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Calzadilla Bertot L, Sòria A, Jimenez-Masip A, Serra I, Broquetas T, Vergara M, Rodriguez A, Aracil C, El Maimouni C, Muñoz-Martinez S, Carrión JA, Pardo A, Pericàs JM, Graupera I, Adams LA. Predicting Hepatic Decompensation in Patients With Metabolic Dysfunction Associated Steatotic Liver Disease-Related Cirrhosis: The ABID-LSM Model. Aliment Pharmacol Ther 2025. [PMID: 40491328 DOI: 10.1111/apt.70215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/18/2025] [Accepted: 05/23/2025] [Indexed: 06/11/2025]
Abstract
BACKGROUND & AIMS Predicting the risk of hepatic decompensation guides prognostication and therapy; however, it is challenging in patients with cirrhosis due to metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to improve a previously developed predictive tool of hepatic decompensation in MASLD cirrhosis (ABIDE) by incorporating liver stiffness measurement (LSM). METHODS A multi-centre retrospective cohort of patients with compensated cirrhosis due to MASLD was identified, with decompensation incidence assessed using competing risk regression. The prognostic accuracy of a modified ABIDE model incorporating LSM (ABID-LSM) was assessed using time-dependent AUC (tAUC) and compared with other predictive models. RESULTS Out of 388 patients, 273 (70.4%) had available LSM. Hepatic decompensation occurred in 54 (20%) patients during follow-up (median 31 months, range: 20-60). The predictive accuracy at 5 years of ABID-LSM (tAUC 0.80) was better than ABIDE (tAUC 0.75, p = 0.03) and LSM (tAUC 0.63, p < 0.001). The ABID-LSM model calibrated well (slope 0.99) with excellent overall performance (Integrated Brier Score 0.15). A cut-off of 8.1 separated those at high and low risk of hepatic decompensation at 5 years (24% vs. 5%, respectively, sHR = 4.8, p < 0.001). The ABID-LSM model had better predictive ability at 5 years than ALBI, FIB-4, NAFLD Decompensation Risk Score and ANTICIPATE models (all p < 0.001) as well as hepatic vein pressure gradient measurement (tAUC 0.78 vs. 0.71, p < 0.001, n = 60). CONCLUSIONS The ABID-LSM model has greater accuracy in predicting hepatic decompensation in patients with cirrhosis due to MASLD than existing predictive models. If externally validated, ABID-LSM may identify those who benefit from pharmacotherapy and close monitoring.
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Affiliation(s)
- Luis Calzadilla Bertot
- Medical School, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Anna Sòria
- Servei d'Hepatologia, Hospital Clínic, Facultat de Medicina i Ciències de la Salut, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain
| | - Alba Jimenez-Masip
- Liver Unit, Vall d'Hebron Institute for Research, Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Isabel Serra
- Departament d'Hepatologia de l'Hospital Dr Josep Trueta Girona, Secció d'Hepatologia, Girona, Spain
| | - Teresa Broquetas
- Liver Section, Gastroenterology Department, Hospital del Mar, Hospital del Mar Medical Research Institute, Barcelona, Spain
| | - Mercedes Vergara
- Unidad Hepatología, Servicio Digestivo, Institut d'Investigació i Innovació Parc Taulí I3PT, Hospital Universitari Parc Taulí, Barcelona, Spain
| | - Adrià Rodriguez
- Servicio de Aparato Digestivo, Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
| | - Carles Aracil
- Secció d'Hepatologia, Servei de Digestiu, Institute of Biomedical Research (IRBLleida), Arnau de Vilanova University Hospital, Lleida, Spain
| | - Cautar El Maimouni
- Servei d'Hepatologia, Hospital Clínic, Facultat de Medicina i Ciències de la Salut, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain
| | - Sergio Muñoz-Martinez
- Liver Unit, Vall d'Hebron Institute for Research, Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jose A Carrión
- Liver Section, Gastroenterology Department, Hospital del Mar, Hospital del Mar Medical Research Institute, Barcelona, Spain
| | - Albert Pardo
- Servicio de Aparato Digestivo, Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
| | - Juan M Pericàs
- Liver Unit, Vall d'Hebron Institute for Research, Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Isabel Graupera
- Servei d'Hepatologia, Hospital Clínic, Facultat de Medicina i Ciències de la Salut, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain
| | - Leon A Adams
- Medical School, University of Western Australia, Nedlands, Western Australia, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
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Villanueva C, Tripathi D, Bosch J. Preventing the progression of cirrhosis to decompensation and death. Nat Rev Gastroenterol Hepatol 2025; 22:265-280. [PMID: 39870944 DOI: 10.1038/s41575-024-01031-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/06/2024] [Indexed: 01/29/2025]
Abstract
Two main stages are differentiated in patients with advanced chronic liver disease (ACLD), one compensated (cACLD) with an excellent prognosis, and the other decompensated (dACLD), defined by the appearance of complications (ascites, variceal bleeding and hepatic encephalopathy) and associated with high mortality. Preventing the progression to dACLD might dramatically improve prognosis and reduce the burden of care associated with ACLD. Portal hypertension is a major driver of the transition from cACLD to dACLD, and a portal pressure of ≥10 mmHg defines clinically significant portal hypertension (CSPH) as the threshold from which decompensating events may occur. In recent years, innovative studies have provided evidence supporting new strategies to prevent decompensation in cACLD. These studies have yielded major advances, including the development of noninvasive tests (NITs) to identify patients with CSPH with reasonable confidence, the demonstration that aetiological therapies can prevent disease progression and even achieve regression of cirrhosis, and the finding that non-selective β-blockers can effectively prevent decompensation in patients with cACLD and CSPH, mainly by reducing the risk of ascites, the most frequent decompensating event. Here, we review the evidence supporting new strategies to manage cACLD to prevent decompensation and the caveats for their implementation, from patient selection using NITs to ancillary therapies.
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Affiliation(s)
- Càndid Villanueva
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
- Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Ministerio de Sanidad, Madrid, Spain.
| | - Dhiraj Tripathi
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham Health Partners, Birmingham, UK
- Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Jaume Bosch
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Ministerio de Sanidad, Madrid, Spain
- Department of Visceral Surgery and Medicine (Hepatology), Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Del Cioppo S, Faccioli J, Ridola L. Hepatic cirrhosis and decompensation: Key indicators for predicting mortality risk. World J Hepatol 2025; 17:104580. [PMID: 40177206 PMCID: PMC11959669 DOI: 10.4254/wjh.v17.i3.104580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 02/28/2025] [Accepted: 03/10/2025] [Indexed: 03/26/2025] Open
Abstract
Liver cirrhosis represents the final stage of liver diseases. The transition from the compensated to the decompensated form is a critical phase, as it is associated with a negative impact on patient prognosis. Therefore, having a tool to identify patients at higher risk of complications and mortality is an ideal goal. Currently, the validated scores for this purpose are the model for end-stage liver disease score and the Child-Pugh score. However, these scores have limitations, as they do not account for other factors associated with liver cirrhosis that are equally relevant from a prognostic perspective. Among these, alterations in body composition, particularly sarcopenia, increase the risk of mortality and should therefore be considered in the comprehensive assessment of patients with liver cirrhosis.
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Affiliation(s)
- Sara Del Cioppo
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome 00185, Italy
| | - Jessica Faccioli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome 00185, Italy
| | - Lorenzo Ridola
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome 00185, Italy.
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Truong E, Alnimer L, Gornbein JA, Yang JD, Alkhouri N, Harrison SA, Noureddin M. Agile 3+ and 4 Scores Accurately Predict Major Adverse Liver Outcomes, Liver Transplant, Progression of MELD Score, the Development of Hepatocellular Carcinoma, and Death in NAFLD. Dig Dis Sci 2025:10.1007/s10620-025-08850-1. [PMID: 40126753 DOI: 10.1007/s10620-025-08850-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 01/04/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND AND AIMS Based on liver stiffness measurement by vibration controlled transient elastography (LSM by VCTE), the Agile 3+ and 4 are novel noninvasive scores that accurately identify advanced fibrosis (≥ F3) and cirrhosis (F4), respectively. We investigated and compared the Agile 3+ and 4 scores' performances in predicting adverse events to LSM alone, FIB-4 and Fibroscan-AST (FAST) score. METHOD This retrospective analysis included NAFLD patients with LSM by VCTE and laboratory testing from a tertiary care center from 2013 to 2022. Adverse events were defined as major adverse liver outcomes (MALO), hepatocellular carcinoma, liver transplant, and death. MALO was defined as ascites, hepatic encephalopathy, or esophageal variceal bleeding. We used the Cox proportional hazard rate model and the Harrell's concordance (C) statistic to compare predictive performances. RESULTS 733 total subjects with median follow-up of 27.0 months were included. Average age was 58.1 years and 32.8% had type 2 diabetes. Average alanine aminotransferase was 46.6 IU/L, aspartate aminotransferase: 34.5 IU/L, albumin: 4.4 g/dL, and platelets: 241.1 × 109/L. Fourteen subjects had 21 adverse outcomes, including 10 MALO, 5 HCC, 4 liver transplants, 3 progression of MELD score, and 6 deaths. Agile 3+ and 4 respectively had the highest C stats of 0.911 (C stat SE 0.028) and 0.909 (C stat SE 0.029) compared to LSM (C stat 0.857, C stat SE 0.045), FIB-4 (C stat 0.843, C stat SE 0.037) or FAST (C stat 0.703, C stat SE 0.085). CONCLUSION The Agile 3+ and 4 scores had the highest likelihood of accurately predicting adverse outcomes including MALO and death compared to LSM alone, FIB-4 or FAST score.
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Affiliation(s)
- Emily Truong
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Lynna Alnimer
- Division of Gastroenterology, Henry Ford Providence Hospital, Michigan State University/College of Human Medicine, Southfield, MI, USA
| | - Jeffrey A Gornbein
- Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | | | | | - Mazen Noureddin
- Houston Methodist Hospital, Houston Research Institute, 1155 Dairy Ashford Suite 200, Houston, TX, 77079, USA.
- Lynda K. and David M. Underwood Center for Digestive Disorders, Department of Medicine, J.C. Walter Jr. Transplant Center, Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, USA.
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van Beurden W, Mendoza YP, Lange NF, Bosch J, Berzigotti A, Rodrigues SG. FIB-4 predicts events in compensated advanced chronic liver disease and type 2 diabetes treated with GLP-1-receptor-agonists. J Diabetes Complications 2025; 39:108978. [PMID: 39999536 DOI: 10.1016/j.jdiacomp.2025.108978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 02/03/2025] [Accepted: 02/19/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND & AIMS Patients with compensated advanced chronic liver disease (cACLD) and treated type 2 diabetes have an increased risk for liver-related events, but data regarding this population is lacking, particularly, taking into account novel treatments. We assessed the role of Fibrosis-4 index and other variables to predict events. METHODS First hepatic decompensation, liver transplantation (OLT), death, hepatocellular carcinoma (HCC) and bacterial infections over a follow-up period of 28.7 (16-49.4) months were retrospectively identified from 106 patients with treated type 2 diabetes and liver stiffness measurement >10 kPa suggesting ACLD. We identified predictors of events using Cox regression. Additionally, we evaluated treatment effect with add-on GLP-1 receptor agonists (GLP-1-RA) compared to other antidiabetic medications. RESULTS FIB-4 was associated with hepatic decompensation, OLT and death (HR 1.517, 95%CI 1.226-1.879, p ≤ 0.001), HCC (HR 1.369, 95%CI 1.046-1.791, p = 0.022) and bacterial infections (HR 1.379, 95%CI 1.118-1.702, p = 0.003). Propensity score adjusted analysis for GLP-1-RA treatment did not show an effect (HR 0.240, 95%CI 0.044-1.315, p = 0.1). Survival was worse in those with more advanced disease defined by FIB-4 > 2.67 (p = 0.02). CONCLUSION FIB-4 is a strong prognostic tool to screen patients and refer them to specialists, in cACLD patients and pharmacologically treated type 2 diabetes, irrespective of treatment.
