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Tavabie OD, Aluvihare VR. Novel biomarkers predicting successful regeneration would likely improve patient selection for plasma exchange in acute liver failure. J Hepatol 2025; 82:e240-e241. [PMID: 39423867 DOI: 10.1016/j.jhep.2024.10.009] [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: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/21/2024]
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Remih K, Hufnagel FM, Karl AS, Durkalski-Mauldin V, Lee WM, Karvellas CJ, Su Z, Rule JA, Tomanová P, Krieg L, Karkossa I, Schubert K, von Bergen M, Tacke F, Luckhardt S, Ziegler N, Kannt A, Engel B, Taubert R, Fontana RJ, Strnad P, the US Acute Liver Failure Study Group. Serum proteomics of adults with acute liver failure provides mechanistic insights and attractive prognostic biomarkers. JHEP Rep 2025; 7:101338. [PMID: 40242314 PMCID: PMC11998117 DOI: 10.1016/j.jhepr.2025.101338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 04/18/2025] Open
Abstract
Background & Aims Acute liver failure (ALF) is defined as rapid onset coagulopathy and encephalopathy in patients without a prior history of liver disease. We performed untargeted and targeted serum proteomics to delineate processes occurring in adult patients with ALF and to identify potential biomarkers. Methods Sera of 319 adult patients with ALF (∼50% acetaminophen [APAP]-related cases) were randomly selected from admission samples of the multicenter USA Acute Liver Failure Study Group consortium and subdivided into discovery/validation cohorts. They were analyzed using untargeted proteomics with mass spectroscopy and a serum cytokine profiling and compared with 30 healthy controls. The primary clinical outcome was 21-day transplant-free survival. Single-cell RNAseq data mapped biomarkers to cells of origin; functional enrichment analysis provided mechanistic insights. Novel prognostic scores were compared with the model for end-stage liver disease and ALFSG prognostic index scores. Results In the discovery cohort, 117 proteins differed between patients with ALF and healthy controls. There were 167 proteins associated with APAP-related ALF, with the majority being hepatocyte-derived. Three hepatocellular proteins (ALDOB, CAT, and PIGR) robustly and reproducibly discriminated APAP from non-APAP cases (AUROCs ∼0.9). In the discovery cohort, 37 proteins were related to 21-day outcome. The key processes associated with survival were acute-phase response and hepatocyte nuclear factor 1α signaling. SERPINA1 and LRG1 were the best individual discriminators of 21-day transplant-free survival in both cohorts. Two models of blood-based proteomic biomarkers outperformed the model for end-stage liver disease and ALFSG prognostic index and were reproduced in the validation cohort (AUROCs 0.83-0.86) for 21-day transplant-free survival. Conclusions Proteomics and cytokine profiling identified new, reproducible biomarkers associated with APAP etiology and 21-day outcome. These biomarkers may improve prognostication and understanding of the etiopathogenesis of ALF but need to be independently validated. Impact and implications Acute liver failure (ALF) is a sudden, and severe condition associated with high fatality. More sensitive and specific prognostic scores are urgently needed to facilitate decision-making regarding liver transplantation in patients with ALF. Our proteomic analysis uncovered marked differences between acetaminophen and non-acetaminophen-related ALF. The identification of routinely measurable biomarkers that are associated with 21-day transplant-free survival and the derivation of novel prognostic scores may facilitate clinical management as well as decisions for/against liver transplantation. Further studies are needed to quantify less abundant proteins. Although we used two cohorts, our findings still need to be independently and prospectively validated.
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Affiliation(s)
- Katharina Remih
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
| | - Franziska-Maria Hufnagel
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
| | - Anna Sophie Karl
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
| | | | - William Martens Lee
- Department of Internal Medicine, Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | | | - Zemin Su
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA
| | - Jody A. Rule
- Department of Internal Medicine, Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Petra Tomanová
- Department of Econometrics, Prague University of Economics and Business, Prague, Czechia
| | - Laura Krieg
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research, Leipzig, Germany
| | - Isabel Karkossa
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research, Leipzig, Germany
| | - Kristin Schubert
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research, Leipzig, Germany
| | - Martin von Bergen
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research, Leipzig, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin, Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany
| | - Sonja Luckhardt
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany
| | - Nicole Ziegler
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany
| | - Aimo Kannt
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany
- Goethe University, Institute of Clinical Pharmacology, Frankfurt am Main, Germany
| | - Bastian Engel
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Richard Taubert
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Robert John Fontana
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
| | - Pavel Strnad
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
| | - the US Acute Liver Failure Study Group
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA
- Department of Internal Medicine, Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
- Department of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada
- Department of Econometrics, Prague University of Economics and Business, Prague, Czechia
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research, Leipzig, Germany
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin, Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany
- Goethe University, Institute of Clinical Pharmacology, Frankfurt am Main, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
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Cardoso FS, Lee WM, Karvellas CJ, U.S. Acute Liver Failure Study Group. Brain CT Scan Diagnostic and Prognostic Value in Patients With Acute Liver Failure and Cerebral Edema: A Multicenter Cohort Study. Crit Care Explor 2025; 7:e1251. [PMID: 40232229 PMCID: PMC12002376 DOI: 10.1097/cce.0000000000001251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2025] Open
Abstract
OBJECTIVE Patients with acute liver failure (ALF) may develop cerebral edema. We aimed to study the CT scan diagnostic and prognostic value among patients with ALF and cerebral edema. DESIGN International multicenter retrospective cohort. SETTING U.S. Acute Liver Failure Study Group prospective registry. PATIENTS Consecutive patients with ALF within the registry from January 1998 to August 2016. INTERVENTIONS The primary exposure was cerebral edema on CT scan. The primary endpoint was 21-day post-inclusion transplant-free survival (TFS). MEASUREMENTS AND MAIN RESULTS Among 2108 patients with ALF, 243 (11.5%) had a brain CT scan. Among those 243 patients, 105 (43.2%) had cerebral edema and 11 (4.5%) later developed tonsillar herniation. Patients with cerebral edema on CT scan were younger (36 vs. 46 yr; p < 0.001) and more often females (81.0% vs. 63.8%; p = 0.003), had more acetaminophen-related ALF (61.0% vs. 39.4%; p < 0.001), required more frequently invasive mechanical ventilation on day 1 (73.3% vs. 55.8%; p = 0.005), and had higher maximum days 1-7 model for end-stage liver disease (MELD) score (39 vs. 35; p = 0.002) than others. Following adjustment for confounders (age, acetaminophen toxicity, and severity of disease by MELD), cerebral edema was associated with lower odds of 21-day TFS (adjusted odds ratio = 0.36 [95% CI, 0.18-0.72]; C-statistic = 0.81 [95% CI, 0.75-0.86]; p = 0.003). However, cerebral edema was not associated with selection for liver transplant (22.9% vs. 16.1%; p = 0.18). CONCLUSIONS In our cohort of patients with ALF, brain CT scan use increased overtime. Among those with a brain CT scan, about two in five had cerebral edema. Cerebral edema on CT scan was independently associated with worse 21-day TFS but did not preclude transplant. Brain CT scan may provide additional diagnostic and prognostic information in selected patients with ALF.
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Affiliation(s)
- Filipe S. Cardoso
- Intensive Care Unit, Transplant Unit, Curry Cabral Hospital, Nova Medical School, Lisbon, Portugal
- Department of Critical Care Medicine and Liver Unit, University of Alberta, Edmonton, AB, Canada
| | - William M. Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX
| | - Constantine J. Karvellas
- Department of Critical Care Medicine and Liver Unit, University of Alberta, Edmonton, AB, Canada
| | - U.S. Acute Liver Failure Study Group
- Intensive Care Unit, Transplant Unit, Curry Cabral Hospital, Nova Medical School, Lisbon, Portugal
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX
- Department of Critical Care Medicine and Liver Unit, University of Alberta, Edmonton, AB, Canada
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Nilsen O, Fisher C, Warrillow S. Update on the management of acute liver failure. Curr Opin Crit Care 2025; 31:219-227. [PMID: 39991852 DOI: 10.1097/mcc.0000000000001253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
PURPOSE OF REVIEW Acute liver failure (ALF) is a rare, life-threatening but potentially reversible clinical syndrome characterized by multiple organ failure secondary to the rapid loss of liver function. Key management challenges include severe cerebral oedema and complex treatments to support multiple organ failure. This review focuses on the fundamental principles of management and recent treatment advances. RECENT FINDINGS Identifying the cause of ALF is key to guiding specific therapies. The early commencement of continuous renal replacement therapy (CRRT) to control hyperammonaemia can now be considered an important standard of care, and plasma exchange may have a role in the sickest of ALF patients; however, other blood purification modalities still lack supporting evidence. Close monitoring, regular investigations, careful attention to neuroprotective measures, as well as optimizing general physiological supports is essential. Where possible, patients should be transferred to a liver transplant centre to achieve the best chance of transplant-free survival, or to undergo emergency liver transplantation if required. SUMMARY This review outlines current principles of ALF management, emerging treatment strategies, and a practical approach to management in the ICU. These recommendations can form the development of local guidelines, incorporating current best evidence for managing this rare but often lethal condition.
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Affiliation(s)
- Oliver Nilsen
- Department of Intensive Care, Austin Health, Heidelberg
| | - Caleb Fisher
- Department of Intensive Care, Austin Health, Heidelberg
- Department of Critical Care, The University of Melbourne, Parkville, Australia
| | - Stephen Warrillow
- Department of Intensive Care, Austin Health, Heidelberg
- Department of Critical Care, The University of Melbourne, Parkville, Australia
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Cardoso FS, Lee WM, Karvellas CJ. Failure to rescue in acute liver failure: A multicenter cohort study. Liver Transpl 2025:01445473-990000000-00573. [PMID: 40062765 DOI: 10.1097/lvt.0000000000000594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 02/27/2025] [Indexed: 05/04/2025]
Abstract
The concept of failure to rescue has been used to measure the quality of care for complications developed following surgery. The concept of failure to rescue has been poorly studied in patients with primary medical diseases, such as sepsis or acute liver failure (ALF). We performed a retrospective multicenter cohort study including consecutive patients with ALF within the United States ALF Study Group (USALFSG) prospective registry from 2010-2016. The failure to rescue rate for 12 medical complications in the registry was calculated as the mortality events up to 21 days after inclusion divided by the complication events registered on the first day after inclusion. The association between these complications and 21-day transplant-free mortality was studied. Among 665 patients with ALF, 478 (71.9%) were females, and the median (IQR) age was 42 (30-55) years. Acetaminophen intoxication was observed in 322 (48.4%) patients. Overall, 461 (69.3%) patients had at least one medical complication on the first day after inclusion (median [IQR] number of 1 [0-3]). The failure to rescue rate for the 12 complications was 32.8%. The complications with the higher failure-to-rescue rates were gastrointestinal bleed (63.6%), non-gastrointestinal bleed (53.9%), requirement for vasopressors (52.5%), and acute respiratory distress syndrome (48.1%). After adjusting for age, sex, etiology, and international normalized ratio, per each added complication present on day 1, the odds of 21-day transplant-free mortality increased by 38% (adjusted OR [95% CI] of 1.38 [1.24-1.54]; c-statistic [95% CI] of 0.77 [0.73-0.81]). In patients with ALF, the concept of failure to rescue highlights the need to improve prevention, early detection, and timely management of medical complications developing early in the hospital stay.
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Affiliation(s)
- Filipe S Cardoso
- Departments of Hepatology and Critical Care, Curry Cabral Hospital, Nova Medical School, Lisbon, Portugal
| | - William M Lee
- Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada
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Lemmer P, Sowa J, Bulut Y, Strnad P, Canbay A. Mechanisms and aetiology-dependent treatment of acute liver failure. Liver Int 2025; 45:e15739. [PMID: 37752801 PMCID: PMC11815625 DOI: 10.1111/liv.15739] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 09/01/2023] [Accepted: 09/05/2023] [Indexed: 09/28/2023]
Abstract
This review compiles the mechanisms of acute liver failure (ALF) as well as the current and potential therapeutic approaches, including aetiology-specific treatment, and the issues encountered with such approaches. On a cellular level, ALF is characterized by massive hepatocyte death due to different types of cellular demise. Compensatory hyperplasia and functional recovery are possible when the regenerative capacity is sufficient to sustain hepatic function. ALF has a high mortality of about 30% and can lead to death in a very short time despite maximum therapeutic intervention. Besides aetiology-specific therapy and intensive care, the therapeutic option of emergency liver transplantation has significantly improved the prognosis of patients with ALF. However, due to limiting factors such as organ shortage, many patients die on the waiting list. In addition to graft assessment, machine perfusion may have the potential to recondition marginal organs and thus expand the organ donor pool.
