AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009...AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)represents the sixteenth most frequent cancer in Argentina.The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.A...BACKGROUND Hepatocellular carcinoma(HCC)represents the sixteenth most frequent cancer in Argentina.The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina.Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC)HCC stages(BCLC B to D).Primary end point analyzed was survival,which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed,with hazard ratios(HR)calculations and 95%confidence intervals(95%CI).RESULTS From 327 HCC patients,41%were BCLC stage B,20%stage C and 39%stage D.Corresponding median survival were 15 mo(IQR 5-26 mo),5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P<0.0001),respectively.Among BCLC-B patients(n=135),57%received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR=0.29(CI:0.21-0.40)than those without TACE.After tumor reassessment by RECIST 1.1 criteria following the first TACE,patients with complete response achieved longer survival(HR=0.15(CI:0.04-0.56,P=0.005))Eighty-two patients were treated with sorafenib,mostly BCLC-B and C(87.8%).However,12.2%were BCLC-D.Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo).A total of 36 BCLC-B patients presented tumor progression after TACE.In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE[HR=0.26(CI:0.09-0.71);P=0.013].CONCLUSION In this real setting,our results were lower than expected.This highlights unmet needs in Argentina,prior to the introduction of new treatments for HCC.展开更多
Chronic kidney disease is a prevalent condition that affects millions of people worldwide and is a major risk factor of cardiovascular morbidity and mortality. The main diseases that lead to chronic kidney disease are...Chronic kidney disease is a prevalent condition that affects millions of people worldwide and is a major risk factor of cardiovascular morbidity and mortality. The main diseases that lead to chronic kidney disease are frequent entities as diabetes mellitus, hypertension and glomerulopathies. One of the clinical markers of kidney disease progression is proteinuria. Moreover, the histological hallmark of kidney disease is sclerosis, located both in the glomerular and in the interstitial compartments. Glomerulosclerosis underscores an irreversible lesion that is clinically accompanied by proteinuria. In this regard, proteinuria and glomerular sclerosis are linked by the cell that has been conserved phylogenetically not only to prevent the loss of proteins in the urine, but also to maintain the health of the glomerular fltration barrier： The podocyte. It can then be concluded that the link between proteinuria, kidney disease progression and chronic kidney disease is mainly related to the podocyte. What is this situation due to？ The podocyte is unable to proliferate under normal conditions, and a complex molecular machinery exists to avoid its detachment and eventual loss. When the loss of podocytes in the urine, or podocyturia, is taking place and its glomerular absolute number decreased, glomerulosclerosis is the predominant histological feature in a kidney biopsy. Therefore, tissular podocyte shortage is the cause of proteinuria and chronic kidney disease. In this regard, podocyturia has been demonstrated to precede proteinuria, showing that the clinical mana-gement of proteinuria cannot be considered an early intervention. The identifcation of urinary podocytes could be an additional tool to be considered by nephrologists to assess the activity of glomerulopathies, for follow-up purposes and also to unravel the pathophysiology of podocyte detachment in order to tailor the therapy of glomerular diseases more appropriately.展开更多
AIM： To assess residual diuresis and diverse variables according to body mass index （BMI）.METHODS： Cross-sectional study （n = 57）, with 3 groups. Group A： BMI 〈 25, n = 22; Group B： BMI 25-30, n = 15; Grou...AIM： To assess residual diuresis and diverse variables according to body mass index （BMI）.METHODS： Cross-sectional study （n = 57）, with 3 groups. Group A： BMI 〈 25, n = 22; Group B： BMI 25-30, n = 15; Group C： BMI 〉 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition infammatory score, Pro-BNP, Troponin T, leptin and in-sulin levels are expressed as median and ranges （r）. RESULTS： Albumin （g/dL）： GA vs GC, 3.70 （r2.20-4.90） vs 3.85 （r3.40-4.90）, P = 0.02. Diuresis （mL/d）： GA 690 （r0-1780）; GB 660 （r60-1800）; GC 840 （r40-2840）. Diuresis GA vs GC, P = 0.01. Leptin （ng/mL）： GA vs GC, 3.81 （r0.78-69.60） vs GC, 32.80 （r0.78-124.50）, P 〈 0.001. Insulin （μU/mL）： GA vs GB, 7 （r2-44） vs 11.50 （r4-38）, P = 0.02; GA vs GC, 7 （r2-44） vs 19.5 （r5-155）, P = 0.0001. Troponin T and Pro-BNP levels were not different. Significant correlations： GC, Insulin-UF： ρ= 0.53; P = 0.03; TroponinT-diuresis： ρ = -0.48, P 〈 0.05; Pro-BNP-diuresis： ρ = -0.39, P 〈 0.01; Troponin T-ProBNP： ρ = 0.77, P 〈 0.0001; albumin-Troponin T： ρ = -0.66, P 〈 0.0001; albumin-ProBNP： ρ = -0.44, P 〈 0.05.CONCLUSION： High BMI associated positively with higher diuresis and albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better survival may be explained by better urinary output, lowering cardiovascular stress.展开更多
Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The differ...Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.展开更多
AIM:To estimate the progression of the hepatitis C virus(HCV)epidemic and measure the burden of HCVrelated morbidity and mortality.METHODS:Age-and gender-defined cohorts were used to follow the viremic population in A...AIM:To estimate the progression of the hepatitis C virus(HCV)epidemic and measure the burden of HCVrelated morbidity and mortality.METHODS:Age-and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence,prevalence,hepatic complications,and mortality.The relative impact of two scenarios on HCV-related outcomes was assessed:(1)increased sustained virologic response(SVR);and(2)increased SVR and treatment.RESULTS:Under scenario 1,SVR raised to 85%-95%in 2016.Compared to the base case scenario,there was a 0.3%reduction in prevalent cases and liverrelated deaths by 2030.Given low treatment rates,cases of hepatocellular carcinoma and decompensated cirrhosis decreased<1%,in contrast to the base case in 2030.Under scenario 2,the same increases in SVR were modeled,with gradual increases in the annual diagnosed and treated populations.This scenario decreased prevalent infections 45%,liver-related deaths 55%,liver cancer cases 60%,and decompensated cirrhosis 55%,as compared to the base case by 2030.CONCLUSION:In Argentina,cases of end stage liver disease and liver-related deaths due to HCV are still growing,while its prevalence is decreasing.Increasing in SVR rates is not enough,and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden.Based on this scenario,strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina.展开更多
Background and Aims:In the REALM (Randomized, Obser-vational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Pa-tients with Chronic HBV Infection) study, 12,378 pa...Background and Aims:In the REALM (Randomized, Obser-vational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Pa-tients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progres-sion events, and deaths. An external event adjudication com-mittee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize poten-tial adverse effects of the large cohort, interdisciplinary out-come assessments, geographic scope, and long duration. Methods:The EAC comprised an international group of hep-atologists and oncologists with expertise in diagnosis of tar-geted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria cap-tured in the EAC charter. Operational processes, including da-ta collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%;hepatocellular carcino-ma (HCC), 83.3%;non-HCC malignancies, 88.0%;non-HCC HBV disease progression, 68.2%. Reasons for lack of con-cordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consis-tency;EAC performance was facilitated by well-defined diag-nostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.展开更多
文摘AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.
文摘BACKGROUND Hepatocellular carcinoma(HCC)represents the sixteenth most frequent cancer in Argentina.The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC.AIM To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic options.METHODS This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina.Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC)HCC stages(BCLC B to D).Primary end point analyzed was survival,which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death.Kaplan Meier survival curves and Cox regression analysis were performed,with hazard ratios(HR)calculations and 95%confidence intervals(95%CI).RESULTS From 327 HCC patients,41%were BCLC stage B,20%stage C and 39%stage D.Corresponding median survival were 15 mo(IQR 5-26 mo),5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P<0.0001),respectively.Among BCLC-B patients(n=135),57%received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR=0.29(CI:0.21-0.40)than those without TACE.After tumor reassessment by RECIST 1.1 criteria following the first TACE,patients with complete response achieved longer survival(HR=0.15(CI:0.04-0.56,P=0.005))Eighty-two patients were treated with sorafenib,mostly BCLC-B and C(87.8%).However,12.2%were BCLC-D.Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo).A total of 36 BCLC-B patients presented tumor progression after TACE.In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE[HR=0.26(CI:0.09-0.71);P=0.013].CONCLUSION In this real setting,our results were lower than expected.This highlights unmet needs in Argentina,prior to the introduction of new treatments for HCC.
