BACKGROUND Careful selection of hepatocellular carcinoma(HCC)patients prior to chemoembolization treatment is a daily reality,and is even more necessary with new available therapeutic options in HCC.To propose two new...BACKGROUND Careful selection of hepatocellular carcinoma(HCC)patients prior to chemoembolization treatment is a daily reality,and is even more necessary with new available therapeutic options in HCC.To propose two new models to better stratify patients and maximize clinical benefit:“6 and 12”and“pre/post-TACE-predict”(TACE,transarterial chemoembolization).METHODS We evaluated and compared their performance in predicting overall survival with other systems{Barcelona Clinic Liver Cancer(BCLC),Albumin-Bilirubin(ALBI)and NIACE[Number of tumor(s),Infiltrative HCC,alpha-fetoprotein,Child-Pugh(CP),and performance status]}in two HCC French cohorts of different stages enrolled between 2010 and 2018.RESULTS The cohorts included 324 patients classified as BCLC stages A/B(cohort 1)and 137 patients classified as BCLC stages B/C(cohort 2).The majority of the patients had cirrhosis with preserved liver function.“Pre-TACE-predict”and“6 and 12”models identified three distinct categories of patients exhibiting different prognosis in cohort 1.However,their prognostic value was no better than the BCLC system or NIACE score.Liver function based on CP and ALBI grades significantly impacted patient survival.Conversely,the“post-TACE-predict”model had a higher predictive value than other models.The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient(cohort 2).CONCLUSION The newly proposed“Pre-TACE-predict”and“6 and 12”models offer an interesting stratification into three categories in a recommended TACE population,as they identify poor candidates,those with partial control and durable response.The models'contribution was reduced in a population with advanced stage HCCs.展开更多
BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma(HCC)is a common situation.The only therapeutic options in France are two broadspectrum tyrosine kinase inhibitors(TKIs),regorafenib(REG...BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma(HCC)is a common situation.The only therapeutic options in France are two broadspectrum tyrosine kinase inhibitors(TKIs),regorafenib(REG)and cabozantinib(CBZ),but no comparative real-life studies are available.AIM To evaluate the progression-free survival(PFS)of patients treated with REG or CBZ,we investigated the disease control rate(DCR),overall survival(OS),and safety of both drugs.To identify the variables associated with disease progression over time.METHODS A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers(Avignon,Marseille,and Nice)between January 2017 and March 2021 using propensity score matching.PFS and OS were assessed using the Kaplan-Meier method.Multivariate analysis(MA)of progression risk factors over time was performed in matched-pair groups.RESULTS Fifty-eight patients 68(62-74)years old with HCC,Barcelona clinic liver cancer(BCLC)B/C(86%),Child-Pugh(CP)-A/B(24%)received REG for 3.4(1.4-10.5)mo as second-line therapy.Twentyeight patients 68(60-73)years,BCLC B/C(75%),CP-A/B(25%)received CBZ for 3.7(1.8-4.9)mo after first-line treatment with sorafenib[3(2-4)(CBZ)vs 4(2.9-11.8)mo(REG),P=0.0226].Twenty percent of patients received third-line therapy.After matching,PFS and DCR were not significantly different after a median follow-up of 6.2(2.7-11.7)mo(REG)vs 5.2(4-7.2)mo(CBZ),P=0.6925.There was no difference in grade 3/4 toxicities,dose reductions,or interruptions.The OS of CP-A patients was 8.3(5.2-24.8)vs 4.9(1.6-11.7)mo(CP-B),P=0.0468.The MA of risk factors for progression over time identified C-reactive protein(CRP)>10 mg/L,neutrophil-to-lymphocyte ratio(NLR)>3,and aspartate aminotransferase(AST)>45 IU as predictive factors.CONCLUSION This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC.Elevated levels of inflammatory markers(CRP and NLR)and AST were associated with non-control of TKIs over time.A 2-mo online progression risk calculation is proposed.展开更多
The“six-and-twelve”(6&12)score is a new hepatocellular carcinoma(HCC)prognostic index designed for recommended transarterial chemoembolization(TACE)candidates.Quick and easy to use by the sum of tumor size(cm)an...The“six-and-twelve”(6&12)score is a new hepatocellular carcinoma(HCC)prognostic index designed for recommended transarterial chemoembolization(TACE)candidates.Quick and easy to use by the sum of tumor size(cm)and number,this model identifies three groups with different survival time(the sum is≤6;or>6 but≤12;or>12);a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve.Recently,Wang ZW et al showed that the“6&12”model was the best system correlated with radiological response after the first TACE.Thus,we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems(Barcelona Clinic Liver Cancer,Hong Kong Liver Cancer(HKLC)staging,Albumin-Bilirubin grade,tumor nodularity,infiltrative nature of the tumor,alpha-fetoprotein,Child-Pugh class,and Performance Status score,Cancer of the Liver Italian Program,Model to Estimate Survival for HCC scores,up-to-seven criteria)different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled.As previously demonstrated,we show that the"6&12”score can classify survival within this French cohort,with a prognostic value comparable to that of other systems,except HKLC staging.More importantly,the“6&12”score simplicity and ability in patients’stratification outperform other systems for a routine clinical practice.展开更多
Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may...Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may be useful in diagnosing NASH,but results across studies have been inconsistent.We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease(NAFLD),and in all patients,circulating CK-18 M30 levels were measured.Individuals with a NAFLD activity score(NAS)≥5 with a score of≥1 for each of steatosis,ballooning,and lobular inflammation were diagnosed as having definite NASH;individuals with a NAS≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver(NAFL).Results:A total of 2571 participants were screened,and 1008(153 with NAFL and 855 with NASH)were finally enrolled.Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL(mean difference 177 U/L;standardized mean difference[SMD]:0.87[0.69–1.04]).There was an interaction between CK-18 M30 levels and serum alanine aminotransferase,body mass index(BMI),and hypertension(P<0.001,P=0.026 and P=0.049,respectively).CK-18 M30 levels were positively associated with histological NAS in most centers.The area under the receiver operating characteristics(AUROC)for NASH was 0.750(95%confidence intervals:0.714–0.787),and CK-18 M30 at Youden’s index maximum was 275.7 U/L.Both sensitivity(55%[52%–59%])and positive predictive value(59%)were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.展开更多
Background and Aims:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)have common features and differences.This real-life study investigated their characteristics,treatment modalities,and prognoses...Background and Aims:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)have common features and differences.This real-life study investigated their characteristics,treatment modalities,and prognoses.Methods:This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020.Overall survival(OS)was estimated by the Kaplan-Meier method.Subclassification of iCCAs after histological and radiological review,and molecular profiling was performed.Results:HCCs patients were more likely to have early-stage disease than iCCA patients.iCCA patients were more likely to be female,especially those patients without cirrhosis(43%vs.17%).Cirrhosis was prominent among HCC patients(89%vs.34%),but no difference in underlying liver disease among cirrhotic patients was found.OS of HCC patients was 18.4(95%CI:6.4,48.3)months,that of iCCA patients was 7.0(95%CI:3.4,20.1)months.OS of Barcelona Clinic Liver Cancer C HCC patients was 7.8(95%CI:4.3,14.2)months,that of advanced/metastatic iCCA patients was 8.5(95%CI:5.7,12.3)months.In patients treated with sorafenib,OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor therapies.No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype.A targetable molecular alteration was detected in 50%of the iCCA patients.Conclusions:In this French series,cirrhosis was common in iCCA,which showed etiological factors comparable to those of HCC,implying a distinct oncogenic pathway.Both entities had a dismal prognosis at advanced stages.However,systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.展开更多
文摘BACKGROUND Careful selection of hepatocellular carcinoma(HCC)patients prior to chemoembolization treatment is a daily reality,and is even more necessary with new available therapeutic options in HCC.To propose two new models to better stratify patients and maximize clinical benefit:“6 and 12”and“pre/post-TACE-predict”(TACE,transarterial chemoembolization).METHODS We evaluated and compared their performance in predicting overall survival with other systems{Barcelona Clinic Liver Cancer(BCLC),Albumin-Bilirubin(ALBI)and NIACE[Number of tumor(s),Infiltrative HCC,alpha-fetoprotein,Child-Pugh(CP),and performance status]}in two HCC French cohorts of different stages enrolled between 2010 and 2018.RESULTS The cohorts included 324 patients classified as BCLC stages A/B(cohort 1)and 137 patients classified as BCLC stages B/C(cohort 2).The majority of the patients had cirrhosis with preserved liver function.“Pre-TACE-predict”and“6 and 12”models identified three distinct categories of patients exhibiting different prognosis in cohort 1.However,their prognostic value was no better than the BCLC system or NIACE score.Liver function based on CP and ALBI grades significantly impacted patient survival.Conversely,the“post-TACE-predict”model had a higher predictive value than other models.The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient(cohort 2).CONCLUSION The newly proposed“Pre-TACE-predict”and“6 and 12”models offer an interesting stratification into three categories in a recommended TACE population,as they identify poor candidates,those with partial control and durable response.The models'contribution was reduced in a population with advanced stage HCCs.
文摘BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma(HCC)is a common situation.The only therapeutic options in France are two broadspectrum tyrosine kinase inhibitors(TKIs),regorafenib(REG)and cabozantinib(CBZ),but no comparative real-life studies are available.AIM To evaluate the progression-free survival(PFS)of patients treated with REG or CBZ,we investigated the disease control rate(DCR),overall survival(OS),and safety of both drugs.To identify the variables associated with disease progression over time.METHODS A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers(Avignon,Marseille,and Nice)between January 2017 and March 2021 using propensity score matching.PFS and OS were assessed using the Kaplan-Meier method.Multivariate analysis(MA)of progression risk factors over time was performed in matched-pair groups.RESULTS Fifty-eight patients 68(62-74)years old with HCC,Barcelona clinic liver cancer(BCLC)B/C(86%),Child-Pugh(CP)-A/B(24%)received REG for 3.4(1.4-10.5)mo as second-line therapy.Twentyeight patients 68(60-73)years,BCLC B/C(75%),CP-A/B(25%)received CBZ for 3.7(1.8-4.9)mo after first-line treatment with sorafenib[3(2-4)(CBZ)vs 4(2.9-11.8)mo(REG),P=0.0226].Twenty percent of patients received third-line therapy.After matching,PFS and DCR were not significantly different after a median follow-up of 6.2(2.7-11.7)mo(REG)vs 5.2(4-7.2)mo(CBZ),P=0.6925.There was no difference in grade 3/4 toxicities,dose reductions,or interruptions.The OS of CP-A patients was 8.3(5.2-24.8)vs 4.9(1.6-11.7)mo(CP-B),P=0.0468.The MA of risk factors for progression over time identified C-reactive protein(CRP)>10 mg/L,neutrophil-to-lymphocyte ratio(NLR)>3,and aspartate aminotransferase(AST)>45 IU as predictive factors.CONCLUSION This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC.Elevated levels of inflammatory markers(CRP and NLR)and AST were associated with non-control of TKIs over time.A 2-mo online progression risk calculation is proposed.
