Hepatocellular carcinoma(HCC)is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself.The prognosis of patients with HCC is determined by intrah...Hepatocellular carcinoma(HCC)is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself.The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function.Hepatitis B virus(HBV)is an established major risk factor of HCC development,and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC.High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways.First,it is associated with more frequent recurrence of HBV-related HCC after treatment.Second,it is associated with more occurrence and severity of potentially life-threatening HBV reactivation.Last,it is associated with more worsened liver function,which limits the therapeutic options for HBV-related HCC.HBV,directly or indirectly,can induce hepatocarcinogenesis.In patients with a high HBV DNA level and subsequent active hepatitis,adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis.HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes.Thus,high HBV viral load can affect the prognosis of patientswith HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression.Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC.Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression,it is expected that long-term antiviral therapy results in the sustained HBV suppression,control of inflammation,reduction in HCC progression,and eventually in improved overall survival.展开更多
AIM To assess the prevalence of possible risk factors of upper gastrointestinal bleeding(UGIB) and their agegroup specific trend among the general population and osteoarthritis patients.METHODS We utilized data from t...AIM To assess the prevalence of possible risk factors of upper gastrointestinal bleeding(UGIB) and their agegroup specific trend among the general population and osteoarthritis patients.METHODS We utilized data from the National Health InsuranceService that included claims data and results of the national health check-up program. Comorbid conditions(peptic ulcer, diabetes, liver disease, chronic renal failure, and gastroesophageal reflux disease), concomitant drugs(aspirin, clopidogrel, cilostazol, non-steroidal anti-inflammatory drugs, steroid, anticoagulants, and SSRI), personal habits(smoking, and alcohol consumption) were considered as possible UGIB risk factors. We randomly imputed the prevalence of infection in the data considering the age-specific prevalence of Helicobacter pylori(H. pylori) infection in Korea. The prevalence of various UGIB risk factors and the age-group specific trend of the prevalence were identified. Prevalence was compared between osteoarthritis patients and others.RESULTS A total of 801926 subjects(93855 osteoarthritis patients) aged 20 and above were included. The prevalence of individual and concurrent multiple risk factors became higher as the age increased. The prevalence of each comorbid condition and concomitant drug were higher in osteoarthritis patients. Thirty-five point zero two percent of the overall population and 68.50% of osteoarthritis patients had at least one or more risk factors of UGIB. The prevalence of individual and concurrent multiple risk factors in younger age groups were also substantial. Furthermore, when personal habits(smoking, and alcohol consumption) and H. pylori infection were included, the prevalence of concurrent multiple risk factors increased greatly even in younger age groups.CONCLUSION Prevalence of UGIB risk factors was high in elderly population, but was also considerable in younger population. Patient with osteoarthritis was at higher UGIB risk than those without osteoarthritis. Physicians s h o u ld c o n s id e r in d i v i d u a li z e d r i s k a s s e s s m e n t regardless of age when prescribing drugs or performing procedures that may increase the risk of UGIB, and take necessary measures to reduce modifiable risk factors such as H. pylori eradication or lifestyle counseling.展开更多
Patients with hepatocellular carcinoma(HCC) accompanying portal vein tumor thrombosis(PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelonaclinic l...Patients with hepatocellular carcinoma(HCC) accompanying portal vein tumor thrombosis(PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelonaclinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival(OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization(TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent metaanalysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization(TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resectionbased multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.展开更多
AIM To examine the association between the timing of endo-scopy and the short-term outcomes of acute variceal bleeding in cirrhotic patients.METHODS This retrospective study included 274 consecutive patients admitted ...AIM To examine the association between the timing of endo-scopy and the short-term outcomes of acute variceal bleeding in cirrhotic patients.METHODS This retrospective study included 274 consecutive patients admitted with acute esophageal variceal bleeding of two tertiary hospitals in Korea. We adjusted confounding factors using the Cox proportional hazards model and the inverse probability weighting （IPW） method. The primary outcome was the mortality of patients within 6 wk.RESULTS A total of 173 patients received urgent endoscopy （ i.e. , ≤ 12 h after admission）, and 101 patients received non-urgent endoscopy （〉 12 h after admission）. The 6-wk mortality rate was 22.5% in the urgent endoscopy group and 29.7% in the non-urgent endoscopy group, and there was no significant difference between the two groups before （P = 0.266） and after IPW （P = 0.639）. The length of hospital stay was statistically different between the urgent group and non-urgent group （P = 0.033）; however, there was no significant difference in the in-hospital mortality rate between the two groups （8.1%vs 7.9%, P = 0.960）. In multivariate analyses, timing of endoscopy was not associated with 6-wk mortality （hazard ratio, 1.297; 95% confdence interval, 0.806-2.089; P = 0.284）.CONCLUSION In cirrhotic patients with acute variceal bleeding, the timing of endoscopy may be independent of short-term mortality.展开更多
