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Janko N, Majeed A, Commins I, Gow P, Kemp W, Roberts SK. Rotational thromboelastometry predicts transplant-free survival in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2025; 37:510-516. [PMID: 39976046 DOI: 10.1097/meg.0000000000002920] [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] [Indexed: 02/21/2025]
Abstract
BACKGROUND AND AIMS Emerging evidence suggests that rotational thromboelastometry (ROTEM) is superior to conventional haemostatic tests in the assessment and management of bleeding risk in patients with cirrhosis. Whether ROTEM may also be useful for assessing the prognosis of these patients is unknown. We aimed to explore the role of ROTEM in predicting the transplant-free survival of patients with cirrhosis. METHODS We conducted a prospective cohort study of patients with cirrhosis at two hospitals. All patients underwent ROTEM analysis at baseline and were followed up until death, liver transplantation or the end of follow-up (28 February 2023). Univariate and multivariate Cox regression analyses were performed to explore the association between transplant-free survivals. RESULTS Between April 2018 and October 2021, 162 patients with cirrhosis were recruited and followed-up for a median of 42 months. During follow-up, 36 patients died and 7 underwent liver transplantation. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in the death/liver transplant group compared to the survivor group (52 vs. 57, P = 0.02; and 51 vs. 55, P = 0.01, respectively). After adjusting for age, sex, presence of clinically significant portal hypertension, hepatocellular carcinoma, care setting, bilirubin, sodium and creatinine, only albumin (hazard ratio: 0.92, 95% CI: 0.85-0.99, P = 0.018) and MCF EXT (hazard ratio: 0.96, 95% CI: 0.92-0.99, P = 0.032) remained significant predictors of transplant-free survival. CONCLUSION ROTEM may be useful in assessing the survival of patients with cirrhosis. Further research is needed to determine the clinical utility of ROTEM parameters as prognostic markers in cirrhosis.
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Affiliation(s)
- Natasha Janko
- Department of Gastroenterology, Alfred Health
- Department of Gastroenterology, School of Translational Medicine, Monash University
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health
- Department of Gastroenterology, School of Translational Medicine, Monash University
| | - Isabella Commins
- Department of Gastroenterology, Alfred Health
- Department of Gastroenterology, School of Translational Medicine, Monash University
| | - Paul Gow
- Department of Hepatology, Victorian Liver Transplant Unit, Austin Health
- Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health
- Department of Gastroenterology, School of Translational Medicine, Monash University
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Health
- Department of Gastroenterology, School of Translational Medicine, Monash University
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2
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Karvellas CJ, Gustot T, Fernandez J. Management of the acute on chronic liver failure in the intensive care unit. Liver Int 2025; 45:e15659. [PMID: 37365997 PMCID: PMC11815614 DOI: 10.1111/liv.15659] [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: 04/30/2023] [Revised: 06/01/2023] [Accepted: 06/15/2023] [Indexed: 06/28/2023]
Abstract
Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.
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Affiliation(s)
- Constantine J. Karvellas
- Department of Critical Care MedicineUniversity of AlbertaEdmontonCanada
- Division of Gastroenterology (Liver Unit)University of AlbertaEdmontonCanada
| | - Thierry Gustot
- Department of Gastroenterology, Hepato‐Pancreatology and Digestive Oncology, H.U.B.CUB Hôpital ErasmeBrusselsBelgium
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital ClinicUniversity of Barcelona, IDIBAPS and CIBERehdBarcelonaSpain
- EF CLIF, EASL‐CLIF ConsortiumBarcelonaSpain
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3
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Zhan L, Yang Y, Nie B, Kou Y, Du S, Tian Y, Huang Y, Ye R, Huang Z, Luo B, Ge L, Ye S. A prolonged activated partial thromboplastin time indicates poor short-term prognosis in patients with hepatic encephalopathy: insights from the MIMIC database. Front Med (Lausanne) 2025; 12:1514327. [PMID: 40018344 PMCID: PMC11865095 DOI: 10.3389/fmed.2025.1514327] [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] [Received: 10/20/2024] [Accepted: 01/23/2025] [Indexed: 03/01/2025] Open
Abstract
Objectives This study investigates serum markers for short-term prognosis in hepatic encephalopathy patients. Background Patients with hepatic encephalopathy face elevated mortality rates and bleak prognoses. However, effective prognostic models or indicators are lacking. This study aims to explore serum markers for predicting short-term prognosis in these patients. Methods We conducted a retrospective analysis of 552 patients with hepatic encephalopathy, categorizing 429 individuals meeting exclusion criteria into normal and high activated partial thromboplastin time (APTT) groups. We assessed 12-day and 25-day survival rates using Kaplan-Meier analysis and Cox regression models to examine associations between groups and outcomes. Results Upon comparing baseline characteristics, the high APTT group exhibited significant disparities in acute kidney injury, sepsis, coagulation disorders, and ascites (p < 0.05). In the multivariate COX regression model, the hazard ratios [HRs; 95% confidence interval (CI)] of 12- and 25-day mortality were 1.012 (1.001, 1.022, p = 0.033) and 1.010 (1.002, 1.018, p = 0.013), respectively. We discovered that APTT demonstrated an independent association with prognosis. Our findings revealed that the ability of APTT to predict short-term prognosis surpasses that of the traditional MELD model. Regarding 12- and 25-day survival, Kaplan-Meier survival curves from these groups demonstrated a lower survival probability for patients in the high APTT group than the normal group (log-rank p < 0.05). The results of subgroup analysis and interaction analysis indicate that APTT is not influenced by other confounding factors. Conclusion A prolonged APTT suggests a poorer short-term prognosis in patients with hepatic encephalopathy.
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Affiliation(s)
- Liping Zhan
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Yuping Yang
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Biao Nie
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
- Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Yanqi Kou
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Shenshen Du
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
- Department of Gastroenterology, Huanghe Sanmenxia Hospital, Sanmenxia, China
| | - Yuan Tian
- Department of Pathology, Guangdong Medical University, Zhanjiang, China
| | - Yujie Huang
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Ruyin Ye
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Zhe Huang
- Department of Colorectal Surgery, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Botao Luo
- Department of Pathology, Guangdong Medical University, Zhanjiang, China
| | - Lei Ge
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Shicai Ye
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
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4
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Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D’Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, et alChoudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D’Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, Chen JJ, Hou JL, Yang JM, Chang J, Trebicka J, Kalf JC, Sollano JD, Varghese J, Arab JP, Li J, Reddy KR, Raja K, Panda K, Kajal K, Kumar K, Madan K, Kalista KF, Thanapirom K, Win KM, Suk KT, Devadas K, Lesmana LA, Kamani L, Premkumar M, Niriella MA, Al Mahtab M, Yuen MF, Sayed MHE, Alla M, Wadhawan M, Sharma MK, Sahu M, Prasad M, Muthiah MD, Schulz M, Bajpai M, Reddy MS, Praktiknjo M, Yu ML, Prasad M, Sharma M, Elbasiony M, Eslam M, Azam MG, Rela M, Desai MS, Vij M, Mahmud N, Choudhary NS, Marannan NK, Ormeci N, Saraf N, Verma N, Nakayama N, Kawada N, Oidov Baatarkhuu, Goyal O, Yokosuka O, Rao PN, Angeli P, Parikh P, Kamath PS, Thuluvath PJ, Lingohr P, Ranjan P, Bhangui P, Rathi P, Sakhuja P, Puri P, Ning Q, Dhiman RK, Kumar R, Vijayaraghavan R, Khanna R, Maiwall R, Mohanka R, Moreau R, Gani RA, Loomba R, Mehtani R, Rajaram RB, Hamid SS, Palnitkar S, Lal S, Biswas S, Chirapongsathorn S, Agarwal S, Sachdeva S, Saigal S, Kumar SE, Violeta S, Singh SP, Mochida S, Mukewar S, Alam S, Lim SG, Alam S, Shalimar, Venishetty S, Sundaram SS, Shetty S, Bhatia S, Singh SA, Kottilil S, Strasser S, Shasthry SM, Maung ST, Tan SS, Treeprasertsuk S, Asthana S, Manekeller S, Gupta S, Acharya SK, K.C. S, Maharshi S, Asrani S, Dadhich S, Taneja S, Giri S, Singh S, Chen T, Gupta T, Kanda T, Tanwandee T, Piratvishuth T, Spengler U, Prasad VGM, Midha V, Rakhmetova V, Arroyo V, Sood V, BR VK, Wong VWS, Pamecha V, Singh V, Dayal VM, Saraswat VA, Kim WR, Jafri W, Gu W, Jun WY, Qi X, Chawla YK, Kim YJ, Shi Y, Abbas Z, Kumar G, Shiina S, Wei L, Omata M, Sarin SK, APASL-ACLF Research Consortium (AARC) for APASL-ACLF working party. Acute-on-chronic liver failure (ACLF): the ‘Kyoto Consensus’—steps from Asia. Hepatol Int 2025; 19:1-69. [DOI: https:/doi.org/10.1007/s12072-024-10773-4] [Show More Authors] [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] [Received: 10/26/2024] [Accepted: 12/29/2024] [Indexed: 04/16/2025]
Abstract
Abstract
Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the “APASL ACLF Research Consortium (AARC)” was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia–Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the ‘Golden Therapeutic Window’, the ‘transplant window’, and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The ‘Kyoto APASL Consensus’ presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
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5
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Riescher-Tuczkiewicz A, Rautou PE. Prediction and prevention of post-procedural bleedings in patients with cirrhosis. Clin Mol Hepatol 2025; 31:S205-S227. [PMID: 39962975 PMCID: PMC11925446 DOI: 10.3350/cmh.2024.0928] [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: 10/19/2024] [Revised: 01/28/2025] [Accepted: 02/17/2025] [Indexed: 03/20/2025] Open
Abstract
Although post-procedural bleedings are infrequent in patients with cirrhosis, they are associated with significant morbidity and mortality. Therefore, predicting and preventing such bleedings is important. Established predictors of post-procedural bleeding include high-bleeding risk procedure, severe cirrhosis and high body mass index; prognostic value of anemia, acute kidney injury and bacterial infection is more uncertain. While prothrombin time and international normalized ratio do not predict post-procedural bleeding, some evidence suggests that platelet count, whole blood thrombin generation assay and viscoelastic tests may be helpful in this context. Prevention of postprocedural bleeding involves careful management of antithrombotic drugs during the periprocedural period. Patients with cirrhosis present unique challenges due to altered pharmacokinetics and pharmacodynamics of antithrombotic drugs, but there is a lack of dedicated studies specifically focused on this patient population. Guidelines for periprocedural management of antithrombotic drugs developed for patients without liver disease are thus applied to those with cirrhosis. Some technical aspects may decrease the risk of post-procedural bleeding, namely ultrasoundguidance, opting for transjugular route rather than percutaneous route, and the level of expertise of the operator. The effectiveness of platelet transfusions or thrombopoietin-receptor agonists remains uncertain. Transfusion of fresh-frozen plasma, of fibrinogen, and administration of tranexamic acid are not recommended for reducing post-procedural bleeding in patients with cirrhosis. In conclusion, prediction of post-procedural requires a global approach taking into account the patients characteristics, the risk of the procedure, and the platelet count. There is little data to support prophylactic correction of hemostasis, and dedicated studies are needed.
