Aims Increased serum creatinine(sCR)is associated with increased mortality in cirrhotic patients,while there remains a lack of evidence-based sCR cutoffs for indicating disease deterioration and predicting 90-day live...Aims Increased serum creatinine(sCR)is associated with increased mortality in cirrhotic patients,while there remains a lack of evidence-based sCR cutoffs for indicating disease deterioration and predicting 90-day liver transplantation(LT)-free mortality in the cirrhotic Chinese population.We aimed to investigate the quantitative relationship between sCR on admission and 90-day mortality in hospitalized patients with cirrhosis in the Chinese population.Methods Data were prospectively collected from two multicenter cohorts,which enrolled hospitalized patients with chronic liver disease.After screening,2582 patients with cirrhosis from January 2015 to December 2016 and from July 2018 to January 2019 were included in the primary analysis.Creatinine values were collected on admission.Patients were regularly followed up at the end of 90 days.The univariate and multivariate Cox proportional hazard model was conducted to explore the relationship between sCR and 90-day LT-free mortality.A generalized additive model and second derivative(acceleration)were used to plot“creatinine-mortality correlation curves”,adjusting for potential confounders.Results Among 2582 hospitalized patients with cirrhosis,428(16.6%)experienced deaths at the end of 90 days.sCR levels on admission were significantly associated with 90-day LT-free mortality in both univariate and multivariate analyses(hazard ratio[HR],1.77,p<0.001;HR,1.22,p=0.003).sCR of 1.1 mg/dL was identified as the starting point(stage 1a)of disease deterioration of acute kidney injury(AKI)in hospitalized patients with cirrhosis.Patients with 1.1 mg/dL<sCR≤1.8 mg/dL had significantly higher 90-day mortality compared to those with sCR≤1.1 mg/dL(HR,1.90,p<0.001).The corresponding 28-day and 90-day LT-free mortality to sCR 1.1 mg/dL were 11%and 18%,respectively.Conclusions sCR was an independent risk factor for 90-day LT-free mortality in hospitalized cirrhotic patients.sCR of 1.1 mg/dL is the starting point of disease deterioration and serves as an important supplement for the diagnostic threshold of AKI stage 1a in the Chinese cirrhotic population without baseline sCR.展开更多
Background The model for end-stage liver disease(MELD)score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure(ACLF).In this study,we identi...Background The model for end-stage liver disease(MELD)score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure(ACLF).In this study,we identified additional predictive parameters and reformed the MELD score to predict ACLF more accurately.Methods A meta-analysis was performed on relevant studies to identify the predictive factors of 28-day/90-day outcomes of ACLF,which were validated in two large prospective cohorts.A prognostic score was developed by incorporating predictive parameters into the MELD score.The model was evaluated with a focus on discrimination and calibration.Results The meta-analysis incorporated 32 cohort studies with a total of 13939 patients,of which 13 risk factors were identified,and 3 risk factors(age,neutrophil count and hepatic encephalopathy(HE)grade)besides MELD score were validated in 751 patients with ACLF derived from two prospective cohorts.A new model(Chinese Acute-on-Chronic Liver Failure Consortium(CATCH-LIFE)-MELD score)was developed as follows:0.028×age+0.3×HE grade+0.039×neutrophil count+0.079×MELD score.CATCH-LIFE-MELD score achieved a concordance index of 0.791/0.788 for 28-day/90-day outcomes,which is superior to other traditional scores.Other discrimination indices,including net reclassification improvement,integrated discrimination improvement and probability density function,and calibration including Nagelkerke’s R2 and Brier scores confirmed its superiority.Moreover,the accuracy of CATCH-LIFE-MELD score remained stable.It was highest in patients with or without hepatitis B virus infection,cirrhosis,liver failure or under the Chinese Group on the Study of Severe Hepatitis B(COSSH)criteria or European Association for the Study of the Liver(EASL)criteria.All results were substantiated by an evaluation using an external cohort.Conclusions CATCH-LIFE-MELD score,a modified MELD score exhibited improved accuracy in predicting the short-term prognosis of ACLF than other traditional scores.展开更多
