Clinical Study Of Rugan Granules Combined With Entecavir In Compensated Cirrhosis With Chronic Hepatitis B

Objective:1?To evaluate the value of the FibroScan?ultrasonic semi-quantitative scoring and combination in diagnosing the compensated cirrhosis with chronic hepatitis B.2?To observe the changes of ALT,AST,PLT,ALB and HBV DNA quantitative after the treatment with Ruangan granules Combined Entecavir in compensated cirrhosis with chronic hepatitis B.The effect of Rugan granule combined with entecavir was evaluated by TCM syndrome ? Liver histopathology ?ultrasonic semi-quantitative scoring ?FibroScan and FIB-4 index.Methods:1.300 patients who were diagnosed compensated cirrhosis with chronic hepatitis B were chosen from 12 hospitals in Guangdong Province.Among them,110 cases were examined by histopathology before and after treatment.2.300 patients were divided into Ruangan granules Combined Entecavir treatment group with 200 cases and Entecavir group with 100 cases,Histopathological examination was performed before and after treatment in 110 cases,80 in combination group and 30 in Entecavir group.3.300 patients were underwent Fibroscan?color doppler ultrasound and routine laboratory tests.The combination group was treated with Ruangan granules Combined Entecavir and Entecavir group was treated with Entecavir onlyfor 48 weeks.4.By taking liver pathological fibrosis staging as gold standard,receiver operating characteristic curve(ROC)of FibroScan,ultrasonic semi-quantitative scoring and their combined diagnosis model were drawn out.The area under the curve(AUROC)?sensitivity,specificity ?positive predictive value(PPV)and negative predictive value(NPV)were used to evaluaterd the diagnose value of FibroScan,ultrasonic semiquantitative scoring and their combined in different stage of liver fibrosis.5.After 48 Weeks treated,the changes of TCM syndrome ? Liver histopathology?ultrasonic semi-quantitative scoring?LSM and FIB-4 index were observation to make sure the clinical efficiency of Ruangan granules Combined Entecavir.Results:1?Application of FibroScan combined with ultrasonic semi-quantitative scoring for compensated cirrhosis with chronic hepatitis B virus.(1)Correlation analysis reveal LSM value and ultrasonic semiquantitative scoring had a positive correlation with Ishakfibrosis score with correlation coefficients of 0.566 and 0.304,respectively and have statistical sense(R=0.566?0.304,P<0.05)).Knodell necroinflammatory score was positively correlated with FibroScan(R=0.206,P=0.032),but there was no significant correlation between Knodell necroinflammatory score and ultrasonic semi-quantitative scoring(R=0.046,P=0.63).(2)The areas under the ROC curve(AUROC value)of FibroScan and ultras onic semi-quantitative scoring and their combination for Ishakfibrosis sc ore(F3-F4)was 0.851(95%CI:0.77-0.912)?0.719(95%CI:0.624-0.801)?0.901(95%CI:0.83-0.95),respectively and for Severe fibrosis(F3)was 0.822(95%CI:0.71-0.91)?0.657(95%CI:0.53-0.77)?0.913(95%CI:0.82-0.97)respectively.Taking F3 or F3-4 diagnostic standard as definition,FibroScan and the combined diagnosis of FibroScan with ultrasonic semi-q uantitative scoring are significantly higher than ultrasonic semi-quantit ative scoring alone(P<0.05),but The combination does not surpass Fibro Scan alone(P>0.05).The AUROC of FibroScan and ultrasonic semi-quantita tive scoring and their combination for early-stage viral liver cirrhosis(F4)was0.868(95%CI:0.79-0.93)?0.832(95%CI:0.75-0.9)?0.901(95%CI:0.83-0.95),Taking F4 diagnostic standard as definition,combined diagn osis of FibroScan with ultrasonic semi-quantitative scoring are significa ntly higher than FibroScan or ultrasonic semi-quantitative scoring alone(P<0.05).