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Affiliation(s)
| | - Pierre-Emmanuel Rautou
- Paris City University, Inserm, Inflammatory Research Center, UMR 1149, Paris, France
- AP-HP, Beaujon Hospital, Hepatology Department, DMU DIGEST, Reference Center for Vascular Diseases of the Liver, FILFOIE, ERN RARE-LIVER, Clichy, France
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6
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Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D'Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, et alChoudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D'Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, Chen JJ, Hou JL, Yang JM, Chang J, Trebicka J, Kalf JC, Sollano JD, Varghese J, Arab JP, Li J, Reddy KR, Raja K, Panda K, Kajal K, Kumar K, Madan K, Kalista KF, Thanapirom K, Win KM, Suk KT, Devadas K, Lesmana LA, Kamani L, Premkumar M, Niriella MA, Al Mahtab M, Yuen MF, Sayed MHE, Alla M, Wadhawan M, Sharma MK, Sahu M, Prasad M, Muthiah MD, Schulz M, Bajpai M, Reddy MS, Praktiknjo M, Yu ML, Prasad M, Sharma M, Elbasiony M, Eslam M, Azam MG, Rela M, Desai MS, Vij M, Mahmud N, Choudhary NS, Marannan NK, Ormeci N, Saraf N, Verma N, Nakayama N, Kawada N, Oidov Baatarkhuu, Goyal O, Yokosuka O, Rao PN, Angeli P, Parikh P, Kamath PS, Thuluvath PJ, Lingohr P, Ranjan P, Bhangui P, Rathi P, Sakhuja P, Puri P, Ning Q, Dhiman RK, Kumar R, Vijayaraghavan R, Khanna R, Maiwall R, Mohanka R, Moreau R, Gani RA, Loomba R, Mehtani R, Rajaram RB, Hamid SS, Palnitkar S, Lal S, Biswas S, Chirapongsathorn S, Agarwal S, Sachdeva S, Saigal S, Kumar SE, Violeta S, Singh SP, Mochida S, Mukewar S, Alam S, Lim SG, Alam S, Shalimar, Venishetty S, Sundaram SS, Shetty S, Bhatia S, Singh SA, Kottilil S, Strasser S, Shasthry SM, Maung ST, Tan SS, Treeprasertsuk S, Asthana S, Manekeller S, Gupta S, Acharya SK, K C S, Maharshi S, Asrani S, Dadhich S, Taneja S, Giri S, Singh S, Chen T, Gupta T, Kanda T, Tanwandee T, Piratvishuth T, Spengler U, Prasad VGM, Midha V, Rakhmetova V, Arroyo V, Sood V, Br VK, Wong VWS, Pamecha V, Singh V, Dayal VM, Saraswat VA, Kim WR, Jafri W, Gu W, Jun WY, Qi X, Chawla YK, Kim YJ, Shi Y, Abbas Z, Kumar G, Shiina S, Wei L, Omata M, Sarin SK. Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia. Hepatol Int 2025; 19:1-69. [PMID: 39961976 PMCID: PMC11846769 DOI: 10.1007/s12072-024-10773-4] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 12/29/2024] [Indexed: 02/23/2025]
Abstract
Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - A S Soin
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | | | - Abhijeet Chowdhury
- Institute of Post-Graduate Medical Education and Research (IPGMER), Kolkata, West Bengal, India
| | - Abraham Koshy
- VPS Lakeshore Hospital and Research Center Ltd, Kochi, Kerala, India
| | - Ajay Duseja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Ajay Kumar
- Govind Ballabh Pant Hospital, New Delhi, India
| | - Ajay Kumar Mishra
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | - Ajit Sood
- Dayanand Medical College, Ludhiana, India
| | - Akash Roy
- Apollo Multispeciality Hospital, Kolkata, India
| | - Akash Shukla
- Seth G S Medical College and K E M Hospital, Mumbai, Maharashtra, India
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Albert Chan
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Amar Mukund
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Amit Goel
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | | | | | - Andrés Cárdenas
- Univerity of Barcelona Institut d'Investigacions Biomèdiques August Pi-Sunyer, Barcelona, Spain
| | | | - Anil Arora
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Anil Chandra Anand
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | | | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anoop Saraya
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anshu Srivastava
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Anupam Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Apurva Pande
- Fortis Hospital, Greater Noida, Uttar Pradesh, India
| | - Archana Rastogi
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Arun Valsan
- Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India
| | - Ashish Goel
- Christian Medical College (CMC), Vellore, India
| | - Ashish Kumar
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Ashwani K Singal
- University of Louisville School of Medicine, Trager Transplant Center and Jewish Hospital, Louisville, KY, USA
| | | | - Audrey Coilly
- Centre Hepato-Biliaire, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Ayaskanta Singh
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Babu Lal Meena
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Bikrant Bihari Lal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - C E Eapen
- Christian Medical College (CMC), Vellore, India
| | - Cesar Yaghi
- Saint Joseph University, Hôtel-Dieu de France University Medical Center, Beirut, Lebanon
| | | | | | | | - Chen Yu
- Capital Medical University, Beijing, China
| | - Chetan R Kalal
- Nanavati Max Super Specialty Hospital, Mumbai, Maharashtra, India
| | - Chhagan Bihari
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Chitranshu Vasishtha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Christian Jansen
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | - Chun Yen Lin
- Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
| | | | - Cosmas Rinaldi Adithya Lesmana
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
- Medistra Hospital, Jakarta, Indonesia
| | | | | | | | | | | | | | | | | | | | - Dong-Sik Kim
- Korea University College of Medicine, Seoul, Republic of Korea
| | | | - Fazal Karim
- Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh
| | - Francois Durand
- Université de Paris, AP-HP, C, DMU DIGEST, Centre de Référence Des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de Recherche Sur L'inflammation, Inserm, Paris, France
| | | | - Gennaro D'Amico
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
- Clinica La Maddalena, Palermo, Italy
| | - George K Lau
- Humanity and Health Medical Center, Hongkong, SAR, China
| | | | - Graciela Elia Castro Narro
- Hospital Médica Sur, Mexico City, Mexico
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran",, Mexico City, Mexico
- Latin-American Association for the Study of the Liver (ALEH), Santiago de Chile, Chile
| | - Guan-Huei Lee
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Gupse Adali
- University of Health Sciences, Ümraniye, Istanbul, Turkey
| | | | - Gyongyi Szabo
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - H C Lin
- Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hai Li
- School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Hari Kumar Nair
- Ernakulam Medical Center (EMC), Kinder Multispeciality Hospital, Kochi, Kerala, India
| | | | - Harshvardhan Tevethia
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | | | - Irsan Hasan
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - J Fernandez
- University of Barcelona, IDIBAPS and CIBEREHD, Barcelona, Spain
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Jaideep Behari
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James Fung
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Jaya Benjamin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Jennifer C Lai
- University of California, San Francisco, San Francisco, CA, USA
| | - Jidong Jia
- Capital Medical University, Beijing, China
| | - Jin Hua Hu
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Jin Jun Chen
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Lin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Mo Yang
- The Catholic University of Korea, Seoul, Korea
| | - Johannes Chang
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jonel Trebicka
- Medizinische Klinik B, Universitätsklinikum Münster, Münster, Germany
| | - Jörg C Kalf
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jose D Sollano
- Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines
| | - Joy Varghese
- Gleneagles Global Hospital, Chennai, Tamil Nadu, India
| | - Juan Pablo Arab
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Schulich School of Medicine, Western University, London, ON, Canada
| | - Jun Li
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | | | - Kaiser Raja
- King's College Hospital London, Dubai, United Arab Emirates
| | - Kalpana Panda
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Kamal Kajal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Karan Kumar
- Mahatma Gandhi Medical College, Jaipur, Rajasthan, India
| | - Kaushal Madan
- Max Super Specialty Hospital Saket, New Delhi, India
| | - Kemal Fariz Kalista
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | | | - Khin Maung Win
- University of Medicine, Yangon Ministry of Health, Yangon, Myanmar
| | - Ki Tae Suk
- Hallym University, Chuncheon, Republic of Korea
| | | | | | - Lubna Kamani
