathy and renal dysfunction. Causes of death mainly include acute liver failure and MODS. Ultrasound and laboratory markers should be reexamined during anticoagulation therapy to identify the patients with progression to severe diseases as early as possible, and in case of progressive deterioration of indices, TIPS should be selected as early as possible to improve the survival rate and prognosis of such patients. In addition, hemobilia should be observed during and after surgery, and intervention measures should be adopted in time to further reduce mortality rate.

Clinical characteristics and outcomes of patients with hepatic veno-occlusive disease induced by Gynura segetum: A retrospective study / 中西医结合学报

OBJECTIVE@#Hepatic veno-occlusive disease (HVOD) has attracted increasing attention in recent years due to its relationship with ingestion of Gynura segetum. The mortality of severe HVOD remains high due to the lack of specific therapies. The aim of the study was to delineate the clinical characteristics and outcomes and explore the potential prognostic factors of HVOD.@*METHODS@#This was a single-center retrospective study. Eighty-nine HVOD patients were screened from the First Affiliated Hospital of Zhejiang University with an ingestion history of G. segetum before developing symptoms from January 2009 to May 2018. The enrolled patients were divided into the survivor and death groups according to the clinical follow-up that ended on September 1, 2019. The demographic variables and clinical data of the patients were recorded. A binary logistic regression analysis and receiver operating characteristic curve were conducted to identify the prognostic factors and assess the prognostic value for predicting death, and a survival analysis was performed to evaluate the clinical outcomes.@*RESULTS@#Sixty-four patients were eligible for further analysis. Most patients showed abdominal distension and were positive for migrating dullness in the abdomen (P = 0.740 and P = 0.732, respectively). The patients who died had higher levels of model for end-stage liver disease score, and higher prothrombin time than those who survived (both P < 0.001). All HVOD patients in both the survival and death groups showed ascites with abnormal imaging presentations of the liver parenchyma and hepatic blood vessels. Unexpectedly, we found that hydrothorax was detected in 21 (65.63%) patients in the death group and 19 (59.38%) patients in the survivor group during hospitalization, which was rarely mentioned in previous studies. Furthermore, international normalized ratio (INR) and creatinine are found to be potential independent prognostic factors for predicting death. Six severe patients achieved clinical improvements and survived after liver transplantation.@*CONCLUSION@#HVOD can be induced by the ingestion of G. segetum, and INR combined with creatinine has prognostic value for predicting death. Liver transplantation may be an effective treatment option for severe HVOD patients.

CT and MRI features of hepatic sinusoidal obstruction syndrome / 中国介入影像与治疗学

Objective: To observe CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS). Methods: Clinical and imaging data of 45 HSOS patients were retrospectively analyzed. Results: Forty-one patients underwent CT examination. Plain CT showed liver enlargement in 20 cases, including enlargement of left lobe and caudate lobe in 7 cases. Decreased density of liver parenchyma was observed in 21 cases, different degrees abdominal effusion in 36 cases, and pleural effusion in 2 cases. Contrast-enhanced CT scan showed uneven enhancement of liver parenchyma in 31 cases, map-like enhancement in 21 cases, patchy uneven enhancement in 9 cases and minor enhancement in 1 case. Patchy map-like enhancement of the portal venous phase was detected in all patients, and the enhancement range further expanded during delayed phase. No bile duct dilatation nor angiogenesis of the medial and lateral hepatic branches was observed. Twelve patients underwent MR examination. Plain MRI showed uneven liver signals, the liver enlargement in 10 cases, and compressed and tapered posterior segment of inferior vena cava in 5 cases. No morphologic abnormality of gallbladder was found in 12 cases. Enhanced MRI showed uneven enhancement of liver parenchyma, and the reduced area of lamellar enhancement and abnormal enhancement foci were all map-shaped. Conclusion: CT and MRI manifestations of HSOS have certain characteristics, which are helpful for clinical diagnosis.