(3)The best cut-off value of FibroScan?ultrasonic semi-quantitative scoring and their combination were 10.1kpa?7point and 0.494 in diagnosis of fibrosis pathological stage(F3-F4),8.9kpa?7 point and and 0.414 in diagnosis of Severe fibrosis(F3)and 11.8kpa?8 point and 0.582 in diagnosis of early-stage viral liver cirrhosis(F4)2?The clinical research of ruangan granulescombined entecavir in treat compensated cirrhosis with chronic hepatitis B virus.(1)Comparison of TCM syndrome score:The TCM symptom of Ruangan granules Combined Entecavir group and Entecavir group reduced after the treatment,with significant differences(P<0.05).The clinical efficiency of the Ruangan granule Combined Entecavir group(80.93%)was much better than Entecavir group(58.33%),with significant differences(P<0.05).(2)Comparison of liver histopathology: There were 67 cases(90.54%)and 16cases(57.14%)with Knodell Hai score decreased>2 points in the Ruangan granule Combined Entecavir group and Entecavir group respectively,the difference was statistically significant(P<0.01).There were 45 cases(60.81%)and 10 cases(35.71%)with Metavir score decreased>1 in the Ruangan granule Combined Entecavir group and the Entecavir group respectively.the difference between the two groups was statistically significant(P<0.05).There were 45 cases(60.81%)and 6 cases(21.43%)with Knodell Hai score decreased>2 points and Metavir score decreased> 1 respectively in the Ruangan granule Combined Entecavir group and Entecavir group respectively,there was a significant difference between the two groups(P<0.01).(3)Comparison of liver FibroScan and ultrasonic semi-quantitative scoring: There were 92 cases(47.42%),28 cases(33.33%)with ultrasonic semi-quantitative scoring decreased > 2 points in the Ruangan granule Combined Entecavir group and Entecavir group respectively,the difference was statistically significant(P<0.05).There were 142 cases(73.2%)and 56 cases(66.67%)with LSM decrease>3 kPa in the Ruangan granule Combined Entecavir group and Entecavir group respectively,with no significant difference(P>0.05).(4)Comparison of FIB-4 index: Ruangan granule Combined Entecavir group had a significant lower FIB-4 index after the treatment(P<0.05),but The difference of FIB-4 before and after entecavir treatment was not statistically significant(P>0.05).The difference between the two groups after treatment was statistically significant(P<0.05).(5)Comparison of HBV DNA:There were 71 cases(36.6%)and 11 cases(13.1%)with HBV DNA were undetected in the Ruangan granule Combined Entecavir group and Entecavir group respectively after 24 weeks treatment,with significant difference(P<0.01).There were 116(59.7%)and 48(57.14%)with HBV DNA were undetected in the Ruangan granule Combined Entecavir group and Entecavir group respectively after 48 weeks treatment,without significant difference(P>0.05).(6)Comparison of ALT?AST?PLT?ALB levels: The levels of ALT and AST in the Ruangan granule Combined Entecavir group were significantly lower than those before treatment,and the levels of PLT and ALB were higher than those before treatment(P<0.05).The levels of ALT and AST in Entecavir group were significantly lower than those before treatment and the levels of ALB was higher than those before treatment(P<0.05).However,The difference of PLT level before and after entecavir treatment was not statistically significant(P>005).Compared with the ETV group,there was no significant difference in the change of the levels ofALT,AST,PLT and ALB in the combination group(P>0.05)Conclusion:1?The Diagnostic value of FibroScan combined with ultrasonic semiquantitative scoring in the diagnosis of severe fibrosis and compensated cirrhosis is higher than they used alone,allowing most patients with Chronic hepatitis B avoiding Liver biopsy histopathology examination.In addition,it is of great significance to guide clinical antiviral therapy and prevent the progress of liver fibrosis.2?Ruangan granules Combined Entecavir can improve the symptoms and signs of patients with severe liver fibrosis,further improve the curative effect of reversing hepatic fibrosis and improve the negative rate of HBV DNA.