AIM:To investigate the diagnostic performance of acoustic radiation force impulse(ARFI) elastography for characterizing focal liver mass by quantifying their stiffness.METHODS:This prospective study included 62 patien...AIM:To investigate the diagnostic performance of acoustic radiation force impulse(ARFI) elastography for characterizing focal liver mass by quantifying their stiffness.METHODS:This prospective study included 62 patients with a focal liver mass that was well visualized on conventional ultrasonography performed in our institution from February 2011 to November 2011.Among them,12 patients were excluded for ARFI measurement failure due to a lesion that was smaller than the region of the interest and at an inaccessible location(deeper than 8 cm)(n = 7) or poor compliance to hold their breath as required(n = 5).Finally,50 patients with valid ARFI measurements were enrolled.If a patient had multiple liver masses,only one mass of interest was chosen.The masses were diagnosed by histological examination or clinical diagnostic criteria.During ultrasonographic evaluation,stiffness,expressed as velocity,was checked 10 times per focal liver mass and the surrounding liver parenchyma.RESULTS:After further excluding three masses that were non-diagnostic on biopsy,a total of 47 focal mass lesions were tested,including 39(83.0%) malignant masses [24 hepatocellular carcinomas(HCC),seven cholangiocellular carcinomas(CCC),and eight liver metastases] and eight(17.0%) benign masses(five hemangiomas and three focal nodular hyperplasias,FNH).Thirty-seven(74.0%) masses were confirmed by histological examination.The mean velocity was 2.48 m/s in HCCs,1.65 m/s in CCCs,2.35 m/s in metastases,1.83 m/s in hemangiomas,and 0.97 m/s in FNHs.Although considerable overlap was still noted between malignant and benign masses,significant differences in ARFI values were observed between malignant and benign masses(mean 2.31 m/s vs 1.51 m/s,P = 0.047),as well as between HCCs and benign masses(mean 2.48 m/s vs 1.51 m/s,P = 0.006).The areas under the receiver operating characteristics curves(AUROC) for discriminating the malignant masses from benign masses was 0.724(95%CI,0.566-0.883,P = 0.048),and the AUROC for discriminating HCCs from benign masses was 0.813(95%CI,0.649-0.976,P = 0.008).To maximize the sum of sensitivity and specificity,an ARFI value of 1.82 m/s was selected as the cutoff value to differentiate malignant from benign liver masses.Furthermore,the cutoff value for distinguishing HCCs from benign masses was also determined to be 1.82 m/s.The diagnostic performance of the sum of the ARFI values for focal liver masses and the surrounding liver parenchyma to differentiate liver masses improved(AUROC = 0.853;95%CI,0.745-0.960;P = 0.002 in malignant liver masses vs benign ones and AUROC = 0.948;95%CI,0.896-0.992,P < 0.001 in HCCs vs benign masses).CONCLUSION:ARFI elastography provides additional information for the differential diagnosis of liver masses.However,our results should be interpreted in clinical context,because considerable overlap in ARFI values existed among liver masses.展开更多
Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which wa...Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.展开更多
AIM:To evaluate long-term clinical course of BuddChiari syndrome(BCS) and predictive factors associated with the development of hepatocellular carcinoma(HCC) and survival.METHODS:We analyzed 67 patients with BCS betwe...AIM:To evaluate long-term clinical course of BuddChiari syndrome(BCS) and predictive factors associated with the development of hepatocellular carcinoma(HCC) and survival.METHODS:We analyzed 67 patients with BCS between June 1988 and May 2008.The diagnosis of BCS was confirmed by hepatic venous outflow obstruction shown on abdominal ultrasound sonography,computed tomography,magnetic resonance imaging,or venography.The median follow-up period was 103 ± 156 [interquartile range(IQR)] mo.RESULTS:The median age of the patients was 47 ± 16(IQR) years.At diagnosis,54 patients had cirrhosis,25(37.3%) Child-Pugh class A,23(34.3%) Child-Pugh class B,and six(9.0%) patients Child-Pugh class C.During the follow-up