Prognostic role of plasma level of angiopoietin-1,angiopoietin-2,and vascular endothelial growth factor in hepatocellular carcinoma

BACKGROUND Most hepatocellular carcinomas(HCCs)are hypervascular,with characteristic features of hepatic arterial supply to the tumor.The factors involved in tumor angiogenesis include angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),and vascular endothelial growth factor(VEGF).AIM To investigate the profiles of plasma levels of angiogenesis markers in patients with HCC and evaluate their roles in predicting overall survival(OS)and progression-free survival(PFS).METHODS Plasma samples from 240 prospectively enrolled HCC patients in the very early to advanced stages were used to measure the levels of Ang-1,Ang-2,and VEGF.Their associations with clinical characteristics,OS,and PFS were analyzed.RESULTS The median plasma levels of Ang-1,Ang-2,and VEGF were 3216 pg/mL,1684 pg/mL,and 26.5 pg/mL,respectively.The plasma level of Ang-2 showed a significant increase from early stage[Barcelona clinic liver cancer(BCLC)A]to intermediate(BCLC B)and advanced stage HCC(BCLC C/D),whereas Ang-1,VEGF,and alpha-fetoprotein(AFP)levels in the plasma did not show any such changes.Multivariable analysis,propensity score-matched analysis,and timedependent receiver operating curve analysis revealed that Ang-2 levels had the highest predictive power for OS and PFS.Neither Ang-1 nor VEGF was significantly associated with OS or PFS.The neutrophil-to-lymphocyte ratio was an independent factor for OS and PFS.CONCLUSION The plasma levels of Ang-2 correlated with liver function,tumor stage,and tumor invasiveness,showing better performance in predicting OS and PFS than AFP,Ang-1,or VEGF.

Hepatocellular carcinoma,decompensation,and mortality based on hepatitis C treatment:A prospective cohort study

BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus(HCV)infection after treatment with interferon-based therapy(IBT)or directacting antivirals(DAA)are limited in many Asian countries.AIM To elucidate the incidences of hepatocellular carcinoma(HCC)and death/transplantation based on treatment with IBT or DAA,to compare the outcomes of the sustained virologic response(SVR)to IBT and DAA,and to investigate outcome-determining factors after SVR.METHODS This cohort included 2054 viremic patients(mean age,57 years;46.5%male;27.4%with cirrhosis)prospectively enrolled at seven hospitals between 2007 and 2019.They were classified as the untreated group(n=619),IBT group(n=578),and DAA group(n=857).Outcomes included the incidences of HCC and death/transplantation.The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution.A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation,followed by propensity score matching to confirm the results.RESULTS During a median of 4.1 years of follow-up,HCC and death/transplantation occurred in 113 and 206 patients,respectively,in the entire cohort.Compared with the untreated group,the incidences of HCC and death/transplantation were significantly lower in the IBT group[adjusted hazard ratio(aHR)0.47,95%CI:0.28-0.80 and aHR 0.28,95%CI:0.18-0.43,respectively]and the DAA group(aHR 0.58,95%CI:0.35-0.96,and aHR 0.19,95%CI:0.20-0.68,respectively).Among 1268 patients who attained SVR with IBT(n=451)or DAA(n=816),the multivariable-adjusted analysis showed no differences in the risks of HCC(HR 2.03;95%CI:0.76-5.43)and death/transplantation(HR 1.38;95%CI:0.55-3.49)between the two groups.This was confirmed by a propensity score-matching analysis.Independent factors for HCC after SVR were age,genotype 1,and the presence of cirrhosis.CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection.The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.