- Liaquat National Hospital, Karachi, Sindh, Pakistan
| | - Madhumita Premkumar
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Mamun Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Man Fung Yuen
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Manasa Alla
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Manoj Sahu
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Manya Prasad
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Mark Dhinesh Muthiah
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Martin Schulz
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Meenu Bajpai
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Ming Lung Yu
- Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine, National Sun Yet-Sen University, Kaohsiung, Taiwan
| | | | - Mithun Sharma
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Mohd Golam Azam
- Endocrine and Metabolic Disorder (BIRDEM) Shahbad, Bangladesh Institute of Research and Rehabilitation in Diabetes, Dhaka, Bangladesh
| | - Mohd Rela
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Moreshwar S Desai
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | - Mukul Vij
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Nadim Mahmud
- University of Pennsylvania, Philadelphia, PA, USA
| | | | | | - Necati Ormeci
- İstanbul Health and Technology University, Istanbul, Turkey
| | - Neeraj Saraf
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | - Nipun Verma
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Norifumi Kawada
- Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Oidov Baatarkhuu
- Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | | | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chuo-Ku, Chiba, Japan
| | - P N Rao
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Paolo Angeli
- Department of Medicine (DIMED), University of Padova, Padua, Italy
| | | | | | | | - Philipp Lingohr
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Piyush Ranjan
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Pravin Rathi
- Topi Wala National (TN) Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | | | - Puneet Puri
- Virginia Commonwealth University, Richmond, VA, USA
| | - Qin Ning
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - R K Dhiman
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Rahul Kumar
- Changi General Hospital, Singapore, Singapore
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- Centre de Recherche Sur L'Inflammation (CRI), INSERM and Université Paris-Cité, Paris, France
- Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Beaujon, Service d'Hépatologie, Clichy, France
| | - Rino Alvani Gani
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - Rohit Loomba
- University of California, San Diego, La Jolla, CA, USA
| | - Rohit Mehtani
- Amrita Institute of Medical Sciences and Research Centre, Faridabad, Haryana, India
| | | | - S S Hamid
- Aga Khan University Hospital, Karachi, Pakistan
| | | | - Sadhna Lal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sagnik Biswas
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Samagra Agarwal
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Sanjiv Saigal
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | | | - Satender Pal Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Saurabh Mukewar
- Midas Multispeciality Hospital Pvt. Ltd, Nagpur, Maharashtra, India
| | - Seema Alam
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seng Gee Lim
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Shahinul Alam
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shalimar
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | | | - Shiran Shetty
- Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shobna Bhatia
- National Institute of Medical Sciences, Jaipur, India
| | | | - Shyam Kottilil
- University of Maryland School of Medicine, Baltimore, USA
| | | | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Soek Siam Tan
- Selayang Hospital, University of Malaysia, Batu Caves, Selangor, Malaysia
| | | | | | | | - Subhash Gupta
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | - Sudhamshu K C
- Bir Hospital, National Academy of Medical Sciences, Kathmandu, Nepal
| | - Sudhir Maharshi
- Sawai Man Singh (SMS) Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sumeet Asrani
- Baylor Simmons Transplant Institute, Dallas, TX, USA
| | - Sunil Dadhich
- Dr Sampuranand Medical College (SNMC), Jodhpur, Rajasthan, India
| | - Sunil Taneja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Suprabhat Giri
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Surender Singh
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Tao Chen
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tarana Gupta
- Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
| | - Tatsuo Kanda
- Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | | | | | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - V G Mohan Prasad
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | | | | | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Vikrant Sood
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vinay Kumar Br
- Mazumdar Shaw Medical Centre, Bangalore, Karnataka, India
| | | | - Viniyendra Pamecha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Virendra Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India
| | - Vishwa Mohan Dayal
- Indira Gandhi Institute of Medical Sciences, (IGIMS), Bely Road Patna, Bihar, India
| | | | - WRay Kim
- Stanford University, Stanford, CA, USA
| | - Wasim Jafri
- Aga Khan University Hospital, Karachi, Pakistan
| | - Wenyi Gu
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Wong Yu Jun
- Changi General Hospital, Singapore, Singapore
| | - Xiaolong Qi
- Medical School, Zhongda Hospital, Southeast University, Nanjing, China
| | - Yogesh K Chawla
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Yoon Jun Kim
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yu Shi
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Zaigham Abbas
- Ziauddin University Hospital Karachi, Karachi, Pakistan
| | - Guresh Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Lai Wei
- Changgung Hospital, Tsinghua University, Beijing, China
| | - Masao Omata
- Yamanashi Central Hospital, Yamanashi, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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7
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Kumar R, Ng LX, Wong YJ, Tan CK, Wang LZ, Qiu TY, Wong B, Lin KW, Li JW, Kwek AB, Ang TL, Gokhle RS, Sivanath TP. Rotational Thromboelastometry Reduces the Need for Preemptive Transfusion in Cirrhosis: A Randomized Controlled Trial (NCT:05698134). J Clin Exp Hepatol 2025; 15:102409. [PMID: 39391324 PMCID: PMC11462181 DOI: 10.1016/j.jceh.2024.102409] [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: 05/25/2024] [Accepted: 09/04/2024] [Indexed: 10/12/2024] Open
Abstract
Backgrounds and aim Viscoelastic tests (VET) like rotational thromboelastometry (ROTEM) assess global hemostasis in cirrhosis. We aimed to assess whether ROTEM-guided blood product transfusion results in lower blood product requirements in patients with cirrhosis undergoing elective invasive procedures as compared to standard of care (SOC) based on conventional coagulation test (CCT). Methods In this open label randomized controlled trial, patients with cirrhosis and abnormal CCT who were undergoing an invasive procedure were randomized to receive blood products either by ROTEM-guidance or SOC. The primary outcome was the difference in blood products (fresh frozen plasma (FFP) or platelets) transfused between the groups. The secondary outcome was procedure-related bleeding or complications within 7 days of the procedure. The trial protocol is registered at clinicaltrails.gov; NCT05698134. Results From August 2021 to January 2023, a total of 40 patients were recruited (ROTEM (n = 20) and SOC (n = 20)). The trial was terminated earlier during interim analyses due to compelling benefit in the ROTEM group after a scheduled interim analysis. The ROTEM group required substantially less blood transfusion than the SOC group (40% [8/20] vs 100% [20/20], P < 0.001). The benefit was consistent across all types of blood product, including fresh frozen plasma (<0.001) and pooled platelets (P = 0.046). No patients experienced clinically significant bleeding events. Transfusion-associated adverse events occurred in one patient (5%) in the SOC group (allergic reaction) and none in the ROTEM group (P = NS). The mortality in both groups at 30 and 90 days was similar. Conclusions Viscoelastic tests like ROTEM provide global assessment of hemostasis in patients with cirrhosis. Institution of ROTEM based transfusion strategy significantly reduces the need for blood product transfusion in patients with cirrhosis undergoing elective procedure without any increased risk of bleeding events. Clinical trial number NCT05698134.