period,HCC was developed in 17 patients,and the annual incidence of HCC in patients with BCS was 2.8%.Patients in HCC group(n = 17) had higher hepatic venous pressure gradient(HVPG) than those in non-HCC group(n = 50)(21 ± 12 mmHg vs 14 ± 7 mmHg,P = 0.019).The survival rate of BCS patients was 86.2% for 5 years,73.8% for 10 years,and 61.2% for 15 years.In patients with BCS and HCC,survival was 79% for 5 years,43.1% for 10 years,and 21.5% for 15 years.CONCLUSION:The incidence of HCC in patients with BCS was similar to that in patients with other etiologic cirrhosis in South Korea.The HVPG is expected to provide additional information for predicting HCC development in BCS patients.展开更多
AIM: To investigate the prevalence of significant liver fibrosis assessed using transient elastography(TE) and its predictors in asymptomatic general population.METHODS: A total of 159 subjects without chronic viral h...AIM: To investigate the prevalence of significant liver fibrosis assessed using transient elastography(TE) and its predictors in asymptomatic general population.METHODS: A total of 159 subjects without chronic viral hepatitis who underwent comprehensive medical health check-up between January 2012 and July 2012 were prospectively recruited. Significant liver fibrosis was defined as liver stiffness value > 7.0 k Pa.RESULTS: The mean age and body mass index(BMI) of the study population(men 54.7%) was 56.0 years and 24.3 kg/m2. Among the study subjects, 11(6.9%) showed significant liver fibrosis. On univariate analysis, BMI, alanine aminotransferase(ALT), homeostasis model assessment of insulin resistance, carotid intimal media thickness(IMT), number of calcified plaques on carotid ultrasound, and visceral fat area on computed tomography were significantly higher in subjects with significant liver fibrosis than in those without(all P < 0.05). However, on multivariate analysis, BMI [odds ratio(OR) =1.487; P = 0.045], ALT(OR = 1.078; P = 0.014), carotid IMT(OR = 3.244; P = 0.027), and the number of calcified carotid plaques(OR = 1.787; P = 0.031) were independent predictors of significant liver fibrosis. CONCLUSION: The prevalence of significant liver fibrosis assessed using TE was 6.9% in apparently healthy subjects. High BMI, high ALT, thicker carotid IMT, and higher numbers of calcified carotid plaqueswere independently associated with the presence of significant liver fibrosis.展开更多
Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of ...Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE(cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drugeluting beads(DEBs) have been imposed as novel drugdelivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEBTACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.展开更多
AIM:To examine the efficacy of telbivudine(LdT)+adefovir(ADV)vs continuation of lamivudine(LAM)+ADV in patients with LAM-resistant chronic hepatitis B(CHB)who show a suboptimal response to LAM+ADV.METHODS:This was a r...AIM:To examine the efficacy of telbivudine(LdT)+adefovir(ADV)vs continuation of lamivudine(LAM)+ADV in patients with LAM-resistant chronic hepatitis B(CHB)who show a suboptimal response to LAM+ADV.METHODS:This was a randomized,active-control,open-label,single-center,parallel trial.All eligible patients were enrolled in this study in Severance Hospital,Yonsei University College of Medicine,Seoul,South Korea,between March 2010 and March 2011.Hepatitis Be antigen(HBeAg)-positive CHB patients whose serum hepatitis B virus(HBV)DNA remained detectable despite at least 6 mo of LAM+ADV therapy were included.Enrolled patients were randomized to either switching to LdT(600 mg/d orally)plus ADV(10 mg/d orally)(LdT+ADV group)or to continuation with LAM(100 mg/d orally)plus ADV(10 mg/d orally)(LAM+ADV group),and were followed for 48 wk.One hundred and six patients completed the 48-wk treatment period.Serum HBV DNA,HBeAg status,liver biochemistry and safety were monitored at baseline and week 12,24,36 and 48.RESULTS:The duration of prior LAM+ADV treatment was 18.3(LdT+ADV)and 14.9 mo(LAM+ADV),respectively(P=0.131).No difference was seen in baseline serum HBV DNA between the two groups[3.66(LdT+ADV)vs 