Correlation Between HVPG And Clinical Stage In Cirrhosis Of Different Etiology And Analysis Of Its Influencing Factors

ObjectivesThe hepatic venous pressure gradient is closely related to the clinical stage of cirrhosis,which can effectively evaluate the severity and prognosis of cirrhosis.The purpose of this study is to explore the correlation between the gradient of hepatic vein pressure and the clinical stages of cirrhosis and the occurrence of liver cancer in Chinese,and to explore the influencing factors of the hepatic vein pressure gradient in different causes of cirrhosis.MethodsA retrospective analysis was made of 257 patients with cirrhosis hospitalized in the Department of Gastroenterology of Shandong Provincial Hospital from April 2010 to April 2019,including 173 patients with hepatitis B cirrhosis,35 patients with alcoholic cirrhosis and 49 patients with cirrhosis of unclear etiology,HVPG was measured in all patients.Through the electronic medical record system,we collected the basic demographic indicators and gastrointestinal bleeding history of patients,the serological indicators and imaging examination and gastroscopy results before HVPG,the measurement methods and results of HVPG,model of end stage liver disease(MELD)score,Child-Pugh score,clinical stages of cirrhosis(stage 1,stage 2,stage 3,stage 4,stage 5)and other data.According to the different causes of cirrhosis,patients were divided into three subgroups:hepatitis B,alcoholic liver disease and unclear etiology.The correlation between HVPG and clinical stages of cirrhosis and the occurrence of liver cancer was statistically analyzed.The cut-off value of HVPG in two adjacent clinical stages of liver cirrhosis was calculated by the receiver operating characteristics curve(ROC),and the predictive value was judged by the area under the ROC curve(AUC).The clinical data were collected to analyze the correlation of HVPG,and to further explore the factors affecting HVPG in the three subgroups of hepatitis B,alcoholic liver disease and unclear etiology.Spss25.0 was used for data analysis.Results:1.Correlation between HVPG and clinical stages of cirrhosis with different etiologies1.1 In the subgroup of hepatitis B,173 patients were included in the study,including 18 patients in 2-stage,42 patients in 3-stage,112 patients in 4-stage and 2 patients in 5-stage(H=18.706,P<0.001).There was a difference in HVPG level between stage 2 and stage 4(P=0.009 after adjustment),between stage 2 and stage 3(P=0.002 after adjustment),and there was no difference in HVPG level between other stages(P>0.05 after adjustment).There was no monotonous correlation between HVPG and clinical stage of liver cirrhosis(rs=0.133,P=0.080);combined stage 3 and stage 4 of liver cirrhosis into the same stage,and analyzed the results again.There was a moderate monotonous correlation between HVPG and clinical stage of liver cirrhosis(rs=0.432,P<0.001).In the hepatitis B subgroup,the best cut-off value of HVPG between stage 2 and stage 3 was 15.75mmHg(AUC=0.821,sensitivity 73.8%,specificity 77.8%),P<0.001,which was statistically significant;the best cut-off value of HVPG between stage 3 and stage 4 was 22.5mmHg(AUC=0.441,sensitivity 15.3%,specificity 90.5%),P=0.051,which was not statistically significant;the best cut-off value of HVPG between stage 4 and stage 5 was 24.5mmHg(AUC=0.964,sensitivity 100%,specificity 92.2%),P=0.026,which was statistically significant.1.2 In the alcoholic liver disease subgroup,there were 35 patients included in the study,including 0 in stage 1,6 in stage 2,6 in stage 3,22 in stage 4 and 1 in stage 5.There were differences in HVPG levels among different clinical stages of cirrhosis(H=12.171,P=0.007),among which there were differences in HVPG levels between 2 and 4 stages(P=0.024 after adjustment),and there were no differences in HVPG levels among other stages(P>0.05 after adjustment).Meanwhile,there was a moderate monotonous correlation between HVPG and clinical stages of cirrhosis(rs=0.592,P=0.001).In the subgroup of alcoholic liver disease,the best cut-off value of HVPG was 15.75mmHg(AUC=0.708,sensitivity 66.7%,specificity 83.3%),P=0.219,which was not statistically significant;the best cut-off value of HVPG was 16.25mmHg(AUC=0.758,sensitivity 77.3%,specificity 83.3%),P=0.089,which was not statistically significant;the best cut-off value of HVPG between stage 4 and stage 5 was 25.75mmHg(AUC=0.955,sensitivity 100%,specificity 95.5%),P=0.235,which was not statistically significant.1.3 In the sub group with unclear etiology,49 patients were included in the study,including 0 in stage 1,9 in stage 2,9:in stage 3,31 in stage 4 and 0 in stage 5.There were differences in HVPG levels among different clinical stages of cirrhosis(H=9.192,P=0.010),among which there were differences in HVPG levels between stage 2 and stage 4(P=0.012 after adjustment),and between stage 2 and stage 3(P=0.036 after adjustment),there was no difference in HVPG level between stage 3 and stage 4(P=1.000 after adjustment).There was a slight monotonous correlation between HVPG and clinical stages of cirrhosis(rs=0.318,P=0.026).The cut-off value of HVPG between stage 2 and stage 3 was 18.5mmHg(AUC=0.833,sensitivity 55.6%,specificity 100%),P=0.003,which was statistically significant;the cut-off value between