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Affiliation(s)
- Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- DUKE-NUS Academic Medical Centre, Singapore
| | - Louis X.L. Ng
- Department of Anesthesia and Critical Care, Changi General Hospital, Singapore
| | - Yu J. Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- DUKE-NUS Academic Medical Centre, Singapore
| | - Chin K. Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Louis Z. Wang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Tian Y. Qiu
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Benny Wong
- Clinical Trials and Research Unit, Changi General Hospital Singapore
| | - Kenneth W. Lin
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - James W. Li
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Andrew B.E. Kwek
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Tiing L. Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Roshni S. Gokhle
- Department of Respiratory Medicine and Critical Care, Changi General Hospital, Singapore
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8
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Tanaka KA, Okada H, Butt AL, Vandyck KB, Ramarapu S, Maier CL, Sniecinski RM, Stewart KE. Use of coagulation factor concentrates and blood transfusion in cardiac surgery: a retrospective cohort study of adults with hereditary and acquired bleeding disorders. Br J Anaesth 2024; 133:1150-1158. [PMID: 39426922 DOI: 10.1016/j.bja.2024.07.041] [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: 03/16/2024] [Revised: 07/19/2024] [Accepted: 07/25/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Cardiac surgery poses a significant risk of perioperative bleeding and allogeneic blood transfusions, particularly in patients with bleeding disorders. Increasingly frequent use of coagulation factor concentrates could impact haemorrhagic risks, thromboembolic events, and costs. We describe the use of coagulation factor concentrates and allogeneic blood products in cardiac surgical patients with hereditary and acquired bleeding disorders to assess pertinent outcomes, including perioperative haemorrhage, thromboembolism, and hospital costs. METHODS We conducted a retrospective cohort study using the Premier Health Database, including adult cardiac surgical patients diagnosed with hereditary or acquired bleeding disorders compared with those without bleeding disorders. RESULTS Patients with acquired bleeding disorders required more extensive use of coagulation factor concentrates and blood products compared with those with hereditary bleeding disorders or without bleeding disorders. The highest exposures to coagulation factor concentrates were found in the acquired bleeding disorders group, with 24% receiving factor VIIa and 11.7% receiving prothrombin complex concentrate. This group also experienced significantly higher rates of complications, including a 15.8% rate of haemorrhage and a 19.2% rate of thromboembolic events. The acquired bleeding disorders group had longer intensive care and hospital stays, and the highest mortality rate (19.2%). The increased use of perioperative replacement of factor VIII and factor IX in the hereditary bleeding disorders group led to increased pharmacy costs but did not significantly impact blood bank charges. CONCLUSIONS Acquired bleeding disorders in cardiac surgery patients are associated with increased use of haemostatic interventions, postoperative complications, and increased healthcare costs. Improved management of perioperative haemostasis and thromboprophylaxis strategies are essential for optimising patient outcomes and reducing expenses.
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Affiliation(s)
- Kenichi A Tanaka
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
| | - Hisako Okada
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Amir L Butt
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Kofi B Vandyck
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Srikiran Ramarapu
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Cheryl L Maier
- Department of Pathology, Emory Healthcare, Atlanta, GA, USA
| | | | - Kenneth E Stewart
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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9
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Ferdinande K, Raevens S, Decaestecker J, De Vloo C, Seynhaeve L, Hoof L, Verhelst X, Geerts A, Devreese KMJ, Degroote H, Van Vlierberghe H. Unravelling the coagulation paradox in liver cirrhosis: challenges and insights. Acta Clin Belg 2024; 79:451-461. [PMID: 39981790 DOI: 10.1080/17843286.2025.2469906] [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: 12/16/2024] [Accepted: 02/15/2025] [Indexed: 02/22/2025]
Abstract
Patients with liver disease experience complex haemostatic changes leading to a state of 'rebalanced haemostasis' that may shift towards bleeding or thrombosis due to complications like kidney dysfunction, bacterial infection, or acute-on-chronic liver failure. Traditional coagulation tests inadequately capture haemostasis in cirrhosis, whereas advanced assays like thrombin generation assay and viscoelastic testing offer better insights but remain limited in clinical outcome prediction or guiding pre-procedural prophylaxis.Contrary to the traditional view of cirrhosis as a bleeding disorder, recent evidence highlights a paradox of higher venous thromboembolism incidence in hospitalised cirrhotic patients. Misconceptions about 'auto-anticoagulation' and concerns about anticoagulation safety hinder consistent thromboprophylaxis. Emerging data suggest that low molecular weight heparin is safe and effective in cirrhotic patients, supporting more evidence-based thromboprophylaxis. For thrombotic events or conditions like atrial fibrillation, therapeutic anticoagulation is recommended, and may offer additional benefits, such as attenuating liver fibrosis and portal hypertension. However, anticoagulation is not established as a core therapy in cirrhosis, given safety concerns in advanced disease.Bleeding remains a significant challenge in cirrhosis, with management focusing on specific aetiologies, including portal hypertension or procedural injuries. In pre-procedural planning, there is a trend of unnecessary blood product use, often based on an assumed bleeding risk. Rational pre-procedural planning should minimize unnecessary transfusions, optimise modifiable risks, and include a plan for managing potential bleeding.This review aims to clarify the 'coagulation paradox' in cirrhosis, promoting a nuanced, individualized approach to managing bleeding and thrombosis in chronic liver disease.
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Affiliation(s)
- K Ferdinande
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
- Department of Gastroenterology and Hepatology, AZ Delta Roeselare, Belgium
| | - S Raevens
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - J Decaestecker
- Department of Gastroenterology and Hepatology, AZ Delta Roeselare, Belgium
| | - C De Vloo
- Department of Gastroenterology and Hepatology, AZ Delta Roeselare, Belgium
| | - L Seynhaeve
- Department of Gastroenterology and Hepatology, AZ Delta Roeselare, Belgium
| | - L Hoof
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - X Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - A Geerts
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - K M J Devreese
- Coagulation Laboratory, Ghent University Hospital, Ghent, Belgium
- Department of Diagnostic Sciences, Ghent University, Belgium
| | - H Degroote
- Department of Gastroenterology and Hepatology, University Hospital Brussels, Belgium
| | - H Van Vlierberghe
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
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10
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Dai J, Su L. Perioperative Application of Point-of-care Test for Blood Viscoelasticity: A Good Choice for Coagulation Management. J Perianesth Nurs 2024:S1089-9472(24)00396-4. [PMID: 39520424 DOI: 10.1016/j.jopan.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 08/08/2024] [Accepted: 08/08/2024] [Indexed: 11/16/2024]
Abstract
Point-of-care test (POCT) of blood viscoelasticity can reflect the coagulation status of patients accurately and timely. POCT can be used to monitor the effect of preoperative antithrombotic drugs on coagulation function, which will inform the selection of appropriate surgical timing. It can also be applied to analyze the reasons of intraoperative bleeding and guide the transfusion of blood products. Also, it is useful to assess the risk of postoperative thromboembolism and hint the need for prophylactic anticoagulation. This article mainly introduces the principles and clinical application of several frequently used POCTs for blood viscoelasticity, with a focus on their role in special types of diseases in which coagulation function changes significantly, such as cardiac disease, trauma, pathological obstetrics, and liver disease. Furthermore, we describe the role of microparticle in coagulation, which is a novel potential biomarker for diagnosing thrombotic disorders and possesses potential to be applied in POCTs of blood viscoelasticity.
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Affiliation(s)
- Jiazhen Dai
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Lin Su
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.
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Blasi A, Calvo A, Mellado R, Torrente MA, Turon F, Garcia-Pagan JC, Hernandez-Gea V, Tassies D, Reverter JC, Lisman T. Comparable hemostatic capacity of blood taken from the portal vein compared with systemic blood in patients with cirrhosis. Res Pract Thromb Haemost 2024; 8:102583. [PMID: 39552771 PMCID: PMC11567948 DOI: 10.1016/j.rpth.2024.102583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/15/2024] [Accepted: 09/29/2024] [Indexed: 11/19/2024] Open
Affiliation(s)
- Annabel Blasi
- Anesthesia Department, Hospital Clinic Barcelona, Institut Investigació per a la Recerca Biomèdica Agustí Pi i Sunyé (IDIBAPS), Barcelona, Spain
| | - Andrea Calvo
- Anesthesia Department, Hospital Clinic Barcelona, Institut Investigació per a la Recerca Biomèdica Agustí Pi i Sunyé (IDIBAPS), Barcelona, Spain
| | - Ricard Mellado
- Anesthesia Department, Hospital Clinic Barcelona, Institut Investigació per a la Recerca Biomèdica Agustí Pi i Sunyé (IDIBAPS), Barcelona, Spain
| | | | - Fanny Turon
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RARE Liver), Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universitat de Barcelona, Barcelona, Spain
| | - Juan Carlos Garcia-Pagan
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RARE Liver), Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universitat de Barcelona, Barcelona, Spain
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RARE Liver), Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universitat de Barcelona, Barcelona, Spain
| | - Dolors Tassies
- Hemostasis Department, Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain
| | | | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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12
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van Dievoet MA, Zouaoui Boudjeltia K, Rousseaux M, Douxfils J, Lisman T, Stephenne X. Fibrinolytic profile depends on disease severity in pediatric patients with cirrhosis: illustration by 2 different plasma-based fibrinolysis assays. Res Pract Thromb Haemost 2024; 8:102551. [PMID: 39290990 PMCID: PMC11406019 DOI: 10.1016/j.rpth.2024.102551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/09/2024] [Accepted: 08/12/2024] [Indexed: 09/19/2024] Open
Affiliation(s)
- Marie-Astrid van Dievoet
- Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium
- Laboratory Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Karim Zouaoui Boudjeltia
- Laboratory of Experimental Medicine (Univeristé libre de Bruxelles, 222 Unit), Faculty of Medicine, Centre Hospitalier Universitaire de Charleroi, André Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul, Belgium
| | - Madeleine Rousseaux
- Laboratory Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Jonathan Douxfils
- Clinical Pharmacology and Toxicology Research Unit, Faculty of Medicine, Namur Research Institute for Life Sciences (NARILIS), Namur Thrombosis and Hemostasis Center, University of Namur, Namur, Belgium
- Research and Development Deparment, QUALIblood s.a., QUALIresearch, Liège, Belgium
| | - Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Deparment of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Xavier Stephenne
- Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Cliniques Universitaires Saint-Luc, Rare Liver European Reference Network, TransplantChild European Reference Network, Brussels, Belgium
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13
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Fernández J, Blasi A, Hidalgo E, Karvellas CJ. Bridging the critically ill patient with acute to chronic liver failure to liver transplantation. Am J Transplant 2024; 24:1348-1361. [PMID: 38548058 DOI: 10.1016/j.ajt.2024.03.026] [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: 12/21/2023] [Revised: 03/16/2024] [Accepted: 03/18/2024] [Indexed: 04/14/2024]
Abstract
Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute-on-chronic liver failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present, adversely impacting the prognosis of these patients. Management of critical care patients with ACLF is complex and requires the participation of different specialties. Once the patient is stabilized, a rapid evaluation for salvage LT should be performed because the time window for LT is often narrow. The development of sepsis and prolonged organ support may preclude LT or diminish its chances of success. The current review describes strategies to bridge severe ACLF patients to LT, highlights the minimal evaluation required for listing and the currently suggested contraindications to proceed with LT, and addresses different aspects of management during the perioperative and early posttransplant period.
