Hepatocellular carcinoma(HCC)is the predominant malignant liver tumor,characterized by high morbidity,mortality,and rapid progression,and it ranks among the leading causes of cancer-related fatalities worldwide.Its tr...Hepatocellular carcinoma(HCC)is the predominant malignant liver tumor,characterized by high morbidity,mortality,and rapid progression,and it ranks among the leading causes of cancer-related fatalities worldwide.Its treatment is facing the severe challenge of resistance to targeted drugs and immunotherapy.Bile acids(BAs)are products of cholesterol metabolism,that not only regulate lipid digestion and absorption,but also influence the development of HCC by modulating inflammation and metabolism.Dysregulation of BA metabolism is closely linked to resistance against targeted therapies and immunotherapies.BAs reduce the efficacy of targeted drugs by influencing enzymes involved in drug metabolism and drug efflux transporters,moreover,BAs also lead to immunotherapeutic resistance by regulating the formation of the immunosuppressive tumor microenvironment.Therefore,regulating BA metabolism has the potential to overcome drug resistance of targeted therapy and immunotherapy,which could be a promising treatment strategy.This review not only summarizes the roles of BA metabolism in HCC development and drug resistance,but also further explores the rationality and necessity of targeting BAs to enhance the survival of HCC patients.展开更多
Aims:Patients with cirrhosis and clinically significant portal hypertension(CSPH)usually have concomitant secondary hypersplenism,and splenectomy(Spx)is an option for treating these patients in the Asia‐Pacific regio...Aims:Patients with cirrhosis and clinically significant portal hypertension(CSPH)usually have concomitant secondary hypersplenism,and splenectomy(Spx)is an option for treating these patients in the Asia‐Pacific region.CSPH is the most important risk factor for postoperative liver dysfunction(PLD)in patients with hepatocellular carcinoma(HCC)and cirrhosis undergoing liver resection.However,the impact of simultaneous Spx and hepatectomy in patients with HCC and CSPH remains unclear.In this study,we aimed to determine the impact of simultaneous Spx on the posthepatectomy outcomes in these patients.Methods:This study included 691 consecutive patients with hepatitis B virusrelated HCC,cirrhosis,and CSPH.These included 565 patients who underwent hepatectomy only(non‐Spx group)and 126 who underwent simultaneous hepatectomy and splenectomy(Spx group).We analyzed the effect of 25 preoperative and 5 intraoperative factors on postoperative outcomes using logistic regression.To overcome any possible selection bias,confounders were balanced by propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses,and subgroup analyses were performed within the PSM‐matched groups.Results:Logistic regression analyses revealed that Spx was an independent protective factor for severe postoperative liver dysfunction(SPLD;odds ratio[OR]=0.22,95%confidence interval[CI]:0.11–0.43,p<0.001)and 90‐day SPLD‐related mortality(OR=0.21,95%CI:0.06–0.55,p=0.004),respectively.Spx was also independently associated with a higher overall survival rate(hazard ratio=0.63,95%CI=0.47–0.85,p=0.002)based on Cox regression analysis.PSM and IPTW models showed that the benefit of Spx was also consistent across the major and minor hepatectomy subgroups examined.Conclusion:Simultaneous Spx improved the outcomes of patients with HCC,cirrhosis,and CSPH treated with hepatectomy,including patients who underwent major and minor hepatectomies.展开更多
基金supported by the National Natural Science Foundation of China(grant No.82270634)Third Affiliated Hospital of Naval Medical University(grant No.tf2024yzyy01)+1 种基金Excellent Doctoral Cultivation Program of Naval Medical University,National Natural Science Foundation of China(No.82503372)China Postdoctoral Science Foundation under Grant Number(GZB20250482).
文摘Hepatocellular carcinoma(HCC)is the predominant malignant liver tumor,characterized by high morbidity,mortality,and rapid progression,and it ranks among the leading causes of cancer-related fatalities worldwide.Its treatment is facing the severe challenge of resistance to targeted drugs and immunotherapy.Bile acids(BAs)are products of cholesterol metabolism,that not only regulate lipid digestion and absorption,but also influence the development of HCC by modulating inflammation and metabolism.Dysregulation of BA metabolism is closely linked to resistance against targeted therapies and immunotherapies.BAs reduce the efficacy of targeted drugs by influencing enzymes involved in drug metabolism and drug efflux transporters,moreover,BAs also lead to immunotherapeutic resistance by regulating the formation of the immunosuppressive tumor microenvironment.Therefore,regulating BA metabolism has the potential to overcome drug resistance of targeted therapy and immunotherapy,which could be a promising treatment strategy.This review not only summarizes the roles of BA metabolism in HCC development and drug resistance,but also further explores the rationality and necessity of targeting BAs to enhance the survival of HCC patients.
基金Shanghai Municipal Health Commission Health Industry Clinical Research Special Project,Grant/Award Number:20214Y0360National Natural Science Foundation of China,Grant/Award Numbers:81970453,81772529+1 种基金Shanghai Science and Technology Innovation Action Plan Project,Grant/Award Numbers:20XD1405100,19441904700State Key Project of China,Grant/Award Numbers:81970453,81772529,82000483。
文摘Aims:Patients with cirrhosis and clinically significant portal hypertension(CSPH)usually have concomitant secondary hypersplenism,and splenectomy(Spx)is an option for treating these patients in the Asia‐Pacific region.CSPH is the most important risk factor for postoperative liver dysfunction(PLD)in patients with hepatocellular carcinoma(HCC)and cirrhosis undergoing liver resection.However,the impact of simultaneous Spx and hepatectomy in patients with HCC and CSPH remains unclear.In this study,we aimed to determine the impact of simultaneous Spx on the posthepatectomy outcomes in these patients.Methods:This study included 691 consecutive patients with hepatitis B virusrelated HCC,cirrhosis,and CSPH.These included 565 patients who underwent hepatectomy only(non‐Spx group)and 126 who underwent simultaneous hepatectomy and splenectomy(Spx group).We analyzed the effect of 25 preoperative and 5 intraoperative factors on postoperative outcomes using logistic regression.To overcome any possible selection bias,confounders were balanced by propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses,and subgroup analyses were performed within the PSM‐matched groups.Results:Logistic regression analyses revealed that Spx was an independent protective factor for severe postoperative liver dysfunction(SPLD;odds ratio[OR]=0.22,95%confidence interval[CI]:0.11–0.43,p<0.001)and 90‐day SPLD‐related mortality(OR=0.21,95%CI:0.06–0.55,p=0.004),respectively.Spx was also independently associated with a higher overall survival rate(hazard ratio=0.63,95%CI=0.47–0.85,p=0.002)based on Cox regression analysis.PSM and IPTW models showed that the benefit of Spx was also consistent across the major and minor hepatectomy subgroups examined.Conclusion:Simultaneous Spx improved the outcomes of patients with HCC,cirrhosis,and CSPH treated with hepatectomy,including patients who underwent major and minor hepatectomies.