Background and Aims:Approximately 10%of patients with acute decompensated(AD)cirrhosis develop acute-on-chronic liver failure(ACLF)within 28 days.Such cases have high mortality and are difficult to predict.Therefore,w...Background and Aims:Approximately 10%of patients with acute decompensated(AD)cirrhosis develop acute-on-chronic liver failure(ACLF)within 28 days.Such cases have high mortality and are difficult to predict.Therefore,we aimed to establish and validate an algorithm to identify these patients on hospitalization.Methods:Hospitalized patients with AD who developed ACLF within 28 days were considered pre-ACLF.Organ dysfunction was defined accord-ing to the chronic liver failure-sequential organ failure as-sessment(CLIF-SOFA)criteria,and proven bacterial infec-tion was taken to indicate immune system dysfunction.A retrospective multicenter cohort and prospective one were used to derive and to validate the potential algorithm,re-spectively.A miss rate of<5%was acceptable for the calcu-lating algorithm to rule out pre-ACLF.Results:In the deri-vation cohort(n=673),46 patients developed ACLF within 28 days.Serum total bilirubin,creatinine,international normalized ratio,and present proven bacterial infection at admission were associated with the development of ACLF.AD patients with≥2 organ dysfunctions had a higher risk for pre-ACLF patients[odds ratio=16.58195%confidence interval:(4.271-64.363),p<0.001].In the derivation co-hort,67.5%of patients(454/673)had≤1 organ dysfunction and two patients(0.4%)were pre-ACLF,with a miss rate of 4.3%(missed/total,2/46).In the validation cohort,65.9%of patients(914/1388)had≤1 organ dysfunction,and four(0.3%)of them were pre-ACLF,with a miss rate of 3.4%(missed/total,4/117).Conclusions:AD patients with≤1 organ dysfunction had a significantly lower risk of developing ACLF within 28 days of admission and could be safely ruled out with a pre-ACLF miss rate of<5%.展开更多
Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.M...Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.Methods:The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies(NCT02457637 and NCT03641872)conducted in highly endemic hepatitis B virus(HBV)areas.Competing risk analysis was used to evaluate the effect of predispositions,including the etiology and severity of CLDs and precipitants;on sequential 28,90,and 365-day liver transplantation(LT)-free mortality.Results:Among all enrolled patients,76.8%of adverse outcomes(including death and LT)within one year occurred within 90 days.Compared with alcoholic etiology,the association of HBV etiology with poorer outcomes was remarkably on the 28th day(hazard ratio[HR],1.81;95%confidence interval[CI],1.07-3.06;p=0.026);however,and dimin-ished or became insignificant at 90 days and 365 days.Cirrhosis increased the adjusted risk for 365-day(HR,1.50;CI,1.13-1.99;p=0.004)LT-free mortality when compared with noncirrhosis.In patients with cirrhosis,prior decompensation(PD)independently increased the adjusted risk of 365-day LT-free mortality by 1.25-fold(p=0.021);however,it did not increase the risk for 90-day mortality.Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90-day LT-free mortality.Conclusions:The 90-day outcome should be considered a significant endpoint for evaluating the short-term prognosis of hospitalized patients with CLD.Predisposing factors,other than etiology,mainly affected the delayed(365-day)outcome.Timely effective therapy for CLD etiology,especially antiviral treatments for HBV,and post-discharge long-term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.展开更多
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(2023A1515010194)Shanghai Hospital Development Commission(SHDC2020CR1037B)+6 种基金National Key R&D Program of China(2017YFC0908100)the National Science and Technology Major Project(2018ZX10302206,2018ZX10723203,2017ZX10202202)Shanghai Municipal Education Commission-Guofeng Clinical Medicine Grant Support,the National Natural Science Foundation of China(82170629,81930061,81900579,81970550,82070613,82070650,81972265)the Chongqing Natural ScienceFoundation(CSTC2019jcyj-zdxmX0004)Beijing Municipal Science&Technology Commission(Z191100006619033)Local Innovative and Research TeamsProject of Guangdong Pearl River Talents Program(2017BT01S131)the Foundation for Innovative Research Groups of Hubei Provincial Natural ScienceFoundation(2018CFA031).