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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.
| | - Annabel Blasi
- Anesthesiology Department, Hospital Clínic, and University of Barcelona, Spain
| | - Ernest Hidalgo
- Hepatolobiliary Surgery Department, Hospital Vall d'Hebron, Barcelona, Spain
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Canada; Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
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14
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Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O'Leary JG, Solà E, Subramanian R, Wong F, Asrani SK. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology 2024; 79:1463-1502. [PMID: 37939273 DOI: 10.1097/hep.0000000000000671] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
| | - Jasmohan S Bajaj
- Virginia Commonwealth University, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Jacqueline G O'Leary
- Department of Medicine, Dallas Veterans Medical Center, University of Texas Southwestern Medical Center Dallas, Texas, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
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15
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Jardim LL, Franco MB, de Oliveira NR, de Carvalho BN, Basques F, Ribeiro DD, Lisman T, Pereira LS, Rezende SM. Hypocoagulability in severe yellow fever infection is associated with bleeding: results from a cohort study. Res Pract Thromb Haemost 2024; 8:102427. [PMID: 38817949 PMCID: PMC11137573 DOI: 10.1016/j.rpth.2024.102427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 04/12/2024] [Accepted: 04/19/2024] [Indexed: 06/01/2024] Open
Abstract
Background Severe yellow fever infection (YFI) may be complicated by a hemorrhagic diathesis. However, the hemostasis profile of YFI has rarely been reported. Objectives The aim of this study was to characterize the hemostatic features of YFI by using a rotational thromboelastometry (ROTEM). Methods We evaluated clinical, laboratory, and ROTEM parameters in adults with severe YFI and their correlation with hemostatic variables according to bleeding and death. Results A total of 35 patients were included (median age, 49 years). ROTEM was performed in 22 patients, of whom 21 (96%) presented bleeding and 4 (18%) died. All patients who died had major bleeding. Patients who died presented prolonged clotting time (CT; median, 2326 seconds; IQR, 1898-2986 seconds) and reduced alpha angle (median, 12°; IQR, 12°-15°) in comparison with patients who had minor (median CT, 644 seconds; IQR, 552-845 seconds and alpha angle, 47°; IQR, 28°-65°) and major (median CT, 719 seconds; IQR, 368-1114 seconds and alpha angle, 43°; IQR, 32°-64°) bleeding who survived. In patients who had bleeding, CT showed a strong negative correlation with factor (F)V (r = -.68), FIX (r = -.84), and FX (r = -.63) as well as alpha angle showed a strong negative correlation with FIX (r = -.92). In patients who died, the correlations were even stronger. A total of 19/21 (90%) patients presented hypocoagulability assessed by ROTEM. Conclusion Hypocoagulabitity is the hallmark of the bleeding diathesis of severe YFI. Abnormal CT and alpha angle associated with death and could be used as potential predictors of adverse outcome in severe YFI.
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Affiliation(s)
- Leticia Lemos Jardim
- Instituto René Rachou (Fiocruz Minas), Belo Horizonte, Minas Gerais, Brazil
- Faculty of Medical Sciences of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Mariana Brandão Franco
- Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Neimy Ramos de Oliveira
- Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Beatriz Nogueira de Carvalho
- Fundação Centro de Hematologia e Hemoterapia do Estado de Minas Gerais (HEMOMINAS), Belo Horizonte, Minas Gerais, Brazil
| | - Fernando Basques
- Fundação Centro de Hematologia e Hemoterapia do Estado de Minas Gerais (HEMOMINAS), Belo Horizonte, Minas Gerais, Brazil
| | - Daniel Dias Ribeiro
- Hematology Unit, University Hospital, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Leonardo Soares Pereira
- Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Suely Meireles Rezende
- Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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16
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Qiu S, Zhang Q, Hu J, Wang L, Chen R, Cao Y, Liu F, Yu Z, Zhao C, Zhang L, Ren W, Xin S, Chen Y, Duan Z, Han T. Impact of Onset Time, Number, Type, and Sequence of Extrahepatic Organ Failure on Prognosis of Acute-on-chronic Liver Failure. J Clin Transl Hepatol 2024; 12:257-265. [PMID: 38426199 PMCID: PMC10899869 DOI: 10.14218/jcth.2023.00379] [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: 08/22/2023] [Revised: 11/02/2023] [Accepted: 12/18/2023] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND AND AIMS The impact of the characteristics of extrahepatic organ failure (EHOF) including the onset time, number, type, and sequence on the prognosis of acute-on-chronic liver failure (ACLF) patients remains unknown. This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients. METHODS ACLF subjects enrolled at six hospitals in China were included in the analysis. The risk of mortality based on the characteristics of EHOF was evaluated. Survival of study groups was compared by Kaplan-Meier analysis and log-rank tests. RESULTS A total of 736 patients with ACLF were included. EHOF was observed in 402 patients (54.6%), of which 295 (73.4%) developed single EHOF (SEHOF) and 107 (26.6%) developed multiple EHOF (MEHOF). The most commonly observed EHOF was coagulation failure (47.0%), followed by renal (13.0%), brain (4.9%), respiratory (4.3%), and circulatory (2.3%) failure. Survival analysis found that MEHOF or SEHOF patients with brain failure had a worse prognosis. However, no significant outcome was found in the analysis of the effect of onset time and sequence of failed organs on prognosis. Patients were further divided into three risk subgroups by the EHOF characteristics. Kaplan-Meier analysis showed that risk stratification resulted in the differentiation of patients with different risks of mortality both in the training and validation cohorts. CONCLUSIONS The mortality of ACLF patients was determined by the number and type, but not the onset time and sequence of EHOF. Risk stratification applicable to clinical practice was established.
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Affiliation(s)
- Shaotian Qiu
- The School of Medicine, Nankai University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, China
| | - Qian Zhang
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin, China
- Tianjin Medical University, Tianjin, China
| | - Jiaxuan Hu
- The School of Medicine, Nankai University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, China
| | - Lewei Wang
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center of Tianjin Medical University, Tianjin, China
| | - Rui Chen
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center of Tianjin Medical University, Tianjin, China
| | - Yingying Cao
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Fang Liu
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Zhenjun Yu
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin, China
| | - Caiyan Zhao
- Department of Infectious Disease, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Liaoyun Zhang
- Department of Infection Disease, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Wanhua Ren
- Infectious Department of Shandong First Medical University Affiliated Shandong Provincial Hospital, Jinan, Shandong, China
| | - Shaojie Xin
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yu Chen
- Liver Disease Center (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Zhongping Duan
- Liver Disease Center (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Tao Han
- The School of Medicine, Nankai University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center Affiliated to Nankai University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin, China
- Tianjin Medical University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center of Tianjin Medical University, Tianjin, China
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
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17
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Tripodi A, Primignani M, D'Ambrosio R, Tosetti G, La Mura V, Lampertico P, Peyvandi F. Reappraisal of the conventional hemostasis tests as predictors of perioperative bleeding in the era of rebalanced hemostasis in cirrhosis. Hepatology 2024:01515467-990000000-00718. [PMID: 38214562 DOI: 10.1097/hep.0000000000000756] [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] [Received: 09/11/2023] [Accepted: 11/24/2023] [Indexed: 01/13/2024]
Abstract
New global laboratory procedures mimicking the in vivo hemostasis process led to the changing paradigm of cirrhosis from the prototype of hemorrhagic diseases to a condition in which hemostasis is normal but fragile, thus justifying the hemorrhagic/thrombotic tendencies that affect these patients. The new paradigm was instrumental to change the management of cirrhosis. For example, international guidelines warn against the entrenched practice of testing patients with conventional hemostasis tests and infusing those with abnormalities with fresh-frozen plasma, coagulation factor concentrates, or platelets, prior to surgery/invasive procedures. These recommendations are, however, largely disattended. The practice of testing patients with the prothrombin time or viscoelastometry and using arbitrary cutoffs to make decisions on perioperative prophylaxis is still common and probably driven by medicolegal issues. There is no doubt that prothrombin time and congeners tests are unable to predict bleeding in cirrhosis. However, it cannot be excluded that some tests may be useful in patients who are severely decompensated. Large prospective collaborative studies are warranted. Enrolled patients should be randomized to receive perioperative prophylaxis based on laboratory testing (eg, viscoelastometry, thrombomodulin-modified thrombin generation) or to usual care. However, for these trials to be useful, a third group of patients who do not receive prophylaxis should be included. In conclusion, until results from these studies are available, physicians attending cirrhosis should refrain from using laboratory tests with arbitrary cutoffs to make decision on perioperative prophylaxis. Decision should be made by considering the clinical history of individual patients and the risk of hemorrhage of specific procedures.