3.76(LAM+ADV)log10IU/mL,P=0.729].At week 48,although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT+ADV group and LAM+ADV group(-0.81 vs-0.47 log10IU/mL,P=0.167),more patients in the LdT+ADV group had undetectable HBV DNA levels compared to those in the LAM+ADV group(30.2%vs 11.5%,P=0.019).Three patients with LdT+ADV treatment and 2 patients with LAM+ADV treatment achieved HBeAg loss.The patients in both groups tolerated the treatment well without serious adverse events.The proportion of patients with estimated glomerular filtration rate≥90 mL/min per 1.73 m2in the LdT+ADV group increased from 49.1%(26/53)at baseline to 58.5%(31/53)at week 48,while that in the LAM+ADV group decreased from 37.7%(20/53)at baseline to 30.2%(16/53)at week 48.CONCLUSION:The switch to LdT+ADV in suboptimal responders to LAM+ADV showed a significantly higher rate of virologic response at week 48.These results suggest that LdT+ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.展开更多
AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC pat...AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC patients who fulfilled the Milan criteria after having received TACE and subsequently underwent LT were included (TACE + LT group) in the study. As controls, 21 patients who also met the Milan criteria and underwent LT without prior treatment were selected (LT group). Post-LT clinical outcomes, such as HCC recurrence, survival rate, and histologic features of explanted livers, were compared between the two groups. RESULTS: Baseline characteristics were not different between the two groups. Pre-LT maximal tumor diameter in TACE + LT group was similar to that of LT group (2.0 ± 0.6 cm vs 2.3 ± 0.9 cm; P = 0.10). Post-LT histologic findings also revealed similar maximal tumor diameter in the two groups (2.4 ± 1.4 cm vs 2.3 ± 0.9 cm; P = 0.70). Explanted livers showed similar incidence of unfavorable pathologic features. The morality within 60 d after transplantation was not different between the two groups (8.3% vs 9.5%; P = 0.99). Post-LT 5-year survival rate (57% vs 74%; P = 0.70) and cumulative recurrence rate (8.3% vs 4.8%; P = 0.90) were not significantly different between the two groups. CONCLUSION: The Milan criteria are still a useful selec- tion criteria showing favorable outcomes in HCC patientsreceiving TACE before LT.展开更多
Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix ...Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin(RSV)/EZE in the treatment of NAFLD.Methods NAFLD mouse models were developed by injecting thioacetamide,fasting,and high-carbohydrate refeeding,highfat diet,and choline-deficient L-amino acid-defined high-fat diet(CDAHFD).Low-dose UDCA(L-UDCA;15 mg/kg)or highdose UDCA(H-UDCA;30 mg/kg)was administered with RSV/EZE.We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.Results Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation,serum alanine aminotransferase(ALT)levels,and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice(all P<0.01).In addition,in the group fasted and refed with a high-carbohydrate diet,UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group(all P<0.05).Subsequently,H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1(SCD-1)mRNA levels(P=0.027)in the liver of high-fat diet-fed mice compared with those observed in the vehicle group.In the CDAHFD-fed mouse model,UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group(all P<0.05).In addition,UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells(all P<0.05).Conclusion Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.展开更多
基金Supported by A Grant of the Korea Healthcare Technology R and D Project,Ministry of Health and Welfare,South Korea, A102065
