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 sinusoi...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.展开更多
BACKGROUND Hepatic sinusoidal obstruction syndrome(SOS)is caused by damage to hepatic sinusoidal endothelial cells that results in fibrous obliteration of intrahepatic venules and necrosis of hepatocytes.Currently the...BACKGROUND Hepatic sinusoidal obstruction syndrome(SOS)is caused by damage to hepatic sinusoidal endothelial cells that results in fibrous obliteration of intrahepatic venules and necrosis of hepatocytes.Currently the diagnosis is primarily based on nonspecific clinical features and invasive liver biopsy.Therefore,noninvasive imaging methods are required for the early diagnosis and severity assessment of hepatic SOS.AIM To determine the effectiveness of supersonic shear wave imaging(SSI)and dual energy computed tomography(DECT)for diagnosing hepatic SOS using a rabbit model.METHODS Among nine New Zealand white rabbits(3-4 kg,male),three in control group ingested normal saline for 20 d and six in the SOS group ingested 6-thioguanine(5 mg/kg/d)for 20 d.Liver stiffness was measured using SSI on days 0,3,10,and 20.On the same days,liver perfusion was evaluated from virtual monochromatic images of 55 keV and iodine map using DECT.Morphologic changes in the liver were assessed using CT.Final pathology scores were compared between the two groups.Liver stiffness and perfusion parameters were compared according to the groups,days,and pathology scores.RESULTS Final pathology scores were significantly higher in the SOS than the control group(median 22 vs 2,P=0.024).No gross morphologic changes were seen in livers.Liver stiffness,Hounsfield Unit values,and iodine concentrations were higher in the SOS compared to the control group on days 10 and 20(all,P≤0.007).Compared to day 0,liver stiffness and perfusion parameters were higher on day 20 in the SOS group(all,P≤0.001).Correlation coefficients for liver stiffness(r=0.635),Hounsfield Unit values(r=0.587),and iodine concentration(r=0.611)with final pathology scores were positive without significance(all,P>0.05).CONCLUSION Liver stiffness and perfusion parameters were significantly increased in the livers of a rabbit SOS model.SSI and DECT might aid in early diagnosis of hepatic SOS.展开更多
BACKGROUND Primary hepatic angiosarcoma(PHA)is a rare malignancy with a poor prognosis.It is difficult to diagnose PHA because of the lack of specific symptoms or tumour markers,and it rapidly progresses and has a hig...BACKGROUND Primary hepatic angiosarcoma(PHA)is a rare malignancy with a poor prognosis.It is difficult to diagnose PHA because of the lack of specific symptoms or tumour markers,and it rapidly progresses and has a high mortality.To our knowledge,PHA has not been reported to mimic hepatic sinusoidal obstruction syndrome.Herein,we present a case of PHA manifesting as hepatic sinusoidal obstruction syndrome,diagnosed using transjugular liver biopsy,that resulted in the death of the patient.CASE SUMMARY A 71-year-old man was admitted with the primary complaint of abdominal distension,decreased appetite,fatigue in the previous month,and loss of 10 kg of weight in the past 2 years.Both the liver and spleen were enlarged,and the liver had a medium-hard texture on percussion.Laboratory examinations were performed,and abdominal plain computed tomography(CT)and contrastenhanced CT showed hepatomegaly and splenomegaly,as well as diffuse lowdensity shadows distributed in the liver and spleen.Contrast-enhanced CT revealed diffuse,hypodense,nodular or flake shadows in the liver and heterogeneous enhancement in the spleen.A transjugular liver biopsy was performed.Based on the pathology results,the patient was diagnosed with hepatic sinusoidal obstruction syndrome secondary to PHA.The patient’s status further deteriorated and he developed serious hepatic failure.The patient was discharged,and died 3 d later.CONCLUSION PHA is rare and has a poor prognosis;however,transjugular liver biopsy can be safely performed to aid in diagnosis.展开更多