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Affiliation(s)
- Armando Tripodi
- IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
| | - Massimo Primignani
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Roberta D'Ambrosio
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giulia Tosetti
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Vincenzo La Mura
- IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, CRC "A. M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Flora Peyvandi
- IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy
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18
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Kampelos G, Alexopoulos T, Vasilieva L, Mani I, Hadziyannis E, Giannouli S, Manioudaki S, Nomikou E, Alexopoulou A. A combination of clot formation abnormalities in thromboelastometry has a high prognostic value in patients with acute-on-chronic liver failure. Eur J Gastroenterol Hepatol 2024; 36:76-82. [PMID: 37823404 DOI: 10.1097/meg.0000000000002630] [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] [Indexed: 10/13/2023]
Abstract
BACKGROUND Global coagulation tests offer a better tool to assess procoagulant and anticoagulant pathways, fibrinolysis and clot firmness and evaluate more accurately coagulation defects compared to conventional coagulation tests. Their prognostic role in acute-on-chronic liver disease (ACLF) or acute decompensation (AD) has not been well established. AIMS To assess the properties and prognostic value of the coagulation profile measured by rotational thromboelastometry (ROTEM) in ACLF and AD. METHODS 84 consecutive patients (35 ACLF and 49 AD) were prospectively studied. Twenty healthy persons matched for age and gender were used as controls. 'Hypocoagulable' or 'hypercoagulable' profiles on admission were assessed based on nine ROTEM parameters and mortality was recorded at 30 and 90 days. RESULTS Individual ROTEM parameters denoted significantly more hypocoagulability in patients compared to controls. 'Hypocoagulable' profile (defined as a composite of 4 or more ROTEM parameters outside the range) was associated with more severe liver disease assessed either as MELD or Child-Pugh scores ( P < 0.001 for both) and higher 30-day mortality (Log-rank P = 0.012). 'Hypocoagulable' profile (HR 3.160, 95% CI 1.003-9.957, P = 0.049) and ACLF status (HR 23.786, 95% CI 3.115-181.614, P = 0.002) were independent predictors of 30-day mortality, in multivariate model. A higher early mortality rate was shown in ACLF patients with 'hypocoagulable' phenotype compared to those without (Log-rank P = 0.017). 'Hypocoagulable' profile was not associated with mortality in AD. CONCLUSION 'Hypocoagulable' profile was associated with more advanced liver disease and higher short-term mortality in patients with ACLF.
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Affiliation(s)
- George Kampelos
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital
| | - Theodoros Alexopoulos
- Gastroenterology Department, National & Kapodistrian University of Athens, Medical School, Laiko General Hospital
| | | | - Iliana Mani
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital
| | - Stavroula Giannouli
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital
| | | | - Efrosyni Nomikou
- Blood Bank and Haemophilia Unit, Hippokratio General Hospital of Athens, Athens, Greece
| | - Alexandra Alexopoulou
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital
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19
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Aiza-Haddad I, Cisneros-Garza LE, Morales-Gutiérrez O, Malé-Velázquez R, Rizo-Robles MT, Alvarado-Reyes R, Barrientos-Quintanilla LA, Betancourt-Sánchez F, Cerda-Reyes E, Contreras-Omaña R, Dehesa-Violante MB, Flores-García NC, Gómez-Almaguer D, Higuera-de la Tijera MF, Lira-Pedrin MA, Lira-Vera JE, Manzano-Cortés H, Meléndez-Mena DE, Muñoz-Ramírez MR, Pérez-Hernández JL, Ramos-Gómez MV, Sánchez-Ávila JF. Guidelines for the management of coagulation disorders in patients with cirrhosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:144-162. [PMID: 38600006 DOI: 10.1016/j.rgmxen.2023.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 08/07/2023] [Indexed: 04/12/2024]
Abstract
Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.
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Affiliation(s)
- I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Mexico City, Mexico.
| | - L E Cisneros-Garza
- Departamento de Gastroenterología y Hepatología, Hospital Christus Muguerza Alta Especialidad, Monterrey, Mexico
| | - O Morales-Gutiérrez
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | | | - M T Rizo-Robles
- Departamento de Gastroenterología y Hepatología, Instituto Mexicano del Seguro Social Centro Médico Nacional «La Raza», Mexico City, Mexico
| | - R Alvarado-Reyes
- Departamento de Hepatología, Hospital San José Tec Salud, Monterrey, Mexico
| | | | | | - E Cerda-Reyes
- Servicio de Gastroenterología, Hospital Central Militar, Mexico City, Mexico
| | - R Contreras-Omaña
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología (CIEHG) Pachuca, Hidalgo, México
| | | | - N C Flores-García
- Escuela de Medicina y Ciencias de la Salud. Tecnológico de Monterrey, Monterrey Nuevo Leon, México
| | | | - M F Higuera-de la Tijera
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | - M A Lira-Pedrin
- Departamento de Gastroenterología, Endoscopía Digestiva, Motilidad y Hepatología, Centro Médico Corporativo Galeana, Tijuana, México
| | - J E Lira-Vera
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | | | - D E Meléndez-Mena
- Hospital General de Especialidades «Maximino Ávila Camacho», IMSS, UMAE, Puebla, México
| | - M R Muñoz-Ramírez
- Departamento de Hepatología, Hospital San José Tec Salud, Monterrey, Mexico
| | - J L Pérez-Hernández
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | - M V Ramos-Gómez
- Departamento Hepatología, ISSSTE, Centro Médico Nacional «20 de noviembre», Ciudad de México, México
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud. Tecnológico de Monterrey, Monterrey Nuevo Leon, México
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20
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Torre A, Cisneros-Garza LE, Castillo-Barradas M, Navarro-Alvarez N, Sandoval-Salas R, González-Huezo MS, Pérez-Hernández JL, Méndez-Guerrero O, Ruiz-Manríquez JA, Trejo-Estrada R, Chavez-Tapia NC, Solís-Gasca LC, Moctezuma-Velázquez C, Aguirre-Valádez J, Flores-Calderón J, Higuera-de-la-Tijera F, García-Juárez I, Canedo-Castillo NA, Malé-Velázquez R, Montalvo-Gordon I, Vilatobá M, Márquez-Guillén E, Córdova-Gallardo J, Flores-García NC, Miranda-Zazueta G, Martínez-Saldívar BI, Páez-Zayas VM, Muñoz-Espinosa LE, Solís-Galindo FA. Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology. Ann Hepatol 2023; 28:101140. [PMID: 37482299 DOI: 10.1016/j.aohep.2023.101140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 07/25/2023]
Abstract
Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - Laura Esthela Cisneros-Garza
- Gastroenterology and Hepatology Department, Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - Nalu Navarro-Alvarez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Osvely Méndez-Guerrero
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Luis Carlos Solís-Gasca
- Gastroenterology Department, Hospital General de Zona #12 Benito Juárez del Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Medicine - Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | | | - Judith Flores-Calderón
- Pediatrics Department, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Iaarah Montalvo-Gordon
- Clinic of Gastrointestinal and Hepatic Specialties, Hospital Faro del Mayab, Mérida, Yucatán, Mexico
| | - Mario Vilatobá
- Transplant Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ernesto Márquez-Guillén
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Ángeles del Pedregal, Mexico City, Mexico
| | - Jacqueline Córdova-Gallardo
- Hepatology Department - General Surgery Service, Hospital General Dr. Manuel Gea González, Mexico City, Mexico
| | - Nayeli Cointa Flores-García
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Linda Elsa Muñoz-Espinosa
- Universidad Autónoma de Nuevo León. Liver Unit, Department of Internal Medicine, University Hospital 'Dr. José E. González', Monterrey, Nuevo León, Mexico
| | - Francisco Alfonso Solís-Galindo
- Gastroenterology Department, Unidad Médica de Alta Especialidad # 71 Instituto Mexicano del Seguro Social, Torreón, Coahuila, Mexico
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21
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Driever EG, Muntz I, Patel V, Adelmeijer J, Bernal W, Koenderink GH, Lisman T. Fibrin clots from patients with acute-on-chronic liver failure are weaker than those from healthy individuals and patients with sepsis without underlying liver disease. J Thromb Haemost 2023; 21:2747-2758. [PMID: 37336436 DOI: 10.1016/j.jtha.2023.06.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/09/2023] [Accepted: 06/04/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND Previous studies identified decreased clot permeability, without differences in fibrin fiber density in clots, from patients with cirrhosis compared with those from healthy controls (HCs). Fibrinogen hypersialylation could be the reason for this discrepancy. OBJECTIVES The aim of this work was to study mechanical properties of clots and reassess clot permeability in relation to hypersialylation in patients with stable cirrhosis, acute decompensation, and acute-on-chronic liver failure (ACLF). Sepsis patients without liver disease were included to distinguish between liver-specific and inflammation-driven phenotypes. METHODS Pooled plasma was used for rheology and permeability experiments. Permeability was assessed with compression using a rheometer and by liquid permeation. Purified fibrinogen treated with neuraminidase was used to study the effects of fibrinogen hypersialylation on liquid permeation. RESULTS Mechanical properties of clots from patients with stable cirrhosis and acute decompensation were similar to those of clots from HCs, but clots from patients with ACLF were softer and ruptured at lower shear stress. Clots from sepsis patients without liver disease were stiffer than those from the other groups, but this effect disappeared after adjusting for increased plasma fibrinogen concentrations. Permeability was similar between clots under compression from HCs and clots under compression from patients but decreased with increasing disease severity in liquid permeation. Removal of fibrinogen sialic acid residues increased permeability more in patients than in controls. CONCLUSION Clots from patients with ACLF have weak mechanical properties despite unaltered fibrin fiber density. Previous liquid permeation experiments may have erroneously concluded that clots from patients with ACLF are prothrombotic as fibrinogen hypersialylation leads to underestimation of clot permeability in this setting, presumably due to enhanced water retention.