文摘AIM:To investigate the diagnostic performance of acoustic radiation force impulse(ARFI) elastography for characterizing focal liver mass by quantifying their stiffness.METHODS:This prospective study included 62 patients with a focal liver mass that was well visualized on conventional ultrasonography performed in our institution from February 2011 to November 2011.Among them,12 patients were excluded for ARFI measurement failure due to a lesion that was smaller than the region of the interest and at an inaccessible location(deeper than 8 cm)(n = 7) or poor compliance to hold their breath as required(n = 5).Finally,50 patients with valid ARFI measurements were enrolled.If a patient had multiple liver masses,only one mass of interest was chosen.The masses were diagnosed by histological examination or clinical diagnostic criteria.During ultrasonographic evaluation,stiffness,expressed as velocity,was checked 10 times per focal liver mass and the surrounding liver parenchyma.RESULTS:After further excluding three masses that were non-diagnostic on biopsy,a total of 47 focal mass lesions were tested,including 39(83.0%) malignant masses [24 hepatocellular carcinomas(HCC),seven cholangiocellular carcinomas(CCC),and eight liver metastases] and eight(17.0%) benign masses(five hemangiomas and three focal nodular hyperplasias,FNH).Thirty-seven(74.0%) masses were confirmed by histological examination.The mean velocity was 2.48 m/s in HCCs,1.65 m/s in CCCs,2.35 m/s in metastases,1.83 m/s in hemangiomas,and 0.97 m/s in FNHs.Although considerable overlap was still noted between malignant and benign masses,significant differences in ARFI values were observed between malignant and benign masses(mean 2.31 m/s vs 1.51 m/s,P = 0.047),as well as between HCCs and benign masses(mean 2.48 m/s vs 1.51 m/s,P = 0.006).The areas under the receiver operating characteristics curves(AUROC) for discriminating the malignant masses from benign masses was 0.724(95%CI,0.566-0.883,P = 0.048),and the AUROC for discriminating HCCs from benign masses was 0.813(95%CI,0.649-0.976,P = 0.008).To maximize the sum of sensitivity and specificity,an ARFI value of 1.82 m/s was selected as the cutoff value to differentiate malignant from benign liver masses.Furthermore,the cutoff value for distinguishing HCCs from benign masses was also determined to be 1.82 m/s.The diagnostic performance of the sum of the ARFI values for focal liver masses and the surrounding liver parenchyma to differentiate liver masses improved(AUROC = 0.853;95%CI,0.745-0.960;P = 0.002 in malignant liver masses vs benign ones and AUROC = 0.948;95%CI,0.896-0.992,P < 0.001 in HCCs vs benign masses).CONCLUSION:ARFI elastography provides additional information for the differential diagnosis of liver masses.However,our results should be interpreted in clinical context,because considerable overlap in ARFI values existed among liver masses.
基金Supported by A grant of the South Korea Healthcare technology R and D projectMinistry of Health and Welfare+1 种基金South KoreaNo.HI10C2020
文摘Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.
基金Supported by A grant of the South Korea Healthcare Technology R and D Project,Ministry of Health and Welfare,South Korea,No.A102065
文摘AIM:To evaluate long-term clinical course of BuddChiari syndrome(BCS) and predictive factors associated with the development of hepatocellular carcinoma(HCC) and survival.METHODS:We analyzed 67 patients with BCS between June 1988 and May 2008.The diagnosis of BCS was confirmed by hepatic venous outflow obstruction shown on abdominal ultrasound sonography,computed tomography,magnetic resonance imaging,or venography.The median follow-up period was 103 ± 156 [interquartile range(IQR)] mo.RESULTS:The median age of the patients was 47 ± 16(IQR) years.At diagnosis,54 patients had cirrhosis,25(37.3%) Child-Pugh class A,23(34.3%) Child-Pugh class B,and six(9.0%) patients Child-Pugh class C.During the follow-up period,HCC was developed in 17 patients,and the annual incidence of HCC in patients with BCS was 2.8%.Patients in HCC group(n = 17) had higher hepatic venous pressure gradient(HVPG) than those in non-HCC group(n = 50)(21 ± 12 mmHg vs 14 ± 7 mmHg,P = 0.019).The survival rate of BCS patients was 86.2% for 5 years,73.8% for 10 years,and 61.2% for 15 years.In patients with BCS and HCC,survival was 79% for 5 years,43.1% for 10 years,and 21.5% for 15 years.CONCLUSION:The incidence of HCC in patients with BCS was similar to that in patients with other etiologic cirrhosis in South Korea.The HVPG is expected to provide additional information for predicting HCC development in BCS patients.