Value of Model for End-Stage Liver Disease and Child-Turcotte-Pugh score in predicting the prognosis of patients with hepatic sinus obstruction syndrome associated with Gynura segetum (Lour.) Merr / 临床肝胆病杂志

ObjectiveTo investigate the value of Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) score in predicting the prognosis of patients with hepatic sinusoidal obstruction syndrome (HSOS) associated with Gynura segetum (Lour.) Merr. MethodsA total of 49 patients with HSOS associated with Gynura segetum (Lour.) Merr. who were admitted to Beijing YouAn Hospital, Beijing Ditan Hospital, The Fifth Medical Center of Chinese PLA General Hospital, Tianjin Third Central Hospital, and The First Affiliated Hospital of Xinxiang Medical University from January 2012 to July 2018 were enrolled and followed up for three years, with death as the outcome event. MELD and CTP scores were calculated according to the laboratory examination and clinical data on admission, and according to CTP score, the patients were divided into CTP class A (CTP score 5-6) group(n=8), CTP class B (CTP score 7-9) group(n=23), and CTP class C (CTP score ≥10) group(n=18). The patients were divided into death group(n=12) and survival group(n=37) according to the clinical outcome during follow-up. The Mann-Whitney U test was used for comparison of continuous data between groups, and the Kruskal-Wallis H test was used for ranked data. The area under the receiver operator characteristic (ROC) curve (AUC) was used to investigate the ability of CTP and MELD scores in predicting death. The Kaplan-Meier survival curves were used to determine the long-term prognosis of patients with different CTP and MELD scores, and the log-rank test was used for comparison. The ROC curve was used to evaluate the performance of these two scoring systems in predicting death. ResultsA total of 12 patients died during the 3-year follow-up period. The patients with HSOS had a median MELD score of 13.443 (8.792-18.379), and the death group had a significantly higher MELD score than the survival group ［19.84 (15.49-25.41) vs 11.58 (8.60-15.79), Z=-3.511, P＜0.001］. The patients with HSOS had a CTP score of 6-12, and of all 49 patients, 8 (16.3%) had CTP class A HSOS, 23 (46.9%) had CTP class B HSOS, and 18 (36.7%) had CTP class C HSOS. The mortality rate of the patients increased significantly with the increase in CTP score (χ2=16.078, P＜0.05). The mortality rates of the patients with CTP class A, B, and C HSOS were 0.0%, 13.0%, and 50.0%, respectively (χ2=10343, P＜0.05). The Kaplan-Meier analysis showed that the patients with a MELD score of ＜14.294 4 had a significantly better 3-year prognosis than those with a MELD score of ≥14.294 4 (χ2=14.893, P＜0.001). The higher the CTP score, the poorer the 3-year prognosis of patients (χ2=11.083, P＜0.05). CTP class had an AUC of 0.780 (95% confidence interval ［CI］: 0.639-0.922) in predicting the prognosis of HSOS patients, while MELD score had an AUC of 0.840 (95%CI: 0.722-0.958), and there was no significant difference between the two scores (Z=2.63, P＞0.05). ConclusionBoth MELD and CTP scores can predict the risk of death in patients with HSOS, with similar performance in predicting the prognosis of patients, and further studies are needed to validate their clinical value.

Clinical characteristics and outcomes of patients with hepatic veno-occlusive disease induced by Gynura segetum: A retrospective study / 中西医结合学报