stage 3 and stage 4 was 22.25mmHg(AUC=0.491,sensitivity 25.8%,specificity 100%),P=0.930,which was not statistically significant.2.The relationship between HVPG and hepatocarcinogenesis in patients with cirrhosisIn this study,there were 257 cases in total,32 cases in compensatory stage of cirrhosis,211 cases in decompensated stage,14 cases in liver cancer.There were differences in HVPG between compensatory stage(12.83 ± 3.33mmhg),decompensated stage(17.71 ± 5.00mmhg)and liver cancer(18.40 ± 3.96mmhg)(H=34.159,P<0.001).There were differences in HVPG between compensatory stage and decompensated stage(P<0.001 after adjustment)There was a difference in HVPG between the two groups(P=0.002 after adjustment),and there was no difference between the two groups(P=1.000 after adjustment).The best cutoff value of HVPG between compensatory stage of cirrhosis and liver cancer was 18.5mmhg(AUC=0.830,sensitivity 64.3%,specificity 96.8%),P<0.001,which was statistically significant.2.1 In the hepatitis B subgroup,there were differences in HVPG between the compensatory stage(12.83 ± 3.33mmhg),the decompensated stage(17.71±5.00mmhg)and the hepatoma(18.40 ± 3.96mmhg)of cirrhosis(H=17.372,P<0.001),among which there were differences in HVPG between compensatory stage and decompensated stage(P<0.001 after adjustment),between compensatory stage and liver cancer(P=0.004 after adjustment),and there was no difference in HVPG between liver cancer and decompensated stage(P=1.000 after adjustment).The best cut-off value of HVPG between compensatory stage of cirrhosis and liver cancer was 18.5mmhg(AUC=0.861,sensitivity 80%,specificity 94.4%),P=0.001,which was statistically significant.2.2 In the alcoholic liver disease subgroup,there were differences in HVPG between the compensatory stage(12.50 ± 2.00mmhg),the decompensated stage(19.10 ±5.24mmhg)and the liver cancer(15.00 ± 1.41mmhg)of cirrhosis(H=8.657,P=0.013),among which there were differences in HVPG between compensatory stage and decompensated stage(P<0.015 after adjustment).And there was no difference in HVPG between compensatory stage and liver cancer(P=1 after adjustment),between liver cancer and decompensated stage(P=0.772 after adjustment).The best cut-off value of HVPG between compensatory stage of cirrhosis and liver cancer was 13.5mmhg(AUC=0.900,sensitivity 100%,specificity 80%),P=0.176,which was not statistically significant.2.3 In the subgroup with unclear etiology,there were differences between HVPG in the compensatory period of liver cirrhosis(9.56+5.48mmHg),decompensated stage(17.83+7.23mmHg),and liver cancer(15+7.07mmHg).(H=9.293,P=0.010).There was a difference in HVPG between the compensatory period and the decompensated period(P=0.005 after adjustment),and there was no difference in the level of HVPG between the compensatory stage and the decompensated stage(P=0.947 after adjustment),between the compensatory stage and the decompensated stage(P=1.000 after adjustment).The best cut-off value of HVPG in compensatory stage of cirrhosis and liver cancer was 17mmHg(AUC=0.661,sensitivity 50%,specificity 100%),P=0.370,which was not statistically significant.3.Analysis of the influencing factors of HVPG in cirrhosis of different etiology.3.1 In the subgroup of hepatitis B,the influencing factors of HVPG were the measurement methods,AST,INR,ALB,ALP,stage of hepatic encephalopathy,Child-Pugh score,ascites grade,MELD score(P=0.012,0.038,0.019,0.003,0.002,0.001,0.027,0.002,0.015,respectively).The other indexes had no significant effect on HVPG(P>0.05).3.2 In the subgroup of alcoholic liver disease,the influencing factors of HVPG were ALB,Hb,INR,gastrointestinal bleeding history,Child-Pugh score(P=0.022,0.008,0.037,0.002,0.041,respectively).The other indexes had no significant effect on HVPG(P>0.05).The best cut-off value of HVPG in bleeding group and non-bleeding group was 16.25mmhg(AUC=0.828,sensitivity 78.3%,specificity 91.6%),P=0.002,which was statistically significant.3.3 In the subgroup with unclear etiology,the factors influencing the level of HVPG were Pt,INR,Child-Pugh score,ascites grade and MELD score(P=0.002,0.001,0.040,0.044 and 0.003,respectively).The other indexes had no significant effect on HVPG(P>0.05).Conclusions:1.The hepatic vein pressure gradient is correlated with the clinical stage of cirrhosis,and it can predict the progression of cirrhosis.With the aggravation of liver cirrhosis clinical stage,the level of hepatic vein pressure gradient is higher.2.The hepatic vein pressure gradient is related to the occurrence of liver cancer,which is of great significance in predicting the risk of liver cancer.3.There are many factors that affect the level of hepatic venous pressure gradient in patients with liver cirrhosis,but the influencing factors of hepatic venous pressure gradient are slightly different in different etiology.In the subgroup of hepatitis B,the influencing factors of HVPG were aspartate aminotransferase,AST,INR,ALB,ALP,stage of hepatic encephalopathy,Child-Pugh score,ascites grade and MELD score;in the subgroup of alcoholic liver disease,the influencing factors of HVPG were ALB,Hb,INR,gastrointestinal bleeding history and Child-Pugh score;in the subgroup of unclear etiology,the influencing factors of HVPG were Pt,INR,Child-Pugh score,ascites grade and MELD score.