Clinicopathologic Analysis In Patients With Hepatic Sinusoidal Obstruction Syndrome Induced By Pyrrole-protein Adducts

BackgroundHepatic sinusoidal obstruction syndrome(HSOS)is a drug induced liver disease,previously known as a hepatic veno-occlusive disease(HVOD),characterized by damages to small hepatic vessels particularly the sinusoidal endothelium,resulting in liver dysfunction and the hypertension of portal vein.Based on etiology,HSOS is mainly classified into pyrrolidine alkaloid-related HSOS,hematopoietic stem cell tansplantation-related HSOS,and HSOS of unknow etiology.In western countries,the most common cause of HSOS is the conditioning treatment with amount of chemotherapy before haematopoietic stem cell transplantation(HSCT)or radiation,and the abundant usage of new chemotherapy medicine of malignant cancer.However,HSOS is usually caused by herbal medicine containing pyrrolizidine alkaloids(PA)in China,which is the most widely distributed natural toxin.The most frequent herbal medicine reported is Tusanqi "(i.e,gynura segetum),which is always mixed with aizoon stonecrop.The widespread herb in China contributes to increasing cases about PA-related HSOS.The pathogenesis of PA-related HSOS remains unclear.The early symptoms of this disease,such as right upper pain,ventosity and ascites,is diverse but non-specific,so that it is easily confused with Budd-Chiari syndrome,dencompensated cirrhosis and acute severe hepatitis,having a bad impact on the prompt diagnose and treatment.And the new serum remarkers have not been widely used.Consequently,Histopathology is still the vital standard for diagnose.However,we have no idea about detailed human histopathological changes of this disease.So we focused on analyzing the clinicopathologic characteristics of patients with HSOS exposed to "Tusanqi" to provide deep insights into development of this disease.ObjectivesHepatic sinusoidal obstruction syndrome(HSOS)induced by pyrrole-protein adducts(PPAs)is uncommon in China.We aimed to investigate histopathological manifestations of PA-HSOS in human,to provide deep insights into development of this disease.MethodsAccording to the criterion described in Expert consensus on diagnosis and treatment of pyrrolidine alkaloids-related sinusoidal obstruction syndrome(2017,Nanjing),we collected the clinical data of 16 patients with PA-HSOS who underwent liver biopsy.6 patients were enrolled in the First Affiliated Hospital of Zhengzhou University between May 2013 and October 2016,and 10 patients were enrolled at the China-Japan Friendship Hospital between February 2012 and May 2017.Patient information included age,gender,the plant part for eating,intake ways;intake time,clinical symptoms and liver function for the time of very beginning and 6 months after fellow up,the duration from the first time intake to symptoms appearance,the duration from the first time intake to liver biopsy,and histopathological information.On the basis of clinical features,we divided the patients into acute stage,subacute stage and chronic stage,observed their histopathology and analysed these date statistically.And we searched the relationship between prognosis and the proportion of severe haemorrhagic in liver lobule.Results1.After 6-month follow up,ALT and AST decreased,which has statistical differences.However,the amount of ALP、GGT、TBIL and ALB did not change statistically.2.Histopathology revealed:in early stage,the integrity of sinusoidal endothelial cells in the perivenular zone was damaged.Erythrocyte entered the space of Disse,and hepatic sinusoid narrowed relatively.In medium stage,hemorrhagic areas are full of fragmented Erythrocyte.Reticular fiber collapsed densely,collagenous fiber deposited gradually,and lumens expanded is covered with sinusoid endothelium(CD31+CD34-).In later stage,deposited collagenous fiber transformed into fibrous scar where existing many expanded lumens covered with vascular endothelium(CD34+CD31-).The injury of central vein endothelium is consistent with the sinusoidal one.3.The ranked number and the duration from drug intake to liver biopsy havethe positive relation.4.Based on the prognosis after 6-month treatment,the PA-HSOS patients are divided into the mild(complete recovery),the moderate(choronicity)and the severe(death or liver translation),Comparied with the severe group,the mild-moderate group has a lower proportion of liver lobule severe haemorrhagic.But there are no statistically significant differences between them.Conclusions1.Based on the consistance of TBIL and ALB,we propose that it may take long time for the recovery of this disease or after stopping drug intake continuous lesion can yet be induced by PA.2.According to the corresponding proportions of the different stages and degrees of hemorrhagic zone,we can predict the duration from drug intake to liver biopsy.3.Different stages of histopathological changes about PA-HSOS were observed.We cannot evaluate prognosis by only basing on the apportion of severe hemorrhagic injury.