Analysis Of Clinical Characteristics In Hepatic Sinusoidal Obstruction Syndrome

Objectives:To summarize and analyze the clinical symptoms,signs,serological,imaging,histopathological features and the response to treatment of hepatic sinusoidal obstruction syndrome（HSOS）patients.Provide guidance for clinicians to recognize,diagnose early and treat effectively.Methods:Enrolled 23 inpatients diagnosed with hepatic sinusoidal obstruction syndrome in the Department of Hepatobiliary and Pancreatic Medicine,Department of Hepatobiliary and Pancreatic Surgery and Department of Hematology of the First Hospital of Jilin University from January 2014 to October 2021.Among them,18patients were related to pyrrole alkaloids.4 cases were related to hematopoietic stem cell transplantation,and 1 case was related to liver transplantation.Collect the clinical data,including:gender,age,specific drugs or plants taken,and time of taking;clinical symptoms and signs:abdominal pain,abdominal distension,ascites,jaundice,hepatomegaly,splenomegaly,liver palm or spider nevus,etc;serological indicators:aspartate aminotransferase（AST）,alanine aminotransferase（ALT）,gamma-glutamine transpeptidase（GGT）,alkaline phosphatase（ALP）,cholinesterase,albumin,total bilirubin hormone,direct bilirubin,platelets（PLT）,prothrombin activity（PTA）,etc.Imaging（unenhanced liver CT scan+three-phase enhancement,hepatic vein color Doppler ultrasound,liver magnetic resonance imaging+enhancement）;liver histopathological features.Analysis from the following aspects:（1）Summarize and analyze the way,time and dose of pyrrole alkaloids in patients with pyrrole alkaloid-related hepatic sinusoidal obstruction syndrome;clinical symptoms,signs,serology,imaging and histopathological characteristics.（2）Summarize and analyze the clinical symptoms,signs and serological characteristics of hematopoietic stem cell transplantation-related hepatic sinusoidal obstruction syndrome at the time of diagnosis.Compared the serological differences with pyrrole alkaloid-related hepatic sinusoidal obstruction syndrome.（3）Compare the serological changes of pyrrole alkaloid-associated hepatic sinusoidal obstruction syndrome before and after 2 weeks of low molecular weight heparin anticoagulation and hepatoprotective therapy.Statistical analysis and related table drawing were carried out by using SPSS 26.0 and Excel software.Results:1.Clinical manifestations of pyrrole alkaloid-associated hepatic sinusoidal obstruction syndrome（PA-HSOS）（1）The basic situation of PA-HSOS patients and the situation of taking drugs or plantsThere were 18 PA-HSOS patients,including 8 male patients（44%）and 10female patients（56%）,with an average age of 57.22±2.05 years old.There were 13patients with clear history of taking"Tusanqi",and 6 cases were taking"Tusanqi"because of the back pain,joint pain,joint replacement,spinal trauma and lumbar disc-herniation.All of them were taken orally,including 2 cases of ingestion,1 case of decoction,and 3 cases of soaking wine.The dosage was variable:1 scoop each time,3-4 times a week for a 1 month;the total dosage was 1 catty.The frequency varies,including:1 time/day,2-3 times/day or 3-4 times/week.The time of first use of"Tusanqi"was uncertain,the shortest time can be traced back to 8 days before the onset of the disease,and the longest can be traced back to 1 year ago.3 cases of oral administration of various Chinese herbal medicine preparations（such as:Dabaidu capsule,snake venom）;1 case of wild herbs;1 case of unknown consumption.（2）PA-HSOS symptoms,signs,serological manifestationsThe most common symptoms and signs of PA-HSOS patients on admission were as follows:abdominal distension（94.44%）,ascites（83.33%）,and hepatomegaly（33.33%）.Serological mean levels:AST:88.00（45.65,143.30）U/L,ALT:45.90（27.80,119.15）U/L,GGT:125.90（49.98,387.23）U/L,ALP:（147.01±15.19）U/L,Albumin:（32.25±0.99）g/L,total Bilirubin:37.15（22.10,48.28）μmol/L,direct bilirubin:15.15（9.55,22.95）μmol/L,PLT（10~9/L）:117.50（87.75,167.25）×10~9/L,PTA:（65.00±3.83）%.