Introduction:Although an association between metabolic dysfunctionassociated fatty liver disease(MAFLD)and cardiovascular disease or overall mortality has been reported,it is unclearwhether there is an association bet...Introduction:Although an association between metabolic dysfunctionassociated fatty liver disease(MAFLD)and cardiovascular disease or overall mortality has been reported,it is unclearwhether there is an association between MAFLD and cancer incidence or mortality.We aimed to investigate the differential risk of all-and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease.Methods:Using the Korean National Health Insurance Service database,we stratified the participants into three groups:(1)single-etiology MAFLD(SMAFLD)or MAFLD of pure metabolic origin;(2)mixed-etiology MAFLD(M-MAFLD)or MAFLD with additional etiological factor(s)(i.e.,concomitant liver diseases and/or heavy alcohol consumption);and(3)non-MAFLD.Hepatic steatosis and fibrosiswere defined using the fatty liver index and the BARDscore,respectively.Cox proportional hazards regression was performed to estimate the risk of cancer events.Results:Among the 9,718,182 participants,the prevalence of S-MAFLD and M-MAFLD was 29.2%and 6.7%,respectively.During the median 8.3 years of follow-up,510,330(5.3%)individuals were newly diagnosed with cancer,and 122,774(1.3%)cancer-related deaths occurred among the entire cohort.Compared with the non-MAFLD group,the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group(incidence,adjusted hazard ratio[aHR]=1.03;95%confidence interval[CI]:1.02−1.04;mortality,aHR=1.06;95%CI:1.04−1.08)and highest among patients with M-MAFLD group(incidence,aHR=1.31;95%CI:1.29−1.32;mortality,aHR=1.45;95%CI:1.42−1.48,respectively).The M-MAFLD with fibrosis group(BARD score≥2)showed the highest relative risk of all-cancer incidence(aHR=1.38,95%CI=1.36–1.39),followed by the M-MAFLD without fibrosis group(aHR=1.09,95%CI=1.06–1.11).Similar trends were observed for cancer-related mortality.Conclusions:MAFLD classification,by applying additional etiologies other than pure metabolic origin,can be used to identify a subgroup of patients with poor cancer-related outcomes.展开更多
Fucoidan is a traditional Chinese medicine suggested to possess anti-tumor effects.In this study the anti-metastatic effects of fucoidan were investigated in vitro in human hepatocellular carcinoma(HCC) cells(Huh-7 an...Fucoidan is a traditional Chinese medicine suggested to possess anti-tumor effects.In this study the anti-metastatic effects of fucoidan were investigated in vitro in human hepatocellular carcinoma(HCC) cells(Huh-7 and SNU-761) under normoxic and hypoxic conditions and in vivo using a distant liver metastasis model involving injection of MH134 cells into spleen via the portal vein.Its ability to protect hepatocytes against bile acid(BA)-induced apoptosis was investigated in primary hepatocytes.Fucoidan was found to suppress the invasion of HCC cells through up-regulation of p42/44 MAPKdependent NDRG-1/CAP43 and partly,under normoxic conditions,through up-regulation of p42/44MAPK-dependent VMP-1 expression.It also significantly decreased liver metastasis in vivo.As regards its hepatoprotective effect,fucoidan decreased BA-induced hepatocyte apoptosis as shown by the attenuation of caspase-8,and-7 cleavages and suppression of the mobilization of caspase-8 and Fas associated death domain(FADD) into the death-inducing signaling complex.In summary,fucoidandisplays inhibitory effects on proliferation of HCC cells and protective effects on hepatocytes.The results suggest fucoidan is a potent suppressor of tumor invasion with hepatoprotective effects.展开更多
文摘Hepatocellular carcinoma(HCC)is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself.The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function.Hepatitis B virus(HBV)is an established major risk factor of HCC development,and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC.High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways.First,it is associated with more frequent recurrence of HBV-related HCC after treatment.Second,it is associated with more occurrence and severity of potentially life-threatening HBV reactivation.Last,it is associated with more worsened liver function,which limits the therapeutic options for HBV-related HCC.HBV,directly or indirectly,can induce hepatocarcinogenesis.In patients with a high HBV DNA level and subsequent active hepatitis,adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis.HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes.Thus,high HBV viral load can affect the prognosis of patientswith HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression.Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC.Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression,it is expected that long-term antiviral therapy results in the sustained HBV suppression,control of inflammation,reduction in HCC progression,and eventually in improved overall survival.