文摘Aims Increased serum creatinine(sCR)is associated with increased mortality in cirrhotic patients,while there remains a lack of evidence-based sCR cutoffs for indicating disease deterioration and predicting 90-day liver transplantation(LT)-free mortality in the cirrhotic Chinese population.We aimed to investigate the quantitative relationship between sCR on admission and 90-day mortality in hospitalized patients with cirrhosis in the Chinese population.Methods Data were prospectively collected from two multicenter cohorts,which enrolled hospitalized patients with chronic liver disease.After screening,2582 patients with cirrhosis from January 2015 to December 2016 and from July 2018 to January 2019 were included in the primary analysis.Creatinine values were collected on admission.Patients were regularly followed up at the end of 90 days.The univariate and multivariate Cox proportional hazard model was conducted to explore the relationship between sCR and 90-day LT-free mortality.A generalized additive model and second derivative(acceleration)were used to plot“creatinine-mortality correlation curves”,adjusting for potential confounders.Results Among 2582 hospitalized patients with cirrhosis,428(16.6%)experienced deaths at the end of 90 days.sCR levels on admission were significantly associated with 90-day LT-free mortality in both univariate and multivariate analyses(hazard ratio[HR],1.77,p<0.001;HR,1.22,p=0.003).sCR of 1.1 mg/dL was identified as the starting point(stage 1a)of disease deterioration of acute kidney injury(AKI)in hospitalized patients with cirrhosis.Patients with 1.1 mg/dL<sCR≤1.8 mg/dL had significantly higher 90-day mortality compared to those with sCR≤1.1 mg/dL(HR,1.90,p<0.001).The corresponding 28-day and 90-day LT-free mortality to sCR 1.1 mg/dL were 11%and 18%,respectively.Conclusions sCR was an independent risk factor for 90-day LT-free mortality in hospitalized cirrhotic patients.sCR of 1.1 mg/dL is the starting point of disease deterioration and serves as an important supplement for the diagnostic threshold of AKI stage 1a in the Chinese cirrhotic population without baseline sCR.
基金supported by the National Key Research and Development Programme of China(No.2022YFC2304501,No.2021YFC2301800)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2022RC141)+5 种基金the Fundamental Research Funds for the Central Universities(No.226-2023-00127,No.2021FZZX001-41)Medical and Health,Science and Technology Planning Project of Zhejiang Province,China(No.2021436801)the National Natural Science Foundation of China(81870425,81930061,81900579,81473641,81271884,81700561,81470038,82070650 and 81660333)the Shanghai Hospital Development Commission(SHDC2020CR1037B)the Chongqing Natural Science Foundation(CSTC2019jcyj-zdxmX0004)Shandong Province Natural Science Foundation(ZR2019PH052).
文摘Background The model for end-stage liver disease(MELD)score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure(ACLF).In this study,we identified additional predictive parameters and reformed the MELD score to predict ACLF more accurately.Methods A meta-analysis was performed on relevant studies to identify the predictive factors of 28-day/90-day outcomes of ACLF,which were validated in two large prospective cohorts.A prognostic score was developed by incorporating predictive parameters into the MELD score.The model was evaluated with a focus on discrimination and calibration.Results The meta-analysis incorporated 32 cohort studies with a total of 13939 patients,of which 13 risk factors were identified,and 3 risk factors(age,neutrophil count and hepatic encephalopathy(HE)grade)besides MELD score were validated in 751 patients with ACLF derived from two prospective cohorts.A new model(Chinese Acute-on-Chronic Liver Failure Consortium(CATCH-LIFE)-MELD score)was developed as follows:0.028×age+0.3×HE grade+0.039×neutrophil count+0.079×MELD score.CATCH-LIFE-MELD score achieved a concordance index of 0.791/0.788 for 28-day/90-day outcomes,which is superior to other traditional scores.Other discrimination indices,including net reclassification improvement,integrated discrimination improvement and probability density function,and calibration including Nagelkerke’s R2 and Brier scores confirmed its superiority.Moreover,the accuracy of CATCH-LIFE-MELD score remained stable.It was highest in patients with or without hepatitis B virus infection,cirrhosis,liver failure or under the Chinese Group on the Study of Severe Hepatitis B(COSSH)criteria or European Association for the Study of the Liver(EASL)criteria.All results were substantiated by an evaluation using an external cohort.Conclusions CATCH-LIFE-MELD score,a modified MELD score exhibited improved accuracy in predicting the short-term prognosis of ACLF than other traditional scores.
基金the National Science and Technology Major Project(2018ZX10723203,2018ZX10302206)National Natural Science Foundation of China(82070650,81270533,81470038)+7 种基金National Key Research and Development Program of China(2017YFC0908100)Local Innova-tive and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01S131)Key Scientific and Technological Program of Guangzhou City(201508020262)Department of Science and Technology of Guangdong Province(2014B020228003,2015B020226004)Clinical Research Program of Nanfang Hospital,Southern Medical University(2018CR037,2020CR026)Key-Area Research and Development Program of Guangdong Province(2019B020227004)Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education(LC2019ZD006,LC2016PY005)President Foundation of Nanfang Hospital,Southern Medical University(2019Z003).