BACKGROUND Hepatic sinusoidal obstruction syndrome(HSOS)is a rare complication in solid organ transplant recipients,especially in liver transplantation recipients.However,the consequences of HSOS occurrence are pernic...BACKGROUND Hepatic sinusoidal obstruction syndrome(HSOS)is a rare complication in solid organ transplant recipients,especially in liver transplantation recipients.However,the consequences of HSOS occurrence are pernicious,which could result in severe liver or renal failure,and even death.In addition to previously reported azathioprine and acute rejection,tacrolimus is also considered as one predisposing factor to induce HSOS after liver transplantation,although the underlying mechanism remains unclear.CASE SUMMARY In this study,we reported three cases of tacrolimus-related HSOS after liver transplantation.The diagnosis of HSOS was firstly based on the typical symptoms including ascites,painful hepatomegaly and jaundice.Furthermore,the features of patchy enhancement on portal vein and delayed phase of abdominal enhanced computed tomography were suspected of HSOS and ultimately confirmed by liver biopsy and histological examination in two patients.A significant decrease in ascites and remission of clinical symptoms of abdominal distention and pain were observed after withdrawal of tacrolimus.CONCLUSION Tacrolimus-induced HSOS is a scarce but severe complication after liver transplantation.It lacks specific symptoms and diagnostic criteria.Timely diagnosis of HSOS is based on clinical symptoms,radiological and histological examinations.Discontinuation of tacrolimus is the only effective treatment.Transplantation physicians should be aware of this rare complication potentially induced by tacrolimus.展开更多
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 ...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.展开更多
Hepatic sinusoidal obstruction syndrome(HSOS)via exposure to pyrrolizidine alkaloids(PAs)is with high mortality and there is no effective treatment in clinics.Bear bile powder(BBP)is a famous traditional animal drug f...Hepatic sinusoidal obstruction syndrome(HSOS)via exposure to pyrrolizidine alkaloids(PAs)is with high mortality and there is no effective treatment in clinics.Bear bile powder(BBP)is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis,inflammation,and fibrosis.Here,we aim to evaluate the protective effect of BBP against HSOS induced by senecionine,a highly hepatotoxic PA compound.Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently,which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells,alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells,as well as decreased conventional serum liver function indicators.In addition,BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts,two well-known markers positively associated with the severity of PA-induced HSOS.Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules.BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines,in which taurours-odeoxycholic acid played an important role.What’s more,BBP treatment also decreased the accumulation of hydrophobic bile acids,such as cholic acid,taurocholic acid,glycocholic acid,as well.We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis,preventing liver fibrosis,and alleviating liver inflammation.Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.展开更多
Background and Aims:Hepatic sinusoidal obstruction syndrome(HSOS)is a life-threatening syndrome,and a cause is exposure to pyrrolizidine alkaloid(PA)-containing products.It is well-established that retrorsine(RTS),a r...Background and Aims:Hepatic sinusoidal obstruction syndrome(HSOS)is a life-threatening syndrome,and a cause is exposure to pyrrolizidine alkaloid(PA)-containing products.It is well-established that retrorsine(RTS),a rep-resentative Pas,insults hepatic sinusoidal endothelial cells and ensues congestion of hepatic sinusoids.However,little known about the impact of Pas on gut microbiota and intesti-nal barrier and inflammation in HSOS.Methods:Mice were gavaged with or without nonabsorbable antibiotics(ABX),followed by a single dose of RTS.The gut microbiota was examined by 16S rDNA sequencing.Results:ABX pretreat-ment significantly reversed RTS-induced liver damage.RTS altered gut microbiota composition,increasing Gram-nega-tive bacteria and resulting in a sharp elevation of circulating lipopolysaccharides(LPS)in HSOS mice.Gut decontamina-tion with ABX alleviated RTS-induced intestine inflamma-tion,protected against disruption of the intestinal epithelial barrier and gut vascular barrier(GVB),and suppressed he-patic LPS-NF-κB pathway activation in RTS-induced HSOS.Importantly,the LPS level was positively correlated with MELD score in patients with HSOS.Elevated LPS in patients with HSOS confirmed that Gram-negative bacteria were in-volved in the pathogenesis of HSOS.Conclusions:RTS,a PA,cooperated with gut dysbiosis to cause intestinal inflam-mation and gut barrier compromise that increased transport of gut-derived LPS into the liver through the portal vein,which contributed to the pathology of HSOS.Modulating the gut microbiota,protecting the intestinal barrier,and sup-pressing intestinal inflammation with prebiotics or antibiot-ics might be a useful pharmacologic intervention in HSOS.展开更多