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Affiliation(s)
- Ellen G Driever
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Iain Muntz
- Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands
| | - Vishal Patel
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Jelle Adelmeijer
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - William Bernal
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Gijsje H Koenderink
- Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
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22
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Intagliata NM, Rahimi RS, Higuera-de-la-Tijera F, Simonetto DA, Farias AQ, Mazo DF, Boike JR, Stine JG, Serper M, Pereira G, Mattos AZ, Marciano S, Davis JPE, Benitez C, Chadha R, Méndez-Sánchez N, deLemos AS, Mohanty A, Dirchwolf M, Fortune BE, Northup PG, Patrie JT, Caldwell SH. Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study. Gastroenterology 2023; 165:717-732. [PMID: 37271290 DOI: 10.1053/j.gastro.2023.05.046] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 05/04/2023] [Accepted: 05/11/2023] [Indexed: 06/06/2023]
Abstract
BACKGROUND & AIMS Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. METHODS Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. RESULTS A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31). CONCLUSIONS Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.
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Affiliation(s)
| | | | | | | | | | - Daniel F Mazo
- School of Medical Sciences of University of Campinas (UNICAMP), São Paulo, Brazil
| | - Justin R Boike
- Northwestern University Feinburg School of Medicine, Chicago, Illinois
| | - Jonathan G Stine
- Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania
| | - Marina Serper
- University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Gustavo Pereira
- Bonsucesso Federal Hospital (Ministry of Health), Rio de Janeiro, Brazil, and Estácio de Sá School of Medicine-Instituto de Educação Médica, Rio de Janeiro, Brazil
| | - Angelo Z Mattos
- Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | | | | | - Carlos Benitez
- Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Nahum Méndez-Sánchez
- Medica Sur Clinic & Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Andrew S deLemos
- Wake Forest University School of Medicine, Atrium Health, Charlotte, North Carolina
| | - Arpan Mohanty
- Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts
| | | | - Brett E Fortune
- Montefiore Einstein Center for Transplantation, New York, New York
| | | | - James T Patrie
- University of Virginia School of Medicine, Charlottesville, Virginia
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23
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Mücke MM, Bruns T, Canbay A, Matzdorff A, Tacke F, Tiede A, Trebicka J, Wedemeyer H, Zacharowski K, Zeuzem S, Lange CM. [Use of Thrombopoetin-Receptor-Agonists (TPO-RA) in patients with liver cirrhosis before invasive procedures]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1225-1234. [PMID: 36377140 DOI: 10.1055/a-1934-1867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Advanced chronic liver disease is accompanied with relevant changes in the corpuscular and plasmatic coagulation system. Due to thrombocytopenia that is regularly observed in these patients, platelet transfusions are often performed prior invasive procedures to prevent possible bleeding complications. However, platelet transfusions are associated with clinically significant adverse events and economically relevant health care costs. Thus, avoiding unnecessary platelet transfusions remains pivotal in daily clinical practice. The first step is to carefully check if increasing platelet counts prior to a planned invasive procedure is really necessary. Nowadays, two well-tolerated thrombopoetin-receptor agonists (TPO-RAs), Avatrombopaq and Lusutrombopaq, to treat thrombocytopenia preemptively before an invasive procedure in patients with liver cirrhosis are available. This review provides a guide for clinician when to increase platelet counts prior an invasive procedure in patients with liver cirrhosis and helps to identify situations in which the use of TPO-RA may be reasonable.
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Affiliation(s)
- Marcus M Mücke
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
| | - Tony Bruns
- Medizinische Klinik III, Uniklinik RWTH Aachen, Rheinisch-Westfaelische Technische Hochschule, Aachen, Germany
| | - Ali Canbay
- Klinik für Innere Medizin, Universitätsklinikum des Knappschaftskrankenhauses Bochum, Bochum, Germany
| | - Axel Matzdorff
- Klinik für Innere Medizin II, Asklepios Klinikum Uckermark GmbH, Schwedt/Oder, Germany
| | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Tiede
- Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule, Hannover, Germany
| | - Jonel Trebicka
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
- Medizinische Klinik B, Universitätsklinikum Münster, Westfälische Wilhelms Universität Münster, Münster, Germany
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Kai Zacharowski
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe Universität, Frankfurt am Main, Germany
| | - Christian M Lange
- Klinik und Poliklinik für Innere Medizin II, LMU Klinikum München, München, Germany
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24
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Vinayagamoorthy V, Srivastava A, Das I, Verma A, Mishra P, Sen Sarma M, Poddar U, Yachha SK. Hypocoagulability in Children With Decompensated Chronic Liver Disease and Sepsis: Assessment by Thromboelastography. JPGN REPORTS 2023; 4:e324. [PMID: 37600623 PMCID: PMC10435032 DOI: 10.1097/pg9.0000000000000324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 04/27/2023] [Indexed: 08/22/2023]
Abstract
Objective To evaluate the coagulation status of children with decompensated chronic liver disease (DCLD) and infection and factors affecting it using thromboelastography (TEG). Methods Coagulation status of children admitted with DCLD and infection was assessed by international normalized ratio (INR), platelet count, and TEG [reaction time (R), kinetic time (K), α-angle (AA), maximum amplitude (MA), coagulation index (CI), and lysis index (LY30)] at admission and at 7-14 days after treatment. CI < -3 represents hypocoagulable state. Clinical profile including systemic inflammatory response syndrome (SIRS), infection severity, bleeding, treatment response, and outcome were noted. Results Thirty children (21 boys, median (IQR) age 78 [15.7-180] months) were studied prospectively. At admission, 29 (96.7%) had prolonged INR, 24 (80%) had thrombocytopenia, and 17 (56.6%) were hypocoagulable by TEG. Nine of 30 (30%) had normal TEG but deranged INR and platelets. Nineteen (63.3%) cases had SIRS, 11 (36.6%) had severe sepsis, and 8 (26.6%) had bleeding. Hypocoagulable state was common in severe sepsis than sepsis/infection (81.1% versus 42.1%; P = 0.05) and persistent (n = 4) versus recovered SIRS (n = 15, 100% versus 33%; P = 0.03). Bleeders had prolonged R-time (7.8 versus 5.4 min; P = 0.03), smaller MA (30.2 versus 47 mm; P = 0.05), and α-angle (40.4 versus 62.9; P = 0.03) but similar INR and platelets than nonbleeders. Six patients (20%) had poor in-hospital outcomes; R-time ≥8.5 min predicted mortality with high sensitivity (83%) and specificity (100%). Conclusions Fifth-seven percent of children with DCLD and infection were hypocoagulable by TEG. Severe sepsis and persistent SIRS worsened the coagulation status. TEG identifies bleeders better than INR and platelet count. R-time ≥8.5 min predicts a poor hospital outcome.
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Affiliation(s)
- Vignesh Vinayagamoorthy
- From the Department of Paediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anshu Srivastava
- From the Department of Paediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Indranil Das
- Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anupam Verma
- Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Prabhakar Mishra
- Department of Biostatistics and Health Informatics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Moinak Sen Sarma
- From the Department of Paediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Ujjal Poddar
- From the Department of Paediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Surender Kumar Yachha
- From the Department of Paediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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25
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Scheinberg AR, Martin P, Bhamidimarri KR. The Clinical Spectrum and Manifestations of Acute-on-Chronic Liver Failure. Clin Liver Dis 2023; 27:671-680. [PMID: 37380290 DOI: 10.1016/j.cld.2023.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is characterized by abrupt decompensation in a patient with chronic liver disease with extrahepatic organ dysfunction and is implicated in an increased risk of mortality. ACLF may be present in approximately 20% to 40% of hospitalized cirrhosis. There are several diagnostic scoring systems for ACLF; one defined by the North American Consortium for Study of End-stage Liver Disease is the presence of acutely decompensated cirrhosis complicated by failure of two or more organ systems: circulatory, renal, neurological, coagulopathy, and/or pulmonary.