OBJECTIVE@#Hepatic veno-occlusive disease (HVOD) has attracted increasing attention in recent years due to its relationship with ingestion of Gynura segetum. The mortality of severe HVOD remains high due to the lack of specific therapies. The aim of the study was to delineate the clinical characteristics and outcomes and explore the potential prognostic factors of HVOD.@*METHODS@#This was a single-center retrospective study. Eighty-nine HVOD patients were screened from the First Affiliated Hospital of Zhejiang University with an ingestion history of G. segetum before developing symptoms from January 2009 to May 2018. The enrolled patients were divided into the survivor and death groups according to the clinical follow-up that ended on September 1, 2019. The demographic variables and clinical data of the patients were recorded. A binary logistic regression analysis and receiver operating characteristic curve were conducted to identify the prognostic factors and assess the prognostic value for predicting death, and a survival analysis was performed to evaluate the clinical outcomes.@*RESULTS@#Sixty-four patients were eligible for further analysis. Most patients showed abdominal distension and were positive for migrating dullness in the abdomen (P = 0.740 and P = 0.732, respectively). The patients who died had higher levels of model for end-stage liver disease score, and higher prothrombin time than those who survived (both P < 0.001). All HVOD patients in both the survival and death groups showed ascites with abnormal imaging presentations of the liver parenchyma and hepatic blood vessels. Unexpectedly, we found that hydrothorax was detected in 21 (65.63%) patients in the death group and 19 (59.38%) patients in the survivor group during hospitalization, which was rarely mentioned in previous studies. Furthermore, international normalized ratio (INR) and creatinine are found to be potential independent prognostic factors for predicting death. Six severe patients achieved clinical improvements and survived after liver transplantation.@*CONCLUSION@#HVOD can be induced by the ingestion of G. segetum, and INR combined with creatinine has prognostic value for predicting death. Liver transplantation may be an effective treatment option for severe HVOD patients.

Clinical features, pathogenesis, and diagnosis and treatment of different types of hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

Hepatic sinusoidal obstruction syndrome (HSOS) is a sinusoidal or small venous fibrous occlusive disease characterized by small hepatic vessel damage, especially sinusoidal endothelial cell injury. Exposure to certain exogenous toxins is the main cause of the disease. Based on etiology, HSOS is mainly classified into pyrrolidine alkaloid-related HSOS, hematopoietic stem cell transplantation-related HSOS, and HSOS of unknown etiology. This article summarizes the types of HSOS and reviews the research advances in clinical manifestations, pathogenesis, diagnosis, and treatment of HSOS.

Efficacy of transjugular intrahepatic portosystemic shunt in the treatment of 21 patients with gynura segetum-related hepatic sinusoidal obstruction syndrome / 中华消化杂志

Objective To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS)in the treatment of patients with hepatic sinusoidal obstruction syndrome (HSOS).Methods From April 2015 to August 2018,at The First Affiliated Hospital of University of Science and Technology of China,21 patients with gynura segetum caused HSOS were selected.All the patients received TIPS treatment because of unresponsiveness to anticoagulant therapy for at least two weeks.After operation patients were followed up with liver and portal vein Doppler ultrasonography examination,liver and kidney function tests,and survival observation.T test,logistic univariate regression analysis and Cox regression analysis were performed for statistical analysis.Results Among the 21 patients with gynura segetum-related HSOS,18 patients were in the subacute phase and three patients in the chronic phase.All of them were moderate or severe patients and all successfully underwent TIPS.The postoperative portal vein pressure was (16.71 ± 4.68) cmH2O (1 cmH2O =0.098 kPa),which was lower than that before operation ((41.52 ±6.27) cmH2O),and the difference was statistically significant (t =16.936,P ＜ 0.01).The postoperation portal vein blood flow velocity was (41.52 ±7.70) cm/s,which was higher than before operation ((11.19 ± 3.29) cm/s),and the difference was statistically significant (t =-15.191,P ＜0.01).At one month after operation,15 of 21 patients were clinically cured;among the remaining six patients,four patients were improved and two patients were ineffective (including one patient died).At four months after operation,two patients died,and the remaining 19 patients were clinically cured.At one month after operation,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBil) and serum creatinine were (23.7 ± 16.8) U/L,(33.9 ±7.4) U/L,(52.7 ± 38.2) μmol/L and (62.7 ± 12.6) μmol/L,respectively,which were lower than those before operation ((60.5 ± 42.4) U/L,(78.4 ± 42.4) U/L,(74.9 ± 38.2) μmol/L and (82.4 ± 19.6) μmol/L,respectively),and the differences were statistically significant (t =3.193,3.493,2.378 and 4.519;all P ＜ 0.05).The level of albumin was (39.0 ±3.1) g/L,which was higher than that before operation ((30.9 ± 3.8) g/L),and the difference was statistically significant (t =-10.283,P ＜ 0.01).Portal vein thrombosis and preoperative TBil level had predictive value for therapeutic efficacy (both P ＜0.05).The one-year cumulative survival rate of patients was 90.5％.Preoperative TBil level and hepatic encephalopathy had effects on the prognosis of patients (both P ＜ 0.05).Conclusion TIPS is a safe,reliable and effective treatment for patients with subacute and chronic gynura segetum-related HSOS who are not responding to ineffective anticoagulant therapy,which can improve the prognosis and survival rate of the patients.

