The phase III clinical trial of the novel molecular targeted agent(MTA)lenvatinib for patients with advanced hepatocellular carcinoma(HCC)(REFLECT trial)found that lenvatinib was non-inferior to sorafenib in overall s...The phase III clinical trial of the novel molecular targeted agent(MTA)lenvatinib for patients with advanced hepatocellular carcinoma(HCC)(REFLECT trial)found that lenvatinib was non-inferior to sorafenib in overall survival.Recently,the efficacy of multiple MTAs,including lenvatinib,in practice has been reported,and therapeutic strategies for Barcelona Clinic Liver Cancer(BCLC)intermediate stage HCC are undergoing major changes.Based on these results,lenvatinib could be recommended for patients with transcatheter arterial chemoembolization(TACE)-refractory,ALBI grade 1,within the up-to-seven criteria in the BCLC intermediate stage.Lenvatinib provides a more favorable outcome than TACE,even in cases with large or multinodular HCC beyond the up-to-seven criteria with Child-Pugh grade A.When patients meet the definitions of TACE-refractory or TACE-unsuitable,switching to systemic chemotherapy,including lenvatinib,is for favorable for preserving liver function.If initial treatment,including MTA,has a significant therapeutic effect and downstaging of HCC is obtained,additional TACE or surgical resection should be considered.Lenvatinib also has a therapeutic effect for poorly differentiated type and non-simple nodular type HCC thanks to the survival-prolonging effect of this drug.Furthermore,a significant therapeutic effect is expected in tumors with more than 50%liver involvement or main portal vein invasion,which have traditionally been considered to have a poor prognosis in patients.This suggests that at the start of lenvatinib treatment,HCC patients with ALBI grade 1 may be able to maintain liver functional reserve.展开更多
BACKGROUND The Mac-2 binding protein glycosylation isomer(M2BPGi),a fibrosis marker in various liver diseases,is reportedly a prognostic marker in patients with hepatocellular carcinoma(HCC)who underwent hepatectomy.A...BACKGROUND The Mac-2 binding protein glycosylation isomer(M2BPGi),a fibrosis marker in various liver diseases,is reportedly a prognostic marker in patients with hepatocellular carcinoma(HCC)who underwent hepatectomy.AIM To evaluate whether the M2BPGi value,M2BP,and pre-sarcopenia before radiofrequency ablation(RFA)could be useful recurrence and prognostic markers in patients with early-stage HCC.METHODS In total,160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus(HCV)-positive and HCV-negative.Factors contributing to recurrence and liver-related death,including M2BP,M2BPGi,and skeletal muscle mass index,were statistically analyzed.Eighty-three patients were HCV-positive and 77 were HCV-negative.RESULTS In HCV-positive patients,only des-γ-carboxy-prothrombin≥23 mAU/mL was a significant poor prognostic factor affecting survival after RFA.In HCV-negative patients,M2BPGi≥1.86 cutoff index was significantly associated with tumor recurrence,while M2BP was not.M2BPGi≥1.86 cutoff index(hazard ratio,4.89;95%confidence interval:1.97-12.18;P<0.001)and pre-sarcopenia(hazard ratio,3.34,95%confidence interval:1.19-9.37;P=0.022)were independent significant poor prognostic factors in HCV-negative patients.CONCLUSION In HCV-negative patients with primary HCC treated with RFA,lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period.Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients.These factors might be useful recurrence and prognostic markers for early-stage primary HCC.展开更多
Prevalence of hepatitis C virus (HCV) infection is high in patients with end-stage renal dysfunction,including patients undergoing hemodialysis (HD).The HCV infection itself can cause glomerulonephritis and puts indiv...Prevalence of hepatitis C virus (HCV) infection is high in patients with end-stage renal dysfunction,including patients undergoing hemodialysis (HD).The HCV infection itself can cause glomerulonephritis and puts individuals at increased risk of developing end-stage renal disease;fortunately,successful HCV eradication sometimes restore HCV-related renal dysfunction.Moreover,the prognosis of dialysis patients infected with HCV is significantly worse and the renal allograft survival in HCV-infected patients is also worse than in dialysis patients without HCV infection.If life prognosis is favorable,therefore,anti-HCV therapy is strongly recommended for HCV-infected patients with severe renal dysfunction.The standard therapy for HCV-infected patients with severe renal dysfunction has historically been interferon-based therapy.However,this therapy remains ineffective in achieving high,sustained viral response rates and the rate of adverse events and treatment discontinuation due to treatment-induced adverse events continues to be high in patients with severe renal dysfunction.Safe and effective anti-HCV therapies are urgently needed,and crucial,for patients with severe renal dysfunction.Recently,direct-acting antivirals (DAAs) that specifically target viral proteins have been developed,and these targets include the NS3,NS5A,and NS5B of HCV.Clinical trials have revealed high efficacy and safety of the DAA-based therapies,but patients with severe renal dysfunction were not included in the majority of these trials.However,several recent reports have shown high efficacy and safety for some regimens of DAA combination therapy for HCV-infected patients with severe renal dysfunction.In this review,we discuss novel treatments for HCV-infected patients with severe renal dysfunction and the pharmacokinetics of these drugs.展开更多