文摘The“six-and-twelve”(6&12)score is a new hepatocellular carcinoma(HCC)prognostic index designed for recommended transarterial chemoembolization(TACE)candidates.Quick and easy to use by the sum of tumor size(cm)and number,this model identifies three groups with different survival time(the sum is≤6;or>6 but≤12;or>12);a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve.Recently,Wang ZW et al showed that the“6&12”model was the best system correlated with radiological response after the first TACE.Thus,we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems(Barcelona Clinic Liver Cancer,Hong Kong Liver Cancer(HKLC)staging,Albumin-Bilirubin grade,tumor nodularity,infiltrative nature of the tumor,alpha-fetoprotein,Child-Pugh class,and Performance Status score,Cancer of the Liver Italian Program,Model to Estimate Survival for HCC scores,up-to-seven criteria)different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled.As previously demonstrated,we show that the"6&12”score can classify survival within this French cohort,with a prognostic value comparable to that of other systems,except HKLC staging.More importantly,the“6&12”score simplicity and ability in patients’stratification outperform other systems for a routine clinical practice.
基金supported by grants from the National Natural Science Foundation of China(No.82070588)High-Level Creative Talents from the Department of Public Health in Zhejiang Province(No.S2032102600032)+4 种基金Project of New Century 551 Talent Nurturing in Wenzhou.G.Targher is supported in part by grants from the University School of Medicine of Verona,Verona,ItalyC.D.Byrne is supported in part by the Southampton NIHR Biomedical Research Centre(No.IS-BRC-20004),UK.MEJG are supported by the Robert W.Storr Bequest to the Sydney Medical Foundation,University of Sydneya National Health and Medical Research Council of Australia(NHMRC)Program Grant(No.APP1053206)Project and ideas grants(Nos.APP2001692,APP1107178,and APP1108422).
文摘Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may be useful in diagnosing NASH,but results across studies have been inconsistent.We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease(NAFLD),and in all patients,circulating CK-18 M30 levels were measured.Individuals with a NAFLD activity score(NAS)≥5 with a score of≥1 for each of steatosis,ballooning,and lobular inflammation were diagnosed as having definite NASH;individuals with a NAS≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver(NAFL).Results:A total of 2571 participants were screened,and 1008(153 with NAFL and 855 with NASH)were finally enrolled.Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL(mean difference 177 U/L;standardized mean difference[SMD]:0.87[0.69–1.04]).There was an interaction between CK-18 M30 levels and serum alanine aminotransferase,body mass index(BMI),and hypertension(P<0.001,P=0.026 and P=0.049,respectively).CK-18 M30 levels were positively associated with histological NAS in most centers.The area under the receiver operating characteristics(AUROC)for NASH was 0.750(95%confidence intervals:0.714–0.787),and CK-18 M30 at Youden’s index maximum was 275.7 U/L.Both sensitivity(55%[52%–59%])and positive predictive value(59%)were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
文摘Background and Aims:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)have common features and differences.This real-life study investigated their characteristics,treatment modalities,and prognoses.Methods:This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020.Overall survival(OS)was estimated by the Kaplan-Meier method.Subclassification of iCCAs after histological and radiological review,and molecular profiling was performed.Results:HCCs patients were more likely to have early-stage disease than iCCA patients.iCCA patients were more likely to be female,especially those patients without cirrhosis(43%vs.17%).Cirrhosis was prominent among HCC patients(89%vs.34%),but no difference in underlying liver disease among cirrhotic patients was found.OS of HCC patients was 18.4(95%CI:6.4,48.3)months,that of iCCA patients was 7.0(95%CI:3.4,20.1)months.OS of Barcelona Clinic Liver Cancer C HCC patients was 7.8(95%CI:4.3,14.2)months,that of advanced/metastatic iCCA patients was 8.5(95%CI:5.7,12.3)months.In patients treated with sorafenib,OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor therapies.No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype.A targetable molecular alteration was detected in 50%of the iCCA patients.Conclusions:In this French series,cirrhosis was common in iCCA,which showed etiological factors comparable to those of HCC,implying a distinct oncogenic pathway.Both entities had a dismal prognosis at advanced stages.However,systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.