Clinical observation of influences of donor HBV infection on allogeneic hematopoietic stem cell transplantation recipients / 西安交通大学学报(医学版)

Objective To investigate the influences of donor HBV infection on allogeneic hematopoietic stem cell transplantation recipients.Methods We made a retrospective analysis of data of four patients without HBV infection who underwent allogeneic hematopoietic stem cell transplantation from January 2015 to December 2016. Among them donors of these patients all had HBV infection.We then observed the influences of HBV infection on hematopoietic reconstruction,hepatic vein occlusive disease and HBV infection.Results HBV serological conditions of two donors were HbsAb,HbeAb and HbcAb positive,and quantitative of HBV-DNA was negative;the donor and the recipient did not use anti-HBV drugs.One donor was HbsAg,HbeAb and HbcAb positive,and the quantitative of HBV-DNA was also positive.Another donor was HbsAg and HbcAb positive,and the quantitative of HBV-DNA was also positive.These two donors received oral nucleoside therapy one month before stem cell collection and the recipients of these two donors also took nucleoside drugs one week before the conditioning.Hepatitis B immune globulin was given after transfusion of stem cells and the third day and seventh day after transplantation.Quantitative of HbsAb was detected each month and if it was less than 150 IU,hepatitis B immune globulin would be given.All the recipients had hematopoietic reconstruction and no VOD or hepatitis B virus infection occurred.Conclusion Oral administration of nucleoside drugs combined with hepatitis B immunoglobulin can effectively prevent HBV infection in recipients with HBV infection donors.

Percutanous transhepatic intrahepatic portosystemic shunt for chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension / 中华放射学杂志

Objective To investigate the efficacy and safety of percutanous transhepatic intrahepatic portosystemic shunt(PTIPS)for chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension.Methods The clinical and imaging data of 38 patients with chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension, who received PTIPS in our hospital from November 2009 to June 2016,were analyzed retrospectively.The differences of the portosystemic pressure gradient(PPG)measured before and after PTIPS procedure was analyzed by a paired samples t-test. All the patients were followed up and the curative effect and operation-correlated complications were observed.Results The PTIPS procedure was technically successful in 36 patients.The other two patients with unsuccessful PTIPS underwent medical treatment,and one of them died of recurrent variceal bleeding 25 months later. Effective portal decompression and free antegrade shunt flow were achieved in 36 patients with successful PTIPS.And the mean PPG was decreased from(25.2±2.9)to(13.2± 1.3) mmHg (1 mmHg=0.133 kPa) before and after PTIPS respectively and the difference was statistically significant(P<0.05).During the procedure,arterial hemorrhage occurred in two patients who subsequently underwent embolization. Biliary injury occurred in one case and percutanous transhepatic biliary drainage (PTBD)was then performed.The mean follow-up period of the 36 patients was(26.7±10.4)months(range from 3.0 to 74.0 months).Hepatic encephalopathy appeared in 4 cases,among which,3 patients recovered after receiving medical treatment, while 1 patient experienced Grade 3 hepatic encephalopathy and recovered after implanting a smaller cover-stent.Shunt dysfunction occurred in 10 cases,of which 8 cases recovered after shunt revision with stent implantation or ballon angioplasty, while 2 cases underwent anticoagulation by warfarin only. During follow-up period, 7 patients died of liver failure(n=4), hepatic cellular carcinoma(n=1), recurrent varicose vein bleeding(n=1), and renal failure(n=1). The other patients remained asymptomatic and shunt patency. Conclusions PTIPS is both safe and effective for the treatment of symptomatic portal hypertension caused by chronic portal vein occlusion and cavernous transformation.The technical success rate is high,and the short-term curative effect is satisfied.