基金Supported by Pfizer Pharmaceutical Korea Ltd,No.A3191378
文摘AIM To assess the prevalence of possible risk factors of upper gastrointestinal bleeding(UGIB) and their agegroup specific trend among the general population and osteoarthritis patients.METHODS We utilized data from the National Health InsuranceService that included claims data and results of the national health check-up program. Comorbid conditions(peptic ulcer, diabetes, liver disease, chronic renal failure, and gastroesophageal reflux disease), concomitant drugs(aspirin, clopidogrel, cilostazol, non-steroidal anti-inflammatory drugs, steroid, anticoagulants, and SSRI), personal habits(smoking, and alcohol consumption) were considered as possible UGIB risk factors. We randomly imputed the prevalence of infection in the data considering the age-specific prevalence of Helicobacter pylori(H. pylori) infection in Korea. The prevalence of various UGIB risk factors and the age-group specific trend of the prevalence were identified. Prevalence was compared between osteoarthritis patients and others.RESULTS A total of 801926 subjects(93855 osteoarthritis patients) aged 20 and above were included. The prevalence of individual and concurrent multiple risk factors became higher as the age increased. The prevalence of each comorbid condition and concomitant drug were higher in osteoarthritis patients. Thirty-five point zero two percent of the overall population and 68.50% of osteoarthritis patients had at least one or more risk factors of UGIB. The prevalence of individual and concurrent multiple risk factors in younger age groups were also substantial. Furthermore, when personal habits(smoking, and alcohol consumption) and H. pylori infection were included, the prevalence of concurrent multiple risk factors increased greatly even in younger age groups.CONCLUSION Prevalence of UGIB risk factors was high in elderly population, but was also considerable in younger population. Patient with osteoarthritis was at higher UGIB risk than those without osteoarthritis. Physicians s h o u ld c o n s id e r in d i v i d u a li z e d r i s k a s s e s s m e n t regardless of age when prescribing drugs or performing procedures that may increase the risk of UGIB, and take necessary measures to reduce modifiable risk factors such as H. pylori eradication or lifestyle counseling.
文摘Patients with hepatocellular carcinoma(HCC) accompanying portal vein tumor thrombosis(PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelonaclinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival(OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization(TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent metaanalysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization(TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resectionbased multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.
