| Objectives:the adverse outcomes of chronic HBV infection are a polygenic trait. We performed a genome-wide screen to identify progression related variants in the respective adverse outcomes including HBV carrier, cirrhosis, liver cancer and acute liver failure.Methods:The initial genome-wide screen by affymatrix SNP 6.0 was done in pooled DNA in randomly selected 86 individual from 100 samples among each outcome. SNPs fulfilling the selection criteria of the pooling stage were genotyped individually in this same sample and additional sample, of which totally included heath HBV carrier 234,cirrhosis 300,liver cancer 300 and acute liver failure 171.Results:we combined two different and stringent statistical approaches (a single-point method and, as a filter for the most significant SNPs, a sliding-window method) to select SNPs of high statistical confidence, finally 7 SNPs is genotyped individually, two genomic loci encoding TBX5 rs382514(additive model P=0.024, dominant model P=0.008 OR 1.8(1.1-2.9)) and SCUBE3 rs 3800385 (additive model P=0.02, dominant model P=0.0076 OR 1.6(1.1-2.32)) was significantly associated with cirrhosis. And SNP rs3800385 of SCUBE3 is significant associated with liver cancer in additive model.Conclusions:Two-stage genetic analysis from above experiments suggests a role for TBX5 and SCUBE3 in HBV-related cirrhosis. Objectives:To describe and analyze the clinical features, complications and follow-up outcomes of HBV-related acute liver failure.To establish prognositic model according to results of follow-up study and compare with current acute liver failure prognositic models such from MELD, Sun, Dhiman prognositic model.To validate accuracy of our model in a indenpent retrospective corhort.Methods:Prospective cohort study consisted of 4 hospital and retrospective cohort included 2 hospital,254 and 43 consecutive patients with acute liver failure admitted over the same 18-month period from the prospective cohort and retrospective cohort respectively.Detailed clinical, Laboratory data and complications collected and analyzed the significant diffence between survival vs. nosurvival group and cirrhosis vs. nocirrhosis group. Logistic regression was also carried out to build prognositic model. Compared our model with current prognostic models by ROC curve, and to validate its predicting accuracy in retrospective independent cohort.Results:The median age of the prospective and retrospective was 40.58 (14-69) and 43.3(20-66) respectively; Cirrhostic rate in prospective group and retrospective group is 27.16% and 27.9% respectively; the overall group was predominantly male 88.89% and 90.7% in prospective group and retrospective group respectively.The follow-up study time is averagely 19.5 (0-30) months from time discharge from hospital and the censored time is Dec,2009. Overall survival rate was 34.68%(103 of total 297), and 35.03% in prospective group and 32.58% in retrospective group Independent risk analysis in survival and nosurvivor goup indicated age, PT, PTA,Fb, Total Bilirubin, DB, GGT, Lactate dehydrogenase, Chlorine, Creatinine,MELD; and Complication of Splenomegaly, Peritonitis, Ascites, Hepatic encephalopathy, Hepatorenal syndrome, Cirrhosis was significant between survival group and death group, the difference of clinical characteristics also existed in cirrhostic and nocirrhostic patients.multiple logistic regression applied to create prognositic model, the model comes to P= eX/1+eX, (X=4.542+0.671*INR+0.003*TB mmol/L-0.025*chlorinemmol/L +0.034*creatinine mmol/L+0.445*Cirrhosis). From the ROC curves, it was found that ROC of our model (0.8, confidence interval 95% 0.75-0.86) is significantly superior to MELD (0.73, confidence interval 95% 0.67-0.8) which is better than Sun Model (0.71, confidence interval 95%0.64-0.77), Dhiman model (0.66, confidence interval 95% 0.61-0.71) and China model (0.58, confidence interval 95% 0.52-0.65), To validite the accuracy of our model in predicting prognosis,43 patients from restrospective group was analyzed, and compared our model with MELD scoring system which was better than other prognostic models in our study, the result displayed AUC of our model was 0.9368 compared to 0.8776 of MELDConclusions:our model is superior to MELD in predicting survival rate of HBV-related acute liver failure.complications of the HBV-induced acute liver can not be proposed as prognostic factors for its low incidence and end-stage occurrence. Consideration of cirrhosis in prognositc model building is feasible and necessary in China.Key Words:prognosis; hepatitis B virus; prognostic model; follow-up study...
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