The Establishment Of A Risk Prediction Model For Chronic Hepatitis B And The Effect Of Integrated Chinese And Western Medicine On The Incidence Of Liver Cancer In Patients With Hepatitis B Cirrhosis

Chronic hepatitis B virus infection increases the risk of developing cirrhosis,liver failure,hepatocellular carcinoma and even death.For patients with chronic hepatitis B,the progression of hepatitis B-related liver cirrhosis,and then further progress for primary liver cancer,is the natural course of disease.A small number of cases can change into hepatocellular carcinoma directly,but most hepatocellular carcinoma cases are based on hepatitis B-related liver cirrhosis.Prevention of hepatocellular carcinoma is an important therapeutic target for chronic hepatitis B virus.In China,the primary cause of liver cancer in the first place that is hepatitis B virus infection,80%of domestic patients with liver cancer is caused by hepatitis B virus infection.Therefore,to creat a HCC risk score for chronic hepatitis B patients based on their demographic characteristics and commom clinical indexes is of great usefulness.A risk score like that can predict the risk of HCC,guide the adjustment of treatments,and search a effective Chinese and Western integration therapy.Objective1 The clinical data of patients with chronic hepatitis B were systematically analyzed.The independent influencing factors of hepatocellular carcinoma were screened by COX single factor and COX multivariate analysis.The risk prediction scale model was established and the accuracy of the model prediction was verified.2 To observe the effect of antiviral combined with traditional Chinese medicine on the occurrence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis,and to provide reference for the clinical prevention of liver cancer in patients with posthepatitic cirrhosis.Methods1 This is a retrospective study of 5148 patients treated for CHB between July 2008 and December 2010 at the Beijing Ditan Hospital,Capital Medical University,China.All cases are divided into two groups by 7:3 through a randomization method.There are 3604 cases in the derivation cohort and 1544 cases in the validation cohort.In the derivation cohort,we use univariable and multivariable Cox proportional hazards regression models to estimate the effect of various variables on the hazard of HCC occurrence.The we creat a risk score for hepatocellular carcinoma based on the independent influencing factors which we filtered out.We use the receiver operator characteristic curve(ROC)to divide the critical value,and use the area under the ROC curve(AUC)to evaluate accuracy of the modle in the derivation cohort and the validation cohort.2 This is a retrospective study of 513 patients treated for hepatitis B-related cirrhosis between July 2008 and December 2010 at the Beijing Ditan Hospital,Capital Medical University,China.The patients are divided into two groups:the western medicine group(n=291)and the integrative medicine group(n=222).The western medicine group is given the anti-viral treatment.The integrative medicine group is added with a kind of Chinese medicine,choosed from 4 kinds of medicines based on patients' syndrome:anluo huaxian pill,fufang biejia ruangan pill,fuzheng huayu capsule,and heluo shugan pill.The incidence of HCC in two groups was compared.The incidence of HCC in two groups under different HCC risk levels was compared.The incidence of HCC in two groups under different clinical stages was compared.The end point of observation is the time point HCC occured or follow-up time of 5 years.Results1 Analysis of datas from 3604 cases in the derivation cohort by univariable Cox proportional hazards regression models shows that:age,sex,cirrhosis,ALT(alanine aminotransferase),TBil(serum total bilirubin),GLB(globulin),ALP(alkaline phosphatase),CHE(cholinesterase),NE#(neutrophil count),LY#(lymphocyte count),PLT(platelet count),Urea,HBeAg,and HBV DNA quantification are parameters associated with the risk of hepatocellular carcinoma.Multivariable Cox proportional hazards regression models shows that:age,sex,cirrhosis,baseline PLT(platelet count)and HBV DNA were independent factors in the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(P<0.05).Calculate the Youden index(sensitivity + specificity-1)of age,PLT(platelet count),and HBV DNA quantification through the sensitivity and specificity of the area under the operating characteristic curve(ROC).Look out the optimal critical values corresponding to the maximum Youden index and stratify the 3 variables:age>46 years and age<46 years,PLT ?120.3×109/L and PLT<120.3×109/L,HBV DNA?5.9 log10copies/ml and HBV DNA<5.9 log10copies/ml.Analyse the 3 stratified variables,gender,whether cirrhosis in Forward LR way of the multivariable Cox proportional hazards regression models.At last we find these 5 factors are independent predictors of HCC and creat a risk score modle to predict the risk of HCC for patients with CHB.The score points of the modle ranges 0-9.The area under the receiver operating characteristic curve(ROC)is 0.803.The optimal critical value corresponding the maximum Youden index is 6,the sensitivity is 71.7%,the specificity is 79.8%.Therefore,the total score of<6 points for the low risk group,?6 points for the high risk group.The model was validated using the cases of the verification cohort,and the area under the receiver operating characteristic curve(ROC)was obtained as 0.807.2 The baseline characteristics of chronic hepatitis B cases before treatment between the the western medicine group and the integrative medicine group are of great comparability.The incidence of hepatocellular carcinoma is significantly lower in the integrative medicine group than that of the western medicine group(26.6%vs 33.7%,P ?0.034<0.05).The incidence of hepatocellular carcinoma in higher risk score points cases is significantly higher in the integrative medicine group than that in the western medicine group(31.9%vs 44.6%,Log-Rank P=0.023<0.05).There is no significant difference in the incidence of HCC between the TCM group and the western medicine group of patients with lower risk score points(P>0.05).The incidence of hepatocellular carcinoma in cases with compensated liver cirrhosis is significantly higher in the integrative medicine group than that in the western medicine group(18.3%vs 33.1%,P = 0.003<0.05).There is no significant difference in the incidence of HCC between the TCM group and the western medicine group of patients with decompensated cirrhosis(P>0.05).Conclusion1 The risk score modle of hepatocellular carcinoma in 5 years for patients with chronic hepatitis B based on age,sex,cirrhosis,baseline PLT(platelet count)and HBV DNA quantification is of relative high clinical value.2 Chinese and Western integration therapy is better than the effect of simple antiviral therapy when used to reduce the incidence of HCC in patients with hepatitis B-related liver cirrhosis.,especially for patients with higher risk core points and compensated liver cirrhosis.