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Affiliation(s)
- Wiebke van Beurden
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Yuly P Mendoza
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Naomi F Lange
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland
| | - Jaime Bosch
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Susana G Rodrigues
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
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Liu Q, He Y, Yang F, Guo G, Yang W, Wu L, Sun C. Development and external validation of Global Leadership Initiative on Malnutrition-dictated nomograms predicting long-term mortality in hospitalized patients with cirrhosis. Sci Prog 2025; 108:368504251320157. [PMID: 39967253 PMCID: PMC11837080 DOI: 10.1177/00368504251320157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
OBJECTIVES Global Leadership Initiative on Malnutrition (GLIM) criteria have gradually accounted for the mainstay evaluating nutritional status. We sought to establish GLIM-dictated nomograms with other prognostic factors influencing long-term mortality and externally validate their predictive performance in decompensated cirrhosis. METHODS The derivation cohort comprised 301 patients presenting with cirrhosis-associated acute insults, while the validation cohort encompassed 101 subjects from another tertiary hospital. Two nomograms were constructed to predict the 1-year all-cause mortality by integrating the GLIM criteria. The study population was stratified into low-, moderate- and high-risk mortality groups according to aforesaid proposed models. RESULTS Adjusting Child-Turcotte-Pugh classification (Nomo#1) or Model for End-stage Liver Disease-Sodium score (Nomo#2) separately, the GLIM criteria were independently associated with 1-year mortality in the multivariate Cox regression analysis (Nomo#1 hazard ratio (HR) = 3.139, p < 0.001; Nomo#2 HR = 3.456, p < 0.001). The C-index and time AUC for Nomo#1 and Nomo#2 performed significantly better than those of the GLIM criteria or conventional scoring systems alone. The survival rate of the low-risk group was significantly higher than those of the moderate- or high-risk groups (Nomo#1: 95% vs 65.8% vs 33.3%, p < 0.001; Nomo#2: 94.3% vs 64.5% vs 25%, p < 0.001). Furthermore, our proposed models exhibited moderate prediction accuracy and may identify malnourished patients with poor survival conditions in the external validation cohort. CONCLUSION GLIM criteria-defined malnutrition negatively impacted long-term mortality in the context of decompensated cirrhosis. Our established nomograms may predict survival status with sufficient discriminatory ability, alongside good consistency and clinical benefits, supporting their effectiveness in daily practice.
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Affiliation(s)
- Qing Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Yumei He
- Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, China
| | - Fang Yang
- Department of Digestive System, Baodi Clinical College of Tianjin Medical University, Tianjin, China
| | - Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Liping Wu
- Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
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Hoppmann H, Zeman F, Wittmann D, Stöckert P, Schlosser-Hupf S, Mehrl A, Pavel V, Müller M, Schmid S. The LIVERAID (LIVER And Infectious Diseases)-ICU score predicts in-hospital mortality in liver cirrhosis patients with infections in the intensive care unit. BMJ Open Gastroenterol 2024; 11:e001482. [PMID: 39384247 PMCID: PMC11481117 DOI: 10.1136/bmjgast-2024-001482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 09/24/2024] [Indexed: 10/11/2024] Open
Abstract
OBJECTIVES The admission of patients with liver cirrhosis to the intensive care unit (ICU) due to infections is a frequent occurrence, often leading to complications such as hepatic encephalopathy, renal failure and circulatory collapse, significantly elevating mortality risks. Accurate and timely diagnosis and intervention are critical for improving therapeutic outcomes. In this context, medical scoring systems in ICUs are essential for precise diagnosis, severity assessment and appropriate therapeutic strategies. There are no specific models for the prediction of mortality in ICU patients with liver cirrhosis-associated infections. This study aims to develop an improved prognostic scoring system for predicting in-hospital mortality among liver cirrhosis patients with infections in the ICU. This scoring system is designed to enhance the predictive accuracy of in-hospital mortality complementing existing sepsis and liver-specific prognostic models. METHODS A retrospective analysis was conducted in 620 patients with liver cirrhosis, treated for infections in the ICU of a German university hospital during 2017-19. Advanced statistical techniques were employed to develop and validate the LIVERAID (LIVER And Infectious Diseases)-ICU score, a novel scoring system specifically tailored for liver cirrhosis patients in the ICU with infections. The development of the multivariable logistic regression model involved selecting variables with the highest prognostic efficacy, and its predictive performance was assessed using calibration plots and the concordance statistic (c-index) to evaluate both calibration and discrimination. RESULTS The LIVERAID-ICU score integrates Child-Pugh class, serum urea levels and respiratory metrics. It is designed for bedside calculation using basic clinical and laboratory data, with no need for additional tools. In the validation cohort, the LIVERAID-ICU score exhibited enhanced sensitivity and specificity (AUC=0.83) in forecasting in-hospital mortality of patients with liver cirrhosis-associated infections when compared with established scores like Sequential Organ Failure Assessment (SOFA) (p=0.045), Model for End-Stage Liver Disease (MELD) (p=0.097), Child (p<0.001) and CLIF consortium acute-on-chronic liver failure (CLIF-C ACLF) (p<0.001). CONCLUSION The newly developed LIVERAID-ICU score represents a robust, streamlined and easy tool for predicting in-hospital mortality in liver cirrhosis patients with infections, surpassing the predictive capabilities of established liver or sepsis scores like SOFA, MELD, Child and CLIF-C ACLF. The reliance of the LIVERAID-ICU score on fundamental clinical and laboratory data facilitates its global application in ICUs, enabling immediate application at the bedside for patients with liver cirrhosis during episodes of suspected or confirmed infections.
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Affiliation(s)
- Hauke Hoppmann
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Florian Zeman
- Center for Clinical Studies, University of Regensburg, Regensburg, Germany
| | - Daniela Wittmann
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Petra Stöckert
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Sophie Schlosser-Hupf
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Alexander Mehrl
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Vlad Pavel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Stephan Schmid
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
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Gananandan K, Singh R, Mehta G. Systematic review and meta-analysis of biomarkers predicting decompensation in patients with compensated cirrhosis. BMJ Open Gastroenterol 2024; 11:e001430. [PMID: 39182920 PMCID: PMC11404266 DOI: 10.1136/bmjgast-2024-001430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 08/06/2024] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND AND AIMS The transition from compensated to decompensated cirrhosis is crucial, drastically reducing prognosis from a median survival of over 10 years to 2 years. There is currently an unmet need to accurately predict decompensation. We systematically reviewed and meta-analysed data regarding biomarker use to predict decompensation in individuals with compensated cirrhosis. METHODS PubMed and EMBASE database searches were conducted for all studies from inception until February 2024. The study was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Quality of Prognosis Studies framework was used to assess the risk of bias. The meta-analysis was conducted with a random effects model using STATA software. RESULTS Of the 652 studies initially identified, 63 studies (n=31 438 patients) were included in the final review, examining 49 biomarkers. 25 studies (40%) were prospective with the majority of studies looking at all-cause decompensation (90%). The most well-studied biomarkers were platelets (n=17), Model for End-Stage Liver Disease (n=17) and albumin (n=16). A meta-analysis revealed elevated international normalised ratio was the strongest predictor of decompensation, followed by decreased albumin. However, high statistical heterogeneity was noted (l2 result of 96.3%). Furthermore, 21 studies were assessed as having a low risk of bias (34%), 26 (41%) moderate risk and 16 (25%) high risk. CONCLUSIONS This review highlights key biomarkers that should potentially be incorporated into future scoring systems to predict decompensation. However, future biomarker studies should be conducted with rigorous and standardised methodology to ensure robust and comparable data.
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Affiliation(s)
| | - Rabiah Singh
- UCL Institute for Liver & Digestive Health, London, UK
| | - Gautam Mehta
- UCL Institute for Liver & Digestive Health, London, UK
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Li XM, Liu SL, He YJ, Shu JC. Using new indices to predict metabolism dysfunction-associated fatty liver disease (MAFLD): analysis of the national health and nutrition examination survey database. BMC Gastroenterol 2024; 24:109. [PMID: 38491451 PMCID: PMC10943835 DOI: 10.1186/s12876-024-03190-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 02/29/2024] [Indexed: 03/18/2024] Open
Abstract
BACKGROUND Metabolism dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease. Few MAFLD predictions are simple and accurate. We examined the predictive performance of the albumin-to-glutamyl transpeptidase ratio (AGTR), plasma atherogenicity index (AIP), and serum uric acid to high-density lipoprotein cholesterol ratio (UHR) for MAFLD to design practical, inexpensive, and reliable models. METHODS The National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle dataset, which contained 12,654 participants, was filtered and randomly separated into internal validation and training sets. This study examined the relationships of the AGTR and AIP with MAFLD using binary multifactor logistic regression. We then created a MAFLD predictive model using the training dataset and validated the predictive model performance with the 2017-2018 NHANES and internal datasets. RESULTS In the total population, the predictive ability (AUC) of the AIP, AGTR, UHR, and the combination of all three for MAFLD showed in the following order: 0.749, 0.773, 0.728 and 0.824. Further subgroup analysis showed that the AGTR (AUC1 = 0.796; AUC2 = 0.690) and the combination of the three measures (AUC1 = 0.863; AUC2 = 0.766) better predicted MAFLD in nondiabetic patients. Joint prediction outperformed the individual measures in predicting MAFLD in the subgroups. Additionally, the model better predicted female MAFLD. Adding waist circumference and or BMI to this model improves predictive performance. CONCLUSION Our study showed that the AGTR, AIP, and UHR had strong MAFLD predictive value, and their combination can increase MAFLD predictive performance. They also performed better in females.
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Affiliation(s)
- Xu Ming Li
- Department of Gastroenterology, Guangzhou Red Cross Hospital(Guangzhou Red Cross Hospital of Jinan University), Jinan University, Guangzhou, China
| | - Song Lian Liu
- Department of Hepatology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ya Jun He
- Department of Gastroenterology, Guangzhou Red Cross Hospital(Guangzhou Red Cross Hospital of Jinan University), Jinan University, Guangzhou, China
| | - Jian Chang Shu
- Department of Gastroenterology, Guangzhou Red Cross Hospital(Guangzhou Red Cross Hospital of Jinan University), Jinan University, Guangzhou, China.
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Dallio M, Romeo M, Vaia P, Auletta S, Mammone S, Cipullo M, Sapio L, Ragone A, Niosi M, Naviglio S, Federico A. Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis. World J Gastroenterol 2024; 30:685-704. [PMID: 38515952 PMCID: PMC10950628 DOI: 10.3748/wjg.v30.i7.685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 12/19/2023] [Accepted: 01/17/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND For compensated advanced chronic liver disease (cACLD) patients, the first decompensation represents a dramatically worsening prognostic event. Based on the first decompensation event (DE), the transition to decompensated advanced chronic liver disease (dACLD) can occur through two modalities referred to as acute decompensation (AD) and non-AD (NAD), respectively. Clinically Significant Portal Hypertension (CSPH) is considered the strongest predictor of decompensation in these patients. However, due to its invasiveness and costs, CSPH is almost never evaluated in clinical practice. Therefore, recognizing non-invasively predicting tools still have more appeal across healthcare systems. The red cell distribution width to platelet ratio (RPR) has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). However, its predictive role for the decompensation has never been explored. AIM In this observational study, we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients. METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up (FUP) semiannually for 3 years. At baseline, biochemical, clinical, and Liver Stiffness Measurement (LSM), Child-Pugh (CP), Model for End-Stage Liver Disease (MELD), aspartate aminotransferase/platelet count ratio index (APRI), Fibrosis-4 (FIB-4), Albumin-Bilirubin (ALBI), ALBI-FIB-4, and RPR were collected. During FUP, DEs (timing and modaities) were recorded. CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines. RESULTS Of 150 MASLD-related cACLD patients, 43 (28.6%) progressed to dACLD at a median time of 28.9 months (29 NAD and 14 AD). Baseline RPR values were significantly higher in cACLD in comparison to controls, as well as MELD, CP, APRI, FIB-4, ALBI, ALBI-FIB-4, and LSM in dACLD-progressing compared to cACLD individuals [all P < 0.0001, except for FIB-4 (P: 0.007) and ALBI (P: 0.011)]. Receiving operator curve analysis revealed RPR > 0.472 and > 0.894 as the best cut-offs in the prediction respectively of 3-year first DE, as well as its superiority compared to the other non-invasive tools examined. RPR (P: 0.02) and the presence of baseline-CSPH (P: 0.04) were significantly and independently associated with the DE. Patients presenting baseline-CSPH and RPR > 0.472 showed higher risk of decompensation (P: 0.0023). CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.