Objective Rifaximin is an effective component of treatment strategies for liver and intestinal diseases.However,the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome(HSOS)has not been explored.The prese...Objective Rifaximin is an effective component of treatment strategies for liver and intestinal diseases.However,the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome(HSOS)has not been explored.The present study aimed to investigate the efficacy and mechanism of rifaximin in HSOS.Methods An HSOS model was established in mice through the administration of monocrotaline(MCT,800 mg/kg),and part of the HSOS mice were intragastrically administered with rifaximin.Then,the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings,liver proinflammatory cytokines,and alanine aminotransferase and aspartate aminotransferase levels.The Ussing chamber was used to evaluate the intestinal permeability,and tight junction(TJ)proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier integrity.Then,the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay.Afterwards,an in vitro experiment was performed to determine the relationship between rifaximin and TJ proteins.Results Rifaximin effectively alleviated the MCT-induced HSOS liver injury,suppressed the expression of liver proinflammatory cytokines,and reduced the serum levels of tumor necrosis factor-alpha and interleukin-6.Furthermore,rifaximin reduced the intestinal permeability,improved the intestinal barrier integrity,and promoted the expression of TJ proteins.Conclusion The results revealed that the intestinal barrier integrity was destroyed in MCT-induced HSOS.The significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.展开更多
Several guidelines have indicated that liver stiffness(LS)assessed by means of shear wave elastography(SWE)can safely replace liver biopsy in several clinical scenarios,particularly in patients with chronic viral hepa...Several guidelines have indicated that liver stiffness(LS)assessed by means of shear wave elastography(SWE)can safely replace liver biopsy in several clinical scenarios,particularly in patients with chronic viral hepatitis.However,an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation,acute hepatitis,obstructive cholestasis,liver congestion,infiltrative liver diseases.This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure,congenital heart diseases or valvular diseases.In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events.The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS)and in the Budd-Chiari syndrome.In the hepatic SOS,an increase of LS is observed some days before the clinical manifestations;therefore,it could allow an early diagnosis to timely start an effective treatment.Moreover,it has been reported that patients that were successfully treated showed a LS decrease,that reached pre-transplantation value within two to four weeks.It has been reported that,in patients with Budd-Chiari syndrome,LS values can be used to monitor short and long-term outcome after angioplasty.展开更多
Pyrrolizidine alkaloids(PAs)are among the most hepatotoxic natural compounds that are widely distributed throughout the world.Most PAs are metabolically activated to trigger toxicity.Exposure to herbal medicine contai...Pyrrolizidine alkaloids(PAs)are among the most hepatotoxic natural compounds that are widely distributed throughout the world.Most PAs are metabolically activated to trigger toxicity.Exposure to herbal medicine containing PAs and food supplements contaminated by PAs is considered to be one of the two main causes of hepatic sinusoidal obstruction syndrome(HSOS),which is a rare hepatic vascular disease with a high mortality rate.PAs-induced HSOS cases have been reported worldwide.However,there is no clinically effective therapy for PAs-induced HSOS,which is partially because the toxic mechanism is not fully understood.This review focuses on updating the information on the metabolism and the molecular mechanisms of PAs hepatotoxicity,including oxidative stress,apoptosis,and dysfunction of bile acid metabolism,and their interactions.展开更多
基金the National Science of Foundation Committee of Zhejiang Province,No.LY22H160003the Zhejiang Provincial Medical and Health Science Foundation,No.2021441200 and No.2021RC083.