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Affiliation(s)
- Peter Lemmer
- Department of Gastroenterology, Hepatology, and Infectious DiseasesOtto‐von‐Guericke University MagdeburgMagdeburgGermany
| | - Jan‐Peter Sowa
- Department of MedicineUniversitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr University BochumBochumGermany
| | - Yesim Bulut
- Department of MedicineUniversitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr University BochumBochumGermany
| | - Pavel Strnad
- Department of Internal Medicine IIIUniversity Hospital RWTH AachenAachenGermany
| | - Ali Canbay
- Department of MedicineUniversitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr University BochumBochumGermany
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Röhlen N, Thimme R. [Acute Liver Failure]. Dtsch Med Wochenschr 2025; 150:371-384. [PMID: 40086863 DOI: 10.1055/a-2301-8259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
Acute liver failure (ALF) is a severe, potentially reversible form of liver insufficiency, which is defined by the occurrence of hepatic coagulopathy and hepatic encephalopathy in patients with no previous hepatic disease. Acute liver failure is preceded by severe acute liver injury (ALI) with an increase in transaminases, jaundice, and deterioration in general condition over a period of hours to weeks. Every year 200-500 people develop ALF in Germany, most frequently on the background of toxic liver injury (e.g. drug induced liver injury). Other potential causes include viral infections (e.g. hepatitis A and B), autoimmune hepatitis, Budd-Chiari Syndrome or Wilson's disease. Patients usually present at the stage of acute liver damage. Initial diagnostics should include a detailed medical history, clinical examination, laboratory diagnostics and abdominal sonography. The course of acute liver failure is very difficult to predict, so all patients with severe acute liver damage should be evaluated for transfer to a center. At the latest when hepatic encephalopathy occurs and thus when all the definition criteria of acute liver failure are met, the patient should be transferred to a liver transplant center immediately. While specific medical therapies may be available in the early stages of the disease, depending on the etiology, the focus in advanced stages is on preventing complications and treating associated organ dysfunctions. In progressive cases, liver transplantation is often the only life-saving measure. Overall, the mortality rate in Germany is 47%, and approximately 8% of annual liver transplants in the European Union are performed due to ALF.
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Triantafyllou E, Gudd CLC, Possamai LA. Immune-mediated liver injury from checkpoint inhibitors: mechanisms, clinical characteristics and management. Nat Rev Gastroenterol Hepatol 2025; 22:112-126. [PMID: 39663461 DOI: 10.1038/s41575-024-01019-7] [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: 11/05/2024] [Indexed: 12/13/2024]
Abstract
Immunotherapy has changed the treatment landscape for patients with cancer in the past decade. Immune checkpoint inhibitor (ICI)-based therapies have proven effective in a range of malignancies, including liver and gastrointestinal cancers, but they can cause diverse off-target organ toxicities. With the increasingly wider application of these drugs, immune-mediated liver injury from ICIs has become a commonly encountered challenge in clinical hepatology and gastroenterology. In this Review, we discuss the evidence from human and animal studies on the immunological mechanisms of immune-mediated liver injury from ICIs and summarize its clinical features and practical considerations for its management.
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Affiliation(s)
- Evangelos Triantafyllou
- Section of Hepatology and Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
| | - Cathrin L C Gudd
- Section of Hepatology and Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Lucia A Possamai
- Section of Hepatology and Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
- Liver and Antiviral Unit, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
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Hudson D, Valentin Cortez FJ, León IHDD, Malhi G, Rivas A, Afzaal T, Rad MR, Diaz LA, Khan MQ, Arab JP. Advancements in MELD Score and Its Impact on Hepatology. Semin Liver Dis 2024. [PMID: 39515784 DOI: 10.1055/a-2464-9543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
There continues to be an ongoing need for fair and equitable organ allocation. The Model for End-Stage Liver Disease (MELD) score has evolved as a calculated framework to evaluate and allocate patients for liver transplantation objectively. The original MELD score has undergone multiple modifications as it is continuously scrutinized for its accuracy in objectively representing the clinical context of patients with liver disease. Several refinements and iterations of the score have been developed, including the widely accepted MELD-Na score. In addition, the most recent updated iteration, MELD 3.0, has been created. The MELD 3.0 calculator incorporates new variables such as patient sex and serum albumin levels and assigns new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is anticipated that the use of MELD 3.0 scores will reduce overall waitlist mortality and enhance access for female liver transplant candidates. However, despite the emergence of the MELD score as one of the most objective measures for fair organ allocation, various countries and healthcare systems employ alternative methods for stratification and organ allocation. This review article will highlight the origins of the MELD score, its iterations, the current MELD 3.0, and future directions for managing liver transplantation organ allocation. LAY SUMMARY: Organ donation is crucial for the management of patients unwell with liver disease, but organs must be allocated fairly and equitably. One method used for this is the Model for End-Stage Liver Disease (MELD) score, which helps objectively decide which patient is a candidate for liver transplant. Over time, the MELD score has been refined to better reflect patients' needs. For example, the latest version, MELD 3.0, now considers factors like nutrition and gender. This should ensure that more patients, especially females, are candidates and receive appropriate access to liver transplantation. However, not every country uses the MELD score. Some countries have created their own scoring systems based on local research. This review will explain where the MELD score came from, how it has changed, the current characteristics of the MELD 3.0 score, and what the future might hold for organ allocation in liver transplants.
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Affiliation(s)
- David Hudson
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | | | - Ivonne Hurtado Díaz de León
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Gurpreet Malhi
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | - Angelica Rivas
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Tamoor Afzaal
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | - Mahsa Rahmany Rad
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology and Hepatology, MASLD Research Center, University of California San Diego, San Diego, California
| | - Mohammad Qasim Khan
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia
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Panackel C, Raja K, Fawas M, Jacob M. Prognostic models in acute liver failure-historic evolution and newer updates "prognostic models in acute liver failure". Best Pract Res Clin Gastroenterol 2024; 73:101957. [PMID: 39709212 DOI: 10.1016/j.bpg.2024.101957] [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: 08/18/2024] [Accepted: 10/22/2024] [Indexed: 12/23/2024]
Abstract
Acute liver failure (ALF) is a rare and dynamic syndrome occurring as a sequela of severe acute liver injury (ALI). Its mortality ranges from 50% to 75% based on the aetiology, patients age and severity of encephalopathy at admission. With improvement in intensive care techniques, transplant-free survival in ALF has improved over time. Timely recognition of patients who are unlikely to survive with medical intervention alone is crucial since these individuals may rapidly develop multiorgan failure and render liver transplantation futile. Various predictive models, biomarkers and AI-based models are currently used in clinical practice, each with its fallacies. The King's College Hospital criteria (KCH) were initially established in 1989 to identify patients with acute liver failure (ALF) caused by paracetamol overdose or other causes who are unlikely to improve with conventional treatment and would benefit from a liver transplant. Since then, various models have been developed and validated worldwide. Most models include age, aetiology of liver disease, encephalopathy grade, and liver injury markers like INR, lactate, factor V level, factor VIII/V ratio and serum bilirubin. But none of the currently available models are dynamic and lack accuracy in predicting transplant free survival. There is an increasing interest in developing prognostic serum biomarkers that when used alone or in combination with clinical models enhance the accuracy of predicting outcomes in ALF. Genomics, transcriptomics, proteomics, and metabolomics as well as machine learning and artificial intelligence (AI) algorithms are areas of interest for developing higher-precision predictive models. Overall, the future of prognostic models in ALF is promising, with ongoing research paving the way for more accurate, personalized, and dynamic risk assessment tools that can potentially save lives in this challenging condition. This article summarizes the history of prognostic models in ALF and future trends.
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Affiliation(s)
| | | | - Mohammed Fawas
- Aster Integrated Liver Care, Aster Medcity, Kochi, India
| | - Mathew Jacob
- Aster Integrated Liver Care, Aster Medcity, Kochi, India
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11
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Gurakar A, Conde Amiel I, Ozturk NB, Artru F, Selzner N, Psoter KJ, Dionne JC, Karvellas C, Rajakumar A, Saner F, Subramanian RM, Sun LY, Dhawan A, Coilly A. An international, multicenter, survey-based analysis of practice and management of acute liver failure. Liver Transpl 2024; 30:1217-1225. [PMID: 38775498 DOI: 10.1097/lvt.0000000000000402] [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] [Received: 02/23/2024] [Accepted: 05/02/2024] [Indexed: 06/30/2024]
Abstract
Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and HE in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on the management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. A total of 267 physicians completed the survey, with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver-intensive or transplant-intensive care unit ( p < 0.001). The median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, 1 week in 37.6%, and more than 1 week in 9.6% ( p < 0.001). Deceased donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria, and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of patients with ALF, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring HE and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare, multicenter studies are valuable for identifying global practice.
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Affiliation(s)
- Ahmet Gurakar
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Isabel Conde Amiel
- Department of Medicine, Hepatology and Liver Transplantation Unit, Hospital Universitario y Politécnico La Fe, IIS La Fe, Valencia, Spain
- Ciberehd, Instituto de Salud Carlos III, Madrid, Spain
| | - N Begum Ozturk
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, Michigan, USA
| | - Florent Artru
- Liver Department, Rennes University Hospital, University of Rennes, Inserm U1241 NuMeCan, Rennes, France
| | - Nazia Selzner
- Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Kevin J Psoter
- Department of Pediatrics, Division of General Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Joanna C Dionne
- Department of Medicine, Department of Health Research Medicine, Evidence and Impact, Divisions of Gastroenterology/Critical Care Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Constantine Karvellas
- Divisions of Hepatology and Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Akila Rajakumar
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, Tamil Nadu, India
| | - Fuat Saner
- Organ Transplant Center of Excellence, King Faisal Specialized Hospital & Research Center, Riyadh, Saudi Arabia
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, Essen, Germany
| | - Ram M Subramanian
- Liver Transplantation & Liver Critical Care Services, Emory University, Atlanta, Georgia, USA
| | - Li-Ying Sun
- Critical Liver Diseases & Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Anil Dhawan
- Department of Pediatrics and Pediatric Liver GI and Nutrition Center and Mowat Labs, King's College Hospital, London, UK
| | - Audrey Coilly
- Paul-Brousse Hospital, Public Hospitals of Paris, FHU Hépatinov, Villejuif, France
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12
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Kulkarni AV, Gustot T, Reddy KR. Liver transplantation for acute liver failure and acute-on-chronic liver failure. Am J Transplant 2024; 24:1950-1962. [PMID: 39094950 DOI: 10.1016/j.ajt.2024.07.012] [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] [Received: 03/12/2024] [Revised: 07/11/2024] [Accepted: 07/11/2024] [Indexed: 08/04/2024]
Abstract
Acute liver failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and, thus, need to be compared and contrasted for appropriate management. There has been a significant improvement in the outcomes of these patients undergoing liver transplantation (LT). Survival post-LT for ALF and ACLF ranges between 90% and 95% and 80% and 90% at 1 year, futility criteria have been described in both ALF and ACLF where organ failures define survival. Plasma exchange and continuous renal replacement therapy may serve as bridging therapies. Identifying the futility of LT is as necessary as the utility of LT in patients with ALF and ACLF. The role of regenerative therapies such as granulocyte colony-stimulating factors in ACLF and hepatocyte and xenotransplantation in both conditions remains uncertain. Measures to increase the donor pool through increasing deceased donor transplants in Asian countries, living donations in Western countries, auxiliary liver transplants, and ABO-incompatible liver transplants are necessary to improve the survival of these patients. In this review, we discuss the similarities and differences in clinical characteristics and the timing and outcomes of LT for ALF and ACLF, briefly highlighting the role of bridging therapies and providing an overview of recent advances in the management of ALF and ACLF.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Thierry Gustot
- Liver Transplant Unit, Department of Gastroenterology, Hepato-Pancreatology and Digestive Oncology, HUB Hôpital Erasme, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium; Inserm Unité 1149, Centre de Recherche sur l'inflammation (CRI), Paris, France; UMR S_1149, Université Paris Diderot, Paris, France
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, USA.
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13
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Hayashi M, Abe K, Sugaya T, Takahata Y, Fujita M, Takahashi A, Ohira H. Circulating myostatin levels as a prognostic biomarker in patients with acute liver failure and late-onset hepatic failure. Hepatol Res 2024; 54:1078-1088. [PMID: 38656751 DOI: 10.1111/hepr.14051] [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: 02/25/2024] [Revised: 03/30/2024] [Accepted: 04/05/2024] [Indexed: 04/26/2024]
Abstract
AIM Myostatin is a myokine involved in muscle mass regulation. The associations between circulating myostatin levels and clinical characteristics in patients with acute liver failure (ALF) and late-onset hepatic failure (LOHF) are unclear. METHODS In this retrospective study, 51 patients with ALF or LOHF were included. Serum myostatin was measured using an enzyme-linked immunosorbent assay. RESULTS Myostatin levels were significantly lower in patients with ALF and LOHF than in controls (ALF/LOHF: 2522 pg/mL, controls: 3853 pg/mL, p = 0.003). The prevalence of low myostatin in deceased patients was significantly higher than that in spontaneous survivors and patients who underwent liver transplantation. Patients with low myostatin levels had a high incidence of complications. There was a positive correlation between the psoas muscle index and serum myostatin levels. Patients with low myostatin levels had shorter 1-year transplant-free survival and shorter 1-year overall survival than patients with high myostatin levels. Low serum myostatin levels were associated with poor prognosis independent of the Japanese scoring system for ALF ≥3, King's College criteria, or model for end-stage liver disease score >30.5. The combination of serum myostatin levels and prognostic models for ALF significantly stratified patients according to 1-year prognosis. CONCLUSIONS Low serum myostatin levels were associated with a low psoas muscle index, complication rate, and poor prognosis in patients with ALF and LOHF. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with ALF and LOHF.