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Affiliation(s)
- Marcello Dallio
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Mario Romeo
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Paolo Vaia
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Salvatore Auletta
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Simone Mammone
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Marina Cipullo
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Luigi Sapio
- Department of Precision Medicine, Clinical Biochemistry Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Angela Ragone
- Department of Precision Medicine, Clinical Biochemistry Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Marco Niosi
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Silvio Naviglio
- Department of Precision Medicine, Clinical Biochemistry Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Alessandro Federico
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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11
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Juanola A, Ma AT, de Wit K, Gananandan K, Roux O, Zaccherini G, Jiménez C, Tonon M, Solé C, Villaseca C, Uschner FE, Graupera I, Pose E, Moreta MJ, Campion D, Beuers U, Mookerjee RP, Francoz C, Durand F, Vargas V, Piano S, Alonso S, Trebicka J, Laleman W, Asrani SK, Soriano G, Alessandria C, Serra-Burriel M, Morales-Ruiz M, Torres F, Allegretti AS, Krag A, Caraceni P, Watson H, Abraldes JG, Solà E, Kamath PS, Hernaez R, Ginès P. Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis. Gut 2023; 73:156-165. [PMID: 37884354 DOI: 10.1136/gutjnl-2023-329923] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 09/18/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Ann Thu Ma
- Toronto Centre for Liver Disease Francis Family Liver Clinic, Toronto General Hospital, Toronto, Ontario, Canada
| | - Koos de Wit
- Gastroenterology and Hepatology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
| | - Kohilan Gananandan
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Olivier Roux
- Department of Hepatology, Beaujon Hospital, Clichy, France
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - César Jiménez
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
| | - Marta Tonon
- Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Cristina Solé
- Department of Gastroenterology and Hepatology, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Clara Villaseca
- Digestive Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Frank E Uschner
- Department of Internal Medicine B, University of Münster, Munster, Germany
| | - Isabel Graupera
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Maria José Moreta
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
| | - Daniela Campion
- Division of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
| | - Ulrich Beuers
- Gastroenterology & Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Rajeshawar P Mookerjee
- Institute of Liver and Digestive Health, University College London Medical School, London, UK
| | - Claire Francoz
- Department of Hepatology, Beaujon Hospital, Clichy, France
| | - Francois Durand
- DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France
- Université Denis Diderot-Paris 7, Paris, France
| | - Victor Vargas
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
| | - Salvatore Piano
- Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Sonia Alonso
- Digestive Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Munster, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Wim Laleman
- Division of Liver and Biliopanreatic Disorders, KU Leuven, University of Leuven, Leuven, Belgium
| | - Sumeet K Asrani
- Division of Hepatology, Department of Medicine, Baylor University Medical Center at Dallas, Dallas, Texas, USA
| | - German Soriano
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
| | - Miquel Serra-Burriel
- University of Zurich Institute of Epidemiology Biostatistics and Prevention, Zurich, Switzerland
| | - Manuel Morales-Ruiz
- Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Ferran Torres
- Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aleksander Krag
- Department of Gastroenterology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, California, USA
| | - Patrick S Kamath
- Gastroenterology and Hepatology, Mayo Medical School, Rochester, Minnesota, USA
| | - Ruben Hernaez
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Pere Ginès
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain
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12
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Gao Y, Yu Q, Li X, Xia C, Zhou J, Xia T, Zhao B, Qiu Y, Zha JH, Wang Y, Tang T, Lv Y, Ye J, Xu C, Ju S. An imaging-based machine learning model outperforms clinical risk scores for prognosis of cirrhotic variceal bleeding. Eur Radiol 2023; 33:8965-8973. [PMID: 37452878 DOI: 10.1007/s00330-023-09938-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 05/08/2023] [Accepted: 05/15/2023] [Indexed: 07/18/2023]
Abstract
OBJECTIVES To develop and validate a machine learning model based on contrast-enhanced CT to predict the risk of occurrence of the composite clinical endpoint (hospital-based intervention or death) in cirrhotic patients with acute variceal bleeding (AVB). METHODS This retrospective study enrolled 330 cirrhotic patients with AVB between January 2017 and December 2020 from three clinical centers. Contrast-enhanced CT and clinical data were collected. Centers A and B were divided 7:3 into a training set and an internal test set, and center C served as a separate external test set. A well-trained deep learning model was applied to segment the liver and spleen. Then, we extracted 106 original features of the liver and spleen separately based on the Image Biomarker Standardization Initiative (IBSI). We constructed the Liver-Spleen (LS) model based on the selected radiomics features. The performance of LS model was evaluated by receiver operating characteristics and calibration curves. The clinical utility of models was analyzed using decision curve analyses (DCA). RESULTS The LS model demonstrated the best diagnostic performance in predicting the composite clinical endpoint of AVB in patients with cirrhosis, with an AUC of 0.782 (95% CI 0.650-0.882) and 0.789 (95% CI 0.674-0.878) in the internal test and external test groups, respectively. Calibration curves and DCA indicated the LS model had better performance than traditional clinical scores. CONCLUSION A novel machine learning model outperforms previously known clinical risk scores in assessing the prognosis of cirrhotic patients with AVB CLINICAL RELEVANCE STATEMENT: The Liver-Spleen model based on contrast-enhanced CT has proven to be a promising tool to predict the prognosis of cirrhotic patients with acute variceal bleeding, which can facilitate decision-making and personalized therapy in clinical practice. KEY POINTS • The Liver-Spleen machine learning model (LS model) showed good performance in assessing the clinical composite endpoint of cirrhotic patients with AVB (AUC ≥ 0.782, sensitivity ≥ 80%). • The LS model outperformed the clinical scores (AUC ≤ 0.730, sensitivity ≤ 70%) in both internal and external test cohorts.
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Affiliation(s)
- Yin Gao
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Qian Yu
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Xiaohuan Li
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Cong Xia
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Jiaying Zhou
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Tianyi Xia
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Ben Zhao
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Yue Qiu
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Jun-Hao Zha
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Yuancheng Wang
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Tianyu Tang
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China
| | - Yan Lv
- Department of Medical Imaging, Subei People's Hospital, Medical School of Yangzhou University, Yangzhou, China
| | - Jing Ye
- Department of Medical Imaging, Subei People's Hospital, Medical School of Yangzhou University, Yangzhou, China
| | - Chuanjun Xu
- Department of Radiology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shenghong Ju
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
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13
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Li F, Wang T, Liang J, Qian B, Tang F, Gao Y, Lv J. Albumin‑bilirubin grade and INR for the prediction of esophagogastric variceal rebleeding after endoscopic treatment in cirrhosis. Exp Ther Med 2023; 26:501. [PMID: 37822588 PMCID: PMC10562956 DOI: 10.3892/etm.2023.12200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 08/18/2023] [Indexed: 10/13/2023] Open
Abstract
Rebleeding following endoscopic treatment in patients with cirrhosis is a serious life-threatening complication. In the present study, a novel, reliable and non-invasive score for prediction of rebleeding following endoscopic therapy for esophagogastric variceal bleeding (EGVB) was developed. The present retrospective study recruited cirrhotic patients with EGVB (n=596) who underwent endoscopic therapy. Patients hospitalized from January 2015 to January 2020 were grouped into a training (n=437) cohort to develop the new score and those hospitalized from February 2020 to February 2022 were grouped into a validation (n=159) cohort to validate the score. The international normalized ratio (INR) and albumin-bilirubin (ALBI) grade were used to develop the INR-ALBI (IALBI) score to predict risk of rebleeding. In the training cohort, the prognostic performance of the IALBI score and other ALBI-associated scores (modified ALBI, platelet-ALBI and ALBI-fibrosis-4) at 1, 3 and 12 months was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. At each time point, most areas under the ROC curve of IALBI were higher than those of other ALBI-associated scores, particularly for prediction of early rebleeding. At 1 month, the rebleeding rates of patients with IALBI grade 2 and 3 were ~10.0- and 19.5-times higher than those of patients with grade 1, respectively. The negative predictive value (NPV) of IALBI for the training and validation cohort at 1 month was 100.0 and 97.8%, respectively. For viral and non-viral patients in the training cohort, IALBI showed good predictive ability and NPV for early rebleeding. The IALBI grading system successfully assessed rebleeding, particularly early rebleeding, in cirrhotic patients with EGVB following endoscopic therapy IALBI grade 1, predicted low risk of rebleeding and may not require endoscopic treatment again in the short-term.
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Affiliation(s)
- Fenghui Li
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-Corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Tao Wang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-Corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-Corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Baoxin Qian
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-Corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Fei Tang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-Corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Yanying Gao
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-Corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Jiayu Lv
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-Corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
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14
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Truong E, Gornbein JA, Yang JD, Noureddin N, Harrison SA, Alkhouri N, Noureddin M. MRI-AST (MAST) Score Accurately Predicts Major Adverse Liver Outcome, Hepatocellular Carcinoma, Liver Transplant, and Liver-Related Death. Clin Gastroenterol Hepatol 2023; 21:2570-2577.e1. [PMID: 36813013 DOI: 10.1016/j.cgh.2023.02.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 01/17/2023] [Accepted: 02/03/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND & AIMS The MRI-AST (MAST) score accurately identifies patients with at-risk nonalcoholic steatohepatitis, defined as nonalcoholic steatohepatitis with nonalcoholic fatty liver disease activity score ≥4 and fibrosis stage ≥2 at highest risk for disease progression. It is important to determine the robustness of the MAST score in predicting major adverse liver outcomes (MALO), hepatocellular carcinoma (HCC), liver transplant, and death. METHODS This retrospective analysis included patients with nonalcoholic fatty liver disease from a tertiary care center who underwent magnetic resonance imaging proton density fat fraction, magnetic resonance elastography, and laboratory testing within 6 months from 2013 to 2022. Other causes of chronic liver disease were excluded. Hazard ratios between logit MAST and MALO (ascites, hepatic encephalopathy, or bleeding esophageal varices), liver transplant, HCC, or liver-related death were computed using a Cox proportional hazards regression model. We computed the hazard ratio of MALO or death associated with MAST scores 0.165-0.242 and 0.242-1.000, using MAST scores 0.000-0.165 as the reference group. RESULTS Among 346 total patients, average age was 58.8 years with 52.9% females and 34.4% with type 2 diabetes. Average alanine aminotransferase was 50.7 IU/L (24.3-60.0 IU/L), aspartate aminotransferase was 38.05 IU/L (22.00-41.00 IU/L), platelets were 242.9 × 109/L (193.8-290.0 × 109/L), proton density fat fraction was 12.90% (5.90%-18.22%), and liver stiffness on magnetic resonance elastography was 2.75 kPa (2.07-2.90 kPa). Median follow-up was 29.5 months. Fourteen had adverse outcomes, including 10 MALO, 1 HCC, 1 liver transplant, and 2 liver-related deaths. The Cox regression of MAST versus adverse event rate had a hazard ratio of 2.01 (95% confidence interval, 1.59-2.54; P < .0001) for each 1 logit unit increases in MAST. The corresponding Harrell concordance statistic (C statistic) was 0.919 (95% confidence interval, 0.865-0.953). The MAST score ranges of 0.165-0.242 and 0.242-1.0, respectively, had adverse event rate hazard ratio of 7.75 (1.40-42.9; P = .0189) and 22.11 (6.59-74.2; P < .0000) relative to MAST 0-0.165. CONCLUSIONS The MAST score noninvasively identifies at-risk nonalcoholic steatohepatitis and accurately predicts MALO, HCC, liver transplant, and liver-related death.
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Affiliation(s)
- Emily Truong
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jeffrey A Gornbein
- Department of Medicine, University of California Los Angeles, Los Angeles, California
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California; Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, California
| | - Nabil Noureddin
- Division of Gasteroenterology, University of California San Diego, San Diego, California
| | | | | | - Mazen Noureddin
- Houston Methodist Hospital, Houston Research Institute, Houston, Texas.
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15
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Navadurong H, Thanapirom K, Wejnaruemarn S, Prasoppokakorn T, Chaiteerakij R, Komolmit P, Treeprasertsuk S. Validation of the albumin-bilirubin score for identifying decompensation risk in patients with compensated cirrhosis. World J Gastroenterol 2023; 29:4873-4882. [PMID: 37701131 PMCID: PMC10494764 DOI: 10.3748/wjg.v29.i32.4873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 07/20/2023] [Accepted: 08/09/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies. AIM To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. METHODS One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020. A total of 113 patients (91.9%) had Child A cirrhosis with a median model for end-stage liver disease (MELD) score of less than 9. Baseline clinical and laboratory variables and decompensation events were collected. The ALBI score was calculated and validated to classify decompensation risk into low-, middle-, and high-risk groups using three ALBI grade ranges (ALBI grade 1: ≤ -2.60; grade 2: > -2.60 but ≤ -1.39; grade 3: > -1.39). Decompensation events were defined as ascites development, variceal bleeding, or grade 3 or 4 hepatic encephalopathy. RESULTS Among 123 cirrhotic patients enrolled, 13.8% (n = 17) developed decompensating events at a median time of 25 [95% confidence interval (CI): 17-31] mo. Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events [-2.768 (-2.956 to -2.453) vs -2.007 (-2.533 to -1.537); P = 0.01]. Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve (tAUC) of 0.86 (95%CI: 0.78-0.92), which was significantly better than that of ALBI-Fibrosis-4 (ALBI-FIB4) score (tAUC = 0.77), MELD score (tAUC = 0.66), Child-Pugh score (tAUC = 0.65), and FIB-4 score (tAUC = 0.48) (P < 0.05 for all). The 3-year cumulative incidence of decompensation was 3.1%, 22.6%, and 50% in the low-, middle-, and high-risk groups, respectively (P < 0.001). The odds ratio for decompensation in patients of the high-risk group was 23.33 (95%CI: 3.88-140.12, P = 0.001). CONCLUSION The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.