基金Supported by The Liver Cirrhosis Clinical Research Centerin part by a grant from the Korea Healthcare Technology RD Project,Ministry of Health and Welfare,Republic of Korea No.HI10C2020
文摘AIM: To investigate the prevalence of significant liver fibrosis assessed using transient elastography(TE) and its predictors in asymptomatic general population.METHODS: A total of 159 subjects without chronic viral hepatitis who underwent comprehensive medical health check-up between January 2012 and July 2012 were prospectively recruited. Significant liver fibrosis was defined as liver stiffness value > 7.0 k Pa.RESULTS: The mean age and body mass index(BMI) of the study population(men 54.7%) was 56.0 years and 24.3 kg/m2. Among the study subjects, 11(6.9%) showed significant liver fibrosis. On univariate analysis, BMI, alanine aminotransferase(ALT), homeostasis model assessment of insulin resistance, carotid intimal media thickness(IMT), number of calcified plaques on carotid ultrasound, and visceral fat area on computed tomography were significantly higher in subjects with significant liver fibrosis than in those without(all P < 0.05). However, on multivariate analysis, BMI [odds ratio(OR) =1.487; P = 0.045], ALT(OR = 1.078; P = 0.014), carotid IMT(OR = 3.244; P = 0.027), and the number of calcified carotid plaques(OR = 1.787; P = 0.031) were independent predictors of significant liver fibrosis. CONCLUSION: The prevalence of significant liver fibrosis assessed using TE was 6.9% in apparently healthy subjects. High BMI, high ALT, thicker carotid IMT, and higher numbers of calcified carotid plaqueswere independently associated with the presence of significant liver fibrosis.
文摘Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE(cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drugeluting beads(DEBs) have been imposed as novel drugdelivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEBTACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.
基金Supported by A Grant under the Bilateral International Collaborative R and D Program from the Ministry of Knowledge Economythe Korea Healthcare Technology R and D Project,Ministry for Health and Welfare,South Korea,No.A102065+1 种基金the Liver Cirrhosis Clinical Research Center,a grant from the Korea Healthcare Technology R and D project,Ministry of Health and Welfare,South Korea,No.HI10C2020a grant to the Bilateral International Collaborative R and D Program from the Ministry of Trade,Industry and Energy,South Korea
文摘AIM:To examine the efficacy of telbivudine(LdT)+adefovir(ADV)vs continuation of lamivudine(LAM)+ADV in patients with LAM-resistant chronic hepatitis B(CHB)who show a suboptimal response to LAM+ADV.METHODS:This was a randomized,active-control,open-label,single-center,parallel trial.All eligible patients were enrolled in this study in Severance Hospital,Yonsei University College of Medicine,Seoul,South Korea,between March 2010 and March 2011.Hepatitis Be antigen(HBeAg)-positive CHB patients whose serum hepatitis B virus(HBV)DNA remained detectable despite at least 6 mo of LAM+ADV therapy were included.Enrolled patients were randomized to either switching to LdT(600 mg/d orally)plus ADV(10 mg/d orally)(LdT+ADV group)or to continuation with LAM(100 mg/d orally)plus ADV(10 mg/d orally)(LAM+ADV group),and were followed for 48 wk.One hundred and six patients completed the 48-wk treatment period.Serum HBV DNA,HBeAg status,liver biochemistry and safety were monitored at baseline and week 12,24,36 and 48.RESULTS:The duration of prior LAM+ADV treatment was 18.3(LdT+ADV)and 14.9 mo(LAM+ADV),respectively(P=0.131).No difference was seen in baseline serum HBV DNA between the two groups[3.66(LdT+ADV)vs 3.76(LAM+ADV)log10IU/mL,P=0.729].At week 48,although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT+ADV group and LAM+ADV group(-0.81 vs-0.47 log10IU/mL,P=0.167),more patients in the LdT+ADV group had undetectable HBV DNA levels compared to those in the LAM+ADV group(30.2%vs 11.5%,P=0.019).Three patients with LdT+ADV treatment and 2 patients with LAM+ADV treatment achieved HBeAg loss.The patients in both groups tolerated the treatment well without serious adverse events.The proportion of patients with estimated glomerular filtration rate≥90 mL/min per 1.73 m2in the LdT+ADV group increased from 49.1%(26/53)at baseline to 58.5%(31/53)at week 48,while that in the LAM+ADV group decreased from 37.7%(20/53)at baseline to 30.2%(16/53)at week 48.CONCLUSION:The switch to LdT+ADV in suboptimal responders to LAM+ADV showed a significantly higher rate of virologic response at week 48.These results suggest that LdT+ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.
