| Objective:Chronic hepatitis B infection is one of the most common causes of end stage liver disease such as liver failure and hepatocellular carcinoma(HCC)in the world.As previous reports accounted more than 400 million people are chronically infected with hepatitis B virus(HBV)globally,and a significant proportion of chronic HBV infections eventually progress to hepatocellular carcinoma(HCC).A poor prognosis is expected owing to limited treatment options,unless HCC is diagnosed in its early stage.Therefore,it is paramount significant to surveillance HCC development to improve long-term prognosis,when curative treatments can be implemented.Until now,The well-known risk factors for development of HCC is cirrhosis.Thus,early detection of cirrhosis in subclinical stage can help identify high-risk individuals of developing HCC earlier,and these patients should be included in the optimized surveillance program accordingly.For these aims,liver biopsy(LB)is traditionally recommended as the gold standard;however,LB has several inherent limitations.Thus,noninvasive surrogates are required for early detection of LC in its subclinical stage.Currently,liver stiffness(LS)measurement(LSM)using transient elastography(TE)is applicable to evaluate the severity of the underlying chronic liver disease,guide treatment decision,assess disease outcome,and evaluate response to therapy.LSM was also found to be useful in define the diagnosis of cirrhosis and substitute clinical cirrhosis as a component of the risk score to predict HCC.The two-dimensional shear wave elastography(2D-SWE)is a novel elastography technique in clinical use and is based on shear waves implemented through a conventional US system.The previous research results of our team found it showed good diagnostic performances in staging liver fibrosis in patients with chronic hepatitis B infection(CHB)and significantly superior to US in detecting liver fibrosis.Some study has demonstrated increased LS measured by SWE was associated with an increased risk of HCC in patients with CHB.However,it has failed to combined with the B-mode image which may lose important diagnostic information.The purpose of this study was to evaluate the individual and combined performances of 2D SWE and US in predicting HCC development in patients with CHB.Methods:Between April 2011 and September 2014,469 patients with CHB infection who were consecutively admitted to our hospital to undergo LB,US and 2D-SWE were prospectively considered for this study.Laboratory data including aspartate aminotransferase(AST),alanine aminotransferase(ALT),albumin(ALB)levels,total bilirubin(TB),prothrombin time(PT),prothrombin activity(PTA),i platelet count(PLT),white blood cell(WBC)and hemoglobin(HGB)level were collected for each patient.After enrolment in this study,subjects underwent periodic surveillance with ultrasonography and laboratory work-ups,including a-foetoprotein(AFP),every 3 or 6 months to screen for the development of HCC and another hepatic decompensation until the end of follow-up.A diagnosis of HCC was established according to the Guidelines of the American Association for the Study of Liver Diseases.2D SWE is a US-based method of elastography for assessment of liver stiffness.All patients underwent 2D S WE examination by using an Aixplorer ultrasonographic(US)system(SuperSonic Imagine,Aix-en-Provence,France)with a convex broadband probe(SC6-1,1-6 MHz).The measurements of 2D SWE were performed by two operators with more than 500 2D SWE examinations.All patients were fasted for about 8 hours and studied in the supine position with the right arm elevated above the head.2D SWE was performed with the intercostal approach during a shallow breath for a few seconds.For the liver stiffness detection,ROI was placed in the right lobe of liver and about 1-2 cm beneath the liver capsule,which was free of large vessels or bile ducts.The value of 2D SWE was defined as the median value of five 2D SWE measurements.Patients underwent 2D-SWE examination within 3 days after LB.Two radiologists(J.Zeng and JY.JIN)performed the procedures independently.After US examination,2D SWE was performed.With 2D SWE system,shear waves are induced by an acoustic radiation force caused by a series of focused US beams transmitted into the liver.Percutaneous LB was performed using a 16 G disposable needle in the right liver lobe under US guidance.Liver fibrosis was evaluated by using the METAVIR scoring system.A US scoring system was used to evaluate the degree of liver cirrhosis.Result:Overall,there were 469 patients enrolled in our study.The mean age of the patients was 36.8(7-69)years,and the median SWE was 7.8(3.8-70.9)kPa.The median follow-up period was 41 months(range 6 to 74 months).During follow-up,HCC developed in 10 patients(2.13%),and the cumulative incidence rates of HCC at 1,3 and 5 years were 0.4%,0.8%and 5.1%respectively.On multivariate analysis,higher SWE value and higher score of liver parenchyma were independently at a significantly greater risk of HCC development,with the following hazard ratios(HR):1.13(95%confidence interval[CI],1.08-1.18;p<0.001);and HR 21.9(95%CI,2.6-197.2;p=0.006).2D SWE demonstrated to have high performance in predicting the potential hazard of CHB patient to develop HCC with AUROC of 0.847.The cutoff point was 15.6kPa calculated by Youden Index and displaying the sensitivity of 70%and specificity of 86.27%.2D SWE appeared higher performance when using cutoff value of 15.6kPa in comparison of F4 in Metavir scoring system in predicting the risk of HCC development(P=0.004).The patients ranked F4 in Metavir scoring system were nearly 46 multiple high risk to develop HCC than the patients stayed F0 to F3 score (P=0.004).2D SWE appeared equal to the FIB-4 and APRI in the detection the high risk group of CHB patients who were susceptible of suffer HCC(P=0.42 and 0.58).Combining 2D SWE when higher than cutoff value of 15.6Kpa,and 2D US with higher than one grade of liver parenchyma in scoring system can improve the diagnostic performance in HCC prediction(ROC,0.92;95%CI:0.89-0.95;p=0.003).When the patients evaluated with over one score in liver parenchyma,the HR were 30 multiple higher of the patients with SWE>15.6kPa compared to<15.6kPa,as well as the cumulative incidence of HCC curves appearing statistical differences between the above two groups(P=0.0008).Conclusion:Increased LS measured by SWE combined with high score in 2D ultrasound scoring system may be highly related to HCC development in patients with CHB. |