文摘Chronic kidney disease is a prevalent condition that affects millions of people worldwide and is a major risk factor of cardiovascular morbidity and mortality. The main diseases that lead to chronic kidney disease are frequent entities as diabetes mellitus, hypertension and glomerulopathies. One of the clinical markers of kidney disease progression is proteinuria. Moreover, the histological hallmark of kidney disease is sclerosis, located both in the glomerular and in the interstitial compartments. Glomerulosclerosis underscores an irreversible lesion that is clinically accompanied by proteinuria. In this regard, proteinuria and glomerular sclerosis are linked by the cell that has been conserved phylogenetically not only to prevent the loss of proteins in the urine, but also to maintain the health of the glomerular fltration barrier： The podocyte. It can then be concluded that the link between proteinuria, kidney disease progression and chronic kidney disease is mainly related to the podocyte. What is this situation due to？ The podocyte is unable to proliferate under normal conditions, and a complex molecular machinery exists to avoid its detachment and eventual loss. When the loss of podocytes in the urine, or podocyturia, is taking place and its glomerular absolute number decreased, glomerulosclerosis is the predominant histological feature in a kidney biopsy. Therefore, tissular podocyte shortage is the cause of proteinuria and chronic kidney disease. In this regard, podocyturia has been demonstrated to precede proteinuria, showing that the clinical mana-gement of proteinuria cannot be considered an early intervention. The identifcation of urinary podocytes could be an additional tool to be considered by nephrologists to assess the activity of glomerulopathies, for follow-up purposes and also to unravel the pathophysiology of podocyte detachment in order to tailor the therapy of glomerular diseases more appropriately.
文摘AIM： To assess residual diuresis and diverse variables according to body mass index （BMI）.METHODS： Cross-sectional study （n = 57）, with 3 groups. Group A： BMI 〈 25, n = 22; Group B： BMI 25-30, n = 15; Group C： BMI 〉 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition infammatory score, Pro-BNP, Troponin T, leptin and in-sulin levels are expressed as median and ranges （r）. RESULTS： Albumin （g/dL）： GA vs GC, 3.70 （r2.20-4.90） vs 3.85 （r3.40-4.90）, P = 0.02. Diuresis （mL/d）： GA 690 （r0-1780）; GB 660 （r60-1800）; GC 840 （r40-2840）. Diuresis GA vs GC, P = 0.01. Leptin （ng/mL）： GA vs GC, 3.81 （r0.78-69.60） vs GC, 32.80 （r0.78-124.50）, P 〈 0.001. Insulin （μU/mL）： GA vs GB, 7 （r2-44） vs 11.50 （r4-38）, P = 0.02; GA vs GC, 7 （r2-44） vs 19.5 （r5-155）, P = 0.0001. Troponin T and Pro-BNP levels were not different. Significant correlations： GC, Insulin-UF： ρ= 0.53; P = 0.03; TroponinT-diuresis： ρ = -0.48, P 〈 0.05; Pro-BNP-diuresis： ρ = -0.39, P 〈 0.01; Troponin T-ProBNP： ρ = 0.77, P 〈 0.0001; albumin-Troponin T： ρ = -0.66, P 〈 0.0001; albumin-ProBNP： ρ = -0.44, P 〈 0.05.CONCLUSION： High BMI associated positively with higher diuresis and albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better survival may be explained by better urinary output, lowering cardiovascular stress.
文摘Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.
文摘AIM:To estimate the progression of the hepatitis C virus(HCV)epidemic and measure the burden of HCVrelated morbidity and mortality.METHODS:Age-and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence,prevalence,hepatic complications,and mortality.The relative impact of two scenarios on HCV-related outcomes was assessed:(1)increased sustained virologic response(SVR);and(2)increased SVR and treatment.RESULTS:Under scenario 1,SVR raised to 85%-95%in 2016.Compared to the base case scenario,there was a 0.3%reduction in prevalent cases and liverrelated deaths by 2030.Given low treatment rates,cases of hepatocellular carcinoma and decompensated cirrhosis decreased<1%,in contrast to the base case in 2030.Under scenario 2,the same increases in SVR were modeled,with gradual increases in the annual diagnosed and treated populations.This scenario decreased prevalent infections 45%,liver-related deaths 55%,liver cancer cases 60%,and decompensated cirrhosis 55%,as compared to the base case by 2030.CONCLUSION:In Argentina,cases of end stage liver disease and liver-related deaths due to HCV are still growing,while its prevalence is decreasing.Increasing in SVR rates is not enough,and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden.Based on this scenario,strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina.
基金This study was funded by Bristol-Myers Squibb,which designed the study,conducted statistical analyses,and provided financial support for the study.
文摘Background and Aims:In the REALM (Randomized, Obser-vational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Pa-tients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progres-sion events, and deaths. An external event adjudication com-mittee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize poten-tial adverse effects of the large cohort, interdisciplinary out-come assessments, geographic scope, and long duration. Methods:The EAC comprised an international group of hep-atologists and oncologists with expertise in diagnosis of tar-geted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria cap-tured in the EAC charter. Operational processes, including da-ta collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%;hepatocellular carcino-ma (HCC), 83.3%;non-HCC malignancies, 88.0%;non-HCC HBV disease progression, 68.2%. Reasons for lack of con-cordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consis-tency;EAC performance was facilitated by well-defined diag-nostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.