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Affiliation(s)
- Huttakan Navadurong
- Division of Gastro-enterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastro-enterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Salisa Wejnaruemarn
- Division of Gastro-enterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Thaninee Prasoppokakorn
- Division of Gastro-enterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Department of Medicine, Queen Savang Vadhana Memorial Hospital, Chonburi 20110, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastro-enterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastro-enterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastro-enterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
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Kim DS, Kim BK, Lee JS, Lee HW, Park JY, Kim DY, Ahn SH, Pyrsopoulos N, Kim SU. Noninvasive risk assessment of hepatic decompensation in patients with hepatitis B virus-related liver cirrhosis. J Gastroenterol Hepatol 2023; 38:1372-1380. [PMID: 37188655 DOI: 10.1111/jgh.16210] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 04/25/2023] [Accepted: 04/27/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND AND AIM Hepatic decompensation is a major complication of liver cirrhosis. We validated the predictive performance of the newly proposed CHESS-ALARM model to predict hepatic decompensation in patients with hepatitis B virus (HBV)-related cirrhosis and compared it with other transient elastography (TE)-based models such as liver stiffness-spleen size-to-platelet (LSPS), portal hypertension (PH), varices risk scores, albumin-bilirubin (ALBI), and albumin-bilirubin-fibrosis-4 (ALBI-FIB-4). METHODS Four hundred eighty-two patients with HBV-related liver cirrhosis between 2006 and 2014 were recruited. Liver cirrhosis was clinically or morphologically defined. The predictive performance of the models was assessed using a time-dependent area under the curve (tAUC). RESULTS During the study period, 48 patients (10.0%) developed hepatic decompensation (median 93 months). The 1-year predictive performance of the LSPS model (tAUC = 0.8405) was higher than those of the PH model (tAUC = 0.8255), ALBI-FIB-4 (tAUC = 0.8168), ALBI (tAUC = 0.8153), CHESS-ALARM (tAUC = 0.8090), and variceal risk score (tAUC = 0.7990). The 3-year predictive performance of the LSPS model (tAUC = 0.8673) was higher than those of the PH risk score (tAUC = 0.8670), CHESS-ALARM (tAUC = 0.8329), variceal risk score (tAUC = 0.8290), ALBI-FIB-4 (tAUC = 0.7730), and ALBI (tAUC = 0.7451). The 5-year predictive performance of the PH risk score (tAUC = 0.8521) was higher than those of the LSPS (tAUC = 0.8465), varices risk score (tAUC = 0.8261), CHESS-ALARM (tAUC = 0.7971), ALBI-FIB-4 (tAUC = 0.7743), and ALBI (tAUC = 0.7541). However, there was no significant difference in the predictive performance among all models at 1, 3, and 5 years (P > 0.05). CONCLUSIONS The CHESS-ALARM score was able to reliably predict hepatic decompensation in patients with HBV-related liver cirrhosis and showed similar performance to the LSPS, PH, varices risk scores, ALBI, and ALBI-FIB-4.
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Affiliation(s)
- David Sooik Kim
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
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Nielsen MJ, Dolman GE, Harris R, Frederiksen P, Chalmers J, Grove JI, Irving WL, Karsdal MA, Patel K, Leeming DJ, Guha IN. PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease. JHEP Rep 2023; 5:100743. [PMID: 37284140 PMCID: PMC10240276 DOI: 10.1016/j.jhepr.2023.100743] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/24/2023] [Accepted: 03/15/2023] [Indexed: 06/08/2023] Open
Abstract
Background & Aims Fibroblast activity is a key feature of fibrosis progression and organ function loss, leading to liver-related complications and mortality. The fibrogenesis marker, PRO-C3, has been shown to have prognostic significance in relation to fibrosis progression and as a treatment efficacy marker. We investigated whether PRO-C3 was prognostic for clinical outcome and mortality in two distinct cohorts of compensated cirrhosis. Methods Cohort 1 was a rapid fibrosis progression cohort including 104 patients with HCV and biopsy-proven Ishak fibrosis stage ≥3 without prior clinical events. Cohort 2 was a prospective cohort including 172 patients with compensated cirrhosis of mixed aetiology. Patients were assessed for clinical outcomes. PRO-C3 was assessed in serum at baseline in cohorts 1 and 2, and compared with model for end-stage liver disease and albumin-bilirubin (ALBI) scores. Results In cohort 1, a 2-fold increase in PRO-C3 was associated with 2.7-fold increased hazard of liver-related events (95% CI 1.6-4.6), whereas a one unit increase in ALBI score was associated with a 6.5-fold increased hazard (95% CI 2.9-14.6). In cohort 2, a 2-fold increase in PRO-C3 was associated with a 2.7-fold increased hazard (95% CI 1.8-3.9), whereas a one unit increase in ALBI score was associated with a 6.3-fold increased hazard (95% CI 3.0-13.2). A multivariable Cox regression analysis identified PRO-C3 and ALBI as being independently associated with the hazard of liver-related outcomes. Conclusions PRO-C3 and ALBI were independent prognostic factors for predicting liver-related clinical outcomes. Understanding the dynamic range of PRO-C3 might enhance its use for both drug development and clinical practice. Impact and Implications We tested novel proteins of liver scarring (PRO-C3) in two groups of liver patients with advanced disease to see if they could predict clinical events. We found that this marker and an established test called ALBI were both independently associated with future liver-related clinical outcomes.
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Affiliation(s)
| | - Grace E. Dolman
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Rebecca Harris
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | | | - Jane Chalmers
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Jane I. Grove
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - William L. Irving
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- School of Life Sciences, University of Nottingham, Nottingham, UK
| | | | - Keyur Patel
- Division of Gastroenterology and Hepatology, University of Toronto Health Network, Toronto, ON, Canada
| | | | - Indra Neil Guha
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
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Marie MS, Shousha HI, Abdelrazek W, Hassany M, Dabees H, Abdelghafour R, Aboganob WM, Said M. Prediction of hepatic decompensation and hepatocellular carcinoma after direct-acting antiviral therapy in patients with hepatitis C-related liver cirrhosis: a cohort study. EGYPTIAN LIVER JOURNAL 2023; 13:12. [DOI: 10.1186/s43066-023-00247-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 02/19/2023] [Indexed: 03/05/2023] Open
Abstract
AbstractAimThis study aimed to evaluate the rate of hepatic decompensation and de novo HCC and identify their independent factors in HCV genotype 4-infected patients with compensated liver cirrhosis following successful direct-acting antiviral (DAA) therapy.MethodsThis prospective cohort study included 1789 patients with HCV genotype 4-related compensated liver cirrhosis who achieved viral eradication after DAAs. Baseline and follow-up clinical, laboratory, albumin-bilirubin score (ALBI), and abdominal ultrasound were recorded to detect hepatic decompensation and de novo HCC. Logistic regression was performed to evaluate the variables associated with decompensation and HCC.ResultsDuring the 24-month period of follow-up, 184 (10.28%) patients developed hepatic decompensation. Ascites was the commonest presentation. Baseline serum albumin, bilirubin, and platelet count were the independent factors associated with hepatic decompensation (P-values 0.022, 0.03, and < 0.001, respectively). A formula was developed for the prediction of decompensation using these 3 factors (AUC: 0.641 at cutoff 0.1098969 with a sensitivity of 59.9% and specificity of 61.7%). Pre-treatment ALBI score could predict decompensation at cutoff value − 2.5184, AUC 0.609, sensitivity 58.3%, and specificity 59.7%. Post-treatment ALBI score could predict hepatic decompensation after DAA therapy at cutoff value − 2.9521, AUC 0.597, sensitivity 48.1%, and specificity 75.5%. Sixteen (0.9%) patients developed de novo HCC. Age (odds ratio: 1.061, 95%, confidence interval: 1–1.126) and male gender (OR 3.450, 95% CI 1.105–10.769) were the independent factors associated with the development of de novo HCC but not the ALBI score.ConclusionBaseline demographic and laboratory data could predict hepatic decompensation and HCC in patients with compensated liver cirrhosis after successful DAA therapy
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Shearer JE, Jones R, Parker R, Ferguson J, Rowe IA. The Natural History of Advanced Chronic Liver Disease Defined by Transient Elastography. Clin Gastroenterol Hepatol 2023; 21:694-703.e8. [PMID: 35337981 DOI: 10.1016/j.cgh.2022.03.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 03/08/2022] [Accepted: 03/14/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The clinical course of cirrhosis does not follow a predictable trajectory. Transient elastography (TE) is commonly used in clinical practice to diagnose liver fibrosis and increasingly to risk stratify patients. The aim of this study was to assess the natural history of advanced chronic liver disease (ACLD) defined by TE using electronic health record (EHR) data in a multistate framework. METHODS TE data were collected between 2008 and 2019. Patients with a liver stiffness measurement (LSM) >10 kPa were included. Disease and procedure code information held in EHR was analyzed. Clinical events including decompensation, hepatocellular carcinoma (HCC), and death were identified. Outcomes were described in a multistate model using flexible parametric survival methods including LSM and the albumin bilirubin (ALBI) score. RESULTS Three thousand and twenty eight patients were included. Median follow up was 3.1 years. LSM and ALBI were associated with the development of varices and decompensation, and ALBI, age, sex, and viral liver disease were associated with the development of HCC from the compensated state. The cumulative incidence of HCC before decompensation was low for patients with alcohol-related liver disease (3.8%) and nonalcoholic fatty liver disease (1.3%) at 5 years after TE. Importantly, death was predicted to occur before decompensation or HCC in most cases. CONCLUSIONS Liver stiffness, ALBI score, and disease etiology are each associated with outcomes in a large contemporary cohort with ACLD. EHR data can be used to define clinical progression in these patients, facilitating large clinical effectiveness trials and cost-effectiveness analyses.
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Affiliation(s)
- Jessica E Shearer
- Leeds Institute for Medical Research, University of Leeds, Leeds, United Kingdom; Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Rebecca Jones
- Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Richard Parker
- Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - James Ferguson
- Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Ian A Rowe
- Leeds Institute for Medical Research, University of Leeds, Leeds, United Kingdom; Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
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Vutien P, Berry K, Feng Z, VoPham T, He Q, Green PK, Ioannou GN. Combining FIB-4 and Liver Stiffness Into the FIB-5, a Single Model that Accurately Predicts Complications of Portal Hypertension. Am J Gastroenterol 2022; 117:1999-2008. [PMID: 35849630 PMCID: PMC9741846 DOI: 10.14309/ajg.0000000000001906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 06/24/2022] [Indexed: 01/30/2023]
Abstract
INTRODUCTION We aimed to combine the fibrosis (FIB)-4 score and fibroscan-derived liver stiffness (LS) into a single score (FIB-5) that predicts incident complications of portal hypertension (PH) in persons with compensated liver disease. METHODS In this retrospective cohort study, we identified 5849 US veterans who underwent LS measurement from May 01, 2014 to June 30, 2019, and laboratory tests enabling FIB-4 calculation within 6 months of LS measurement. Patients were followed up from the LS measurement date until February 05, 2020, for incident complications of PH. We combined LS values and the individual components of the FIB-4 score (i.e. age, aspartate aminotransferase, alanine aminotransferase, and platelet count) using multivariable Cox proportional hazards modeling and the machine learning algorithm eXtreme gradient boosting to develop the C-FIB-5 and X-FIB-5 models, respectively. Models were internally validated using optimism-corrected measures. RESULTS Among 5,849 patients, the mean age was 62.8 years, 95.9% were men, and the mean follow-up time was 2.14 ± 1.21 years. Within 3 years after LS measurement date, 116 (2.0%) patients developed complications of PH. The X-FIB-5 (area under the receiver operating characteristic [AUROC] 0.845) and C-FIB-5 scores (AUROC 0.868) demonstrated superior discrimination over LS (AUROC 0.688) and FIB-4 (AUROC 0.672) for predicting incident complications of PH. Both the X-FIB-5 and C-FIB-5 models demonstrated higher classification accuracy across all sensitivity cutoffs when compared with LS or FIB-4 alone. DISCUSSION We combined LS and the individual components of the FIB-4 into a single scoring system (FIB-5, www.fib5.net ), which can help identify patients with compensated liver disease at risk of developing complications of PH.