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Affiliation(s)
- Manabu Hayashi
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan
| | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan
| | - Tatsuro Sugaya
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan
| | - Yosuke Takahata
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan
| | - Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan
| | - Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University, Fukushima, Japan
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14
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Wang L, Liu P, Han Y. Serum microRNA-181a Expression Level in Patients with Acute Liver Failure and Its Correlation with Prognosis. Int J Gen Med 2024; 17:4815-4822. [PMID: 39440101 PMCID: PMC11495206 DOI: 10.2147/ijgm.s478709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 09/13/2024] [Indexed: 10/25/2024] Open
Abstract
Objective This paper examined miR-181a expression in the serum of patients with acute liver failure (ALF) and investigated the impact of its expression in the prognosis of ALF patients. Methods A total of 112 ALF patients (ALF group) and 100 healthy controls during the same period (control group) were recruited as study subjects, and ALF patients were separated into the survival group and the death group. Serum ALT, AST, SCr, TBil, PTA, and International Normalized Ratio (INR) indices as well as serum miR-181a expression were assessed by using a fully automated biochemistry analyzer and RT-qPCR. Patients in the ALF group were evaluated using the Model for End-Stage Liver Disease (MELD) score. Correlation between serum miR-181a expression and MELD scores of ALF patients was processed by Pearson correlation analysis, and the diagnostic value of miR-181a level for the occurrence of ALF was estimated by ROC curve analysis. Multivariate logistic regression analysis was executed to assess the factors influencing the occurrence of death in ALF patients. Results ALF patients had higher levels of ALT, AST, TBiL, SCr, INR and miR-181a and lower PTA levels in comparison to healthy controls. Serum miR-181a expression level in ALF patients revealed a significant positive correlation with MELD score. Multivariate logistic regression analysis unveiled that TBil, INR, SCr, and miR-181a were the independent risk factors for the occurrence of death in ALF patients, and that PTA was an independent protective factor for the prognosis of ALF patients. miR-181a exhibited a favorable diagnostic value in ALF and its prognosis. Conclusion miR-181a expression is upregulated in the serum of ALF patients, and it can be utilized as an indicator for ALF diagnostic and prognostic assessment.
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Affiliation(s)
- Lili Wang
- Department of Liver Disease, Qingdao Sixth People’s Hospital, Qingdao, Shandong, 266033, People’s Republic of China
| | - Pingping Liu
- Clinical Laboratory, Qingdao Sixth People’s Hospital, Qingdao, Shandong, 266033, People’s Republic of China
| | - Yidi Han
- Department of Liver Disease, Qingdao Sixth People’s Hospital, Qingdao, Shandong, 266033, People’s Republic of China
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15
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Cardoso FS, Toapanta D, Jimenez N, Fidalgo P, Figueiredo A, Valdivieso M, Germano N, Rule JA, Lee WM, Abraldes JG, Reverter E, Karvellas CJ. Ammonia and urea metabolism in acute liver failure: A multicentre cohort study. Liver Int 2024; 44:2651-2659. [PMID: 39016195 PMCID: PMC11610480 DOI: 10.1111/liv.16043] [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: 01/05/2024] [Revised: 06/29/2024] [Accepted: 07/06/2024] [Indexed: 07/18/2024]
Abstract
BACKGROUND & AIMS Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied. METHODS Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight. RESULTS Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p < .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R2 of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p = .024) or lower (p < .001) urea was independently associated with lower explanted liver weight. CONCLUSIONS Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.
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Affiliation(s)
- Filipe S. Cardoso
- Transplant Unit, Intensive Care Unit, Curry Cabral Hospital, Nova Medical School, Lisbon, Portugal
- Intensive Care Unit, Curry Cabral Hospital, Lisbon, Portugal
| | - David Toapanta
- Liver ICU, Liver Unit, Clinic Hospital, Barcelona, Spain
| | | | - Pedro Fidalgo
- Intensive Care Unit, São Francisco Xavier Hospital, Lisbon, Portugal
| | - António Figueiredo
- Pathological Anatomy Department, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Nuno Germano
- Intensive Care Unit, Curry Cabral Hospital, Lisbon, Portugal
| | - Jody A. Rule
- Department of Internal Medicine, University of Texas Southwestern Medical Center, TX, US
| | - William M. Lee
- Department of Internal Medicine, University of Texas Southwestern Medical Center, TX, US
| | | | - Enric Reverter
- Liver ICU, Liver Unit, Clinic Hospital, Barcelona, Spain
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16
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Wang X, Zheng MY, He HY, Zhu HL, Zhao YF, Chen YH, Xu ZY, Yang JH, Sun DL. Quality Evaluation of Guidelines for the Diagnosis and Treatment of Liver Failure. Crit Care Med 2024; 52:1624-1632. [PMID: 38832833 PMCID: PMC11392122 DOI: 10.1097/ccm.0000000000006346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2024]
Abstract
OBJECTIVES This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.
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Affiliation(s)
- Xia Wang
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Meng-Yao Zheng
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Hai-Yu He
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Hui-Ling Zhu
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Ya-Fang Zhao
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yu-Hang Chen
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Zhi-Yuan Xu
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jin-Hui Yang
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Da-Li Sun
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming, China
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17
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Ludusanu A, Ciuntu BM, Tanevski A, Fotache M, Radu VD, Burlacu A, Tinica G. Liver Status Assessment After Coronary Artery Bypass Grafting. Cureus 2024; 16:e72210. [PMID: 39583384 PMCID: PMC11583995 DOI: 10.7759/cureus.72210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/23/2024] [Indexed: 11/26/2024] Open
Abstract
Background Coronary artery bypass grafting (CABG) is a common surgical intervention used to treat severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has become a widely used prognostic index for assessing the severity of liver disease and prioritizing liver transplantation. However, its utility in predicting outcomes in cardiac surgery procedures has not been extensively evaluated. Methods This retrospective study gathered data on patients who underwent CABG or CABG combined with other concomitant surgical interventions, such as carotid common or external carotid artery endarterectomy, thoracic aortic aneurysm repair, and aortic or mitral valve replacement or decalcification procedures, at a single tertiary care facility from January 2011 to December 2020. Researchers collected demographic, clinical, and laboratory information, including MELD score and European System for Cardiac Operative Risk Evaluation (EuroSCORE) data. The patients were divided into two groups: the first group included only those who underwent CABG, while the second group comprised patients who underwent CABG along with other concomitant cardiac interventions. Results The MELD score at discharge was significantly higher in the CABG and other interventions group compared to the CABG-only group (median = 14.09, IQR = 7.41-18.7 vs. median = 6.41, IQR = 4.61-9.44, p < 0.001). However, the difference in MELD score at admission between the two groups was not statistically significant (p = 0.328). A p-value < 0.05 was considered statistically relevant, indicating that liver function worsened postoperatively in the patients with additional interventions. The EuroSCORE was also significantly higher in the CABG and other interventions group, suggesting a higher surgical risk as expected (median = 5.74, IQR = 3.54-11.47 vs. median = 3.34, IQR = 1.97-5.66, p < 0.001). Additionally, differences in laboratory parameters, especially coagulation and hemostasis indicators throughout the postoperative period, including the ICU stay (divided into four equal periods based on each patient's total ICU length of stay) and at discharge, indicate a more complex biological state in patients with additional interventions. These findings may have implications for perioperative management and long-term outcomes. Conclusions The elevated MELD score in patients undergoing CABG with additional interventions emphasizes the need for close monitoring of liver function and coagulation status. Evaluating hepatic status preoperatively would be beneficial, and incorporating liver-protective strategies could help mitigate postoperative repercussions. It may also be useful to include liver function parameters in existing cardiovascular risk scores to improve risk assessment.
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Affiliation(s)
- Andreea Ludusanu
- Anatomy, Grigore T. Popa University of Medicine and Pharmacy, Iași, ROU
| | - Bogdan M Ciuntu
- General Surgery, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iași, ROU
| | - Adelina Tanevski
- General Surgery, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iași, ROU
| | - Marin Fotache
- Faculty of Economics and Business Administration, Alexandru Ioan Cuza University, Iași, ROU
| | - Viorel D Radu
- Urology, Grigore T. Popa University of Medicine and Pharmacy, Iași, ROU
| | - Alexandru Burlacu
- Cardiology, Institute of Cardiovascular Diseases "Prof. Dr. George I. M. Georgescu", Iași, ROU
| | - Grigore Tinica
- Cardiac Surgery, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iași, ROU
- Cardiac Surgery, Faculty of Medicine, Institute of Cardiovascular Diseases "Prof. Dr. George I. M. Georgescu", Iași, ROU
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18
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Bhatti ABH, ul Haq N, Mehmood N, Hassan D, Ahmed A, Malik WT, Zia HH, Salih M, Khan NY, Ilyas A, Khan NA. Impact of Renal Replacement Therapy on Outcomes of Living Donor Liver Transplantation for Acute Liver Failure: A Cohort Study. Int J Hepatol 2024; 2024:8422308. [PMID: 39268546 PMCID: PMC11392576 DOI: 10.1155/2024/8422308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 07/30/2024] [Accepted: 08/21/2024] [Indexed: 09/15/2024] Open
Abstract
Despite the promising role of renal replacement therapy (RRT) in acute liver failure (ALF), high-risk patients need liver transplantation and remain at risk for death due to cerebral complications. The objective of this study was to report outcomes of living donor liver transplantation (LDLT) for ALF with perioperative RRT. This was a single-center retrospective cohort study. Out of 1167 LDLTs, 24 patients had ALF and met the King's College criteria for transplantation. They were categorized into no-RRT (n = 13) and RRT (n = 11) groups. We looked at 1-year posttransplant survival in these patients. The median serum ammonia level at the time of transplant in the no-RRT and RRT groups was 259.5 mcg/dL (222.7-398) and 70.6 mcg/dL (58.1-92.6) (p = 0.005). In the RRT group, serum ammonia level < 100 mcg/dL was achieved in all patients. Seven (53.8%) patients in the no-RRT group and 11/11 (100%) in the RRT group were extubated and regained full consciousness after LDLT (p = 0.013). The 90-day mortality was 6/13 (46.1%) and 2/11 (18.1%) (p = 0.211). There was no brainstem herniation-related mortality in the RRT group, that is, 5/13 (38.4%) and 0/11 (0%) (p = 0.030). The 1-year posttransplant survival was also significantly higher in the RRT group (p = 0.031). The use of RRT lowers serum ammonia levels and might reduce posttransplant mortality due to brainstem herniation.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Department of HPB Surgery and Liver TransplantationShifa International Hospital, Islamabad, Pakistan
| | - Nauman ul Haq
- Department of HPB Surgery and Liver TransplantationShifa International Hospital, Islamabad, Pakistan
| | - Nayyer Mehmood
- Department of NephrologyShifa International Hospital, Islamabad, Pakistan
| | - Danyal Hassan
- Department of NephrologyShifa International Hospital, Islamabad, Pakistan
| | - Arsalan Ahmed
- Department of NeurologyShifa International Hospital, Islamabad, Pakistan
| | - Wasim Tariq Malik
- Department of NeurologyShifa International Hospital, Islamabad, Pakistan
| | - Haseeb Haider Zia
- Department of HPB Surgery and Liver TransplantationShifa International Hospital, Islamabad, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and HepatologyShifa International Hospital, Islamabad, Pakistan
| | - Nusrat Yar Khan
- Department of HPB Surgery and Liver TransplantationShifa International Hospital, Islamabad, Pakistan
| | - Abid Ilyas
- Department of Surgical Critical CareShifa International Hospital, Islamabad, Pakistan
| | - Nasir Ayub Khan
- Department of AnesthesiologyShifa International Hospital, Islamabad, Pakistan
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19
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Fernández J, Bassegoda O, Toapanta D, Bernal W. Acute liver failure: A practical update. JHEP Rep 2024; 6:101131. [PMID: 39170946 PMCID: PMC11337735 DOI: 10.1016/j.jhepr.2024.101131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/17/2024] [Accepted: 05/22/2024] [Indexed: 08/23/2024] Open
Abstract
Acute liver failure is a rare and dynamic condition, with a broad aetiology and an incompletely understood pathophysiology. Management of this life-threatening disease requires critical care and organ support and frequently early liver transplantation. Proper identification, prevention and treatment of complications such as intracranial hypertension and sepsis are critical to optimising outcomes. The identification of the cause of acute liver failure and the prompt initiation of the aetiological treatment can also improve prognosis. Survival has progressively improved in parallel to advances in medical treatment. Intracranial hypertension complicating hepatic encephalopathy is less frequent than in the past and intracranial pressure monitoring now relies on non-invasive techniques. Current prognostic models have good accuracy to identify patients who will die without liver transplantation but are not able to identify those in whom transplantation is futile. New prognostic markers to select patients for transplantation are still in the pipeline. Therapeutic plasma exchange and, in some centers, early renal replacement therapy are well established treatments for the disease. The use of other artificial liver devices in clinical practice is not supported by evidence. This review is intended to provide a clinical update on the management of acute liver failure, incorporating the most recent advances in the field.