文摘AIM: To evaluate whether the Milan criteria are useful in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before liver transplantation (LT). METHODS: Thirty-six HCC patients who fulfilled the Milan criteria after having received TACE and subsequently underwent LT were included (TACE + LT group) in the study. As controls, 21 patients who also met the Milan criteria and underwent LT without prior treatment were selected (LT group). Post-LT clinical outcomes, such as HCC recurrence, survival rate, and histologic features of explanted livers, were compared between the two groups. RESULTS: Baseline characteristics were not different between the two groups. Pre-LT maximal tumor diameter in TACE + LT group was similar to that of LT group (2.0 ± 0.6 cm vs 2.3 ± 0.9 cm; P = 0.10). Post-LT histologic findings also revealed similar maximal tumor diameter in the two groups (2.4 ± 1.4 cm vs 2.3 ± 0.9 cm; P = 0.70). Explanted livers showed similar incidence of unfavorable pathologic features. The morality within 60 d after transplantation was not different between the two groups (8.3% vs 9.5%; P = 0.99). Post-LT 5-year survival rate (57% vs 74%; P = 0.70) and cumulative recurrence rate (8.3% vs 4.8%; P = 0.90) were not significantly different between the two groups. CONCLUSION: The Milan criteria are still a useful selec- tion criteria showing favorable outcomes in HCC patientsreceiving TACE before LT.
基金supported by Daewoong Pharmaceutical company,and was supported by a Faculty Research Grant from the Yonsei University College of Medicine(6-2019-0068 to S.H.Bae)by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)+2 种基金funded by the Ministry of Health&Welfare,Republic of Korea(HI17C0913 and HI16C0257 to S.H.Bae)supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(NRF-2022R1A2C2003438 to S.H.Bae,NRF-2021R1C1C2095694 to D.H.Lee)by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(2019R1A2C4070136 to S.U.Kim).
文摘Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin(RSV)/EZE in the treatment of NAFLD.Methods NAFLD mouse models were developed by injecting thioacetamide,fasting,and high-carbohydrate refeeding,highfat diet,and choline-deficient L-amino acid-defined high-fat diet(CDAHFD).Low-dose UDCA(L-UDCA;15 mg/kg)or highdose UDCA(H-UDCA;30 mg/kg)was administered with RSV/EZE.We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.Results Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation,serum alanine aminotransferase(ALT)levels,and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice(all P<0.01).In addition,in the group fasted and refed with a high-carbohydrate diet,UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group(all P<0.05).Subsequently,H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1(SCD-1)mRNA levels(P=0.027)in the liver of high-fat diet-fed mice compared with those observed in the vehicle group.In the CDAHFD-fed mouse model,UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group(all P<0.05).In addition,UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells(all P<0.05).Conclusion Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.