Relationship Between Plasma HGF/s-Met With The Severity And Prognosis Of Sepsis Patients

Objective:To investigate the relationship between plasma hepatocyte growth factor?HGF?/soluble cellular-Mesenchymal to epithelial transition factor?s-Met?with the severity and prognosis of sepsis patientsMethods:A single-center,prospective,observational clinical research was conducted.Patients admitted to the Department of Critical Medicince,Zhongda Hospital,Southeast University from November 2017 to March 2018,with the diagnosis of sepsis were prospectively enrolled.The demographic and baseline characteristics including gender,age,body mass index?BMI?,co-morbidities,source of infection,Acute Physiology and Chronic Health Evaluation II?APACHE II?score,Sequential Organ Failure Assessment?SOFA?score,lactic acid,central venous blood oxygen saturation?ScVO₂?,arteriovenous CO₂ partial pressure difference?Pv-aCO₂?,complications including acute kidney injury?AKI?and shock;management including the use of invasive mechanical ventilation,continuous renal replacement therapy?CRRT?,vasoprssor,norepinephrine,fluid intake and balance;patermeters reflexing vascular endothelial injury and organ function were recorded.The plasma HGF and s-Met at Day1 and Day3 were measured by enzyme linked immunosorbent assay?ELISA?.The patients were followed up to 28-day with mortality recoreded.?1?Patients were divided into survivor and nonsurvivor group according to 28-day survival,and the level of plasma HGF and s-Met and vascular endothelial injury and organ function indicators at Day1 and Day3 were compared;?2?Patients were grouped according to the severity of sepsis ?shock or not,SOFA?8 or not,APACHE II?15 or not?,and the plasm HGF and s-Met at Day1and Day3 were compared.Result1.Baseline CharacteristicsA total of 141 sepsis patients were admitted during study,and 86 patients were enrolled finally.Among them,64 patients survived,22 patients deceased,50 patients with septic shock,APACHE II score was 24±10,SOFA score was 8±4,with the 28-day mortality of 25.6%.There was no significant difference in age,gender,co-morbidities and source of infection between the survival and the nonsurvival group?P>0.05?.Compared with the survivor group,the APACHE II score,Day1 fluid balance,lactic acid were all significantly increased?P<0.05?;ScVO₂was significantly decreased?P=0.018?;the use of invasive mechanical ventilation,CRRT,vasoconstrictor,norepinephrine dosage,the incidence of AKI and shock increased significantly in nonsurvival group?P<0.05?.2.Comparison of plasma HGF and s-Met levels in survivor and nonsurvivor groups at Day1 and Day3.2.1 Comparison of plasma HGF levels in survivor and nonsurvivor groups at Day1 and Day3The plasma HGF level of Day1 and Day 3 was significantly increased in nosurvivor group compared with survivor group[pg/mL,1872?1619,2170?vs.1667?1456,1917?,P=0.002,and1808?1481,2149?vs.1309?864,1572?,P=0.001,respectively].The plasma HGF levels in the survival group were significantly reduced at Day3[pg/mL,1309?864,1572?vs.1667?1456,1917?,P=0.000]in survivor group but no significant difference in the nonsurvivor group[pg/mL,1808?1481,2149?vs.1872?1619,2170?,P=0.375].2.2 Comparison of plasma s-Met levels at Day1 and Day3 in survivor and nonsurvivor groupsThe plasma s-Met in the nonsurvivor group at Day1 and Day 3 was significantly increased compared with survivor group[pg/mL,1985?1806,2705?vs.1807?1603,1974?,P=0.017,and2141?1924,2572?vs.1740?1519,2296?,P=0.028,respectively].Compared with Day1,there was no significant difference in plasma s-Met level in survival group of Day3?P=0.394?.Compared with Day1,there was no significant difference in the plasma s-Met level of Day3 in the death group?P=0.442?.3.Comparison of organ function between the survival group and the nonsurvivor group.3.1 Comparison of vascular endothelial injury indicators in the survival group and nonsurvivor group:Compared with survival group,the group of death in patients with Day1 liquid balance increased significantly?P=0.007?.there was no significant difference in Day1 liquid intake,EVLWI,PVPI,SVRI?P>0.05?.At Day3,compared with survival group and nonsurvivor group the liquid intake increased significantly?P=0.005?,and SVRI decreased?P=0.042?,there was no obvious difference in EVLWI,PVPI,liquid balance in Day3?P>0.05?.3.2 Comparison of immune inflammatory markers in survival group and nonsurvivor group:Compared with the survival group,the levels of Day1 CRP and IL-6 in the nonsurvivor group were significantly increased?P<0.05?.Compared with the survival group,the level of HLA-DR in the nonsurvivor group was significantly reduced?P=0.001?.There was no statistically significant difference between the two groups in T,HR,WBC,PCT at Day1?P>0.05?.In the nonsurvivor group,PCT level was significantly higher than the survival group at Day3?P=0.02?.There was no statistically significant difference between T,HR,WBC,CRP,IL-6 and HLA-DR in the two groups at Day3?P>0.05?.3.3 Comparison of coagulation function indicators in the survivor group and the nonsurvivor group:compared with the survival group,PT in the nonsurvivor group was significantly prolonged?P=0.006?,and the D-dimer,FDP,PLT were significantly reduced in Day1?P<0.05?.There was no statistically significant difference between the two groups in the APTT and