Incidence And Predictors Of Hepatocellular Carcinoma In Hepatitis B Virus-related Cirrhotic Patients Receiving Antiviral Therapy:A Propensity Score Matching Study

Background:According to the report of WHO,more than 2 billion people had been exposed to HBV in the world,in which there are 350 million people developed to chronic HBV carriers.Hepatitis B virus(HBV)infection is a major cause of chronic hepatitis,liver cirrhosis and hepatocellular carcinoma(HCC)worldwide,which result in about 1 million deaths every year before the widely use of antiviral therapy.For untreated chronic hepatitis B(CHB)patients,the cumulative risk of developing cirrhosis over five years is about 8-20%,meanwhile,for cirrhotic patients,an approximately 1%to 5%annual incidence of hepatitis B-related HCC reveals a poor prognosis.Over the past two decades,several antiviral agents,especially oral nucleos(t)ide analogues(NAs),have been approved for the treatment of CHB patients and improved their long-time outcome dramatically.The principal goal of treatment for CHB patients is to achieve sustained suppression of HBV replication and prevention of cirrhosis,hepatic decompensation and HCC.Clinical data had shown that antiviral therapy significantly reduces the incidence of HCC compared with CHB patients without antiviral treatment,including patients developing cirrhosis.However,several studies also demonstrated that HCC still developed in CHB patients treated with antiviral agents.Furthermore,HCC risk remained increasing in patients with cirrhosis even if they have achieved virological remission.The aims of our cohort study were(1)to evaluate the incidence of hepatitis B-related HCC and to explore independent predictors of HCC in Chinese HBV-related cirrhotic patients receiving antiviral therapy.(2)to explore the different effect of entecavir and low genetic barrier antivirals on the development of hepatocellular carcinoma in hepatitis B viral cirrhotic patients by a propensity score matching study.Part ? Incidence and predictors of hepatocellular carcinoma in Chinese hepatitis B virus-related cirrhotic patients receiving antiviral therapyAim:To evaluate the incidence and predictors of hepatocellular carcinoma(HCC)in Chinese hepatitis B virus-related cirrhotic patients receiving antiviral therapy.Materials and Methods:Consecutive HBV-related cirrhotic patients receiving antiviral therapy for at least 12 months were enrolled.Multivariable Cox proportional hazards models were used to evaluate independent prognostic factors for developing HCC.Result:A total of 207 patients were included:95 patients with compensated cirrhosis and 112 patients with decompensated cirrhosis.The cumulative incidence rate of HCC at months 24,36,48,60 and 72 were 6.9%,11.2%,16.6%,23.4%and 42.6%,In multivariable Cox regression analysis,the HCC risk was independently associated with older age(?48 years,HR:2.42,95%Cl 1.05-5.58,p=0.038),male gender(HR:2.85,95%CI 1.12-7.25,p=0.028),higher AST levels(?55U/L,HR:2.92,95%CI 1.33-6.42,p=0.008)and lower platelet counts(<80×109/L,HR:2.86,95%CI 1.20-6.80,p=0.017).Additionally,subgroup analyses identified resistance of nucleos(t)ide analogues(NAs)as an independent risk factor for patients with compensated cirrhosis(p=0.020)but not in those with decompensated cirrhosis.Conclusion:Our study indicates that risk of HCC remains high in hepatitis B virus-related cirrhotic patients,particularly for those with older age,male gender,higher AST levels and lower platelet counts.All cirrhotic patients should remain under HCC surveillance even treated with NAs.Part ?:Effect of Entecavir and Low Genetic Barrier Antivirals on the Development of Hepatocellular Carcinoma in Hepatitis B Viral Cirrhotic Patients:a Propensity Score Matching StudyAim:To compare the reduction of hepatocellular carcinoma(HCC)risk between long-term treatment of high genetic barrier drug(entecavir)and low genetic barrier drugs in Hepatitis B virus(HBV)-related cirrhotic patients.Methodology:HBV-related cirrhotic patients with antiviral treatment for at least 12 months were consecutively included.Propensity score matching(PSM)analysis was performed to improve comparability of the data from both entecavir group and the control group(low genetic barrier drugs).Log-rank test was used to compare influence of various nucleos(t)ide analogs(NAs)for incidence of HCC.Independent risk factors were estimated by multivariable Cox proportional hazards models.Results:The total cohort included 207 HBV-related cirrhotic patients,of which 83 patients were treated with entecavir initially.The present study found no statistical difference for the incidence of HCC between entecavir group and the control group in total cohort(p=0.525),however,the difference became statistically.significant(p=0.014)after propensity score matching.Multivariable Cox regression in propensity score matching cohort revealed older age(>48y,HR:1.066,p=0.041),NAs of low generic barrier(HR:6.944,p=0.016),NAs resistance(HR:3.648,p=0.041)and lower platelet counts(<80×109/L,HR:6.718,p=0.009)as independent risk factors for HCC incidence.Conclusions:Entecavir is more efficient in reducing the incident HCC risk for HBV-related cirrhotic patients in comparison to low genetic barrier NAs.