文摘AIM To examine the association between the timing of endo-scopy and the short-term outcomes of acute variceal bleeding in cirrhotic patients.METHODS This retrospective study included 274 consecutive patients admitted with acute esophageal variceal bleeding of two tertiary hospitals in Korea. We adjusted confounding factors using the Cox proportional hazards model and the inverse probability weighting （IPW） method. The primary outcome was the mortality of patients within 6 wk.RESULTS A total of 173 patients received urgent endoscopy （ i.e. , ≤ 12 h after admission）, and 101 patients received non-urgent endoscopy （〉 12 h after admission）. The 6-wk mortality rate was 22.5% in the urgent endoscopy group and 29.7% in the non-urgent endoscopy group, and there was no significant difference between the two groups before （P = 0.266） and after IPW （P = 0.639）. The length of hospital stay was statistically different between the urgent group and non-urgent group （P = 0.033）; however, there was no significant difference in the in-hospital mortality rate between the two groups （8.1%vs 7.9%, P = 0.960）. In multivariate analyses, timing of endoscopy was not associated with 6-wk mortality （hazard ratio, 1.297; 95% confdence interval, 0.806-2.089; P = 0.284）.CONCLUSION In cirrhotic patients with acute variceal bleeding, the timing of endoscopy may be independent of short-term mortality.
基金Seoul National University Hospital,Grant/Award Numbers:04-2022-3140,30-2022-0340Liver Research Foundation of Korea。
文摘Introduction:Although an association between metabolic dysfunctionassociated fatty liver disease(MAFLD)and cardiovascular disease or overall mortality has been reported,it is unclearwhether there is an association between MAFLD and cancer incidence or mortality.We aimed to investigate the differential risk of all-and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease.Methods:Using the Korean National Health Insurance Service database,we stratified the participants into three groups:(1)single-etiology MAFLD(SMAFLD)or MAFLD of pure metabolic origin;(2)mixed-etiology MAFLD(M-MAFLD)or MAFLD with additional etiological factor(s)(i.e.,concomitant liver diseases and/or heavy alcohol consumption);and(3)non-MAFLD.Hepatic steatosis and fibrosiswere defined using the fatty liver index and the BARDscore,respectively.Cox proportional hazards regression was performed to estimate the risk of cancer events.Results:Among the 9,718,182 participants,the prevalence of S-MAFLD and M-MAFLD was 29.2%and 6.7%,respectively.During the median 8.3 years of follow-up,510,330(5.3%)individuals were newly diagnosed with cancer,and 122,774(1.3%)cancer-related deaths occurred among the entire cohort.Compared with the non-MAFLD group,the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group(incidence,adjusted hazard ratio[aHR]=1.03;95%confidence interval[CI]:1.02−1.04;mortality,aHR=1.06;95%CI:1.04−1.08)and highest among patients with M-MAFLD group(incidence,aHR=1.31;95%CI:1.29−1.32;mortality,aHR=1.45;95%CI:1.42−1.48,respectively).The M-MAFLD with fibrosis group(BARD score≥2)showed the highest relative risk of all-cancer incidence(aHR=1.38,95%CI=1.36–1.39),followed by the M-MAFLD without fibrosis group(aHR=1.09,95%CI=1.06–1.11).Similar trends were observed for cancer-related mortality.Conclusions:MAFLD classification,by applying additional etiologies other than pure metabolic origin,can be used to identify a subgroup of patients with poor cancer-related outcomes.
文摘Fucoidan is a traditional Chinese medicine suggested to possess anti-tumor effects.In this study the anti-metastatic effects of fucoidan were investigated in vitro in human hepatocellular carcinoma(HCC) cells(Huh-7 and SNU-761) under normoxic and hypoxic conditions and in vivo using a distant liver metastasis model involving injection of MH134 cells into spleen via the portal vein.Its ability to protect hepatocytes against bile acid(BA)-induced apoptosis was investigated in primary hepatocytes.Fucoidan was found to suppress the invasion of HCC cells through up-regulation of p42/44 MAPKdependent NDRG-1/CAP43 and partly,under normoxic conditions,through up-regulation of p42/44MAPK-dependent VMP-1 expression.It also significantly decreased liver metastasis in vivo.As regards its hepatoprotective effect,fucoidan decreased BA-induced hepatocyte apoptosis as shown by the attenuation of caspase-8,and-7 cleavages and suppression of the mobilization of caspase-8 and Fas associated death domain(FADD) into the death-inducing signaling complex.In summary,fucoidandisplays inhibitory effects on proliferation of HCC cells and protective effects on hepatocytes.The results suggest fucoidan is a potent suppressor of tumor invasion with hepatoprotective effects.