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Affiliation(s)
- Javier Fernández
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Spain
- EF Clif, EASL-CLIF Consortium, Barcelona, Spain
| | - Octavi Bassegoda
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Spain
| | - David Toapanta
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Spain
| | - William Bernal
- Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital, London, United Kingdom
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20
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Brozat JF, Pohl J, Engelmann C, Tacke F. [Liver transplantation in acute and acute-on-chronic liver failure]. Med Klin Intensivmed Notfmed 2024; 119:484-492. [PMID: 39043956 DOI: 10.1007/s00063-024-01158-4] [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] [Received: 05/08/2024] [Accepted: 06/04/2024] [Indexed: 07/25/2024]
Abstract
Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are diseases with a rapidly progressive course and high mortality. Apart from treating the underlying triggers and intensive care measures, there are very limited therapeutic options for either condition. Liver transplantation is often the only life-saving treatment, but it cannot always be employed due to contraindications and severe disease progression. ACLF is characterized by underlying liver cirrhosis and typical triggers such as bacterial infections, bleeding, or alcohol binges. ALF occurs in previously healthy livers, usually as a result of purely hepatotoxic events. Disease differences are also reflected in the course and regulations of liver transplantation. Newer prognostic parameters and prioritization programs for ACLF can help improve both waiting list mortality and outcomes after transplantation.
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Affiliation(s)
- Jonathan F Brozat
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland
| | - Julian Pohl
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland
| | - Cornelius Engelmann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland
| | - Frank Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland.
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21
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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22
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Maiwall R, Kulkarni AV, Arab JP, Piano S. Acute liver failure. Lancet 2024; 404:789-802. [PMID: 39098320 DOI: 10.1016/s0140-6736(24)00693-7] [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] [Received: 09/12/2023] [Revised: 03/13/2024] [Accepted: 04/03/2024] [Indexed: 08/06/2024]
Abstract
Acute liver failure (ALF) is a life-threatening disorder characterised by rapid deterioration of liver function, coagulopathy, and hepatic encephalopathy in the absence of pre-existing liver disease. The cause of ALF varies across the world. Common causes of ALF in adults include drug toxicity, hepatotropic and non-hepatotropic viruses, herbal and dietary supplements, antituberculosis drugs, and autoimmune hepatitis. The cause of liver failure affects the management and prognosis, and therefore extensive investigation for cause is strongly suggested. Sepsis with multiorgan failure and cerebral oedema remain the leading causes of death in patients with ALF and early identification and appropriate management can alter the course of ALF. Liver transplantation is the best current therapy, although the role of artificial liver support systems, particularly therapeutic plasma exchange, can be useful for patients with ALF, especially in non-transplant centres. In this Seminar, we discuss the cause, prognostic models, and management of ALF.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Juan Pablo Arab
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
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23
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Sato-Espinoza K, Berrospi D, Diaz-Ferrer J. Case report: liver failure as a debut of autoimmune hepatitis triggered by dengue virus in a pregnant woman. Rev Peru Med Exp Salud Publica 2024; 41:209-213. [PMID: 39166644 PMCID: PMC11300697 DOI: 10.17843/rpmesp.2024.412.13485] [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] [Received: 11/26/2023] [Accepted: 04/17/2024] [Indexed: 08/23/2024] Open
Abstract
Autoimmune hepatitis (AIH) is a complex condition with unclear origins, involving genetic susceptibility and environmental triggers that lead to immune system dysfunction. We report a case of a pregnant woman from a mosquito-borne disease-endemic area who presented jaundice, abdominal pain, and pruritus, complicated by acute liver failure. Immunological markers showed AIH triggered by dengue virus infection, which was confirmed by a positive IgM test. Treatment with supportive care followed by steroids and azathioprine resulted in favorable outcomes, averting the need for a liver transplant. Although AIH can be triggered by viruses, the role of dengue in its pathogenesis remains poorly understood. Regular clinical monitoring is vital for managing AIH, particularly during pregnancy, due to variable immune status and treatment responses. Further research is necessary to understand the link between dengue infection and AIH. Individualized treatment strategies are crucial, especially during pregnancy, in order to ensure favorable outcomes.
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Affiliation(s)
- Karina Sato-Espinoza
- Escuela de Medicina. Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru.Universidad Peruana de Ciencias AplicadasEscuela de MedicinaUniversidad Peruana de Ciencias Aplicadas (UPC)LimaPeru
| | - Diego Berrospi
- Facultad de Medicina, Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru.Universidad Peruana Cayetano HerediaFacultad de MedicinaUniversidad Peruana Cayetano Heredia (UPCH)LimaPeru
| | - Javier Diaz-Ferrer
- Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.Hospital Nacional Edgardo Rebagliati MartinsLimaPeru
- Facultad de Medicina, Universidad San Martín de Porres, Lima, Peru.Universidad de San Martín de PorresFacultad de MedicinaUniversidad San Martín de PorresLimaPeru
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24
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Cavazza A, Triantafyllou E, Savoldelli R, Mujib S, Jerome E, Trovato FM, Artru F, Sheth R, Huang XH, Ma Y, Dazzi F, Pirani T, Antoniades CG, Lee WM, McPhail MJ, Karvellas CJ, the US Acute Liver Failure Study Group. Macrophage activation markers are associated with infection and mortality in patients with acute liver failure. Liver Int 2024; 44:1900-1911. [PMID: 38588014 PMCID: PMC11466005 DOI: 10.1111/liv.15928] [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: 11/03/2023] [Revised: 03/18/2024] [Accepted: 03/21/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND AND AIMS Acute liver failure is a multisystem disorder with a high mortality and frequent need for emergency liver transplantation. Following massive innate immune system activation, soluble markers of macrophage activation are released during liver damage and their association with disease severity and prognosis requires exploration. METHODS Patients ALF from the United States Acute Liver Failure Study Group (USALFSG, n = 224) and King's College Hospital (n = 40) together with healthy controls (HC, n = 50) were recruited. Serum from early (Days 1-3) and late (>Day 3) time points were analysed for MAMs by enzyme-linked immunosorbent assay correlated to markers of illness severity and 21-day spontaneous survival. Surface expression phenotyping was performed via Flow Cytometry on CD14+ monocytes. RESULTS All MAMs serum concentrations were significantly higher in ALF compared to controls (p < .0001). sCD206 concentration was higher in early and late stages of the disease in patients with bacteraemia (p = .002) and infection in general (p = .006). In MELD-adjusted multivariate modelling, sCD206 and sCD163 were independently associated with mortality. CD14+ monocyte expression of CD206 (p < .001) was higher in patients with ALF compared with controls and correlated with SOFA score (p = .018). sCD206 was independently validated as a predictor of infection in an external cohort. CONCLUSIONS sCD206 is increased in serum of ALF patients with infections and poor outcome and is upregulated on CD14+ monocytes. Later measurements of sCD163 and sCD206 during the evolution of ALF have potential as mechanistic predictors of mortality. sCD206 should be explored as a biomarker of sepsis and mortality in ALF.
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Affiliation(s)
- Anna Cavazza
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Evangelos Triantafyllou
- Section of Hepatology and Gastroenterology, Department of Metabolism, Digestion and ReproductionImperial College LondonLondonUK
| | - Roberto Savoldelli
- School of Cardiovascular and Metabolic Medicine and ScienceKing's College LondonLondonUK
| | - Salma Mujib
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Ellen Jerome
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Francesca M. Trovato
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Florent Artru
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Roosey Sheth
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Xiao Hong Huang
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
| | - Yun Ma
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
| | - Francesco Dazzi
- School of Cardiovascular and Metabolic Medicine and ScienceKing's College LondonLondonUK
| | - Tasneem Pirani
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Charalambos G. Antoniades
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - William M. Lee
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Mark J. McPhail
- Department of Inflammation Biology, School of Inflammation and Microbial Science, Institute of Liver StudiesKing's College LondonLondonUK
- Liver Intensive Therapy UnitInstitute of Liver Studies, King's College HospitalLondonUK
| | - Constantine J. Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care MedicineUniversity of AlbertaEdmontonCanada
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25
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Umbaugh DS, Nguyen NT, Curry SC, Rule JA, Lee WM, Ramachandran A, Jaeschke H, Acute Liver Failure Study Group.. The chemokine CXCL14 is a novel early prognostic biomarker for poor outcome in acetaminophen-induced acute liver failure. Hepatology 2024; 79:1352-1364. [PMID: 37910653 PMCID: PMC11061265 DOI: 10.1097/hep.0000000000000665] [Citation(s) in RCA: 1] [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: 08/29/2023] [Accepted: 10/12/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND AND AIMS Patients with acetaminophen-induced acute liver failure are more likely to die while on the liver transplant waiting list than those with other causes of acute liver failure. Therefore, there is an urgent need for prognostic biomarkers that can predict the need for liver transplantation early after an acetaminophen overdose. APPROACH AND RESULTS We evaluated the prognostic potential of plasma chemokine C-X-C motif ligand 14 (CXCL14) concentrations in patients with acetaminophen (APAP) overdose (n=50) and found that CXCL14 is significantly higher in nonsurviving patients compared to survivors with acute liver failure ( p < 0.001). Logistic regression and AUROC analyses revealed that CXCL14 outperformed the MELD score, better discriminating between nonsurvivors and survivors. We validated these data in a separate cohort of samples obtained from the Acute Liver Failure Study Group (n = 80), where MELD and CXCL14 had similar AUC (0.778), but CXCL14 demonstrated higher specificity (81.2 vs. 52.6) and positive predictive value (82.4 vs. 65.4) for death or need for liver transplantation. Next, combining the patient cohorts and using a machine learning training/testing scheme to mimic the clinical scenario, we found that CXCL14 outperformed MELD based on AUC (0.821 vs. 0.787); however, combining MELD and CXCL14 yielded the best AUC (0.860). CONCLUSIONS We find in 2 independent cohorts of acetaminophen overdose patients that circulating CXCL14 concentration is a novel early prognostic biomarker for poor outcomes, which may aid in guiding decisions regarding patient management. Moreover, our findings reveal that CXCL14 performs best when measured soon after patient presentation to the clinic, highlighting its importance for early warning of poor prognosis.
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Affiliation(s)
- David S. Umbaugh
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
| | - Nga T. Nguyen
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
| | - Steven C. Curry
- Department of Medical Toxicology, Banner – University Medical Center Phoenix, Phoenix, AZ, USA
- Department of Medicine, and Division of Clinical Data Analytics and Decision Support, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA
| | - Jody A. Rule
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - William M. Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Anup Ramachandran
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
| | - Hartmut Jaeschke
- Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
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Verma SK, Upadhyay P, Shukla S, Jain A, Shukla S, Patwa AK. Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model. Indian J Gastroenterol 2024; 43:459-467. [PMID: 38568354 DOI: 10.1007/s12664-024-01551-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 02/01/2024] [Indexed: 05/28/2024]
Abstract
OBJECTIVES Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. METHODS The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. RESULTS As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). CONCLUSION INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. CLINICAL TRIAL REGISTRY NUMBER Not applicable as this is a retrospective study.
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Affiliation(s)
- Sanjeev Kumar Verma
- Department of Pediatrics, King George Medical University, Lucknow, 226 003, India.
| | - Piyush Upadhyay
- Department of Pediatrics, Ram Manohar Lohiya Institute of Medical Sciences, Lucknow, 226 010, India
| | - Stuti Shukla
- Department of Pediatrics, King George Medical University, Lucknow, 226 003, India
| | - Amita Jain
- Department of Microbiology, King George Medical University, Lucknow, 226 003, India
| | - Suruchi Shukla
- Department of Microbiology, King George Medical University, Lucknow, 226 003, India
| | - Ajay Kumar Patwa
- Department of Medicine, King George Medical University, Lucknow, 226 003, India
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27
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Sithamparapillai K, Zachariah U, Eapen CE, Goel A. Plasma exchange improves survival in acute liver failure - An updated systematic review and meta-analysis focussed on comparing within single etiology. Indian J Gastroenterol 2024; 43:397-406. [PMID: 38691239 DOI: 10.1007/s12664-024-01557-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 02/15/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND AND OBJECTIVE Therapeutic plasma exchange (PLEX) is increasingly used in patients with acute liver failure (ALF) as either stand-alone therapy or bridge to liver transplantation. Etiology plays a major role in prognosis of these patients and benefit of PLEX may consequently differ across etiologies. This systematic review and meta-analysis aims to evaluate the efficacy of PLEX in treating ALF, focussing on studies with single etiology. METHODS We conducted a systematic literature search and identified studies comparing PLEX vs. standard medical therapy (SMT) for patients with ALF across all age groups. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023442383). Pooled risk-ratios were determined by Mantel-Haenszel method within a random effect model. Primary outcome was mortality at ≤ 60-days and 90 days. Secondary outcome was adverse events attributable to PLEX. RESULTS Eight studies (pooled sample size in PLEX arm: 284; randomized trials: 2; Comparative cohorts: 6) with retrievable data on ALF were included in this systematic review. Analysis showed that PLEX was associated with significant reduction in mortality at ≤ 60-days (RR 0.64; CI, 0.51-0.80; P < 0.001) and at 90-days (RR 0.67; CI, 0.50-0.90; P = 0.008) as compared to SMT. On sub-group analysis, the survival benefit was noted irrespective of the volume of plasma exchanged during PLEX. Three studies (pooled sample size in PLEX arm: 110; all comparative cohorts) were identified, which included patients with a single etiology for ALF. These studies included patients with Wilson's disease, rodenticidal hepatotoxicity and acute fatty liver of pregnancy. Pooled analysis of studies with single etiology ALF showed better reduction in ≤ 90-day mortality with PLEX (RR 0.53; CI, 0.37-0.74; P < 0.001). Studies reported no major side-effects attributable to PLEX. CONCLUSION PLEX is safe and improves survival, independent of the volumes utilized, in patients with ALF as compared to standard medical treatment. The survival benefit is especially pronounced in studies restricted to single etiology.