文摘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.
基金Supported by a Faculty Research Grant of Yonsei University College of Medicine for 2017,No.6-2017-0090
文摘BACKGROUND Hepatic sinusoidal obstruction syndrome(SOS)is caused by damage to hepatic sinusoidal endothelial cells that results in fibrous obliteration of intrahepatic venules and necrosis of hepatocytes.Currently the diagnosis is primarily based on nonspecific clinical features and invasive liver biopsy.Therefore,noninvasive imaging methods are required for the early diagnosis and severity assessment of hepatic SOS.AIM To determine the effectiveness of supersonic shear wave imaging(SSI)and dual energy computed tomography(DECT)for diagnosing hepatic SOS using a rabbit model.METHODS Among nine New Zealand white rabbits(3-4 kg,male),three in control group ingested normal saline for 20 d and six in the SOS group ingested 6-thioguanine(5 mg/kg/d)for 20 d.Liver stiffness was measured using SSI on days 0,3,10,and 20.On the same days,liver perfusion was evaluated from virtual monochromatic images of 55 keV and iodine map using DECT.Morphologic changes in the liver were assessed using CT.Final pathology scores were compared between the two groups.Liver stiffness and perfusion parameters were compared according to the groups,days,and pathology scores.RESULTS Final pathology scores were significantly higher in the SOS than the control group(median 22 vs 2,P=0.024).No gross morphologic changes were seen in livers.Liver stiffness,Hounsfield Unit values,and iodine concentrations were higher in the SOS compared to the control group on days 10 and 20(all,P≤0.007).Compared to day 0,liver stiffness and perfusion parameters were higher on day 20 in the SOS group(all,P≤0.001).Correlation coefficients for liver stiffness(r=0.635),Hounsfield Unit values(r=0.587),and iodine concentration(r=0.611)with final pathology scores were positive without significance(all,P>0.05).CONCLUSION Liver stiffness and perfusion parameters were significantly increased in the livers of a rabbit SOS model.SSI and DECT might aid in early diagnosis of hepatic SOS.
基金Supported by Tianjin Science and Technology Plan Project,No.19ZXDBSY00030Beijing iGandan Foundation,No.RGGJJ-2021-014.
文摘BACKGROUND Primary hepatic angiosarcoma(PHA)is a rare malignancy with a poor prognosis.It is difficult to diagnose PHA because of the lack of specific symptoms or tumour markers,and it rapidly progresses and has a high mortality.To our knowledge,PHA has not been reported to mimic hepatic sinusoidal obstruction syndrome.Herein,we present a case of PHA manifesting as hepatic sinusoidal obstruction syndrome,diagnosed using transjugular liver biopsy,that resulted in the death of the patient.CASE SUMMARY A 71-year-old man was admitted with the primary complaint of abdominal distension,decreased appetite,fatigue in the previous month,and loss of 10 kg of weight in the past 2 years.Both the liver and spleen were enlarged,and the liver had a medium-hard texture on percussion.Laboratory examinations were performed,and abdominal plain computed tomography(CT)and contrastenhanced CT showed hepatomegaly and splenomegaly,as well as diffuse lowdensity shadows distributed in the liver and spleen.Contrast-enhanced CT revealed diffuse,hypodense,nodular or flake shadows in the liver and heterogeneous enhancement in the spleen.A transjugular liver biopsy was performed.Based on the pathology results,the patient was diagnosed with hepatic sinusoidal obstruction syndrome secondary to PHA.The patient’s status further deteriorated and he developed serious hepatic failure.The patient was discharged,and died 3 d later.CONCLUSION PHA is rare and has a poor prognosis;however,transjugular liver biopsy can be safely performed to aid in diagnosis.
