Validation Of "Nanjing Criteria" For Pyrrolizidine Alkaloids Induced Hepatic Sinusoidal Obstruction Syndrome

Background&Aims:Hepatic sinusoidal obstruction syndrome(HSOS),also called hepatic veno-occlusive disease(HVOD),is a hepatic vascular disease characterized by oedema,necrosis,detachment of endothelial cells in small sinusoidal hepatic and interlobular veins,intrahepatic congestion,portal hypertension and liver dysfunction.In China,the major cause of HSOS has been the ingestion of products containing pyrrolizidine alkaloids(PAs),such as Tusanqi.The manifestations of patients with HSOS is nonspecific and prone to be misdiagnosed,and severe cases can lead to multiple organ dysfunction/failure with a high fatality rate.Liver biopsy might be needed to make the definite diagnosis.Nevertheless,since nearly all patients with PA-HSOS had ascites and coagulation disorders,transjugular liver biopsy(TJLB)might be more proper for these patients.However,TJLB is a difficult and expensive technology that cannot be routinely carried out in most hospitals.To some extent,the diagnosis for PA-HSOS can be made according to the improved Seattle and Baltimore criteria.However,the significant differences in epidemiology,ethnicity,etiology,and underlying diseases between patients with PA-HSOS in China and patients with HSCT-HSOS in Western countries suggest that the clinical characteristics of PA-HSOS are specific.The diagnostic criteria based on hematopoietic stem cell transplantation related hepatic sinusoidal obstruction syndrome(HSCT-HSOS)have been controversial for the diagnosis of pyrrolizidine alkaloids induced hepatic sinusoidal obstruction syndrome(PA-HSOS).Therefore,in 2017,the "Nanjing criteria" was put forward in the relevant consensus issued by the hepatobiliary group of the Chinese Medical Association for the diagnosis of PA-HSOS,but there were few validation studies of the new diagnostic criteria.The aim of this study was to validate the efficacy of "Nanjing criteria" for the diagnosis of PA-HSOS.Methods:Medical records of 379 eligible cases from 904 consecutive patients in 3 hospitals,who had abnormal liver function and ascites or abdominal distension,anorexia for less than six months,were collected from November 2011 to December 2018.The reference standard used to define the presence of true PA-HSOS was based on the liver pathological findings and a definite history of PA intake or detection of blood pyrrole-protein adducts(PPAs).Diagnosis of other liver diseases was based on the diagnostic criteria from EASL or ACG guidelines in recent years.Diagnostic performance of Nanjing criteria and simplified Nanjing criteria(several items in Nanjing criteria)were evaluated.Sensitivity,specificity,positive and negative predictive values(PPV and NPV)along with 95%CI,positive likelihood ratio,negative likelihood ratio,Kappa value and area under the ROC curves(AUROC)were calculated.Data were analyzed using the SPSS software,version 22.0.Results:There were 71 patients with PA-HSOS,144 patients with decompensated cirrhosis,33 patients with drug-induced liver injury(DILI),42 patients with Budd-Chiari syndrome(BCS),88 patients with acute liver failure(ALF)or subacute liver failure(SALF),and one patient with cardiogenic ascites.Nanjing criteria had sensitivity and specificity of 92.96%(95%CI:86.86-99.06)and 100%,respectively,for the diagnosis of PA-HSOS.The sensitivity and specificity of simplified Nanjing criteria(ii&iii&iv or ii&iv or iii&iv in Nanjing criteria)for the diagnosis of HSOS were 95.77%(95%CI:90.98-100)and 99.35%(95%CI:98.45-100),respectively.The Kappa value between "Nanjing criteria" and golden standard for diagnosis of PA-HSOS was 0.955.And the Kappa value of simplified "Nanjing criteria"(ii&iii&iv or ii&iv or iii&iv in"Nanjing criteria")were 0.956,as compared to the golden standard.The AUROC of Nanjing criteria in the diagnosis of PA-HSOS was 0.965(95%CI:0.930-1.000,P<0.01).The AUROC of simplified Nanjing criteria(ii&iii&iv or ii&iv or iii&iv in Nanjing criteria)was 0.976(95%CI:0.948-1.000,P<0.01).In addition,the combination of any binomial in ii,iii,iv of Nanjing Criteria,as long as the iv item was included,had a good diagnostic performance.Conclusions:Nanjing criteria and simplified Nanjing criteria have excellent performance in the diagnosis of PA-HSOS.In addition,the characteristic images of CT or MRI are of great significance for the diagnosis of PA-HSOS so that simplified Nanjing criteria containing this item have satisfying diagnostic accuracy.Differential diagnosis between PA-HSOS and part of BCS should be careful for their similar clinical characteristics and image findings.Angiography,history of ingesting PA-containing plants,detection of blood pyrrole-protein adducts,and liver histology are critical for the differential diagnosis between HSOS and BCS.