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Affiliation(s)
| | - Uday Zachariah
- Department of Hepatology, Christian Medical College, Vellore 632 004, India
| | - C E Eapen
- Department of Hepatology, Christian Medical College, Vellore 632 004, India
| | - Ashish Goel
- Department of Hepatology, Christian Medical College, Vellore 632 004, India.
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Singh KA, Kumar SE, Zachariah UG, Daniel D, David V, Subramani K, Pichamuthu K, Jacob E, Kodiatte TA, Eapen CE, Goel A. Single-Centre Experience With Low-Volume Plasma Exchange and Low-Dose Steroid to Treat Patients With Idiosyncratic Drug-Induced Acute Liver Failure. J Clin Exp Hepatol 2024; 14:101303. [PMID: 38076447 PMCID: PMC10698001 DOI: 10.1016/j.jceh.2023.11.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 11/03/2023] [Indexed: 02/07/2025] Open
Abstract
Background Idiosyncratic drug-induced liver injury (iDILI) causing acute liver failure (ALF) carries high short-term mortality and patients who meet King's College criteria for liver transplantation have 1-month survival of 34% without liver transplantation (PMID: 20949552). We present our experience with low-volume plasma exchange (PLEX-LV, 50% of estimated plasma volume exchanged per session) and low-dose steroid to treat iDILI ALF. Methods We retrospectively analysed data of patients with iDILI (diagnosed as per RUCAM score), treated with PLEX-LV and low-dose steroid (prednisolone: 10 mg OD, with rapid taper) in our department from 2016 to 2022. Baseline and dynamic parameters (post-PLEX) were assessed as predictors of 1-month liver transplantation-free survival. Results Twenty-two iDILI patients [probable: possible iDILI: 20:2, males: 9, age: 30 (14-84) years, median (range); MELD score: 30.5 (19-43)] underwent PLEX-LV for ALF during the study period. Causative agents were complementary and alternative medications (36%), antiepileptics (18%) antimicrobials (14%), antitubercular drugs (14%), antifungal drugs (9%) and others (9%). All patients had jaundice and encephalopathy; 9 patients also had ascites. None of the patients underwent liver transplantation. Study patients underwent 3 (1-7) PLEX sessions and 1.4 (0.6-1.6) litres of plasma was exchanged per session. One-month transplant-free survival was 59% (13/22) in the study population and 63% (12/19) among patients who fulfilled Kings College criteria for liver transplantation. Reduction of ≥25% in plasma von Willebrand factor (VWF) levels after PLEX-LV predicted improved survival (HR: 0.09, 95% CI: 0.01-0.65; AUROC: 0.81; 95% CI: 0.6-1.0). Conclusion Low-volume PLEX and low-dose steroid appears a promising treatment option in patients with iDILI-induced ALF not opting for liver transplantation. Dynamic changes in VWF level after PLEX predict 1-month survival in these patients.
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Affiliation(s)
- Kunwar A. Singh
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Santhosh E. Kumar
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Uday G. Zachariah
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Dolly Daniel
- Department of Transfusion Medicine, and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Vinoi David
- Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Kandasamy Subramani
- Department of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
| | - Kishore Pichamuthu
- Department of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
| | - Ebor Jacob
- Department of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
| | - Thomas A. Kodiatte
- Department of General Pathology, Christian Medical College, Vellore, Tamil Nadu, India
| | | | - Ashish Goel
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
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29
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Trovato FM, Artru F, Miquel R, Pirani T, McPhail MJW. Liver Elastography in Acute Liver Failure: A Pilot Study. Crit Care Explor 2024; 6:e1048. [PMID: 38343443 PMCID: PMC10857654 DOI: 10.1097/cce.0000000000001048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2024] Open
Abstract
OBJECTIVES We aimed to assess the feasibility and reliability of sequential ultrasonographic and elastographic monitoring in acute liver failure (ALF). DESIGN Observational study. SETTING ALF is a rare, life-threatening disease that requires intensive care admission and often liver transplant, where the accurate selection of patients is crucial. Liver elastography is a noninvasive tool that can measure hepatic stiffness, but previous results have been inconclusive in ALF. PATIENTS Patients admitted between October 2021 and March 2023 to the Liver Intensive Therapy Unit at King's College Hospital with ALF were recruited, with healthy control (HC) individuals and acute-on-chronic liver failure (ACLF) used as controls. INTERVENTION None. MEASUREMENTS Average shear wave velocity was recorded with ElastPQ on the right and left liver lobes and the spleen. Portal vein flow, hepatic artery resistive index, and peak systolic velocity were also recorded. Physiologic and histologic data were used for comparison. MAIN RESULTS Forty patients with ALF, 22 patients with ACLF, and 9 HC individuals were included in the study. At admission, liver stiffness measurement (LSM) of the right lobe was statistically different between HC individuals (5.6 ± 2 kPa), ALF (31.7 ± 17 kPa), and ACLF (76.3 ± 71 kPa) patients (ALF vs. ACLF, p = 0.0301). Spleen size and stiffness discriminated between ALF (10.4 ± 2 cm and 21.4 ± 16.6 kPa) and ACLF (14 ± 2.3 cm and 42.6 ± 26 kPa). At admission, LSM was not different between ALF patients who spontaneously survived versus patients who died or were transplanted in the following 90 days. However, the trend over the first 10 days of admission was different with a peak of LSM at day 5 in spontaneous survivors followed by reduction during the recovery phase. ALF patients with poor prognosis showed a persistently increased LSM. CONCLUSIONS In ALF stiffness peaks at day 5 of admission with subsequent reduction in patients spontaneously surviving, showing significant difference according to the prognosis at day 7 of admission. LSM might be useful in distinguishing acute from acute-on-chronic liver failure together with spleen volume and stiffness.
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Affiliation(s)
- Francesca M Trovato
- School of Immunology and Microbial Sciences, Department of Inflammation Biology, Kings College London, London, United Kingdom
- Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, United Kingdom
| | - Florent Artru
- School of Immunology and Microbial Sciences, Department of Inflammation Biology, Kings College London, London, United Kingdom
- Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, United Kingdom
| | - Rosa Miquel
- Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, United Kingdom
| | - Tasneem Pirani
- School of Immunology and Microbial Sciences, Department of Inflammation Biology, Kings College London, London, United Kingdom
- Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, United Kingdom
| | - Mark J W McPhail
- School of Immunology and Microbial Sciences, Department of Inflammation Biology, Kings College London, London, United Kingdom
- Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, United Kingdom
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Tavabie OD, Salehi S, Aluvihare VR. The challenges and potential in developing microRNA associated with regeneration as biomarkers to improve prognostication for liver failure syndromes and hepatocellular carcinoma. Expert Rev Mol Diagn 2024; 24:5-22. [PMID: 38059597 DOI: 10.1080/14737159.2023.2292642] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 12/05/2023] [Indexed: 12/08/2023]
Abstract
INTRODUCTION Determining the need for liver transplantation remains critical in the management of hepatocellular carcinoma (HCC) and liver failure syndromes (including acute liver failure and decompensated cirrhosis states). Conventional prognostic models utilize biomarkers of liver and non-liver failure and have limitations in their application. Novel biomarkers which predict regeneration may fulfil this niche. microRNA are implicated in health and disease and are present in abundance in the circulation. Despite this, they have not translated into mainstream clinical biomarkers. AREAS COVERED We will discuss current challenges in the prognostication of patients with liver failure syndromes as well as for patients with HCC. We will discuss biomarkers implicated with liver regeneration. We then provide an overview of the challenges in developing microRNA into clinically tractable biomarkers. Finally, we will provide a scoping review of microRNA which may have potential as prognostic biomarkers in liver failure syndromes and HCC. EXPERT OPINION Novel biomarkers are needed to improve prognostic models in liver failure syndromes and HCC. Biomarkers associated with liver regeneration are currently lacking and may fulfil this niche. microRNA have the potential to be developed into clinically tractable biomarkers but a consensus on standardizing methodology and reporting is required prior to large-scale studies.
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Affiliation(s)
| | - Siamak Salehi
- Institute of Liver Studies, King's College Hospital, London, UK
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Ozturk NB, Herdan E, Saner FH, Gurakar A. A Comprehensive Review of the Diagnosis and Management of Acute Liver Failure. J Clin Med 2023; 12:7451. [PMID: 38068503 PMCID: PMC10707329 DOI: 10.3390/jcm12237451] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/27/2023] [Accepted: 11/28/2023] [Indexed: 04/27/2025] Open
Abstract
Acute liver failure (ALF) is a rare and specific form of severe hepatic dysfunction characterized by coagulopathy and hepatic encephalopathy in a patient with no known liver disease. ALF carries a high morbidity and mortality. Careful attention should be given to hemodynamics and metabolic parameters along with the active surveillance of infections. Timely transfer and supportive management are important in an intensive care unit in a liver transplant center. Identifying patients who will and will not improve with medical management and may need emergent liver transplantation is critical. In this review, we provide a comprehensive update on the etiology, diagnosis, and management of ALF.
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Affiliation(s)
- Nazli Begum Ozturk
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, MI 48073, USA
| | - Emre Herdan
- Division of Gastroenterology and Hepatology, Johns Hopkins University Hospital, Baltimore, MD 21287, USA
| | - Fuat H. Saner
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, 45147 Essen, Germany
- Organ Transplant Center of Excellence, King Faisal Specialized Hospital & Research Center, Riyadh 11211, Saudi Arabia
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University Hospital, Baltimore, MD 21287, USA
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Kwan R, Chen L, Park MJ, Su Z, Weerasinghe SVW, Lee WM, Durkalski-Mauldin VL, Fontana RJ, Omary MB. The Role of Carbamoyl Phosphate Synthetase 1 as a Prognostic Biomarker in Patients With Acetaminophen-induced Acute Liver Failure. Clin Gastroenterol Hepatol 2023; 21:3060-3069.e8. [PMID: 37054752 PMCID: PMC10656042 DOI: 10.1016/j.cgh.2023.03.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 02/04/2023] [Accepted: 03/01/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND & AIMS Carbamoyl phosphate synthetase 1 (CPS1) is a highly abundant mitochondrial urea cycle enzyme that is expressed primarily in hepatocytes. CPS1 is constitutively and physiologically secreted into bile but is released into the bloodstream upon acute liver injury (ALI). Given its abundance and known short half-life, we tested the hypothesis that it may serve as a prognostic serum biomarker in the setting of acute liver failure (ALF). METHODS CPS1 levels were determined using enzyme-linked immunosorbent assay and immunoblotting of sera collected by the ALF Study Group (ALFSG) from patients with ALI and ALF (103 patients with acetaminophen and 167 non-acetaminophen ALF etiologies). A total of 764 serum samples were examined. The inclusion of CPS1 was compared with the original ALFSG Prognostic Index by area under the receiver operating characteristic curve analysis. RESULTS CPS1 values for acetaminophen-related patients were significantly higher than for non-acetaminophen patients (P < .0001). Acetaminophen-related patients who received a liver transplant or died within 21 days of hospitalization exhibited higher CPS1 levels than patients who spontaneously survived (P = .01). Logistic regression and area under the receiver operating characteristic analysis of CPS1 enzyme-linked immunosorbent assay values improved the accuracy of the ALFSG Prognostic Index, which performed better than the Model for End-Stage Liver Disease, in predicting 21-day transplant-free survival for acetaminophen- but not non-acetaminophen-related ALF. An increase of CPS1 but not alanine transaminase or aspartate transaminase, when comparing day 3 with day 1 levels was found in a higher percentage of acetaminophen transplanted/dead patients (P < .05). CONCLUSION Serum CPS1 determination provides a new potential prognostic biomarker to assess patients with acetaminophen-induced ALF.
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Affiliation(s)
- Raymond Kwan
- Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ; Switch Therapeutics, Inc, San Francisco, CA
| | - Lu Chen
- Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ; Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min-Jung Park
- Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea
| | - Zemin Su
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | | | - William M Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX
| | | | - Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI
| | - M Bishr Omary
- Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ; Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI.
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Biswas S, Shalimar. Liver Transplantation for Acute Liver Failure- Indication, Prioritization, Timing, and Referral. J Clin Exp Hepatol 2023; 13:820-834. [PMID: 37693253 PMCID: PMC10483009 DOI: 10.1016/j.jceh.2023.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 01/17/2023] [Indexed: 09/12/2023] Open
Abstract
Acute liver failure (ALF) is a major success story in gastroenterology, with improvements in critical care and liver transplant resulting in significant improvements in patient outcomes in the current era compared to the dismal survival rates in the pretransplant era. However, the ever-increasing list of transplant candidates and limited organ pool makes judicious patient selection and organ use mandatory to achieve good patient outcomes and prevent organ wastage. Several scoring systems exist to facilitate the identification of patients who need a liver transplant and would therefore need an early referral to a specialized liver unit. The timing of the liver transplant is also crucial as transplanting a patient too early would lead to those who would recover spontaneously receiving an organ (wastage), and a late decision might result in the patient becoming unfit for transplant (delisted) or have an advanced disease which would result in poor post-transplant outcomes. The current article reviews the indications and contraindications of liver transplant in ALF patients, the various prognostic scoring systems, etiology-specific outcomes, prioritization and timing of referral.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences New Delhi, India
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Shingina A, Mukhtar N, Wakim-Fleming J, Alqahtani S, Wong RJ, Limketkai BN, Larson AM, Grant L. Acute Liver Failure Guidelines. Am J Gastroenterol 2023; 118:1128-1153. [PMID: 37377263 DOI: 10.14309/ajg.0000000000002340] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 04/04/2023] [Indexed: 06/29/2023]
Abstract
Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.