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Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, Washington, USA
- Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
| | - Kristin Berry
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
| | - Ziding Feng
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Trang VoPham
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Qianchuan He
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Pamela K Green
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
| | - George N Ioannou
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, Washington, USA
- Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
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Rabiee A, Deng Y, Ciarleglio M, Chan JL, Pons M, Genesca J, Garcia-Tsao G. Noninvasive predictors of clinically significant portal hypertension in NASH cirrhosis: Validation of ANTICIPATE models and development of a lab-based model. Hepatol Commun 2022; 6:3324-3334. [PMID: 36214066 PMCID: PMC9701481 DOI: 10.1002/hep4.2091] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/15/2022] [Accepted: 08/17/2022] [Indexed: 01/21/2023] Open
Abstract
Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg, identifies patients with compensated cirrhosis at a high risk of decompensation. However, HVPG is an invasive and nuanced method. The ANTICIPATE models, which include liver stiffness measurements by transient elastography (TE) and platelet count ± body mass index, are robust noninvasive surrogates of CSPH but required external validation in patients with nonalcoholic steatohepatitis (NASH) cirrhosis. Additionally, TE is not widely available worldwide. The aims of the study were: (1) to externally validate the ANTICIPATE models using baseline data from patients with compensated NASH cirrhosis screened/enrolled in a multicenter international randomized controlled trial; and (2) to develop and externally validate a model using only laboratory values. Regarding aim 1, both ANTICIPATE models showed good calibration and discrimination (area under the curve [AUC] > 0.8) in our cohort (n = 222). Regarding aim 2, a new lab-based model using the Fibrosis-4 index (FIB-4 [age, aspartate aminotransferase, alanine aminotransferase, platelet count]) plus serum albumin was developed. The discrimination in the training cohort (n = 309) was good (AUC of 0.78 [95% confidence interval [CI]:0.72-0.83]). It was then externally validated in a separate cohort of 245 patients with compensated NASH cirrhosis (AUC of 0.8 [95% CI: 0.75-0.86]). Given the difference in the prevalence of CSPH between training (74%) and validation (39%) cohorts, the model required an update of the baseline risk to achieve a good calibration. The updated model was named FIB4+. In conclusion, both ANTICIPATE models performed well in predicting the presence of CSPH in NASH cirrhosis. A model using FIB-4 plus albumin (FIB4+) can be used to predict CSPH where TE is not available.
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Affiliation(s)
- Anahita Rabiee
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
| | - Yanhong Deng
- Department of Biostatistics, School of Public Health, Yale University, New Haven, Connecticut, USA
| | - Maria Ciarleglio
- Department of Biostatistics, School of Public Health, Yale University, New Haven, Connecticut, USA
| | - Jean L Chan
- Conatus Pharmaceuticals at the time of study conduct, San Diego, California, USA
| | - Monica Pons
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Joan Genesca
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigacion Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Guadalupe Garcia-Tsao
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA.,VA-CT Healthcare System, New Haven, Connecticut, USA
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Yu Q, Xu C, Li Q, Ding Z, Lv Y, Liu C, Huang Y, Zhou J, Huang S, Xia C, Meng X, Lu C, Li Y, Tang T, Wang Y, Song Y, Qi X, Ye J, Ju S. Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701). JHEP Rep 2022; 4:100575. [PMID: 36204707 PMCID: PMC9531280 DOI: 10.1016/j.jhepr.2022.100575] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/14/2022] [Accepted: 08/16/2022] [Indexed: 11/30/2022] Open
Abstract
Background & Aims Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. Methods This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I–III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. Results The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1–52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index ≥0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2–12.8) in the training and 5.8 (95% CI 3.9–8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (≤1%), and the model had a competitive performance compared with the Baveno VII criteria. Conclusions This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. Lay summary People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.
Spleen volume is a predictor for decompensation by rapid risk increasement after spleen volume >364 cm3. The spleen-based model revealed incremental prognostic improvement (C-index >0.84). Low-risk patients identified by the spleen-based model had a negligible 3-year risk (≤1%) of decompensation.
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Affiliation(s)
- Qian Yu
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Chuanjun Xu
- Department of Radiology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qinyi Li
- Department of Radiology, The Affiliated Third Hospital of Jiangsu University, Zhenjiang, China
| | - Zhimin Ding
- Department of Radiology, Yijishan Hospital of Wannan Medical College, Wuhu, China
| | - Yan Lv
- Department of Medical Imaging, Subei People’s Hospital, Medical School of Yangzhou University, Yangzhou, China
| | - Chuan Liu
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yifei Huang
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Jiaying Zhou
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Shan Huang
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Cong Xia
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiangpan Meng
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Chunqiang Lu
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yuefeng Li
- Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Tianyu Tang
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yuancheng Wang
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yang Song
- MR Scientific Marketing, Siemens Healthineers Ltd., Shanghai, China
| | - Xiaolong Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jing Ye
- Department of Medical Imaging, Subei People’s Hospital, Medical School of Yangzhou University, Yangzhou, China
| | - Shenghong Ju
- Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Corresponding author. Address: Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. Tel.: +86-83272121.
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Allen AM, Therneau TM, Ahmed OT, Gidener T, Mara KC, Larson JJ, Canning RE, Benson JT, Kamath PS. Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design. J Hepatol 2022; 77:1237-1245. [PMID: 35843374 PMCID: PMC9974107 DOI: 10.1016/j.jhep.2022.07.004] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 06/26/2022] [Accepted: 07/04/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. METHODS This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. RESULTS A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. CONCLUSION In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. LAY SUMMARY For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.
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Affiliation(s)
- Alina M Allen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States.
| | - Terry M Therneau
- Division of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Omar T Ahmed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Tolga Gidener
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Kristin C Mara
- Division of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Joseph J Larson
- Division of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Rachel E Canning
- Division of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Joanne T Benson
- Division of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
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Liu C, Cao Z, Yan H, Wong YJ, Xie Q, Hirooka M, Enomoto H, Kim TH, Hanafy AS, Liu Y, Huang Y, Li X, Kang N, Koizumi Y, Hiasa Y, Nishimura T, Iijima H, Jung YK, Yim HJ, Guo Y, Zhang L, Ma J, Kumar M, Jindal A, Teh KB, Sarin SK, Qi X. A Novel SAVE Score to Stratify Decompensation Risk in Compensated Advanced Chronic Liver Disease (CHESS2102): An International Multicenter Cohort Study. Am J Gastroenterol 2022; 117:1605-1613. [PMID: 35973168 PMCID: PMC9531993 DOI: 10.14309/ajg.0000000000001873] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 04/12/2022] [Indexed: 02/05/2023]
Abstract
INTRODUCTION In patients with compensated advanced chronic liver disease (cACLD), the invasive measurement of hepatic venous pressure gradient is the best predictor of hepatic decompensation. This study aimed at developing an alternative risk prediction model to provide a decompensation risk assessment in cACLD. METHODS Patients with cACLD were retrospectively included from 9 international centers within the Portal Hypertension Alliance in China (CHESS) network. Baseline variables from a Japanese cohort of 197 patients with cACLD were examined and fitted a Cox hazard regression model to develop a specific score for predicting hepatic decompensation. The novel score was validated in an external cohort (n = 770) from 5 centers in China, Singapore, Korea, and Egypt, and was further assessed for the ability of predicting clinically significant portal hypertension in a hepatic venous pressure gradient cohort (n = 285). RESULTS In the derivation cohort, independent predictors of hepatic decompensation were identified including Stiffness of liver, Albumin, Varices, and platElets and fitted to develop the novel score, termed "SAVE" score. This score performed significantly better (all P < 0.05) than other assessed methods with a time-dependent receiver operating characteristic curve of 0.89 (95% confidence interval [CI]: 0.83-0.94) and 0.83 (95% CI: 0.73-0.92) in the derivation and validation cohorts, respectively. The decompensation risk was best stratified by the cutoff values at -6 and -4.5. The 5-year cumulative incidences of decompensation were 0%, 24.9%, and 69.0% in the low-risk, middle-risk, and high-risk groups, respectively ( P < 0.001). The SAVE score also accurately predicted clinically significant portal hypertension (AUC, 0.85 95% CI: 0.80-0.90). DISCUSSION The SAVE score can be readily incorporated into clinical practice to accurately predict the individual risk of hepatic decompensation in cACLD.
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Affiliation(s)
- Chuan Liu
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Zhujun Cao
- Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
| | - Huadong Yan
- Department of Infectious Disease, Shulan Hospital, Hangzhou, China;
| | - Yu Jun Wong
- Department of Gastroenterology & Hepatology, Changi General Hospital, SingHealth, Singapore;
- Duke-NUS Medical School, Singapore;
| | - Qing Xie
- Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Hirayuki Enomoto
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan;
| | - Tae Hyung Kim
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea;
| | - Amr Shaaban Hanafy
- Division of Gastroenterology, Hepatology and Endoscopy, Internal Medicine, Zagazig University Faculty of Medicine, Egypt
| | - Yanna Liu
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Yifei Huang
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Xiaoguo Li
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Ning Kang
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Takashi Nishimura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan;
- Ultrasound Imaging Center, Hyogo College of Medicine Hospital, Nishinomiya, Japan;
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan;
- Ultrasound Imaging Center, Hyogo College of Medicine Hospital, Nishinomiya, Japan;
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea;
| | - Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea;
| | - Ying Guo
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China;
| | - Linpeng Zhang
- Department of Interventional Radiology, The Third People's Hospital of Taiyuan, Taiyuan, China;
| | - Jianzhong Ma
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China;
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Kok Ban Teh
- Department of Gastroenterology & Hepatology, Changi General Hospital, SingHealth, Singapore;
- Duke-NUS Medical School, Singapore;
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Xiaolong Qi
- CHESS Center, Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China;
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25
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Liu C, Li J, Wong YJ, Xie Q, Hirooka M, Enomoto H, Kim TH, Hanafy AS, He R, Koizumi Y, Hiasa Y, Nishimura T, Iijima H, Jung YK, Yim HJ, Ma J, Zeng QL, Sarin SK, Qi X. ABC: a novel algorithm to stratify decompensation risk in patients with compensated advanced chronic liver disease (CHESS2108): an international, multicenter cohort study. Hepatol Int 2022; 16:1105-1115. [PMID: 35606627 DOI: 10.1007/s12072-022-10345-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 04/16/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Liver-related death is preceded by clinical decompensation; therefore, the risk stratification of decompensation in compensated advanced chronic liver disease (cACLD) is extraordinary significant. METHODS The international, multicenter study included three cohorts from January 2009 to August 2021. In training cohort, the unfavorable Baveno VI criteria patients were used to develop the novel CHESS criteria to stratify decompensation risk. The Algorithm based on Baveno VI criteria plus CHESS criteria (ABC model) was validated in validation cohort, and used to diagnose clinically significant portal hypertension (CSPH) in hepatic venous pressure gradient (HVPG)-performed cohort. RESULTS A total of 1377 cACLD patients were enrolled. In training cohort, multivariate analysis revealed that liver stiffness measurement (LSM), platelet count (PLT), albumin, alanine aminotransferase (ALT) and varices were the independent risk factors for hepatic decompensation. The novel CHESS criteria was produced (0.036 × LSM [kPa]) + (- 0.013 × PLT [109/L]) + (- 0.068 × Albumin [g/L])) + (- 0.016 × ALT [U/L]) + (0.651 × Varices [present: 1, absent: 0]), and < - 4.4, - 4.4 to - 3.1 and > - 3.1 indicated the low risk, medium risk, and high risk of decompensation, with a 3 year-time-dependent area under the curve (tAUC) of 0.851 (0.800-0.901). In validation cohort, the 3 year-tAUC of ABC model was 0.843 (0.742-0.943). Notably, in HVPG cohort, the high risk group was used to rule in CSPH with a positive predictive value of 93.0%. CONCLUSIONS The ABC model can stratify the risk of decompensation in cACLD. HVPG evaluation can be waived in both low risk and high risk cACLD patients as they can be managed by Baveno VI criteria and non-selective β-blockers intervention, respectively, and the remaining medium risk patients need further HVPG evaluation.