A clinical analysis of hepatic veno-occlusive disease after hematopoietic stem cell transplantation / 中华内科杂志

Objective To analyze the outcome and the prognostic factors of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). Methods A total of 797 patients receiving HSCT were analyzed retrospectively. The prophylaxis regimen of HVOD in the First Affiliated Hospital of Guangxi Medical University consisted of low molecular weight heparin and lipoprostaglandin E1 (PGE1). Results Fifty-nine patients (7.4%) developed HVOD at 3-49 days after HSCT (median 12 days). Age younger than 15 years at transplant( HR=6.47, P<0.001), busulphan conditioning ( HR=6.40, P<0.001), thalassemia major ( HR=6.35,P<0.001), allogeneic transplantation ( HR=7.74, P=0.005) were univariate risk factors for HVOD. Multivariate analyses suggested that thalassemia major and busulphan conditioning were independently correlated with the development of HVOD. Conclusion Thalassemia major and busulphan conditioning are independent risk factors for HVOD after HSCT.

Research advances in sinusoidal obstruction syndrome / 临床肝胆病杂志

Sinusoidal obstruction syndrome (SOS) is a sinusoidal or small venous fibrous occlusive disease. This article reviews the research advances in the etiology, pathogenesis, clinical manifestations, auxiliary examinations, and treatment of SOS, and points out that the pathogenesis of SOS remains unknown and there are no specific therapeutic methods. How to identify SOS and provide intervention and treatment as early as possible becomes the hot research topic.

Treatment for Gynura segetum caused hepatic vein occlusive disease: a single-center retrospective study / 中华消化杂志

Objective To explore the effects of different treatments on prognosis of patients with Gynura segetum caused hepatic vein occlusion disease (HVOD).Methods From July 2008 to January 2016,85 patients with Gynura segetum caused HVOD were enrolled and received treatment of liver function protection and microcirculation improvement.According to different treatment options,patients were divided into non-anticoagulation group,nowanticoagulation transfered to transjugular intrahepatic portosystem stent-shunt (TIPS) group,anticoagulation group,anticoagulation transfered to TIPS group and anticoagulation-TIPS step-by-step treatment group.The efficacy of each group was observed.Chi square test was performed for statistical analysis.Results Among 22 patients who received nonanticoagulation treatment,six (27.3％) patients were cured and 14 (63.6％) patients died during the treatment period;besides two (9.1 ％) patients received TIPS because of ineffective treatment and achieved longterm survival.Among 63 patients treated with combination of low-molecular-weight heparin and warfarin,six (9.5％) patients died and 36(57.1％) patients were cured.The cure rate was higher than that of nonanticoagulation group (x2 =5.820,P=0.016).Other 21 patients received TIPS treatment,achieved longterm survival except one patient died from surgical complications.The cure rate of anticoagulation-TIPS step treatment group was 88.9 ％ (56/63) which was higher than that of non-anticoagulation group,and the difference was statistically significant (x2 =31.350,P＜0.01).Conclusions Compared to conventional liver function protection treatment and symptomatic treatment,anticoagulation therapy significantly increases the cure rate of patients with Gynura segetum caused HVOD.Anticoagulation-TIPS step-by-step treatment further improves the cure rate.