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Affiliation(s)
- Alexandra Shingina
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Nizar Mukhtar
- Department of Gastroenterology, Kaiser Permanente, San Francisco, California, USA
| | - Jamilé Wakim-Fleming
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland Ohio, USA
| | - Saleh Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
- Liver Transplantation Unit, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
| | | | - Anne M Larson
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, Washington, USA
| | - Lafaine Grant
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
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Rakela JL, Karvellas CJ, Koch DG, Vegunta S, Lee WM. Acute Liver Failure: Biomarkers Evaluated by the Acute Liver Failure Study Group. Clin Transl Gastroenterol 2023; 14:e00565. [PMID: 36716224 PMCID: PMC10132708 DOI: 10.14309/ctg.0000000000000565] [Citation(s) in RCA: 2] [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: 12/19/2022] [Accepted: 01/20/2023] [Indexed: 01/31/2023] Open
Abstract
There has been a growing interest in identifying prognostic biomarkers that alone or with available prognostic models (King's College Criteria, KCC; MELD and ALFSG Prognostic Index) would improve prognosis in acute liver failure (ALF) patients being assessed for liver transplantation. The Acute Liver Failure Study Group (ALFSG) has evaluated 15 potential prognostic biomarkers: serum AFP; apoptosis-associated proteins; serum actin-free Gc-globulin; serum glycodeoxycholic acid; sRAGE/RAGE ligands; plasma osteopontin; circulating MBL, M-, L-, H-ficolin and CL-1; plasma galectin-9; serum FABP1; serum Lct2; miRNAs; factor V; thrombocytopenia, and sCD163. The ALFSG also has reported on 4 susceptibility biomarkers: keratins 8 and 18 (K8/K18) gene variants; polymorphisms of genes encoding putative APAP-metabolizing enzymes ( UGT1A1 , UGT 1A0 , UGT 2B15 , SULT1A1 , CYP2E1 , and CYP3A5 ) as well as CD44 and BHMT1 ; single nucleotide polymorphisms (SNPs) of genes associated with human behavior, rs2282018 in the arginine vasopressin ( AVP ) gene and rs11174811 in the AVP receptor 1A gene. Finally, rs2277680 of the CSCL16 gene in HBV-ALF patients. In conclusion, we have reviewed the prognostic and susceptibility biomarkers studied by the ALFSG. We suggest that a better approach to predicting the clinical outcome of an ALF patient will require a combination of biomarkers of pathogenic processes such as cell death, hepatic regeneration, and degree of inflammation that could be incorporated into prognostic models such as KCC, MELD or ALFSG PI.
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Affiliation(s)
- Jorge L. Rakela
- Division of Gastroenterology and Hepatology, Mayo Clinic in Arizona, Phoenix, Arizona, USA
| | - Constantine J. Karvellas
- Division of Gastroenterology (Liver Unit), Division of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - David G. Koch
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Suneela Vegunta
- Department of Internal Medicine, Mayo Clinic in Arizona, Phoenix, Arizona, USA
| | - William M. Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA
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Goel A, Lalruatsanga D, Himanshu D, Bharti V, Sharma D. Acute Liver Failure Prognostic Criteria: It's Time to Revisit. Cureus 2023; 15:e33810. [PMID: 36819396 PMCID: PMC9929612 DOI: 10.7759/cureus.33810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/15/2023] [Indexed: 01/18/2023] Open
Abstract
INTRODUCTION Acute liver failure (ALF) is a devastating disease, and patients are at a higher risk of death without liver transplantation. Indicators are needed to identify the risk of death in ALF, which will help in the timely referral of patients to specialized centers. Clichy criteriaand King's College Hospital (KCH) criteria are the most widely used prognostic criteria. Real-life application of Clichy criteria is limited due to the non-availability of factor V level measurement. KCH criteria have good specificity but low sensitivity to predict outcomes. Therefore, we attempted to use the model for end-stage liver disease (MELD) score and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in ALF patients as prognostic indicators and need for liver transplantation. METHODS Forty-one patients with ALF were enrolled in the study. On the day of admission, MELD and CLIF-SOFA scores were calculated for each patient. Area under receiver operating characteristics (AUROC) curve, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy (DA) of MELD and CLIF-SOFA score were calculated to predict the outcome of the patients. RESULTS Out of 41 patients, nine patients left against medical advice. The sensitivity, specificity, PPV, NPV, and DA for the MELD score of enrolled patients in the study were 81.5%, 62.5%, 59.5%, 83.3%, 70.1%, and for the CLIF-SOFA score of enrolled patients in the study were 88.9%, 90.0%, 85.7%, 92.3%, 89.6% respectively. Patients who did not survive had higher INR, MELD, CLIF-SOFA scores, and hepatic encephalopathy (HE) grades. Five patients who had a combination of MELD ≥30 and CLIF-SOFA ≥10, expired. CONCLUSION In our study, we used MELD score and CLIF-SOFA as prognostic markers, and we concluded that CLIF-SOFA is a better predictor of mortality than MELD score in terms of sensitivity, specificity, NPV, PPV, and diagnostic accuracy. AUROC for CLIF-SOFA score is higher when compared to the MELD score.
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Affiliation(s)
- Amit Goel
- Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow, IND
| | | | - D Himanshu
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Vipin Bharti
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Deepak Sharma
- Internal Medicine, King George's Medical University, Lucknow, IND
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Lim H, Kang Y, Park S, Koh H. Effectiveness of High-Volume Therapeutic Plasma Exchange for Acute and Acute-on-Chronic Liver Failure in Korean Pediatric Patients. Pediatr Gastroenterol Hepatol Nutr 2022; 25:481-488. [PMID: 36451692 PMCID: PMC9679303 DOI: 10.5223/pghn.2022.25.6.481] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/04/2022] [Indexed: 11/22/2022] Open
Abstract
PURPOSE Liver transplantation (LT) is the only curative treatment for acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). In high-volume therapeutic plasma exchange (HV-TPE), extracorporeal liver support filters accumulate toxins and improve the coagulation factor by replacing them. In this study, we aimed to evaluate the effectiveness of HV-TPE in pediatric patients with ALF and ACLF. METHODS We reviewed the records of children waiting for LT at Severance Hospital who underwent HV-TPE between 2017 and 2021. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin (TB and DB), gamma-glutamyl transferase (GGT), ammonia, and coagulation parameter-international normalized ratio (INR) were all measured before and after HV-TPE to analyze the liver function. The statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Co., Armonk, NY, USA). RESULTS Nine patients underwent HV-TPE with standard medical therapy while waiting for LT. One had neonatal hemochromatosis, four had biliary atresia, and the other four had ALF of unknown etiology. Significant decreases in AST, ALT, TB, DB, GGT, and INR were noted after performing HV-TPE (930.38-331.75 IU/L, 282.62-63.00 IU/L, 11.75-5.59 mg/dL, 8.10-3.66 mg/dL, 205.62-51.75 IU/L, and 3.57-1.50, respectively, p<0.05). All patients underwent LT, and two expired due to acute complications. CONCLUSION HV-TPE could remove accumulated toxins and improve coagulation. Therefore, we conclude that HV-TPE can be regarded as a representative bridging therapy before LT.
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Affiliation(s)
- Hyeji Lim
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.,Severance Pediatric Liver Diseases Research Group, Severance Children's Hospital, Seoul, Korea
| | - Yunkoo Kang
- Department of Pediatrics, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Sowon Park
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.,Severance Pediatric Liver Diseases Research Group, Severance Children's Hospital, Seoul, Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.,Severance Pediatric Liver Diseases Research Group, Severance Children's Hospital, Seoul, Korea
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Cardoso FS, Fidalgo P, Bagshaw SM, Gottfried M, Tujios S, Olson JC, Lee WM, Karvellas CJ. Persistent But Not Transient Acute Kidney Injury Was Associated With Lower Transplant-Free Survival in Patients With Acute Liver Failure: A Multicenter Cohort Study. Crit Care Med 2022; 50:1329-1338. [PMID: 35446272 PMCID: PMC10681629 DOI: 10.1097/ccm.0000000000005563] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acute liver failure (ALF) is an orphan disease often complicated by acute kidney injury (AKI). We assessed the impact of transient versus persistent AKI on survival in patients with ALF. DESIGN International multicenter retrospective cohort. SETTING U.S. ALF Study Group prospective registry. PATIENTS Patients with greater than or equal to 18 years and ALF in the registry from 1998 to 2016 were included. Patients with less than 3 days of follow-up, without kidney function evaluation on day 3, or with cirrhosis were excluded. INTERVENTIONS AKI was defined by Kidney Disease Improving Global Outcomes guidelines on day 1. Kidney recovery was defined on day 3 as transient AKI, by a return to no-AKI within 48 hours or persistent AKI if no such recovery or renal replacement therapy (RRT) was observed. Primary outcome was transplant-free survival (TFS) at 21 days. MEASUREMENTS AND MAIN RESULTS Among 1,071 patients with ALF, 339 (31.7%) were males, and median (interquartile range) age was 39 years (29-51 yr). Acetaminophen-related ALF was found in 497 patients (46.4%). On day 1, 485 of 1,071 patients (45.3%) had grade 3-4 hepatic encephalopathy (HE), 500 of 1,070 (46.7%) required invasive mechanical ventilation (IMV), 197 of 1,070 (18.4%) were on vasopressors, and 221 of 1,071 (20.6%) received RRT. On day 1, 673 of 1,071 patients (62.8%) had AKI. On day 3, 72 of 1,071 patients (6.7%) had transient AKI, 601 of 1,071 (56.1%) had persistent AKI, 71 of 1,071 (6.6%) had late onset AKI, and 327 of 1,071 (30.5%) remained without AKI. Following adjustment for confounders (age, sex, race, etiology, HE grade, use of IMV and vasopressors, international normalized ratio, and year), although persistent acute kidney injury (adjusted odds ratio [aOR] [95% CI] 0.62 [0.44-0.88]) or late onset AKI (aOR [95% CI] 0.48 [0.26-0.89]) was associated with lower TFS, transient AKI was not (aOR [95% CI] 1.89 [0.99-3.64]). CONCLUSIONS In a multicenter cohort of patients with ALF, persistent but not transient AKI was independently associated with lower short-term TFS.
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Affiliation(s)
- Filipe S Cardoso
- Intensive Care Unit and Transplant Unit, Curry Cabral Hospital, Nova Medical School, Nova University, Lisbon, Portugal
| | - Pedro Fidalgo
- Intensive Care Unit, São Francisco Xavier Hospital, Lisbon, Portugal
| | - Sean M Bagshaw
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, AB, Canada
| | - Michelle Gottfried
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - Shannan Tujios
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX
| | - Jody C Olson
- Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS
| | - William M Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX
| | - Constantine J Karvellas
- Department of Critical Care Medicine and Division of Gastroenterology (Liver Unit), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
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Ye QX, Huang JF, Xu ZJ, Yan YY, Yan Y, Liu LG. Short-term prognostic factors for hepatitis B virus-related acute-on-chronic liver failure. World J Clin Cases 2022; 10:8186-8195. [PMID: 36159528 PMCID: PMC9403684 DOI: 10.12998/wjcc.v10.i23.8186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 05/12/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is the abrupt exacerbation of declined hepatic function in patients with chronic liver disease.
AIM To explore the independent predictors of short-term prognosis in patients with hepatitis B virus (HBV)-related ACLF and to establish a predictive short-term prognosis model for HBV-related ACLF.
METHODS From January 2016 to December 2019, 207 patients with HBV-related ACLF attending the 910th Hospital of Chinese People's Liberation Army were continuously included in this retrospective study. Patients were stratified based on their survival status 3 mo after diagnosis. Information was collected regarding gender and age; coagulation function in terms of prothrombin time and international normalized ratio (INR); hematological profile in terms of neutrophil-to-lymphocyte ratio (NLR) and platelet count (PLT); blood biochemistry in terms of alanine aminotransferase, aspartate aminotransferase, total bilirubin (Tbil), albumin, cholinesterase, blood urea nitrogen (BUN), creatinine, blood glucose, and sodium (Na); tumor markers including alpha-fetoprotein (AFP) and Golgi protein 73 (GP73); virological indicators including HBV-DNA, HBsAg, HBeAg, Anti-HBe, and Anti-HBc; and complications including hepatic encephalopathy, hepatorenal syndrome, spontaneous peritonitis, gastrointestinal bleeding, and pulmonary infection.