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Affiliation(s)
- Chuan Liu
- Department of Radiology, Center of Portal Hypertension, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, SingHealth, Singapore, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Qing Xie
- Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Hirayuki Enomoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tae Hyung Kim
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan, Gyeonggi, Republic of Korea
| | - Amr Shaaban Hanafy
- Division of Gastroenterology, Hepatology and Endoscopy, Internal Medicine, Zagazig University Faculty of Medicine, Zagazig, Egypt
| | - Ruiling He
- Department of Radiology, Center of Portal Hypertension, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Takashi Nishimura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
- Ultrasound Imaging Center, Hyogo College of Medicine Hospital, Nishinomiya, Japan
| | - Hiroko Iijima
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
- Ultrasound Imaging Center, Hyogo College of Medicine Hospital, Nishinomiya, Japan
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan, Gyeonggi, Republic of Korea
| | - Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Korea University Ansan Hospital, Ansan, Gyeonggi, Republic of Korea
| | - Jianzhong Ma
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Qing-Lei Zeng
- Department of Infectious Diseases and Hepatology, The First Affiliated Hospital of Zhengzhou University, No.1, Eastern Jianshe Road, Zhengzhou, 450052, China.
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Xiaolong Qi
- Department of Radiology, Center of Portal Hypertension, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, No.1, Donggang Road, Lanzhou, 730000, China.
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Toyoda H, Johnson PJ. The ALBI score: From liver function in patients with HCC to a general measure of liver function. JHEP Rep 2022; 4:100557. [PMID: 36124124 PMCID: PMC9482109 DOI: 10.1016/j.jhepr.2022.100557] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 01/27/2023] Open
Abstract
The (albumin-bilirubin) ‘ALBI’ score is an index of ‘liver function’ that was recently developed to assess prognosis in patients with hepatocellular carcinoma, irrespective of the degree of underlying liver fibrosis. Other measures of liver function, such as model for end-stage liver disease (MELD) and Child-Pugh score, which were introduced for specific clinical scenarios, have seen their use extended to other areas of hepatology. In the case of ALBI, its application has been increasingly extended to chronic liver disease in general and in some instances to non-liver diseases where it has proven remarkably accurate in terms of prognosis. With respect to chronic liver disease, numerous publications have shown that ALBI is highly prognostic in patients with all types and stages of chronic liver disease. Outside of liver disease, ALBI has been reported as being of prognostic value in conditions ranging from chronic heart failure to brain tumours. Whilst in several of these reports, explanations for the relationship of liver function to a clinical condition have been proposed, it has to be acknowledged that the specificity of ALBI for liver function has not been clearly demonstrated. Nonetheless, and similar to the MELD and Child-Pugh scores, the lack of any mechanistic basis for ALBI’s clinical utility does not preclude it from being clinically useful in certain situations. Why albumin and bilirubin levels, or a combination thereof, are prognostic in so many different diseases should be studied in the future.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Philip J Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
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27
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Wong YJ, Li J, Liu C, Chen Z, Chan YH, Putera M, Teh KB, Ang TL, Zhao L, Yan Z, Kumar R, Li X, Qi X. CHESS-ALARM score to stratify decompensation risk in compensated advanced chronic liver disease patients: An international multicenter study. J Gastroenterol Hepatol 2022; 37:1043-1051. [PMID: 35253271 DOI: 10.1111/jgh.15819] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/31/2022] [Accepted: 02/08/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM A combination of platelet and elastography (PE criteria) was proposed to identify compensated advanced chronic liver disease (cACLD) patients at risk of liver decompensation. We aim to validate and refine PE criteria by developing a new predictive score to predict decompensation in Asian cACLD patients. METHODS An international cohort of 633 cACLD patients with liver stiffness measurement (LSM) and esophagogastroduodenoscopy performed were included. We validated PE criteria to predict first liver decompensation using competing risk analysis, with death and hepatocellular carcinoma as competing events. We developed a predictive model using proportional subdistribution hazard regression. Prognostic accuracy was compared with the model of end-stage liver disease (MELD), albumin-bilirubin (ALBI), and ALBI-FIB-4 score using time-dependent area under operative characteristic curve (tAUC). RESULTS Sixty patients developed decompensation over the median follow-up of 39 months. Favorable Baveno VI status ruled out cACLD patients at risk of liver decompensation. LSM > 25 kPa was suboptimal to predict cACLD patients who will develop liver decompensation. We developed CHESS-ALARM score by incorporating age, platelet, and gender into LSM. CHESS-ALARM score (tAUC = 0.86, 95% confidence interval [CI]: 0.79-0.94) has significantly higher accuracy than MELD (tAUC: 0.61), ALBI (tAUC: 0.62), ALBI-FIB-4 (tAUC: 0.70), and LSM > 25 kPa (tAUC: 0.54) to predict liver decompensation at 5 years (P < 0.05 for all). Patients with CHESS-ALARM score ≥ -0.37 had an 11-fold higher risk of decompensation (subdistribution hazard ratio = 11.2, 95% CI: 5.1-24.5). CONCLUSION CHESS-ALARM score can be readily incorporated into clinical practice of cACLD patients to estimate individual risk of liver decompensation; however, more data are required in morbidly obese cACLD patients of nonviral etiology.
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Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Duke-NUS Academic Medical Program, SingHealth, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Chuan Liu
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zhaojin Chen
- Biostatistic Unit, Yong Loo Lin School of Medicine, Singapore
| | - Yiong Huak Chan
- Biostatistic Unit, Yong Loo Lin School of Medicine, Singapore
| | - Martin Putera
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Kok Ban Teh
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Duke-NUS Academic Medical Program, SingHealth, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Lili Zhao
- Department of Gastroenterology and Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Zhongfang Yan
- Department of Radiology, Tianjin Second People's Hospital, Tianjin, China
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Duke-NUS Academic Medical Program, SingHealth, Singapore
| | - Xin Li
- Department of Clinical Nutrition, Tianjin Second People's Hospital, Tianjin, China
| | - Xiaolong Qi
- CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
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Fujiwara N, Fobar AJ, Raman I, Li QZ, Marrero JA, Parikh ND, Singal AG, Hoshida Y. A Blood-Based Prognostic Liver Secretome Signature Predicts Long-term Risk of Hepatic Decompensation in Cirrhosis. Clin Gastroenterol Hepatol 2022; 20:e1188-e1191. [PMID: 33727162 PMCID: PMC8435537 DOI: 10.1016/j.cgh.2021.03.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 12/13/2022]
Abstract
Cirrhosis is the terminal stage of progressive liver fibrosis, affecting 1%-2% of the global population and accounting for 1.3 million deaths annually.1,2 Median survival for persons with compensated cirrhosis is approximately 12 years, compared with only 2 years for those with hepatic decompensation. Accurate prediction of hepatic decompensation is an unmet need to enable identification of patients with cirrhosis who could benefit from close monitoring and timely medical interventions. Besides, risk stratification of patients with cirrhosis could help inform patient selection for trials evaluating therapies to prevent hepatic decompensation. Although various clinical scores, such as the albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4) indices (ALBI-FIB4 score) have been proposed to predict long-term risk of hepatic decompensation,3 external validation has often shown suboptimal prognostic capability and revealed room for improvement.4.
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Affiliation(s)
- Naoto Fujiwara
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Austin J Fobar
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Indu Raman
- Microarray Core Facility, Department of Immunology, BioCenter, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Quan-Zhen Li
- Microarray Core Facility, Department of Immunology, BioCenter, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Jorge A Marrero
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Yujin Hoshida
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
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Elshaarawy O, Abdelaziz R, Zayed N, Hany A, Hammam Z, Mueller S, Yosry A, Shousha HI. Acoustic radiation force impulse to measure liver stiffness and predict hepatic decompensation in pregnancy with cirrhosis: A cohort study. Arab J Gastroenterol 2022; 23:89-94. [PMID: 35153176 DOI: 10.1016/j.ajg.2022.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/15/2021] [Accepted: 01/14/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS Pregnancy in association with cirrhosis is a rather uncommon and highly risky situation for both mother and child. We aim to study all factors and the utility of liver stiffness (LS) measurement by Acoustic Radiation Force Impulse elastography (ARFI) to predict hepatic decompensation in pregnant cirrhotic patients. PATIENTS AND METHODS We prospectively recruited 224 pregnant women at the multidisciplinary clinic of liver disease with pregnancy, Cairo University. LS was measured using ARFI (Siemens ACUSON S3000 ultrasound system) during the second trimester and 8-12 weeks post-delivery. The outcome of pregnancy and the incidence of hepatic decompensation were assessed. RESULTS Our cohort comprised 128 normal pregnancies, 37 patients with pregnancy-related liver disease (Intrahepatic cholestasis (n = 6), preeclampsia (n = 23), and hyperemesis gravidarum (n = 8)) and 59 patients with an established chronic liver disease not related to pregnancy. In all patients, LS significantly decreased after delivery from 1.19 m/s to 0.94 m/s (P < 0.001). In multivariate analysis, LS was an independent predictor for the outcome of pregnancy in all patients (odds ratio (OR) = 5.442 (3.01-6.82), cut-off = 1.21 m/s). Patients with cirrhosis, mean LS was 1.57 ± 0.66 m/s and 26 (44%) patients had hepatic decompensation (hepatocellular jaundice (n = 8), ascites (n = 9) and variceal bleeding (n = 6)). In multivariate analysis; LS, platelets, albumin, and bilirubin were independent predictors of decompensation post-delivery and the OR for LS was 6.141(4.32-7.98). The optimal cut off value of LS to predict decompensation was 1.46 m/s (8.4 kPa) with AUROC of 0.827. CONCLUSION LS can be used to predict hepatic decompensation after delivery in pregnant women with manifest cirrhosis.
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Affiliation(s)
- Omar Elshaarawy
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Egypt; Department of Internal Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Germany
| | - Rasha Abdelaziz
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Naglaa Zayed
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ayman Hany
- Gynecology and Obstetrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Zainab Hammam
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sebastian Mueller
- Department of Internal Medicine, Salem Medical Center and Center for Alcohol Research and Liver Disease, University of Heidelberg, Germany
| | - Ayman Yosry
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hend Ibrahim Shousha
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
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30
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Qian T, Fujiwara N, Koneru B, Ono A, Kubota N, Jajoriya AK, Tung MG, Crouchet E, Song WM, Marquez CA, Panda G, Hoshida A, Raman I, Li QZ, Lewis C, Yopp A, Rich NE, Singal AG, Nakagawa S, Goossens N, Higashi T, Koh AP, Bian CB, Hoshida H, Tabrizian P, Gunasekaran G, Florman S, Schwarz ME, Hiotis SP, Nakahara T, Aikata H, Murakami E, Beppu T, Baba H, Warren A, Bhatia S, Kobayashi M, Kumada H, Fobar AJ, Parikh ND, Marrero JA, Rwema SH, Nair V, Patel M, Kim-Schulze S, Corey K, O’Leary JG, Klintmalm GB, Thomas DL, Dibas M, Rodriguez G, Zhang B, Friedman SL, Baumert TF, Fuchs BC, Chayama K, Zhu S, Chung RT, Hoshida Y. Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development. Gastroenterology 2022; 162:1210-1225. [PMID: 34951993 PMCID: PMC8934284 DOI: 10.1053/j.gastro.2021.12.250] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND & AIMS There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. METHODS A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122). RESULTS A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. CONCLUSION The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.
