Clinical Features Of Patients With Portal Pulmonary Hypertension And Expression Analysis Of Serum BMP9 And ET-1

Objective:（1）To screen the patients with portal pulmonary hypertension of the First Hospital of Jilin University,collect their clinical data and serum samples.（2）The concentrations of BMP9 and ET-1 in different groups were detected by ELISA experiment to explore the correlation between BMP9 and ET-1 and POPH.Research objects and methods:（1）Research objects:1)Analysis 57 patients with POPH of First Hospital of Jilin University from January 2018 to February 2023.2)A total of 28 POPH patients with serum collected were selected,and 29 patients with PAH caused by left heart disease,28 patients with PAH caused by lung disease,55 patients with cirrhosis（Including:15patients with alcoholic cirrhosis;14 patients with hepatitis B cirrhosis;11 patients with hepatitis C cirrhosis;15 patients with PBC）,25 patients with chronic HBV infection,3 patients with hepatitis B liver failure.Simultaneously,select 30 healthy patients as controls.（2）Method:Based on the inclusion criteria and exclusion criteria,57 sick persons with POPH were enrolled for 3591 cirrhosis patients with portal hypertensive in the First Hospital of Jilin University.Clinical data of patients were analyzed:（age,sex,etiology,MELD score,hypertension,diabetes,liver cancer,splenectomy,test aspects（PO₂,PCO₂,HGB,PLT,CREA,ALT,AST,ALB,TBIL,PT,INR）,examination（electrocardiogram,heart color ultrasound,lung CT,abdominal examination）,complications of cirrhosis（hepatic encephalopathy,gastrointestinal bleeding,liver failure,etc）,serum samples of patients were collected.The levels of BMP9 and ET-1in POPH patients and the above control group were detected by ELISA,and the differences of BMP9 and ET-1 levels among multiple groups were compared.Results:（1）Between January 2018 and February 2023,57 sick persons with POPH（1.59%）were selected from the First Hospital of Jilin University.Clinical data were as follows:the mean age was 58.74±11.52 years old,there were 26 females（45.61%）,MELD score was 13.84（9.86-18.50）points.11 patients（19.3%）had hypertension,12 patients（21.05%）had diabetes,and 7 patients（12.28%）had a history of splenectomy.Among the different causes of POPH,alcohol was the most common cause（19 cases,33.33%）,followed by hepatitis B（16 cases,28.07%）,and the number of autoimmune factors was the same as that of hepatitis C（8 cases,14.04%）.The complications of liver cirrhosis of POPH patients were analyzed:19 patients had gastrointestinal bleeding,12 patients（21.05%）had liver cancer or had viable tumors in their liver,10patients（17.54%）had hepatic encephalopathy,and 8 patients（14.04%）had portal vein thrombosis.Laboratory results:PO₂:77.66±25.76mm Hg（n=44）,PCO₂:32.37±6.04mm Hg（n=44）,HGB:96.32±28.07g/L,PLT:77.00（44.50-108.00）*10^9/L,ALB:28.42±5.80g/L,TBIL:38.50（19.80-86.70）umol/L,ALT:24.60（16.20-33.90）U/L,AST:41.4（30.80-65.30）U/L,PT:15.50（13.70-19.30）s,INR:1.30（1.17-1.63）,CREA:64.50（50.85-90.10）umol/L.More than half of POPH patients had normal ECG results;tricuspid regurgitation,left atrium enlargement,and mitral regurgitation were the most common abnormal results of cardiac color ultrasound.The relevant parameters of lung CT were measured as follows:the diameter of pulmonary trunk was 34.14±5.41mm,the diameter of aortic trunk was32.00（30.00-36.00）mm,and the diameter of pulmonary trunk/aortic trunk was1.04±0.20.（2）In the BMP9-related experiment,1）Compared with the healthy,the serum concentration of BMP9 in patients with POPH was lower（P<0.001）;2)Compared with PAH caused by left heart disease（P<0.001）and PAH caused by lung disease（P<0.001）,the serum BMP9 concentration in POPH group was also significantly lesser;2)Compared with the healthy person,the serum BMP9 concentration in the cirrhotic patients with non-POPH was also significantly fewer（P<0.001）;3)Compared with patients with chronic HBV infection,the serum BMP9 concentration of hepatitis B POPH（P<0.001）,hepatitis B cirrhosis with non-POPH（P<0.001）,hepatitis B liver failure（P=0.003）was significantly lower.（3）In the ET-1 related experiment,1)Compared with the healthy group,the PAH caused by left heart disease（P=0.006）,the PAH caused by lung disease（P<0.001）,the liver cirrhosis with non-POPH group was significantly increased（P<0.001）,POPH group was not significantly increased,but the overall ET-1 level was higher（P=0.219）;2)Compared with patients with alcoholic cirrhosis,hepatitis C cirrhosis and PBC,the serum ET-1 concentration in patients with hepatitis B cirrhosis was significantly higher（P<0.001）.Conclusion:（1）In this study,the incidence of POPH in patients with cirrhosis was about1.59%.In the POPH population,tricuspid regurgitation,left atrium enlargement,and mitral regurgitation are the most common abnormal results of cardiac color ultrasound.In terms of causes,alcohol is the most common cause,followed by hepatitis B virus infection,autoimmune liver disease and hepatitis C virus infection.Among the complications related to cirrhosis of POPH patients,gastrointestinal bleeding is the most common complication,followed by liver cancer and hepatic encephalopathy.（2）BMP9 concentration in the patients of POPH was significantly lesser than that in the left heart disease caused PAH and lung disease caused PAH groups.Considering the application of BMP9,POPH could be distinguished from the common clinical left heart disease caused PAH and lung disease caused PAH.Compared with chronic HBV infection,serum BMP9 concentration was significantly lower in patients with hepatitis B POPH,hepatitis B cirrhosis with non-POPH,and hepatitis B liver failure,suggesting that low BMP9 is more likely to be associated with liver hypofunction.（3）Compared with the healthy group,the serum ET-1 concentration in the PAH group caused by left heart disease and the PAH group caused by lung disease was significantly increased,while the POPH group had no significant increase,but the overall ET-1 level was higher,which again confirmed that the increase of ET-1 was related to the onset of PAH.