RESULTS There were 157 and 50 patients in the survival and death categories, respectively. Univariate analysis revealed significant differences in age, PLT, Tbil, BUN, NLR, HBsAg, AFP, GP73, INR, stage of liver failure, classification of liver failure, and incidence of complications (pulmonary infection, hepatic encephalopathy, spontaneous bacterial peritonitis, and upper gastrointestinal bleeding) between the two groups (P < 0.05). GP73 [hazard ratio (HR): 1.009, 95% confidence interval (CI): 1.005-1.013, P = 0.000], middle stage of liver failure (HR: 5.056, 95%CI: 1.792-14.269, P = 0.002), late stage of liver failure (HR: 22.335, 95%CI: 8.544-58.388, P = 0.000), pulmonary infection (HR: 2.056, 95%CI: 1.145-3.690, P = 0.016), hepatorenal syndrome (HR: 6.847, 95%CI: 1.930-24.291, P = 0.003), and HBsAg (HR: 0.690, 95%CI: 0.524-0.908, P = 0.008) were independent risk factors for short-term prognosis in patients with HBV-related ACLF. Following binary logistics regression analysis, we arrived at the following formula for predicting short-term prognosis: Logit(P) = Ln(P/1-P) = 0.013 × (GP73 ng/mL) + 1.907 × (middle stage of liver failure) + 4.146 × (late stage of liver failure) + 0.734 × (pulmonary infection) + 22.320 × (hepatorenal syndrome) - 0.529 × (HBsAg) - 5.224. The predictive efficacy of the GP73-ACLF score was significantly better than that of the Model for End-Stage Liver Disease (MELD) and MELD-Na score models (P < 0.05).
CONCLUSION The stage of liver failure, presence of GP73, pulmonary infection, hepatorenal syndrome, and HBsAg are independent predictors of short-term prognosis in patients with HBV-related ACLF, and the GP73-ACLF model has good predictive value among these patients.
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Affiliation(s)
- Qiao-Xia Ye
- Department of Infectious Diseases, The 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Quanzhou 362000, Fujian Province, China
| | - Jin-Fa Huang
- Department of Infectious Diseases, The 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Quanzhou 362000, Fujian Province, China
| | - Zheng-Ju Xu
- Department of Infectious Diseases, The 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Quanzhou 362000, Fujian Province, China
| | - Yan-Yan Yan
- Department of Infectious Diseases, The 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Quanzhou 362000, Fujian Province, China
| | - Yan Yan
- Department of Infectious Diseases, The 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Quanzhou 362000, Fujian Province, China
| | - Li-Guan Liu
- Department of Infectious Diseases, The 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Quanzhou 362000, Fujian Province, China
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40
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Abstract
Abbreviated pathogenesis and clinical course of the acute liver failure syndrome. The pathogenesis and clinical course of the syndrome of acute liver failure (ALF) differs depending upon the etiology of the primary liver injury. In turn, the severity of the liver injury and resulting synthetic failure is often the primary determinant of whether a patient is referred for emergency liver transplantation. Injuries by viral etiologies trigger the innate immune system via pathogen-associated molecular patterns (PAMPs), while toxin-induced (and presumably ischemia-induced) injuries do so via damage-associated molecular patterns (DAMPs). The course of the clinical syndrome further depends upon the relative intensity and composition of cytokine release, resulting in an early proinflammatory phenotype (SIRS) and later compensatory anti-inflammatory response phenotype (CARS). The outcomes of overwhelming immune activation are the systemic (extrahepatic) features of ALF (cardiovascular collapse, cerebral edema, acute kidney injury, respiratory failure, sepsis) which ultimately determine the likelihood of death.Acute liver failure (ALF) continues to carry a high risk of mortality or the need for transplantation despite recent improvements in overall outcomes over the past two decades. Optimal management begins with identifying that liver failure is indeed present and its etiology, since outcomes and the need for transplantation vary widely across the different etiologies. Most causes of ALF can be divided into hyperacute (ischemia and acetaminophen) and subacute types (other etiologies), based on time of evolution of signs and symptoms of liver failure; the former evolve in 3 to 4 days and the latter typically in 2 to 4 weeks. Both involve intense release of cytokines and hepatocellular contents into the circulation with multiorgan effects/consequences.Management involves optimizing fluid balance and cardiovascular support, including the use of continuous renal replacement therapy, vasopressors, and pulmonary ventilation. Early evaluation for liver transplantation is advised particularly for acetaminophen toxicity, which evolves so rapidly that delay is likely to lead to death.Vasopressor support, high-grade hepatic encephalopathy, and unfavorable (subacute) etiologies heighten the need for urgent listing for liver transplantation. Prognostic scores such as Kings Criteria, Model for End-Stage Liver Disease, and the Acute Liver Failure Group prognostic index take these features into account and provide reasonable but imperfect predictive accuracy. Future treatments may include liver support devices and/or agents that improve hepatocyte regeneration.
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Affiliation(s)
- Shannan Tujios
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - R. Todd Stravitz
- Section of Hepatology, Department of Internal Medicine, Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, Virginia
| | - William M. Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
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Ning Q, Chen T, Wang G, Xu D, Yu Y, Mao Q, Li T, Li L, Li J, Lu X, Li J, Li Z, Zhang W, Xiao Y, Meng Q, Mi Y, Shang J, Yu Y, Zhao Y, Zhao C, Zhao H, Huang J, Peng J, Tang H, Tang X, Hu J, Hu B, Guo W, Zheng B, Chen B, Zhang Y, Wei J, Sheng J, Chen Z, Wang M, Xie Q, Wang Y, Wang FS, Hou J, Duan Z, Wei L, Jia J, Chinese Society of Infectious Disease of Chinese Medical Association. Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infections. INFECTIOUS DISEASES & IMMUNITY 2022; 2:168-178. [DOI: 10.1097/id9.0000000000000055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Indexed: 10/13/2023]
Abstract
Abstract
End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.
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Affiliation(s)
- Qin Ning
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Tao Chen
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Dong Xu
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yanyan Yu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Qing Mao
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Taisheng Li
- Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jun Li
- Department of Infectious Disease, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
| | - Xiaoju Lu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Jiabin Li
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei 230031, China
| | - Zhiwei Li
- Department of Infectious Diseases, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang 110801, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Institute of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Yonghong Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Qinghua Meng
- Department of Severe Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Yuqiang Mi
- Nankai University Second People's Hospital, Tianjin 300071, China
| | - Jia Shang
- Department of Infectious Disease, People's Hospital of Henan Province, Zhengzhou 450003, China
| | - Yunsong Yu
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Caiyan Zhao
- Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang 050051, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
| | - Jianrong Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jie Peng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xiaoping Tang
- Research Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
| | - Jinhua Hu
- Liver Failure Treatment and Research Center, The Fifth Medical Center, China PLA General Hospital, Beijing 100039, China
| | - Bijie Hu
- Department of Infectious Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Wei Guo
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Bo Zheng
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China
| | - Baiyi Chen
- Department of Infectious Diseases, The First Hospital of China Medical University, Shenyang 110002, China
| | - Yuexin Zhang
- Center of Infectious Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
| | - Jia Wei
- Department of Infectious Disease, The Second People's Hospital, Kunming 650201, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Minggui Wang
- Department of Infectious Diseases, Institute of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yuming Wang
- Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Fu-Sheng Wang
- Liver Failure Treatment and Research Center, The Fifth Medical Center, China PLA General Hospital, Beijing 100039, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Lai Wei
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People's Hospital, Beijing 100044, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis & National Clinical Research Center for Digestive Diseases, Beijing 100050, China
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42
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Jacob R, Liu K, Marinelli T. Successful liver transplantation for hepatitis B-related acute liver failure in a patient with active COVID-19. Transpl Infect Dis 2022; 24:e13889. [PMID: 35751133 PMCID: PMC9350301 DOI: 10.1111/tid.13889] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 05/29/2022] [Accepted: 05/31/2022] [Indexed: 12/01/2022]
Abstract
The emergence of coronavirus disease 19 (COVID‐19) has significantly disrupted liver transplantation worldwide. Despite significant, collective experience in treating liver transplant recipients with COVID‐19, there remains a paucity of data to guide the management of transplant candidates with acute COVID‐19 who require urgent transplantation. We present the case of an otherwise well, 39‐year‐old female presenting for urgent liver transplantation for acute liver failure secondary to hepatitis B, with concomitant acute, mild COVID‐19 due to Omicron BA.2. COVID‐19 antivirals were not administered pre‐transplant as the potential risk of hepatotoxicity precipitating further deterioration of liver function was not felt to outweigh the small, potential benefit of antiviral therapy. No effective SARS‐CoV‐2 monoclonal antibodies were available; however, the patient was previously vaccinated against SARS‐CoV‐2 with evidence of anti‐spike antibodies at the time of COVID‐19. Transplantation surgery and recovery were uncomplicated with no progression of COVID‐19 post‐transplant, hospital discharge was at day 14. At 30 days post‐transplant the patient had recovered, with normal liver function and SARS‐CoV‐2 was not detectable on nasopharyngeal PCR. While the safety of transplantation of patients with acute COVID‐19 cannot be assured by a single case, ours highlights the complex decision‐making process undertaken and competing priorities that need to be balanced when assessing patients with acute COVID‐19 who require urgent transplantation.
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Affiliation(s)
- Rachael Jacob
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Tina Marinelli
- Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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43
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Abstract
PURPOSE OF REVIEW To review the surgical and critical care management of liver trauma; one of the most common abdominal injuries sustained due to its size and location. RECENT FINDINGS Hepatic injuries range from negligible to life threatening: in the acute phase, the most common cause of morbidity and mortality is hemorrhage; however, severe traumatic hepatic injuries can also lead to biochemical abnormalities, altered coagulation, and ultimately liver failure. This brief review will review the classification of traumatic liver injuries by mechanism, grade, and severity. Most Grades I-III injuries can be managed nonoperatively, whereas the majority of Grades IV-VI injuries require operative management. Therapeutic strategies for traumatic liver injury including nonoperative, operative, radiologic will be described. The primary goal of liver trauma management in the acute setting is hemorrhage control, then the management of secondary factors such as bile leaks. The rapid restoration of homeostasis may prevent further damage to the liver and allow for deferred nonoperative management, which has been shown to be associated with good clinical outcomes. SUMMARY A multidisciplinary approach to the care of these patients at an experienced liver surgery center is warranted.
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44
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Feighery AM, Aseem SO, Huebert RC. 55-Year-Old Man Presenting With Jaundice. Mayo Clin Proc 2022; 97:795-800. [PMID: 35287955 DOI: 10.1016/j.mayocp.2021.09.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 09/06/2021] [Accepted: 09/10/2021] [Indexed: 12/24/2022]
Affiliation(s)
- Aoife M Feighery
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Sayed Obaidullah Aseem
- Resident in Gastroenterology and Hepatology, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Robert C Huebert
- Advisor to residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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45
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Pop TL, Aldea CO, Delean D, Bulata B, Boghiţoiu D, Păcurar D, Ulmeanu CE, Grama A. The Role of Predictive Models in the Assessment of the Poor Outcomes in Pediatric Acute Liver Failure. J Clin Med 2022; 11:432. [PMID: 35054127 PMCID: PMC8778932 DOI: 10.3390/jcm11020432] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/05/2022] [Accepted: 01/13/2022] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES In children, acute liver failure (ALF) is a severe condition with high mortality. As some patients need liver transplantation (LT), it is essential to predict the fatal evolution and to refer them early for LT if needed. Our study aimed to evaluate the prognostic criteria and scores for assessing the outcome in children with ALF. METHODS Data of 161 children with ALF (54.66% female, mean age 7.66 ± 6.18 years) were analyzed based on final evolution (32.91% with fatal evolution or LT) and etiology. We calculated on the first day of hospitalization the PELD score (109 children), MELD, and MELD-Na score (52 children), and King's College Criteria (KCC) for all patients. The Nazer prognostic index and Wilson index for predicting mortality were calculated for nine patients with ALF in Wilson's disease (WD). RESULTS PELD, MELD, and MELD-Na scores were significantly higher in patients with fatal evolution (21.04 ± 13.28 vs. 13.99 ± 10.07, p = 0.0023; 36.20 ± 19.51 vs. 20.08 ± 8.57, p < 0.0001; and 33.07 ± 8.29 vs. 20.08 ± 8.47, p < 0.0001, respectively). Moreover, age, bilirubin, albumin, INR, and hemoglobin significantly differed in children with fatal evolution. Function to etiology, PELD, MELD, MELD-Na, and KCC accurately predicted fatal evolution in toxic ALF (25.33 vs. 9.90, p = 0.0032; 37.29 vs. 18.79, p < 0.0001; 34.29 vs. 19.24, p = 0.0002, respectively; with positive predicting value 100%, negative predicting value 88.52%, and accuracy 89.23% for King's College criteria). The Wilson index for predicting mortality had an excellent predictive strength (100% sensibility and specificity), better than the Nazer prognostic index. CONCLUSIONS Prognostic scores may be used to predict the fatal evolution of ALF in children in correlation with other parameters or criteria. Early estimation of the outcome of ALF is essential, mainly in countries where emergency LT is problematic, as the transfer to a specialized center could be delayed, affecting survival chances.
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Affiliation(s)
- Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Center of Expertise in Pediatric Liver Rare Disorders, 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Cornel Olimpiu Aldea
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (C.O.A.); (D.D.); (B.B.)
| | - Dan Delean
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (C.O.A.); (D.D.); (B.B.)
| | - Bogdan Bulata
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (C.O.A.); (D.D.); (B.B.)
| | - Dora Boghiţoiu
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.B.); (D.P.); (C.E.U.)
- Department of Pediatrics, Grigore Alexandrescu Emergency Clinical Hospital for Children, 011743 Bucharest, Romania
| | - Daniela Păcurar
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.B.); (D.P.); (C.E.U.)