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Affiliation(s)
- Tongqi Qian
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Naoto Fujiwara
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S.,Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Bhuvaneswari Koneru
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Atsushi Ono
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S.,Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naoto Kubota
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Arun K Jajoriya
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Matthew G Tung
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, U.S
| | - Emilie Crouchet
- Institut de Recherche sur les Maladies Virales et Hépatiques, Inserm U1110, University of Strasbourg, Strasbourg, France
| | - Won-Min Song
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Cesia Ammi Marquez
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Gayatri Panda
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Ayaka Hoshida
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Indu Raman
- Microarray Core Facility, Department of Immunology, BioCenter, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Quan-Zhen Li
- Microarray Core Facility, Department of Immunology, BioCenter, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Cheryl Lewis
- Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Adam Yopp
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Nicole E Rich
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Nicolas Goossens
- Division of Gastroenterology and Hepatology, Geneva University Hospital, Switzerland
| | - Takaaki Higashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Anna P Koh
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - C Billie Bian
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Hiroki Hoshida
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Ganesh Gunasekaran
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Sander Florman
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Myron E Schwarz
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Spiros P Hiotis
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toru Beppu
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, U.S
| | - Hideo Baba
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, U.S
| | | | | | | | | | - Austin J Fobar
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, U.S
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, U.S
| | - Jorge A Marrero
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, U.S.,Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, U.S
| | | | - Venugopalan Nair
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Manishkumar Patel
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, U.S
| | | | - Kathleen Corey
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, U.S
| | | | | | - David L Thomas
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, U.S
| | | | | | - Bin Zhang
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Scott L Friedman
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, U.S
| | - Thomas F Baumert
- Institut de Recherche sur les Maladies Virales et Hépatiques, Inserm U1110, University of Strasbourg, Strasbourg, France.,IHU, Pole hépato-digestif, Strasbourg University Hospitals, Strasbourg, France
| | - Bryan C Fuchs
- Department of Surgery, Massachusetts General Hospital, Boston, U.S., Ferring Pharmaceuticals, San Diego, U.S
| | - Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Shijia Zhu
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
| | - Raymond T Chung
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Yujin Hoshida
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
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Innes H, Walker AJ, Benselin J, Grove JI, Pedergnana V, Azim Ansari M, Lin SK, McLauchlan J, Hutchinson SJ, Barnes E, Irving WL, Guha IN. Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis. Clin Transl Gastroenterol 2022; 13:e00462. [PMID: 35142723 PMCID: PMC8963831 DOI: 10.14309/ctg.0000000000000462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 12/06/2021] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Risk-stratifying patients with hepatitis C virus (HCV) cirrhosis according to medium-term prognosis will inform clinical decision-making. It is unclear which biomarkers/models are optimal for this purpose. We quantified the discriminative ability of 14 diverse biomarkers for prognosis prediction over a 4-year time. METHODS We recruited 1196 patients with HCV cirrhosis from the United Kingdom for a prospective study. Genetic risk score, collagen (e.g., PROC3), comorbidity (e.g., CirCom), and validated biomarkers from routine data were measured at enrollment. Participants were linked to UK hospital admission, cancer, and mortality registries. Primary endpoints were (i) liver-related outcomes for patients with compensated cirrhosis and (ii) all-cause mortality for decompensated cirrhosis. The discriminative ability of all biomarkers was quantified individually and also by the fraction of new prognostic information provided. RESULTS At enrollment, 289 (24%) and 907 (76%) had decompensated and compensated cirrhosis, respectively. Participants were followed for 3-4 years on average, with >70% of the follow-up time occurring post-HCV cure. Seventy-five deaths in the decompensated subgroup and 98 liver-related outcomes in the compensated subgroup were reported. The discriminative ability of the albumin-bilirubin-fibrosis-4 index (C-index: 0.71-0.72) was superior to collagen biomarkers (C-index = 0.58-0.67), genetic risk scores (C-index = 0.50-0.57), and comorbidity markers (0.53-0.60). Validated biomarkers showed the greatest prognostic improvement when combined with a comorbidity or a collagen biomarker (generally >30% of new prognostic information added). DISCUSSION Inexpensive biomarkers such as the albumin-bilirubin-fibrosis-4 index predict medium-term cirrhosis prognosis moderately well and outperform collagen, genetic, and comorbidity biomarkers. Improvement of performance was greatest when a validated test was combined with comorbidity or collagen biomarker.
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Affiliation(s)
- Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
- Public Health Scotland, Glasgow, UK
| | - Alex J. Walker
- The DataLab, Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, UK
| | - Jennifer Benselin
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Jane I. Grove
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Vincent Pedergnana
- Laboratoire MIVEGEC (UMR CNRS 5290, UR IRD 224, UM), Montpellier, France
| | - M. Azim Ansari
- Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the Oxford NIHR Biomedical Research Centre, Oxford University, UK
| | - Shang-Kuan Lin
- Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the Oxford NIHR Biomedical Research Centre, Oxford University, UK
| | - John McLauchlan
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Sharon J. Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
- Public Health Scotland, Glasgow, UK
| | - Eleanor Barnes
- Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the Oxford NIHR Biomedical Research Centre, Oxford University, UK
| | - William L. Irving
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Indra Neil Guha
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
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Liver stiffness can predict decompensation and need for beta-blockers in compensated cirrhosis: a step beyond Baveno-VI criteria. Hepatol Int 2022; 16:89-98. [DOI: 10.1007/s12072-021-10280-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 11/12/2021] [Indexed: 11/30/2022]
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33
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Palaniyappan N, Fallowfield JA. Emerging Non-invasive Markers: Imaging, Blood, and Liver Clearance Tests. PORTAL HYPERTENSION VII 2022:135-151. [DOI: 10.1007/978-3-031-08552-9_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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34
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Hsu CY, Parikh ND, Huo TI, Tapper EB. Comparison of Seven Noninvasive Models for Predicting Decompensation and Hospitalization in Patients with Cirrhosis. Dig Dis Sci 2021; 66:4508-4517. [PMID: 33387126 DOI: 10.1007/s10620-020-06763-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 12/06/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND/AIM Patients with cirrhosis have poor outcomes once decompensation occurs; however, we lack adequate predictors of decompensation. To use a national claim database to compare the predictive accuracy of seven models for decompensation and hospitalization in patients with compensated cirrhosis. METHODS We defined decompensation as ascites, hepatic encephalopathy, hepato-renal syndrome, and variceal bleeding. Patients without decompensation at the time of cirrhosis diagnosis were enrolled from 2001 to 2015. Patients with hepatitis B and/or C were grouped as viral cirrhosis. We compared the predictive accuracy of models with the AUC (area under the curve) and c-statistic. The cumulative incidence of decompensation and incidence risk ratios of hospitalization were calculated with the Fine-Gray competing risk and negative binomial models, respectively. RESULTS A total of 3722 unique patients were enrolled with a mean follow-up time of 524 days. The mean age was 59 (standard deviation 12), and the majority were male (55%) and white (65%). Fifty-three percent of patients had non-viral cirrhosis. Sixteen and 20 percent of patients with non-viral and viral cirrhosis, respectively, developed decompensation (P = 0.589). The FIB-4 model had the highest 3-year AUC (0.73) and overall c-statistic (0.692) in patients with non-viral cirrhosis. The ALBI-FIB-4 model had the best 1-year (AUC = 0.741), 3-year (AUC = 0.754), and overall predictive accuracy (c-statistic = 0.681) in patients with viral cirrhosis. The MELD score had the best predictive power for hospitalization in both non-viral and viral patients. CONCLUSIONS FIB-4-based models provide more accurate prediction for decompensation, and the MELD model has the best predictive ability of hospitalization.
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Affiliation(s)
- Chia-Yang Hsu
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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35
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Ieda S, Miyamoto T, Hosomi K, Takegami M, Kawabata A. Identification of Remaining Life Expectancy Less Than Two Weeks by C-Reactive Protein/Albumin Ratio, Prognostic Nutritional Index, Fibrosis-4 Index, and Albumin-Bilirubin Score in Terminal Cancer Patients. J Palliat Med 2021; 25:570-576. [PMID: 34612718 DOI: 10.1089/jpm.2021.0243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background: Accurate prognosis in terminal cancer patients is useful to improve their quality of life and also to decide the cessation of fluid administration. Nonetheless, few prognostic indicators are available for prediction of such a short-term life expectancy. Objectives: The present study aimed at evaluating the efficacy of C-reactive protein (CRP)/albumin (CRP/Alb) ratio, prognostic nutritional index (PNI), fibrosis-4 (FIB-4) index, and albumin-bilirubin (ALBI) score in identifying terminal cancer patients who have a life expectancy less than two weeks. Design: Retrospective study. Setting/Subjects: Of 483 patients who died between April 2019 and March 2020 at a single center in Japan, 102 who met the inclusion criteria were enrolled in this study. Measurements: CRP/Alb, PNI, FIB-4, and ALBI were calculated from the laboratory data collected 1-13, 14-27, 28-83, and 168-365 days before death and subjected to statistical analyses. Results: CRP/Alb, PNI, FIB-4, and ALBI values were significantly associated with the time before death during terminal 365 days. CRP/Alb ≥4.4, PNI <30, FIB-4 ≥ 9.4, and ALBI ≥ -1.26 were significantly associated with the transition from the first half to the second half of terminal four weeks. Of those prognostic indicators, three and four combinations provided significantly reliable estimation of a life expectancy less than two weeks. Conclusions: CRP/Alb, PNI, FIB-4, ALBI, and their combinations are considered to help identify cancer patients who have a life expectancy less than two weeks, which is useful to make appropriate end-stage treatment decisions, for example, cessation of artificial hydration therapy.
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Affiliation(s)
- Shoko Ieda
- Department of Pharmacy, Kindai University Hospital, Osakasayama, Japan
| | - Tomoyoshi Miyamoto
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan.,Department of Pharmacy, Seichokai Fuchu Hospital, Izumi, Japan
| | - Kouichi Hosomi
- Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
| | - Manabu Takegami
- Department of Pharmacy, Kindai University Hospital, Osakasayama, Japan
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Yoo SH, Lim TS, Lee HW, Kim JK, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Lee JI, Lee KS, Kim SU. Risk assessment of hepatocellular carcinoma and liver-related events using ultrasonography and transient elastography in patients with chronic hepatitis B. J Viral Hepat 2021; 28:1362-1372. [PMID: 34185929 DOI: 10.1111/jvh.13560] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 06/18/2021] [Indexed: 12/09/2022]
Abstract
Cirrhosis has prognostic value. We investigated whether the combined use of ultrasonography (US) and transient elastography (TE) to diagnose cirrhosis is beneficial for the risk assessment of hepatocellular carcinoma (HCC) and liver-related events in patients with chronic hepatitis B (CHB). A total of 9300 patients with CHB who underwent US and TE in two institutions between 2006 and 2018 were enrolled. TE value ≥13 kPa was set to indicate cirrhosis. Patients were divided into four groups: US(+)TE(+) (cirrhosis by US and TE), US(+)TE(-) (cirrhosis by US, but not by TE), US(-)TE(+) (cirrhosis by TE, but not by US) and US(-)TE(-) (non-cirrhosis by US and TE).The patients were predominantly male (n = 5474, 58.9%) with a mean age of 47.5 years. The proportions of patients with cirrhosis diagnosed by US and TE were 17.2% (n = 1595) and 13.2% (n = 1225), respectively. The proportion of patients with discordant results in diagnosing cirrhosis by US and TE was 18.7% (n = 1740). During follow-up (median: 60.0 months), HCC and liver-related events developed in 481 (5.2%) and 759 (8.2%) patients, respectively. The cumulative incidence rates of HCC and liver-related events were highest in the US(+)TE(+) group, intermediate-high in the US(-)TE(+) group, intermediate-low in the US(+)TE(-) group and lowest in the US(-)TE(-) group (overall p < .001). Cirrhosis assessed using US and TE was a major predictor of HCC and liver-related event development in patients with CHB. Cirrhosis assessed using TE seemed better in predicting HCC or liver-related events than using US, when cirrhosis diagnosis was discordant by US and TE.
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Affiliation(s)
- Sung Hwan Yoo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Yongin Severance Hospital, Yongin, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Yongin Severance Hospital, Yongin, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Kwan Sik Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
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37
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Calzadilla-Bertot L, Vilar-Gomez E, Wong VWS, Romero-Gomez M, Aller-de la Fuente R, Wong GLH, Castellanos M, Eslam M, Desai AP, Jeffrey GP, George J, Chalasani N, Adams LA. ABIDE: An Accurate Predictive Model of Liver Decompensation in Patients With Nonalcoholic Fatty Liver-Related Cirrhosis. Hepatology 2021; 73:2238-2250. [PMID: 32978796 DOI: 10.1002/hep.31576] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 08/28/2020] [Accepted: 09/07/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is an increasingly important cause of liver cirrhosis and subsequent complications. We retrospectively developed and validated a model to predict hepatic decompensation in patients with NAFLD and cirrhosis and compared this with currently available models. APPROACH AND RESULTS Baseline variables from an international cohort of 299 patients with biopsy-proven NAFLD with compensated cirrhosis were examined to construct a model using competing risk multivariate regression and Akaike/Bayesian information criteria. Validation was performed in 244 patients with biopsy-proven NAFLD cirrhosis from the United States. Prognostic accuracy was compared with the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4), Model for End-Stage Liver Disease (MELD), Child-Turcotte-Pugh (CTP), and albumin-bilirubin (ALBI)-FIB-4 score using time-dependent area under the curve (tAUC) analysis. During a median follow-up of 5.6 years (range 2.4-14.1) and 5.4 years (range 1.5-13.8), hepatic decompensation occurred in 81 and 132 patients in the derivation and validation cohorts, respectively. In the derivation cohort, independent predictors of hepatic decompensation (Aspartate aminotransferase/alanine aminotransferase ratio, Bilirubin, International normalized ratio, type 2 Diabetes, and Esophageal varices) were combined into the ABIDE model. Patients with a score ≥4.1 compared with those with a score <4.1 had a higher risk of decompensation (subhazard ratio, 6.7; 95% confidence interval [CI], 4.0-11.2; P < 0.001), a greater 5-year cumulative incidence (37% vs. 6%, P < 0.001), and shorter mean duration to decompensation (3.8 vs 6.7 years, P < 0.001). The accuracy of the ABIDE model at 5 years was good in the derivation (tAUC, 0.80; 95% CI, 0.73-0.84) and validation cohorts (0.78; 95% CI, 0.74-0.81) and was significantly more accurate than the NFS (0.72), FIB-4 (0.74), MELD (0.69), CTP (0.72), and ALBI-FIB-4 (0.73) (all P < 0.001). CONCLUSIONS In patients with NAFLD and compensated cirrhosis, ABIDE, a predictive model of routine clinical measures, predicts future hepatic decompensation.