（3）PA-HSOS imaging featuresLiver CT plain scan and three-phase enhancement:18 patients with PA-HSOS underwent liver CT plain scan and three-phase enhancement,which directly considered HSOS in 12 cases,manifested as:uneven reduction of liver parenchyma density or liver congestion,with a map pattern after enhancement heterogeneous enhancement or diffuse patchy,nodular hypoenhancement shadows.Hepatic veins or hepatic venules were not shown clearly.The remaining 6 cases were reported as:abnormal perfusion,chronic liver damage,heterogeneous fatty liver,inflammatory or localized fatty liver.1 case did the liver MRI scan and enhancement,manifested as:full liver shape,liver parenchyma signal and enhancement changed,and unclear display of left,middle and right hepatic veins and intrahepatic venules,HSOS was considered;1 case of plain scan was reported as:chronic liver disease damage.15 patients underwent color Doppler ultrasonography of hepatic veins,and 11patients showed hepatic sinusoidal obstruction syndrome,manifested as:liver parenchyma changed,hepatic vein slender diameter/spectrum showed increased resistance.（4）Histopathological manifestations of PA-HSOSAmong the 18 patients with PA-HSOS,7 patients had finished liver histopathological examination,and were diagnosed HSOS directly,and 3 patients were in acute stage.One of the more typical manifestations was as follows:zone III and zone II hepatic sinusoids around the central hepatic vein were highly dilated,most of the hepatocytes in zone III disappear,and the surrounding hepatocytes obviously shrinked and disappeared.After liver protection,anticoagulation,and symptomatic and supportive treatment,the histopathological examination after 6 months showed that the hepatic acinar structure remained generally normal,diffuse fibrosis around the focal central veins,more focal peri-sinusoidal fibers,and intermediate hepatic fibrosis.The cells were located in zone III,with irregular expansion of the hepatic sinusoids.2.Clinical symptoms,signs and serological characteristics at the time of diagnosis of hematopoietic stem cell transplantation-related hepatic sinusoidal obstruction syndrome,and serological differences with pyrrole alkaloid-related hepatic sinusoidal obstruction syndrome.When HSCT-HSOS patients were diagnosed,the most obvious clinical symptoms were ascites,hepatomegaly,abdominal distension,and abdominal pain.Mean levels of serological indexes:AST:（1417.48±821.38）U/L,ALT:（818.85±343.57）U/L,GGT:（158.15±72.96）U/L,ALP:（102.45±26.22）U/L,albumin:（26.60±2.23）g/L,total bilirubin:（31.38±14.55）μmol/L,direct bilirubin:（22.00±10.57）μmol/L,PTA:（47.00±9.09）%.Albumin in PA-HSOS group and HSCT-HSOS group was（32.25±0.99）g/L and（26.60±2.23）g/L,respectively;the fibrinogen was（2.49±0.17）g/L and（3.55±2.23）g/L,respectively.Albumin in PA-HSOS group was higher than that in HSCT-HSOS group,and fibrinogen was lower than that in HSCT-HSOS group,and the difference was statistically significant（P<0.05）.There was no statistical difference in liver serology among the remaining included groups（P>0.05）.3.Serological change before and after 2 weeks of low molecular weight heparin anticoagulation combined with hepatoprotective drugs in patients with pyrrole alkaloid-related hepatic sinusoidal obstruction syndrome.After 2 weeks of treatment with low molecular weight heparin anticoagulation combined with hepatoprotective drugs in 5 PA-HSOS patients,APTT and PTA were higher than before（P<0.05）,cholinesterase,hematocrit（HCT）,and hemoglobin were lower than before（P<0.05）,and there was no statistical difference in the other included liver enzymes（P>0.05）.Conclusions:1.In this study,the common age of onset of PA-HSOS patients is 55-64 years old,the youngest is 34 years old and the oldest is 68 years old.The time from the first use of"Tusanqi"to the onset is 8 days to 1 year.2.Among the PA-HSOS patients,most patients could have a clear history of taking"Tusanqi".A small number of patients take Chinese herbal medicines and wild vegetables,and the etiology of some patients is unknown.3.In this study,the most common clinical symptoms and signs of PA-HSOS patients are abdominal distension,ascites and hepatomegaly.Liver enzymes and bilirubin are slightly elevated,and platelets and PTA are slightly decreased.4.In PA-HSOS patients,typical liver CT manifestations are:uneven density reduction on plain scan,and uneven or diffuse patchy enhancement after enhancement.The typical pathological manifestations are:high degree of expansion of the hepatic sinusoids around the central veins of the hepatic lobules,and the disappearance of most of the hepatocytes in the hepatic lobules.5.In this study,the most common clinical symptoms of HSCT-HSOS patients are ascites,hepatomegaly,abdominal distension and abdominal pain.Liver enzymes show severe elevation.Compared with PA-HSOS patients,HSCT-HSOS patients have lower albumin and higher fibrinogen levels.6.In this study,the PTA of PA-HSOS patients is higher than before,after the treatment with hepatoprotective drugs combined with 2 weeks low molecular weight heparin.