Clinical effect of spleen aminopeptide on improving liver function damage and immune function in children with infant hepatitis syndrome

BACKGROUND Infant hepatitis syndrome(IHS)is a clinical syndrome in infants less than one year of age with generalized skin jaundice,abnormal liver function,and hepato-megaly due to various etiologies such as infection.AIM To investigate the effect of IHS patients,after treatment with arsphenamine-based peptides,on patients'liver function damage and immune function.METHODS Of 110 patients with IHS treated in our hospital from January 2019 to January 2021 were grouped according to the randomized residual grouping method,with 5 cases in each group shed due to transfer,etc.Ultimately,50 cases remained in each group.The control group was treated with reduced glutathione,and the treat-ment group was treated with sesquiterpene peptide based on the control group.Observe and compare the differences in indicators after treatment.RESULTS The comparison of serum total bilirubin,direct bilirubin,and serum alanine transferase after treatment was significantly different and lower in the treatment group than in the control group(P<0.05).The comparison of CD4+,CD3+,CD4+/CD8+after treatment was significantly different and higher in the treatment group than in the control group,and the comparison was statist-ically significant(P<0.05).The complication of the two groups showed that the rash,cough and sputum,elevated platelets,and gastrointestinal reactions in the treatment group were significantly lower than those in the control group,and the differences were statistically significant by test(P<0.05).CONCLUSION The comparative study of IHS treated with arsphenamine combined with reduced glutathione is more effective.

Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome

AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01 or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitisgroup. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-α levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.

Noninvasive evaluation of hepatic fibrosis in children with infant hepatitis syndrome

AIM： To elucidate the impact of hemodynamic parameters on ultrasonography and serum fibrosis markers for the assessment of liver fibrosis in the children with infant hepatitis syndrome （IHS）. METHODS： Forty-one children with IHS and 46 healthy infants were examined by ultrasonography, and several hemodynamic indices such as peak systolic velocity （PSV） and resistant index （RI） of proper hepatic artery （PHA） were measured. Serum fibrosis markers including hyaluronic acid （HA）, pre-collagen type-Ⅲ （PC-Ⅲ）, collagen type Ⅳ （C-Ⅳ）, and laminin （LN） were assayed by radioimmunoassays. In children with IHS, liver tissues were obtained either by ultrasound-guided liver biopsy （n = 35） or in the course of operation （n = 6）. The stages of hepatic fibrosis were scored as mild （S1 and S2）, moderate （S3）, or severe （S4） according to liver histological diagnosis. Multiple groups comparative and Spearman correlative analyses were carried out. RESULTS： Histopathologically, 39 children （95.1%） were found to have hepatic fibrosis, 12 of them stage Sl or S2, 12 stage S3, and 15 stage S4. PSV, RI of the PHA, and serum HA showed a consecutive increase from mild to severe hepatic fibrosis and a close positive correlation with hepatic fibrosis in IHS group （r = 0.717, 0.745 and 0.712, respectively, P = 0.001）. The Doppler waveform of HV was also positively correlated with the degree of hepatic fibrosis in IHS group （r = 0.783, P 〈 0.001）.CONCLUSION： Combination of ultrasonic studies on the hepatic hemodynamics with the evaluation of serum HA may provide an indicator for hepatic fibrosis in patients with IHS, This may be a useful noninvasive method for the diagnosis and evaluation of the prognosis of IHS.

A Study of the Mechanism of Yinzhihuang（菌栀黄）Injection in the Treatment of Infantile Hepatitis Syndrome

The content of serum total bilirubin, serum alanine aminotransferase and hepatic enlarge-ment were observed before and affer the treatment for intantile hepatitis syndrome by using injections ofYinzhihuang. Peripheral blood T cell subproportions and levels of duodenal bilirubin were also detected insome patients. The results of this study suggest the injections of Yinzhihuang had a significant effect in re-solving jaundice, but no effect in improving the disturbance of cellular immunity.

Clinical Observations on Treatment of Infantile Cholestatic Hepatitis Syndrome by Rhubarb

Objective: To evaluate the role of rhubarb in treating infantile cholestatic hepatitis syndrome (ICHS).Methods: Forty-four patients of the treatment group were treated with rhubarb taken orally and (or) by duodenal infusion, 20 cases of the control group were treated with general liver protecting therapy such as inosine, vitamin C and glucose. Serum bilirubin, alanine aminotransferase and γ-glutamyl transpeptidase level, bilirubin in duodenal juice and liver size were observed before and after treatment.Results: In the treatment group, 18 cases were markedly effective, 21 effective, 3 ineffective and 2 deteriorated, while in the control group, the respective numbers were 0, 4, 13 and 3. Conclusion: Rhubarb was markedly effective in cholagoging and abating jaundice, it could promote the recovery of liver function, dredge the cholestasis in cholangiole and micro-cholangiole so as to promote the bile secretion.

Idiopathic hypereosinophilic syndrome with hepatic sinusoidal obstruction syndrome:A case report and literature review

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.

Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities,such as major hepatic resections and liver transplantation.In addition to the organ’s post reperfusion injury,this syndrome appears to play a central role in the dysfunction of distant tissues and systems.Thus,continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates.Treprostinil is a synthetic analog of prostaglandin I2,and its experimental administration has shown encouraging results.It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation,where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min.Treprostinil improves renal and hepatic function,diminishes hepatic oxidative stress and lipid peroxidation,reduces hepatictoll-like receptor 9 and inflammation,inhibits hepatic apoptosis and restores hepatic adenosine triphosphate(ATP)levels and ATP synthases,which is necessary for functional maintenance of mitochondria.Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflam-matory cytokines;therefore,it can potentially minimize ischemia-reperfusion injury.Additionally,it may have beneficial effects on cardiovascular parameters,and much current research interest is concentrated on this compound.

Pathogenesis and significance of hepatitis C virus steatosis:An update on survival strategy of a successful pathogen

Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host&#x02019;s metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as &#x0201c;hepatitis C-associated dysmetabolic syndrome&#x0201d; (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.

Liver stiffness and perfusion changes for hepatic sinusoidal obstruction syndrome in rabbit model

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.

Primary hepatic angiosarcoma manifesting as hepatic sinusoidal obstruction syndrome:A case report

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.

The right hepatic artery syndrome

Various benign and malignant conditions could cause biliary obstruction. Compression of extrahepatic bile duct (EBD) by right hepatic artery was reported as a right hepatic artery syndrome but all cases were compressed EBD from stomach side. Our case compressed from dorsum was not yet reported, so it was thought to be a very rare case. We present here the first case of bile duct obstruction due to the compression of EBD from dorsum by right hepatic artery.

Hepatic sinusoidal obstruction syndrome induced by tacrolimus following liver transplantation:Three case reports

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.

Rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice

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.

Ultrasound liver elastography beyond liver fibrosis assessment

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.

Acute-on-chronic liver failure：recent update

Acute on chronic liver failure（ACLF） was first described in 1995 as a clinical syndrome distinct to classic acute decompensation.Characterized by complications of decompensation,ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between45%and 90%.Despite the clinical relevance of the condition,it still remains largely undefined with continued disagreement regarding its precise etiological factors,clinical course,prognostic criteria and management pathways.It is concerning that,despite our relative lack of understanding of the condition,the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%.This paper highlights our current understanding of ACLF,including its etiology,diagnostic and prognostic criteria and pathophysiology.It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates.The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters,while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF.

A Case of Autoimmune Hepatitis and Primary Biliary Cirrhosis Overlap Syndrome Treated with Chinese Herbs

Some patients present with overlapping features between disorders within the spectrum of autoimmune liver diseases, i.e., autoimmune hepatitis （AIH）, primary biliary cirrhosis （PBC）, and primary sclerosing cholangitis （PSC）, and are commonly classified as having an ＂overlap syndrome＂. The pathophysiological mechanisms underlying AIH-PBC overlap remain unclear.^（1） Due to the lack of standardization and variations in the populations under study,

Efficacy of ursodeoxycholic acid alone or combined with immunosuppressant in primary biliray cirrhosis- autoimmune hepatitis overlap syndrome

Objective To evaluate the efficacy of ursodeoxycholic acid(UDCA)alone or combined with immunosuppressant in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome(PBC-AIH).Methods From January2001 to December 2014,41 patients with PBC-AIH were screened out from patients with autoimmune hepatitis(AIH)and retrospectively analyzed.According to

Expression of MMP-9 in hepatic sinusoidal obstruction syndrome induced by Gynura segetum

Background and objective： Hepatic sinusoidal obstruction syndrome （HSOS） is characterized by painful hepatomegaly, ascites, increased body weight, and jaundice. Gynura segetum （Compositae）, a plant widely used in Chinese traditional medicine, often leads to the development of HSOS. However, the mechanism is unclear. The aim was to study the role of matrix metalloproteinase-9 （MMP-9） in the onset of HSOS induced by Gynura segetum. Methods： Twenty-five male Sprague-Dawley rats were randomly divided into two groups. Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone. Liver sections were evaluated by light microscopy with a modified scoring system. Routine transmission electron microscopy （TEM） methods were used to evaluate the ultrastructual features of fixed liver tissue, and blood samples were collected to determine liver enzyme concentrations. MMP-9 expression was assessed by both immunohisto- chemical staining and enzyme-linked immunosorbent assay （ELISA） methods. Results： A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract. The treated rats presented clinical symptoms and the histopathological manifestation of HSOS, including abnormal liver enzyme concentrations （alanine aminotransferase （ALT）： （84.8＋13.62） vs. （167.0±72.63） U/L, P〈0.05; aspartate aminotransferase （AST）： （27.6±6.31） vs. （232.8±108.58） U/L, P〈0.05）. Hematoxylin and eosin （H＆E） staining and TEM together revealed deposition of red blood cells, the damage and destruction of hepatic sinusoidal endothelial cells, collapse of hepatic sinusoids, hem- orrhage of subendothelial cells, atrophy and destruction of hepatocytes, etc. Compared with controls, the expression of MMP-9 in the blood sample, the lung and liver tissues of HSOS rats was increased. Conclusions： MMP-9 may have an important role in early patholoclical chanqes of HSOS, and thus the onset of the disease.

Validation of the Nanjing Criteria for Diagnosing Pyrrolizidine Alkaloids-induced Hepatic Sinusoidal Obstruction Syndrome

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.

Retrorsine Cooperates with Gut Microbiota to Promote Hepatic Sinusoidal Obstruction Syndrome by Disrupting the Gut Barrier

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.