FIB?P>0.05?.Compared with the survival group,APTT and PT were significantly prolonged and PLT significantly reduced in the nonsurvivor group in Day3?P<0.05?.There was no significant difference in D-dimer,FDP and FIB in the two groups?P>0.05?.3.4 Comparison of liver and kidney function indicators in survival group and nonsurvivor group:Compared with the survival group,the total bilirubin?TBIL?in the nonsurvivor group was significantly increased?P=0.039?.Compared with the survival group,TBIL and BUN were significantly elevated in the nonsurvivor group at Day3?P<0.05?.4.Relationship between plasma HGF,s-Met level and severity of sepsis patients.4.1 Comparison of plasma HGF and s-Met levels in patients with sepsis and septic shockCompared with the sepsis group,the serum HGF level of the patients in the septic shock group was significantly increased[pg/mL,1793?1568,2030?vs.1588?1298,1859?,P=0.002].There was no significant in plasma HGF level difference between the two groups of Day3?P=0.791?.Compared with the sepsis group,there was no significant difference in plasma s-Met evels in septic shock group both Day1 and Day3?P>0.05?.4.2 Comparison of SOFA?8 and SOFA<8 of plasma HGF,s-Met level in Day1 and Day3Compared with SOFA<8 group,the plasma HGF level of patients in Day1 of SOFA?8 was significantly increased[pg/mL,1817?1580,2030?vs.1568?1314,1857?,P=0.002].Compared with SOFA<8 group,there was no significant difference in plasma HGF level in patients with SOFA?8?P=0.193?.Compared with SOFA<8 group,there was no significant difference between Day1 and Day3 plasma s-Met level in SOFA?P>0.05?.4.3 Comparison of the plasma HGF and s-Met level between APACHE II?15 and APACHE II<15Compared with the APACHE II<15 group,the plasma HGF level in the APACHE II group was significantly higher than that in APACHE II?15 groups[pg/mL,1744?1540,1988?vs.1494?1346,1667?,P=0.017].Compared with the APACHE II<15 group,there was no significant difference in the serum HGF level in the APACHE II?15 group?P=0.378?.Compared with the APACHE II<15group,there was no significant difference in the plasma s-Met level between the APACHE II?15and the APACHE II<15 groups at Day1 and Day3?P>0.05?.4.4 Comparison of plasma HGF and s-met levels in patients with liver or kidney dysfunctionCompared with the normal liver function group,the plasma HGF level of Day1 in patients with liver dysfunction increased significantly[pg/mL,1872?1639,2214?vs.1667?1499,1889?,P=0.032].The plasma HGF level of Day3 showed an upward trend[pg/mL,1571?1367,2069?vs.1353?867,1655?,P=0.072].The plasma s-Met levels of Day1 and Day3 showed no significant difference?P>0.05?.Compared with the non-AKI group,the plasma s-Met level of Day1 in patients in the AKI group increased significantly[pg/mL,1968?1807,2838?vs.1756?1611,1871?,P=0.007].There was no significant difference in plasma s-Met level of Day3?P=0.506?.There was no significant difference in plasma HGF levels of Day1 and Day3 in the AKI group compared with the non-AKI group?P>0.05?.5.Predictive value of plasma HGF and s-Met levels in patients with sepsis for 28-day mortality risk.The ROC curve analysis was employed on plasma HGF,s-Met at Day1.The cut-off value of HGF was 1832pg/mL,which predicted that the sensitivity,specificity was 63.6%,71.9%.The cut-off value of s-met was 1923pg/mL,which predicted the sensitivity,specificity was 63.6%,65.6%,respectively.The ROC curve analysis was performed for the plasma HGF,s-Met at Day3.The cut-off value of HGF was 1380pg/mL,which predicted that the sensitivity,specificity was 93.8%,60%respectively.The cut-off value of s-Met was 1854pg/mL,which predicted that the sensitivity,specificity was81.3%,55.6%respectively.6.Comparison of the severity and prognosis of patients which gouped by the joint of plasma HGF and s-Met in Day1.Based on mortality risk prediction cut-offs of plasma HGF and s-Met?1832 pg/mL and 1923pg/mL?of Day1 in patients with sepsis,the patients were divided into high HGF high s-Met,high HGF low s-Met,low HGF high s-Met and low HGF low s-Met group.Compared with high HGF high s-Met group,SOFA score,norepinephrine dosage,the 28 day mortality significantly decreased?P<0.05?.There was no significant difference between the four groups in the APACHE II score,the use of invasive mechanical ventilation and CRRT,the incidence of shock,and the length of hospitalization in the ICU?P>0.05?.7.Relationship between plasma HGF,s-Met level and vascular endothelial injury in sepsis patients.In terms of vascular endothelial permeability,plasma HGF and PVPI,fluid intake and balance were positively correlated?P<0.05?,and negatively correlated with SVRI?P=0.494?,no obvious correlation with EVLWI?P=0.649?.There was no significant correlation between plasma s-Met and SVRI,PVPI,EVLWI,fluid intake,and fluid balance?P>0.05?.In terms of inflammation response,plasma HGF level was positively correlated with IL-6 and PCT?P<0.05?.In terms of coagulation function,plasma HGF level was positively correlated with APTT?P=0.012?.The plasma s-Met level was positively correlated with PT?P=0.002?.Conclusions:Plasma HGF were associated with the severity and prognosis in patients with sepsis.The higher the level of HGF,the worse the condition and prognosis of sepsis patients.Plasma s-Met.was associated with the poor prognosis in patients with sepsis.