Mechanism of Therapeutic Effect of Ligustrazine on Hepatic Veno-occlusive Disease Induced by Sedum aizoon in Mice / 胃肠病学

Background:Hepatic veno-occlusive disease( HVOD) is a disease characterized by hepatomegaly,jaundice, ascites,weight gain and lack of effective treatment currently. Our prophase research showed that ligustrazine had therapeutic effect on Sedum aizoon induced HVOD in mice. Aims:To investigate the mechanism of therapeutic effect of ligustrazine on Sedum aizoon induced HVOD in mice. Methods:A total of 115 mice were randomly divided into 4 groups:mice in group A were intragastrically administrated with 30 mg·kg-1 ·d-1 Sedum aizoon to induce HVOD and served as model group;mice in group B were given 30 mg·kg-1 ·d-1 Sedum aizoon + 100 mg·kg-1 ·d-1 ligustrazine and served as low dose ligustrazine intervention group;mice in group C were given 30 mg·kg-1 ·d-1 Sedum aizoon + 200 mg·kg-1 ·d-1 ligustrazine and served as high dose ligustrazine intervention group;mice in group D were given 30 mg·kg-1 ·d-1 PBS and served as normal control group. After 30 days,all the mice were sacrificed. HE staining and Masson staining were performed for histological examination. The mRNA and protein expressions of tissue factor(TF),nuclear factor(NF)-κBp65 and early growth response factor( Egr)-1 in liver tissue were determined by RT-PCR and Western blotting, respectively. Results:HE staining and Masson staining histological examination showed that ligustrazine could obviously ameliorate the pathological injury of liver tissue in HVOD mice. Compared with group D,the mRNA and protein expressions of TF,NF-κBp65,Egr-1 were significantly increased in group A( P 0. 05). Conclusions:Ligustrazine has therapeutic effect on HVOD,the possible mechanism is that ligustrazine could interrupt the activation of coagulation system by reducing the expression of TF via down regulating the expressions of NF-κBp65 and Egr-1,especially in high dose ligustrazine group.

Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide / Journal of the Korean Cancer Association, 대한암학회지

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Research advances in cavernous transformation of portal vein / 临床肝胆病杂志

Cavernous transformation of the portal vein (CTPV) is considered a rare condition. However, with the development of radiological technology, an increasing number of patients have been diagnosed with CTPV, thus causing wide attention in clinical practice. This article elaborates on the research advances in CTPV from etiology to treatment, discusses the etiology of portal vein thrombosis and the mechanism by which portal vein thrombosis leads to CTPV, and summarizes the clinical manifestations of CTPV and the main methods of diagnosing this disease. Besides, this article analyses various methods in treating CTPV, and believes that surgical shunts are still the most extensively used method in treating CTPV.

Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation

BACKGROUND: The outcome of hematopoietic stem cell transplantation (HSCT) is poor in patients with secondary iron overload (SIO). We evaluated the relationship between SIO and veno-occlusive disease (VOD) in an animal model with radiation for HSCT. METHODS: We used a 6-week-old female BDF1 (H-2b/d) and a male C57/BL6 (H-2b) as recipient and donor, respectively. Recipient mice were injected intraperitoneally with 10 mg of iron dextran (cumulative doses of 50 mg, 100 mg, and 200 mg). All mice received total body irradiation for HSCT. We obtained peripheral blood for alanine transaminase (ALT) and liver for pathologic findings, lipid hyperoxide (LH) as reactive oxygen species (ROS), and liver iron content (LIC) on post-HSCT day 1 and day 7. The VOD score was assessed by pathologic findings. RESULTS: ALT levels increased depending on cumulative iron dose, with significant differences between days 1 and 7 for mice loaded with 200 mg of iron (P<0.01). LH levels significantly increased in mice loaded with 200 mg of iron compared to those in other groups (P<0.01). For mice loaded with 100 mg of iron, the LH level depended on the radiation dose (P<0.01). There was a statistically significant relationship among ALT, LH, and LIC parameters (P<0.05). Pathologic scores for VOD correlated with LIC (P<0.01). CONCLUSION: Livers with SIO showed high ROS levels depending on cumulative iron dose, and correlations with elevated liver enzyme and LIC. The pathologic score for VOD was associated with the LIC. Our results suggest that SIO may induce VOD after HSCT with irradiation.