文摘The phase III clinical trial of the novel molecular targeted agent(MTA)lenvatinib for patients with advanced hepatocellular carcinoma(HCC)(REFLECT trial)found that lenvatinib was non-inferior to sorafenib in overall survival.Recently,the efficacy of multiple MTAs,including lenvatinib,in practice has been reported,and therapeutic strategies for Barcelona Clinic Liver Cancer(BCLC)intermediate stage HCC are undergoing major changes.Based on these results,lenvatinib could be recommended for patients with transcatheter arterial chemoembolization(TACE)-refractory,ALBI grade 1,within the up-to-seven criteria in the BCLC intermediate stage.Lenvatinib provides a more favorable outcome than TACE,even in cases with large or multinodular HCC beyond the up-to-seven criteria with Child-Pugh grade A.When patients meet the definitions of TACE-refractory or TACE-unsuitable,switching to systemic chemotherapy,including lenvatinib,is for favorable for preserving liver function.If initial treatment,including MTA,has a significant therapeutic effect and downstaging of HCC is obtained,additional TACE or surgical resection should be considered.Lenvatinib also has a therapeutic effect for poorly differentiated type and non-simple nodular type HCC thanks to the survival-prolonging effect of this drug.Furthermore,a significant therapeutic effect is expected in tumors with more than 50%liver involvement or main portal vein invasion,which have traditionally been considered to have a poor prognosis in patients.This suggests that at the start of lenvatinib treatment,HCC patients with ALBI grade 1 may be able to maintain liver functional reserve.
文摘BACKGROUND The Mac-2 binding protein glycosylation isomer(M2BPGi),a fibrosis marker in various liver diseases,is reportedly a prognostic marker in patients with hepatocellular carcinoma(HCC)who underwent hepatectomy.AIM To evaluate whether the M2BPGi value,M2BP,and pre-sarcopenia before radiofrequency ablation(RFA)could be useful recurrence and prognostic markers in patients with early-stage HCC.METHODS In total,160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus(HCV)-positive and HCV-negative.Factors contributing to recurrence and liver-related death,including M2BP,M2BPGi,and skeletal muscle mass index,were statistically analyzed.Eighty-three patients were HCV-positive and 77 were HCV-negative.RESULTS In HCV-positive patients,only des-γ-carboxy-prothrombin≥23 mAU/mL was a significant poor prognostic factor affecting survival after RFA.In HCV-negative patients,M2BPGi≥1.86 cutoff index was significantly associated with tumor recurrence,while M2BP was not.M2BPGi≥1.86 cutoff index(hazard ratio,4.89;95%confidence interval:1.97-12.18;P<0.001)and pre-sarcopenia(hazard ratio,3.34,95%confidence interval:1.19-9.37;P=0.022)were independent significant poor prognostic factors in HCV-negative patients.CONCLUSION In HCV-negative patients with primary HCC treated with RFA,lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period.Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients.These factors might be useful recurrence and prognostic markers for early-stage primary HCC.
文摘Prevalence of hepatitis C virus (HCV) infection is high in patients with end-stage renal dysfunction,including patients undergoing hemodialysis (HD).The HCV infection itself can cause glomerulonephritis and puts individuals at increased risk of developing end-stage renal disease;fortunately,successful HCV eradication sometimes restore HCV-related renal dysfunction.Moreover,the prognosis of dialysis patients infected with HCV is significantly worse and the renal allograft survival in HCV-infected patients is also worse than in dialysis patients without HCV infection.If life prognosis is favorable,therefore,anti-HCV therapy is strongly recommended for HCV-infected patients with severe renal dysfunction.The standard therapy for HCV-infected patients with severe renal dysfunction has historically been interferon-based therapy.However,this therapy remains ineffective in achieving high,sustained viral response rates and the rate of adverse events and treatment discontinuation due to treatment-induced adverse events continues to be high in patients with severe renal dysfunction.Safe and effective anti-HCV therapies are urgently needed,and crucial,for patients with severe renal dysfunction.Recently,direct-acting antivirals (DAAs) that specifically target viral proteins have been developed,and these targets include the NS3,NS5A,and NS5B of HCV.Clinical trials have revealed high efficacy and safety of the DAA-based therapies,but patients with severe renal dysfunction were not included in the majority of these trials.However,several recent reports have shown high efficacy and safety for some regimens of DAA combination therapy for HCV-infected patients with severe renal dysfunction.In this review,we discuss novel treatments for HCV-infected patients with severe renal dysfunction and the pharmacokinetics of these drugs.