基金Supported by Surface Project of National Natural Science Foundation of China,No.81972760The Joint Project of Chongqing Health Commission and Science and Technology Bureau,No.2022QNXM020Doctoral Through Train Scientific Research Project of Chongqing,No.CSTB2022BSXM-JCX0004。
文摘BACKGROUND Hepatic sinusoidal obstruction syndrome(HSOS)is a rare complication in solid organ transplant recipients,especially in liver transplantation recipients.However,the consequences of HSOS occurrence are pernicious,which could result in severe liver or renal failure,and even death.In addition to previously reported azathioprine and acute rejection,tacrolimus is also considered as one predisposing factor to induce HSOS after liver transplantation,although the underlying mechanism remains unclear.CASE SUMMARY In this study,we reported three cases of tacrolimus-related HSOS after liver transplantation.The diagnosis of HSOS was firstly based on the typical symptoms including ascites,painful hepatomegaly and jaundice.Furthermore,the features of patchy enhancement on portal vein and delayed phase of abdominal enhanced computed tomography were suspected of HSOS and ultimately confirmed by liver biopsy and histological examination in two patients.A significant decrease in ascites and remission of clinical symptoms of abdominal distention and pain were observed after withdrawal of tacrolimus.CONCLUSION Tacrolimus-induced HSOS is a scarce but severe complication after liver transplantation.It lacks specific symptoms and diagnostic criteria.Timely diagnosis of HSOS is based on clinical symptoms,radiological and histological examinations.Discontinuation of tacrolimus is the only effective treatment.Transplantation physicians should be aware of this rare complication potentially induced by tacrolimus.
基金This study was funded in full by the National Natural Science Foundation of China,with grant numbers 8157040652 and 81900552the Key Project of Nanjing Health and Technology Development,with grant number ZKX19015。
文摘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.
基金This work was supported by Shanghai Natural Science Foundation(20ZR1473300)Shanghai Talents Development Foundation(2020099)+1 种基金the Program of Shanghai Municipal Commission of Health and Family Planning(ZY(2018-2020)-CCCX-5002)the Xinglin Scholar Program of Shanghai University of Traditional Chinese Medicine(B1-GY21-409-04-06).
文摘Hepatic sinusoidal obstruction syndrome(HSOS)via exposure to pyrrolizidine alkaloids(PAs)is with high mortality and there is no effective treatment in clinics.Bear bile powder(BBP)is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis,inflammation,and fibrosis.Here,we aim to evaluate the protective effect of BBP against HSOS induced by senecionine,a highly hepatotoxic PA compound.Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently,which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells,alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells,as well as decreased conventional serum liver function indicators.In addition,BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts,two well-known markers positively associated with the severity of PA-induced HSOS.Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules.BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines,in which taurours-odeoxycholic acid played an important role.What’s more,BBP treatment also decreased the accumulation of hydrophobic bile acids,such as cholic acid,taurocholic acid,glycocholic acid,as well.We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis,preventing liver fibrosis,and alleviating liver inflammation.Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.
基金the National Natural Science Foundation of China(No.81974078,81570530,81370550 to LY,No.8190034336 to WW)Natural Science Founda-tion of Hubei Province(No.2019ACA133 to LY)。
文摘Background and Aims:Hepatic sinusoidal obstruction syndrome(HSOS)is a life-threatening syndrome,and a cause is exposure to pyrrolizidine alkaloid(PA)-containing products.It is well-established that retrorsine(RTS),a rep-resentative Pas,insults hepatic sinusoidal endothelial cells and ensues congestion of hepatic sinusoids.However,little known about the impact of Pas on gut microbiota and intesti-nal barrier and inflammation in HSOS.Methods:Mice were gavaged with or without nonabsorbable antibiotics(ABX),followed by a single dose of RTS.The gut microbiota was examined by 16S rDNA sequencing.Results:ABX pretreat-ment significantly reversed RTS-induced liver damage.RTS altered gut microbiota composition,increasing Gram-nega-tive bacteria and resulting in a sharp elevation of circulating lipopolysaccharides(LPS)in HSOS mice.Gut decontamina-tion with ABX alleviated RTS-induced intestine inflamma-tion,protected against disruption of the intestinal epithelial barrier and gut vascular barrier(GVB),and suppressed he-patic LPS-NF-κB pathway activation in RTS-induced HSOS.Importantly,the LPS level was positively correlated with MELD score in patients with HSOS.Elevated LPS in patients with HSOS confirmed that Gram-negative bacteria were in-volved in the pathogenesis of HSOS.Conclusions:RTS,a PA,cooperated with gut dysbiosis to cause intestinal inflam-mation and gut barrier compromise that increased transport of gut-derived LPS into the liver through the portal vein,which contributed to the pathology of HSOS.Modulating the gut microbiota,protecting the intestinal barrier,and sup-pressing intestinal inflammation with prebiotics or antibiot-ics might be a useful pharmacologic intervention in HSOS.