文摘Background and Aims:Approximately 10%of patients with acute decompensated(AD)cirrhosis develop acute-on-chronic liver failure(ACLF)within 28 days.Such cases have high mortality and are difficult to predict.Therefore,we aimed to establish and validate an algorithm to identify these patients on hospitalization.Methods:Hospitalized patients with AD who developed ACLF within 28 days were considered pre-ACLF.Organ dysfunction was defined accord-ing to the chronic liver failure-sequential organ failure as-sessment(CLIF-SOFA)criteria,and proven bacterial infec-tion was taken to indicate immune system dysfunction.A retrospective multicenter cohort and prospective one were used to derive and to validate the potential algorithm,re-spectively.A miss rate of<5%was acceptable for the calcu-lating algorithm to rule out pre-ACLF.Results:In the deri-vation cohort(n=673),46 patients developed ACLF within 28 days.Serum total bilirubin,creatinine,international normalized ratio,and present proven bacterial infection at admission were associated with the development of ACLF.AD patients with≥2 organ dysfunctions had a higher risk for pre-ACLF patients[odds ratio=16.58195%confidence interval:(4.271-64.363),p<0.001].In the derivation co-hort,67.5%of patients(454/673)had≤1 organ dysfunction and two patients(0.4%)were pre-ACLF,with a miss rate of 4.3%(missed/total,2/46).In the validation cohort,65.9%of patients(914/1388)had≤1 organ dysfunction,and four(0.3%)of them were pre-ACLF,with a miss rate of 3.4%(missed/total,4/117).Conclusions:AD patients with≤1 organ dysfunction had a significantly lower risk of developing ACLF within 28 days of admission and could be safely ruled out with a pre-ACLF miss rate of<5%.
基金Clinical Research Plan of SHDC,Grant/Award Number:SHDC2020CR1037BShanghai Municipal Key Clinic Specialty,Grant/Award Number:shslczdzk00602+16 种基金National Key R&D Program of China,Grant/Award Number:2017YFC0908100National Science and Technology Major Project,Grant/Award Numbers:2018ZX10302206,2018ZX10723203,2017ZX10202202Shanghai Municipal Education Commission–Guofeng Clinical Medicine Grant Support,Grant/Award Number:20152213National Natural Science Foundation of China,Grant/Award Numbers:82170629,81930061,81900579,81970550,82070613,82070650,81972265,81870425,81774234Shanghai Hospital Development Commission,Grant/Award Number:16CR1024BChongqing Natural Science Foundation,Grant/Award Number:CSTC2019jcyjzdxmX0004Beijing Municipal Science&Technology Commission,Grant/Award Number:Z191100006619033Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program,Grant/Award Number:2017BT01S131Clinical Research Program of Nanfang Hospital,Southern Medical University,Grant/Award Numbers:2018CR037,2020CR026Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education,Grant/Award Number:LC2019ZD006President Foundation of Nanfang Hospital,Southern Medical University,Grant/Award Number:2019Z003Foundation for Innovative Research Groups of Hubei Provincial Natural Science Foundation,Grant/Award Number:2018CFA031Hubei Province's Outstanding Medical Academic Leader Program and Project of Hubei University of Medicine,Grant/Award Numbers:FDFR201902,2020XGFYZR05Fundamental Research Funds for the Central Universities,Grant/Award Number:2021FZZX001-41Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2020A1515010052Natural Fund of Guangdong Province,Grant/Award Number:2016A030313237Guangzhou City Science and Technology Project,Grant/Award Number:201607010064。
文摘Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.Methods:The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies(NCT02457637 and NCT03641872)conducted in highly endemic hepatitis B virus(HBV)areas.Competing risk analysis was used to evaluate the effect of predispositions,including the etiology and severity of CLDs and precipitants;on sequential 28,90,and 365-day liver transplantation(LT)-free mortality.Results:Among all enrolled patients,76.8%of adverse outcomes(including death and LT)within one year occurred within 90 days.Compared with alcoholic etiology,the association of HBV etiology with poorer outcomes was remarkably on the 28th day(hazard ratio[HR],1.81;95%confidence interval[CI],1.07-3.06;p=0.026);however,and dimin-ished or became insignificant at 90 days and 365 days.Cirrhosis increased the adjusted risk for 365-day(HR,1.50;CI,1.13-1.99;p=0.004)LT-free mortality when compared with noncirrhosis.In patients with cirrhosis,prior decompensation(PD)independently increased the adjusted risk of 365-day LT-free mortality by 1.25-fold(p=0.021);however,it did not increase the risk for 90-day mortality.Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90-day LT-free mortality.Conclusions:The 90-day outcome should be considered a significant endpoint for evaluating the short-term prognosis of hospitalized patients with CLD.Predisposing factors,other than etiology,mainly affected the delayed(365-day)outcome.Timely effective therapy for CLD etiology,especially antiviral treatments for HBV,and post-discharge long-term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.
