Objective：We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation（LT）for hepatocellular carcinoma（HCC）.Methods：We retrospectively analyzed HCC recipients withou...Objective：We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation（LT）for hepatocellular carcinoma（HCC）.Methods：We retrospectively analyzed HCC recipients without steroids after LT（SF group,n=368）based on the China Liver Transplant Registry（CLTR）database.These recipients were matched 1：2 with patients using steroids（S group,n=736）for the same period after LT for HCC,according to propensity scores.Results：Multivariate analysis indicates that recipients with younger age[odds ratio（OR）,1.053;P=0.011],preoperative hepatitis B virus（HBV）DNA≥1,000 copies/mL（OR,2.597;P=0.004）and beyond Milan criteria（OR,4.255;P〈0.001）were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT.The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group（P〈0.05）.Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival（OR,1.690;P〈0.001）and tumor-free survival（OR,2.066;P〈0.001）.The incidences of new-onset diabetes mellitus（21.20% vs.33.29%,P〈0.001）,new-onset hypertension（10.05%vs.18.61%,P〈0.001）and hyperlipidemia（4.08% vs.7.20%,P=0.042）were significantly lower in the SF group.Conclusions：Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT.Age,HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients.Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.展开更多
BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis i...BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy.However,its prognostic value in patients with HBV-associated HCC after liver transplantation（LT）is not clear.The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT.METHODS： A cohort of 104 HCC patients with HBV-associ- ated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohis- tochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS： GPC-3 was expressed in samples from 74 （71.2%） of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size （P=0.004）, encapsulation （P=0.018）, pathological stage （P--0.027）, portal vein invasion （P=0.043）, tumor differentiation （P=0.002） and the Milan criteria （P=0.016）. The 5-year survival rate and dis- ease-free survival rate of patients with GPC-3-positive were lower than those （38.2% vs 75.4%, P〈0.001; 30.8% vs 69.7%, P=0.001） of patients with GPC-3-negative. Multivariate Coxregression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate （P=0.031） and disease-free survival rate （P=0.047）, together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein.CONCLUSION： GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.展开更多
基金supported by the Cheung Kong Scholars Programthe Zhejiang Provincial Program for the Cultivation of Highlevel Innovative Health Talentsthe Projects of Medical and Health Technology Program in Zhejiang Province (No. 2015KYB151 and 2017RC002)
文摘Objective：We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation（LT）for hepatocellular carcinoma（HCC）.Methods：We retrospectively analyzed HCC recipients without steroids after LT（SF group,n=368）based on the China Liver Transplant Registry（CLTR）database.These recipients were matched 1：2 with patients using steroids（S group,n=736）for the same period after LT for HCC,according to propensity scores.Results：Multivariate analysis indicates that recipients with younger age[odds ratio（OR）,1.053;P=0.011],preoperative hepatitis B virus（HBV）DNA≥1,000 copies/mL（OR,2.597;P=0.004）and beyond Milan criteria（OR,4.255;P〈0.001）were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT.The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group（P〈0.05）.Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival（OR,1.690;P〈0.001）and tumor-free survival（OR,2.066;P〈0.001）.The incidences of new-onset diabetes mellitus（21.20% vs.33.29%,P〈0.001）,new-onset hypertension（10.05%vs.18.61%,P〈0.001）and hyperlipidemia（4.08% vs.7.20%,P=0.042）were significantly lower in the SF group.Conclusions：Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT.Age,HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients.Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.
基金supported by grants from the Special Fund Research of the Ministry of Health(2010.201002015)Specialized Research Fund of the Ministry of Education(20110001110044)Beijing Key Laboratory Special Fund(Z141107004414042)
文摘BACKGROUND：Glypican-3（GPC-3）is frequently overexpressed in hepatocellular carcinoma（HCC）.Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy.However,its prognostic value in patients with HBV-associated HCC after liver transplantation（LT）is not clear.The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT.METHODS： A cohort of 104 HCC patients with HBV-associ- ated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohis- tochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS： GPC-3 was expressed in samples from 74 （71.2%） of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size （P=0.004）, encapsulation （P=0.018）, pathological stage （P--0.027）, portal vein invasion （P=0.043）, tumor differentiation （P=0.002） and the Milan criteria （P=0.016）. The 5-year survival rate and dis- ease-free survival rate of patients with GPC-3-positive were lower than those （38.2% vs 75.4%, P〈0.001; 30.8% vs 69.7%, P=0.001） of patients with GPC-3-negative. Multivariate Coxregression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate （P=0.031） and disease-free survival rate （P=0.047）, together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein.CONCLUSION： GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.