基金the National Natural Science Foundation of China(No.81800480 and NO.81770582)the Graduates’Innovation Fund,Huazhong University of Science and Technology(No.2021yjsCXCY106).
文摘Objective Rifaximin is an effective component of treatment strategies for liver and intestinal diseases.However,the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome(HSOS)has not been explored.The present study aimed to investigate the efficacy and mechanism of rifaximin in HSOS.Methods An HSOS model was established in mice through the administration of monocrotaline(MCT,800 mg/kg),and part of the HSOS mice were intragastrically administered with rifaximin.Then,the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings,liver proinflammatory cytokines,and alanine aminotransferase and aspartate aminotransferase levels.The Ussing chamber was used to evaluate the intestinal permeability,and tight junction(TJ)proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier integrity.Then,the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay.Afterwards,an in vitro experiment was performed to determine the relationship between rifaximin and TJ proteins.Results Rifaximin effectively alleviated the MCT-induced HSOS liver injury,suppressed the expression of liver proinflammatory cytokines,and reduced the serum levels of tumor necrosis factor-alpha and interleukin-6.Furthermore,rifaximin reduced the intestinal permeability,improved the intestinal barrier integrity,and promoted the expression of TJ proteins.Conclusion The results revealed that the intestinal barrier integrity was destroyed in MCT-induced HSOS.The significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.
文摘Several guidelines have indicated that liver stiffness(LS)assessed by means of shear wave elastography(SWE)can safely replace liver biopsy in several clinical scenarios,particularly in patients with chronic viral hepatitis.However,an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation,acute hepatitis,obstructive cholestasis,liver congestion,infiltrative liver diseases.This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure,congenital heart diseases or valvular diseases.In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events.The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS)and in the Budd-Chiari syndrome.In the hepatic SOS,an increase of LS is observed some days before the clinical manifestations;therefore,it could allow an early diagnosis to timely start an effective treatment.Moreover,it has been reported that patients that were successfully treated showed a LS decrease,that reached pre-transplantation value within two to four weeks.It has been reported that,in patients with Budd-Chiari syndrome,LS values can be used to monitor short and long-term outcome after angioplasty.
基金supported by the National Natural Science Foundation of China(grant number 81603384)the Shanghai Nature Science Foundation(grant number 16ZR1434200)+2 种基金Shanghai Rising-Star Program(grant number 17QA1403600)Program of Shanghai Academic/Technology Research Leader(grant number 17XD1403500)Programof Shanghai Municipal Commission of Health and Family Planning(grant number ZY(2018e2020)-CCCX-5002).
文摘Pyrrolizidine alkaloids(PAs)are among the most hepatotoxic natural compounds that are widely distributed throughout the world.Most PAs are metabolically activated to trigger toxicity.Exposure to herbal medicine containing PAs and food supplements contaminated by PAs is considered to be one of the two main causes of hepatic sinusoidal obstruction syndrome(HSOS),which is a rare hepatic vascular disease with a high mortality rate.PAs-induced HSOS cases have been reported worldwide.However,there is no clinically effective therapy for PAs-induced HSOS,which is partially because the toxic mechanism is not fully understood.This review focuses on updating the information on the metabolism and the molecular mechanisms of PAs hepatotoxicity,including oxidative stress,apoptosis,and dysfunction of bile acid metabolism,and their interactions.