- Department of Pediatrics, Grigore Alexandrescu Emergency Clinical Hospital for Children, 011743 Bucharest, Romania
| | - Coriolan Emil Ulmeanu
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.B.); (D.P.); (C.E.U.)
- Department of Pediatrics, Grigore Alexandrescu Emergency Clinical Hospital for Children, 011743 Bucharest, Romania
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Center of Expertise in Pediatric Liver Rare Disorders, 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
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Wu J, Shi C, Sheng X, Xu Y, Zhang J, Zhao X, Yu J, Shi X, Li G, Cao H, Li L. Prognostic Nomogram for Patients with Hepatitis E Virus-related Acute Liver Failure: A Multicenter Study in China. J Clin Transl Hepatol 2021; 9:828-837. [PMID: 34966646 PMCID: PMC8666371 DOI: 10.14218/jcth.2020.00117] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 03/14/2021] [Accepted: 04/16/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND AND AIMS Timely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present study aimed to establish an effective nomogram for predicting the mortality of HEV-ALF patients. METHODS The nomogram was based on a cross-sectional set of 404 HEV-ALF patients who were identified and enrolled from a cohort of 650 patients with liver failure. To compare the performance with that of the model for end-stage liver disease (MELD) scoring and CLIF-Consortium-acute-on-chronic liver failure score (CLIF-C-ACLFs) models, we assessed the predictive accuracy of the nomogram using the concordance index (C-index), and its discriminative ability using time-dependent receiver operating characteristics (td-ROC) analysis, respectively. RESULTS Multivariate logistic regression analysis of the development set carried out to predict mortality revealed that γ-glutamyl transpeptidase, albumin, total bilirubin, urea nitrogen, creatinine, international normalized ratio, and neutrophil-to-lymphocyte ratio were independent factors, all of which were incorporated into the new nomogram to predict the mortality of HEV-ALF patients. The area under the curve of this nomogram for mortality prediction was 0.671 (95% confidence interval: 0.602-0.740), which was higher than that of the MELD and CLIF-C-ACLFs models. Moreover, the td-ROC and decision curves analysis showed that both discriminative ability and threshold probabilities of the nomogram were superior to those of the MELD and CLIF-C-ACLFs models. A similar trend was observed in the validation set. CONCLUSIONS The novel nomogram is an accurate and efficient mortality prediction method for HEV-ALF patients.
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Affiliation(s)
- Jian Wu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Laboratory Medicine, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Cuifen Shi
- Department of Infectious Disease, The Second People’s Hospital of Yancheng City, Yancheng, Jiangsu, China
| | - Xinyu Sheng
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yanping Xu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jinrong Zhang
- Department of Laboratory Medicine, The People’s Hospital of Dafeng City, Yancheng, Jiangsu, China
| | - Xinguo Zhao
- Department of Respiration, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Jiong Yu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xinhui Shi
- Department of Laboratory Medicine, The First People’s Hospital of Yancheng City, Yancheng, Jiangsu, China
| | - Gongqi Li
- Department of Clinical Laboratory, Linyi Traditional Hospital, Linyi, Shandong, China
| | - Hongcui Cao
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, Hangzhou, Zhejiang, China
| | - Lanjuan Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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47
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Pailleux F, Maes P, Jaquinod M, Barthelon J, Darnaud M, Lacoste C, Vandenbrouck Y, Gilquin B, Louwagie M, Hesse AM, Kraut A, Garin J, Leroy V, Zarski JP, Bruley C, Couté Y, Samuel D, Ichai P, Faivre J, Brun V. Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury. Int J Mol Sci 2021; 22:ijms222011071. [PMID: 34681731 PMCID: PMC8540689 DOI: 10.3390/ijms222011071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/03/2021] [Accepted: 10/11/2021] [Indexed: 12/18/2022] Open
Abstract
Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10–48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.
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Affiliation(s)
- Floriane Pailleux
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Pauline Maes
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Michel Jaquinod
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Justine Barthelon
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
- Clinique Universitaire d’Hépato-gastroentérologie, Centre Hospitalier Universitaire Grenoble, 38000 Grenoble, France; (V.L.); (J.-P.Z.)
| | - Marion Darnaud
- Hepatobiliary Centre, Paul-Brousse University Hospital, INSERM U1193, 94800 Villejuif, France; (M.D.); (C.L.); (D.S.); (P.I.)
- Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France
| | - Claire Lacoste
- Hepatobiliary Centre, Paul-Brousse University Hospital, INSERM U1193, 94800 Villejuif, France; (M.D.); (C.L.); (D.S.); (P.I.)
- Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France
| | - Yves Vandenbrouck
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Benoît Gilquin
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
- Univ. Grenoble Alpes, CEA, LETI, Clinatec, 38000 Grenoble, France
| | - Mathilde Louwagie
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Anne-Marie Hesse
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Alexandra Kraut
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Jérôme Garin
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Vincent Leroy
- Clinique Universitaire d’Hépato-gastroentérologie, Centre Hospitalier Universitaire Grenoble, 38000 Grenoble, France; (V.L.); (J.-P.Z.)
- Institute for Advanced Biosciences, Université Grenoble Alpes, CNRS, INSERM U1209, 38000 Grenoble, France
| | - Jean-Pierre Zarski
- Clinique Universitaire d’Hépato-gastroentérologie, Centre Hospitalier Universitaire Grenoble, 38000 Grenoble, France; (V.L.); (J.-P.Z.)
- Institute for Advanced Biosciences, Université Grenoble Alpes, CNRS, INSERM U1209, 38000 Grenoble, France
| | - Christophe Bruley
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Yohann Couté
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
| | - Didier Samuel
- Hepatobiliary Centre, Paul-Brousse University Hospital, INSERM U1193, 94800 Villejuif, France; (M.D.); (C.L.); (D.S.); (P.I.)
- Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France
| | - Philippe Ichai
- Hepatobiliary Centre, Paul-Brousse University Hospital, INSERM U1193, 94800 Villejuif, France; (M.D.); (C.L.); (D.S.); (P.I.)
- Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France
| | - Jamila Faivre
- Hepatobiliary Centre, Paul-Brousse University Hospital, INSERM U1193, 94800 Villejuif, France; (M.D.); (C.L.); (D.S.); (P.I.)
- Faculté de Médecine, Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France
- Assistance Publique-Hôpitaux de Paris (AP-HP), Pôle de Biologie Médicale, Paul-Brousse University Hospital, 94800 Villejuif, France
- Correspondence: (J.F.); (V.B.)
| | - Virginie Brun
- Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France; (F.P.); (P.M.); (M.J.); (J.B.); (Y.V.); (B.G.); (M.L.); (A.-M.H.); (A.K.); (J.G.); (C.B.); (Y.C.)
- Univ. Grenoble Alpes, CEA, LETI, Clinatec, 38000 Grenoble, France
- Correspondence: (J.F.); (V.B.)
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Nash E, Sabih AH, Chetwood J, Wood G, Pandya K, Yip T, Majumdar A, McCaughan GW, Strasser SI, Liu K. Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements. Med J Aust 2021; 215:261-268. [PMID: 34272737 DOI: 10.5694/mja2.51173] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 06/03/2021] [Accepted: 06/04/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements. DESIGN Retrospective electronic medical record data analysis. SETTING, PARTICIPANTS Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. MAIN OUTCOME MEASURES 90-day transplant-free survival; drugs implicated as causal agents in DILI. RESULTS A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36). CONCLUSION In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.
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Affiliation(s)
- Emily Nash
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
| | - Abdul-Hamid Sabih
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
| | - John Chetwood
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
| | - Georgette Wood
- Sydney Medical School, University of Sydney, Sydney, NSW
| | - Keval Pandya
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
| | - Terry Yip
- Medical Data Analytic Centre and Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong
| | - Avik Majumdar
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
- Sydney Medical School, University of Sydney, Sydney, NSW
| | - Geoffrey W McCaughan
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
- Sydney Medical School, University of Sydney, Sydney, NSW
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
- Sydney Medical School, University of Sydney, Sydney, NSW
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
- Sydney Medical School, University of Sydney, Sydney, NSW
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Uhlig M, Hein M, Habigt MA, Tolba RH, Braunschweig T, Helmedag MJ, Klinge U, Koch A, Trautwein C, Mechelinck M. Acute myocardial injury secondary to severe acute liver failure: A retrospective analysis supported by animal data. PLoS One 2021; 16:e0256790. [PMID: 34460845 PMCID: PMC8405020 DOI: 10.1371/journal.pone.0256790] [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] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 08/17/2021] [Indexed: 11/29/2022] Open
Abstract
To investigate whether acute liver failure (ALF) leads to secondary acute myocardial injury, 100 ALF patients that were retrospectively identified in a single center based on ICD 10 codes and 8 rats from an experimental study that died early after bile duct ligation (BDL) were examined. Creatine kinase (CK), creatine kinase-MB isoenzyme (CKMB) and cardiac troponin-I (cTnI) were analyzed as markers of myocardial injury. For histological analysis, hematoxylin-eosin (HE), elastic Van Gieson (EVG), CD41 and myeloperoxidase were used to stain rat hearts. Major adverse cardiac events (MACEs) were a critical factor for mortality (p = 0.037) in human ALF. Deceased patients exhibited higher levels of CKMB than survivors (p = 0.023). CKMB was a predictor of mortality in ALF (p = 0.013). Animals that died early after BDL exhibited increased cTnI, CKMB, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels compared to controls (cTnI: p = 0.011, CKMB: p = 0.008, TNFα: p = 0.003, IL-6: p = 0.006). These animals showed perivascular lesions and wavy fibers, microthrombi and neutrophilic infiltration in the heart. MACEs are decisive for mortality in human ALF, and elevated CKMB values indicate that this might be due to structural myocardial damage. Accordingly, CKMB was found to have predictive value for mortality in ALF. The results are substantiated by data from a rat BDL model demonstrating diffuse myocardial injury.
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Affiliation(s)
- Moritz Uhlig
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Marc Hein
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Moriz A. Habigt
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - René H. Tolba
- Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Till Braunschweig
- Department of Pathology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Marius J. Helmedag
- Department of General, Visceral and Transplantation Surgery, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Uwe Klinge
- Department of General, Visceral and Transplantation Surgery, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Alexander Koch
- Department of Gastroenterology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Christian Trautwein
- Department of Gastroenterology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
| | - Mare Mechelinck
- Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
- Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
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50
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Fontana RJ, Stravitz RT, Durkalski V, Hanje J, Hameed B, Koch D, Ganger D, Olson J, Liou I, McGuire BM, Clasen K, Lee WM. Prognostic Value of the 13 C-Methacetin Breath Test in Adults with Acute Liver Failure and Non-acetaminophen Acute Liver Injury. Hepatology 2021; 74:961-972. [PMID: 33660316 PMCID: PMC10683007 DOI: 10.1002/hep.31783] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 01/08/2021] [Accepted: 02/01/2021] [Indexed: 01/16/2023]
Abstract
BACKGROUND AND AIMS The 13 C-methacetin breath test (MBT) is a noninvasive, quantitative hepatic metabolic function test. The aim of this prospective, multicenter study was to determine the utility of initial and serial 13 C-MBT in predicting 21-day outcomes in adults with acute liver failure (ALF) and non-acetaminophen acute liver injury (ALI). APPROACH AND RESULTS The 13 C-MBT BreathID device (Exalenz Biosciences, Ltd.) provided the percent dose recovery (PDR) for a duration of 60 minutes after administration of 13 C-methacetin solution as the change in exhaled 13 CO2 /12 CO2 compared with pre-ingestion ratio on study days 1, 2, 3, 5, and 7. Results were correlated with 21-day transplant-free survival and other prognostic indices. A total of 280 subjects were screened for enrollment between May 2016 and August 2019. Median age of the 62 enrolled patients with adequate data was 43 years, 79% were Caucasian, 76% had ALF with the remaining 24% having ALI. The mean PDR peak on day 1 or day 2 was significantly lower in nonsurvivors compared with transplant-free survivors (2.3%/hour vs. 9.1%/hour; P < 0.0001). In addition, serial PDR peaks were consistently lower in nonsurvivors versus survivors (P < 0.0001). The area under the receiver operating characteristic curve (AUROC) of the 13 C-MBT in the combined cohort was 0.88 (95% CI: 0.79-0.97) and higher than that provided by King's College (AUROC = 0.70) and Model for End-Stage Liver Disease scores (AUROC = 0.83). The 13 C-MBT was well tolerated with only two gastrointestinal adverse events reported. CONCLUSIONS The 13 C-MBT is a promising tool to estimate the likelihood of hepatic recovery in patients with ALF and ALI. Use of the PDR peak data from the 13 C-MBT point-of-care test may assist with medical decision making and help avoid unnecessary transplantation in critically ill patients with ALF and ALI.
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Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - R. Todd Stravitz
- Lee-Hume Transplant Center, Virginia Commonwealth University, Richmond, VA
| | - Valerie Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - James Hanje
- Department of Medicine, The Ohio State University, Columbus, OH
| | - Bilal Hameed
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - David Koch
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - Daniel Ganger
- Division of Gastroenterology, Northwestern University, Chicago, IL
| | - Jody Olson
- Division of Gastroenterology, University of Kansas Medical Center, Kansas City, KS
| | - Iris Liou
- Department of Medicine, University of Washington, Seattle, WA
| | | | - Kristen Clasen
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC
| | - William M. Lee
- Department of Internal Medicine, University of Texas Southwestern, Dallas, TX
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