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Affiliation(s)
- Luis Calzadilla-Bertot
- Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
- Unit for the Clinical Management of Digestive Diseases, Centro para la Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Virgen del Rocio University Hospital, University of Seville, Seville, Spain
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Manuel Romero-Gomez
- Unit for the Clinical Management of Digestive Diseases, Centro para la Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Virgen del Rocio University Hospital, University of Seville, Seville, Spain
| | - Rocio Aller-de la Fuente
- Department of Digestive Disease, Institute of Endocrinology and Nutrition, University of Valladolid, Valladolid, Spain
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Marlen Castellanos
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Archita P Desai
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Gary P Jeffrey
- Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Leon A Adams
- Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, WA, Australia
- Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
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Bernardo S, Crespo R, Saraiva S, Barata R, Gonçalves S, Nogueira P, Cortez-Pinto H, Machado MV. Outcomes of excessive alcohol drinkers without baseline evidence of chronic liver disease after 15 years follow-up: Heavy burden of cancer and liver disease mortality. PLoS One 2021; 16:e0252218. [PMID: 34033642 PMCID: PMC8148371 DOI: 10.1371/journal.pone.0252218] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/12/2021] [Indexed: 12/20/2022] Open
Abstract
Background Most long-term heavy drinkers do not have clinically evident chronic liver disease (CLD). However, at any time-point, their risk of developing CLD remains unknown. We aimed to evaluate the long-term outcomes of a group of heavy drinkers, without evidence of CLD at baseline. Methods A cohort of 123 long-term heavy drinkers without CLD were prospectively recruited in 2002 and retrospectively followed until 2018. Results At baseline (2002), median alcohol consumption was 271±203g/day during 21.5±20 years, 65% being abstinent during the previous 1.75±5 months. Patients were followed for 14±3 years. During follow-up, 53% reported any alcohol intake. Alcohol consumption during follow-up associated weakly with either 1- or 6-months previous abstinence at baseline. Until 2018, progression to CLD occurred in 6%, associating with years of alcohol intake during follow-up (OR 1.15 [1.01–1.31]) and baseline alkaline-phosphatase (OR 1.05 [1.01–1.10]). During follow-up, being abstinent for at least 1 year positively associated with CLD-free survival. 27% died (55% of cancer–mostly oropharyngeal cancer, 27% of cardiovascular disease, and 9% of liver disease), with a mean age of 71 years [69–74] (10 years less than the expected in the Portuguese population). Achieving abstinence for at least 1 year positively associated with overall survival, while smoking, and hepatic steatosis at baseline associated negatively. Conclusion Long-term heavy drinkers seemed to have a decreased life expectancy compared with the overall Portuguese population. Cancer was the main cause of death. Our results suggest that progression to CLD depends mostly on continued alcohol intake. Alcohol abstinence, even if temporary, seems to decrease the risks of CLD and mortality.
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Affiliation(s)
- Sónia Bernardo
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
| | - Ricardo Crespo
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
| | - Sofia Saraiva
- Nephrology Department, Hospital de Curry Cabral, CHULC, Lisbon, Portugal
| | - Rui Barata
- Gastroenterology Department, Portuguese Oncology Institute, Lisbon, Portugal
| | - Sara Gonçalves
- Nephrology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
| | - Paulo Nogueira
- Biostatistics’ Department, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Helena Cortez-Pinto
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Mariana Verdelho Machado
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- * E-mail:
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Nishikawa H, Enomoto H, Yoh K, Iwata Y, Sakai Y, Kishino K, Ikeda N, Takashima T, Aizawa N, Takata R, Hasegawa K, Ishii N, Yuri Y, Nishimura T, Iijima H, Nishiguchi S. Combined albumin-bilirubin grade and Mac-2 binding protein glycosylation isomer as a useful predictor in compensated liver cirrhosis. Medicine (Baltimore) 2019; 98:e18366. [PMID: 31852142 PMCID: PMC6922458 DOI: 10.1097/md.0000000000018366] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 10/25/2019] [Accepted: 11/13/2019] [Indexed: 01/27/2023] Open
Abstract
We aimed to compare the impact on survival among albumin-bilirubin (ALBI) grade, modified ALBI (mALBI) and our proposed combined ALBI grade and Mac-2 binding protein glycosylation isomer (M2BPGi) or FIB4 index grading system in chronic hepatitis C (CHC) related compensated liver cirrhosis (n = 165, 93 men and 72 women, median age = 67 years). Patients with ALBI grade 1, 2, and 3 were allocated a score of 1, 2, and 3 points, respectively. Patients with mALBI grade 1, 2A, and 2B were allocated a score of 1, 2, and 3 points, respectively. Patients with a high or low M2BPGi were allocated a score of 1 and 0 point. Patients with a high or low FIB4 index were allocated a score of 1 and 0 point. Sum of the point of ALBI (1, 2, or 3) and M2BPGi (0 or 1) or FIB4 index (0 or 1) was defined as ALBI-M2BPGi grade or ALBI-FIB4 grade. Prognostic accuracy was compared using the Akaike information criterion (AIC) value and time dependent receiver operating characteristics (ROC) curve analysis. The median follow-up duration was 5.422 years. AIC value for survival by ALBI-M2BPGi grade was the lowest among 4 prognostic models (AIC: 205.731 in ALBI grade, 200.913 in mALBI grade, 189.816 in ALBI-M2BPGi grade, and 204.671 in ALBI-FIB4 grade). All area under the ROC curves of ALBI-M2BPGi grade in each time point were higher than those of ALBI grade, mALBI grade, and ALBI-FIB4 grade. In conclusion, our proposed ALBI-M2BPGi grading system seems to be helpful for estimating prognosis in patients with CHC related compensated LC.
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Affiliation(s)
- Hiroki Nishikawa
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Hirayuki Enomoto
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Kazunori Yoh
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Yoshinori Iwata
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Yoshiyuki Sakai
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Kyohei Kishino
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Naoto Ikeda
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Tomoyuki Takashima
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Nobuhiro Aizawa
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Ryo Takata
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Kunihiro Hasegawa
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Noriko Ishii
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Yukihisa Yuri
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Takashi Nishimura
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
| | - Shuhei Nishiguchi
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine
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40
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Fragaki M, Sifaki-Pistolla D, Orfanoudaki E, Kouroumalis E. Comparative evaluation of ALBI, MELD, and Child-Pugh scores in prognosis of cirrhosis: is ALBI the new alternative? Ann Gastroenterol 2019; 32:626-632. [PMID: 31700241 PMCID: PMC6826070 DOI: 10.20524/aog.2019.0417] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 07/31/2019] [Indexed: 12/28/2022] Open
Abstract
Background: The existence of reliable prognostic indices is of paramount importance in the management of cirrhosis. Both the model for end-stage liver disease (MELD) score and the older Child-Pugh (CP) scores are widely used. The albumin-bilirubin (ALBI) score, initially used in hepatocellular carcinoma, has not been thoroughly investigated in cirrhosis. The aim of this study was to compare the prognostic accuracy of ALBI, MELD, MELD with sodium (MELD-Na), CP, and the corrected for creatinine CP scores in a genetically homogeneous Cretan cirrhotic population. Methods: One hundred ninety-five outpatients or hospitalized cirrhotics (127 male, median age 66 years) were studied over a period of 2 years and ALBI, platelet-albumin-bilirubin, MELD, MELD-Na, CP score, and 2 types of modified CP score (CP-I and CP-II) with serum creatinine were calculated and correlated with survival. Results: ALBI had an optimum balance between sensitivity and specificity (area under the curve 0.704, 95% confidence interval [CI] 0.630-0.778) compared to the other scores. In the multivariate analysis, the only factors independently associated with death were the ALBI score (hazard ratio [HR] 2.51, 95%CI 1.69-3.73; P<0.001), the MELD-Na score (HR 1.04, 95%CI 1.00-1.09; P=0.045), and age (HR 1.05, 95%CI 1.03-1.07; P<0.001). When only decompensated cirrhosis was evaluated, the multivariate analysis showed that the ALBI score (HR 3.03; 95%CI 1.92-4.78; P<0.001), and age (HR 1.05, 95%CI 1.03-1.07; P<0.001) were independently associated with death. Conclusion: ALBI score might be a better prognostic indicator of mortality in cirrhosis and given its simplicity could substitute for the CP, MELD, and MELD-Na scores.
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Affiliation(s)
- Maria Fragaki
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion and University of Crete, Medical School (Maria Fragaki, Eleni Orfanoudaki, Elias Kouroumalis)
| | - Dimitra Sifaki-Pistolla
- Clinic of Social and Family Medicine, University of Crete, Medical School (Dimitra Sifaki-Pistolla), Crete, Greece
| | - Eleni Orfanoudaki
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion and University of Crete, Medical School (Maria Fragaki, Eleni Orfanoudaki, Elias Kouroumalis)
| | - Elias Kouroumalis
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion and University of Crete, Medical School (Maria Fragaki, Eleni Orfanoudaki, Elias Kouroumalis)
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Abraldes JG, Garcia-Tsao G. Simple Clinical Tools to Predict Decompensation in Patients With Compensated Cirrhosis: An Unmet Need. Clin Gastroenterol Hepatol 2019; 17:2179-2181. [PMID: 31004761 PMCID: PMC11090165 DOI: 10.1016/j.cgh.2019.04.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 04/09/2019] [Indexed: 02/07/2023]
Affiliation(s)
- Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
| | - Guadalupe Garcia-Tsao
- Digestive Diseases Section, Yale University School of Medicine, New Haven, Connecticut
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Nishikawa H, Enomoto H, Yoh K, Iwata Y, Sakai Y, Kishino K, Ikeda N, Takashima T, Aizawa N, Takata R, Hasegawa K, Ishii N, Yuri Y, Nishimura T, Iijima H, Nishiguchi S. Combined Albumin-Bilirubin Grade and Skeletal Muscle Mass as a Predictor in Liver Cirrhosis. J Clin Med 2019; 8:782. [PMID: 31159435 PMCID: PMC6617543 DOI: 10.3390/jcm8060782] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 05/30/2019] [Accepted: 05/31/2019] [Indexed: 01/27/2023] Open
Abstract
We aimed to compare the prognostic impact among albumin-bilirubin (ALBI) grade, the Child-Pugh classification and our proposed combined ALBI grade and skeletal muscle mass (SMM) grading system in patients with liver cirrhosis (LC) (n = 468, 254 males and 214 females) using the Akaike information criterion (AIC) and time-dependent receiver operating characteristics (ROC) curve analysis. SMM was tested using bioimpedance analysis. Male subjects with skeletal muscle mass index (SMI) <7.0 cm2/m2 and female subjects with SMI <5.7 cm2/m2 were defined as having low SMM. Patients with ALBI grade 1, 2 and 3 were given 1, 2 and 3 points. Patients with and without low SMM were given 1 and 0 point, respectively. The sum of the point of ALBI (1, 2, or 3) and SMM (0 or 1) was defined as the ALBI-SMM grade. The value obtained with the AIC for survival by the ALBI-SMM grade was the lowest among three assessment methods (AIC: 513.418 in ALBI grade, 533.584 in Child-Pugh classification and 493.72 in ALBI-SMM grade). In time-dependent ROC analysis, all area under the ROCs of the ALBI-SMM grade in each time point were the highest among three assessment methods. In conclusion, the ALBI-SMM grading system can be helpful for LC patients.
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Affiliation(s)
- Hiroki Nishikawa
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
- Center for clinical research and education, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Hirayuki Enomoto
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Kazunori Yoh
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Yoshinori Iwata
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Yoshiyuki Sakai
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Kyohei Kishino
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Naoto Ikeda
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Tomoyuki Takashima
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Nobuhiro Aizawa
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Ryo Takata
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Kunihiro Hasegawa
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Noriko Ishii
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Yukihisa Yuri
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Takashi Nishimura
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Shuhei Nishiguchi
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
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43
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D’Amico G, Perricone G. Prediction of Decompensation in Patients with Compensated Cirrhosis: Does Etiology Matter? ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s11901-019-00473-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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