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Affiliation(s)
- Andrew R Scheinberg
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA.
| | - Kalyan Ram Bhamidimarri
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA
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26
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Reverter E, Toapanta D, Bassegoda O, Zapatero J, Fernandez J. Critical Care Management of Acute-on-Chronic Liver Failure: Certainties and Unknowns. Semin Liver Dis 2023; 43:206-217. [PMID: 37369227 DOI: 10.1055/s-0043-1769907] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
Intensive care unit (ICU) admission is frequently required in patients with decompensated cirrhosis for organ support. This entity, known as acute-on-chronic liver failure (ACLF), is associated with high short-term mortality. ICU management of ACLF is complex, as these patients are prone to develop new organ failures and infectious or bleeding complications. Poor nutritional status, lack of effective liver support systems, and shortage of liver donors are also factors that contribute to increase their mortality. ICU therapy parallels that applied in the general ICU population in some complications but has differential characteristics in others. This review describes the current knowledge on critical care management of patients with ACLF including organ support, prognostic assessment, early liver transplantation, and futility rules. Certainties and knowledge gaps in this area are also discussed.
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Affiliation(s)
- Enric Reverter
- Liver ICU, Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - David Toapanta
- Liver ICU, Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Octavi Bassegoda
- Liver ICU, Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Juliana Zapatero
- Liver ICU, Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
- European Foundation for the Study of Chronic Liver Failure, EASL-CLIF, Consortium, Barcelona, Spain
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27
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Abstract
Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness.
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Affiliation(s)
- Thomas N Smith
- Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Alice Gallo de Moraes
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
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28
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Ngu NLY, Flanagan E, Bell S, Le ST. Acute-on-chronic liver failure: Controversies and consensus. World J Gastroenterol 2023; 29:232-240. [PMID: 36687118 PMCID: PMC9846945 DOI: 10.3748/wjg.v29.i2.232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/01/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease. Consequences include high short-term morbidity, mortality, and healthcare resource utilisation. ACLF encompasses a dysregulated, systemic inflammatory response, which can precipitate extra hepatic organ failures. Common precipitants include infection, alcoholic hepatitis, and reactivation of viral hepatitis although frequently no cause is identified. Heterogenous definitions, diagnostic criteria, and treatment guidelines, have been proposed by international hepatology societies. This can result in delayed or missed diagnoses of ACLF, significant variability in clinical management, and under-estimation of disease burden. Liver transplantation may be considered but the mainstay of treatment is organ support, often in the intensive care unit. This review will provide clarity around where are the controversies and consensus in ACLF including: Epidemiology and resource utilisation, key clinical and diagnostic features, strategies for management, and research gaps.
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Affiliation(s)
- Natalie L Y Ngu
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
- Department of Gastroenterology and Hepatology, Alfred Health, Melbourne 3004, Victoria, Australia
| | - Eliza Flanagan
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
- Monash digital Therapeutics and Innovation Laboratory (MoTILa), Monash University, Clayton 3168, Victoria, Australia
| | - Sally Bell
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
| | - Suong T Le
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
- Monash digital Therapeutics and Innovation Laboratory (MoTILa), Monash University, Clayton 3168, Victoria, Australia
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29
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Llancalahuen FM, Vallejos A, Aravena D, Prado Y, Gatica S, Otero C, Simon F. α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1408:65-82. [PMID: 37093422 DOI: 10.1007/978-3-031-26163-3_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/25/2023]
Abstract
Stimulation of a1-adrenergic nervous system is increased during systemic inflammation and other pathological conditions with the consequent adrenergic receptors (ARs) activation. It has been reported that a1-stimulation contributes to coagulation since a1-AR blockers inhibit coagulation and its organic consequences. Also, coagulation induced by a1-AR stimulation can be greatly decreased using a1-AR blockers. In health, endothelial cells (ECs) perform anticoagulant actions at cellular and molecular level. However, during inflammation, ECs turn dysfunctional promoting a procoagulant state. Endothelium-dependent coagulation progresses at cellular and molecular levels, promoting endothelial acquisition of procoagulant properties to potentiate coagulation by means of prothrombotic and antifibrinolytic proteins expression increase in ECs releasing them to circulation, the thrombus formation is strengthened. Calcium signaling is a main feature of coagulation. Inhibition of ion channels involved in Ca2+ entry severely decreases coagulation. The transient receptor potential canonical 6 (TRPC6) is a non-selective Ca2+-permeable ion channel. TRPC6 activity is induced by diacylglycerol, suggesting that is regulated by a1-ARs. Furthermore, a1-ARs stimulation elicits a TRPC-like current in rat mesenteric artery smooth muscle and mesangial cells. However, whether TRPC6 could promote an ECs-mediated platelet adhesion induced by a1-adrenergic stimulation is currently not known. Therefore, the aim of this study was to examine if the TRPC6 calcium channel mediates platelet adhesion induced by a1-adrenergic stimulation. Our results suggest that platelet adhesion to ECs is enhanced by the a1-adrenergic stimulation evoked by phenylephrine mediated by TRPC6 activity. We conclude that TRPC6 is a molecular determinant in platelet adhesion to ECs with implications in systemic inflammatory diseases treatment.
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Affiliation(s)
- Felipe M Llancalahuen
- Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Alejando Vallejos
- Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Diego Aravena
- Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Yolanda Prado
- Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Sebastian Gatica
- Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Carolina Otero
- Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
| | - Felipe Simon
- Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
- Millennium Nucleus of Ion Channel-Associated Diseases, Santiago, Chile.
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Lisman T. Bleeding and thrombosis in cirrhosis. CARDIO-HEPATOLOGY 2023:165-202. [DOI: 10.1016/b978-0-12-817394-7.00010-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Tomić Mahečić T, Baronica R, Mrzljak A, Boban A, Hanžek I, Karmelić D, Babić A, Mihaljević S, Meier J. Individualized Management of Coagulopathy in Patients with End-Stage Liver Disease. Diagnostics (Basel) 2022; 12:3172. [PMID: 36553179 PMCID: PMC9777026 DOI: 10.3390/diagnostics12123172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/02/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Over the last decades, individualized approaches and a better understanding of coagulopathy complexity in end-stage liver disease (ESLD) patients has evolved. The risk of both thrombosis and bleeding during minimally invasive interventions or surgery is associated with a worse outcome in this patient population. Despite deranged quantitative and qualitative coagulation laboratory parameters, prophylactic coagulation management is unnecessary for patients who do not bleed. Transfusion of red blood cells (RBCs) and blood products carries independent risks for morbidity and mortality, including modulation of the immune system with increased risk for nosocomial infections. Optimal coagulation management in these complex patients should be based on the analysis of standard coagulation tests (SCTs) and viscoelastic tests (VETs). VETs represent an individualized approach to patients and can provide information about coagulation dynamics in a concise period of time. This narrative review will deliver the pathophysiology of deranged hemostasis in ESLD, explore the difficulties of evaluating the coagulopathies in liver disease patients, and examine the use of VET assays and management of coagulopathy using coagulation factors. Methods: A selective literature search with PubMed as the central database was performed with the following.
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Affiliation(s)
- Tina Tomić Mahečić
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Robert Baronica
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Liver Transplant Center, Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Ana Boban
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Department of Hematology, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Ivona Hanžek
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Dora Karmelić
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Anđela Babić
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Slobodan Mihaljević
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Jens Meier
- Clinic of Anesthesiology and Intensive Care Medicine, Kepler University Clinic, Johannes Kepler University, 4040 Linz, Austria
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Li X, Zhang L, Pu C, Tang S. Liver transplantation in Acute-on-Chronic liver failure: Timing of transplantation and selection of patient population. Front Med (Lausanne) 2022; 9:1030336. [PMID: 36569133 PMCID: PMC9773247 DOI: 10.3389/fmed.2022.1030336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 11/21/2022] [Indexed: 12/13/2022] Open
Abstract
Acute-on-Chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality. Alcoholic ACLF is prevalent in European and American countries, while hepatitis B virus (HBV)-related ACLF is more common in the Asia-Pacific region. There is still a lack of a unified definition standard for ACLF, due to various etiologies and pathogeneses in different continents. Currently, liver transplantation (LT) is the most effective treatment for liver failure. However, the shortage of liver sources is still a global problem, which seriously limits the clinical application of an LT. Premature LT aggravates the shortage of liver resources to a certain extent, and too much delay significantly increases the risk of complications and death. Therefore, this study reviews the current literature on LT in the treatment of ACLF and discusses further the challenges for ACLF patients, the timing of LT for ACLF, and the choice of the patient population.
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Affiliation(s)
- Xue Li
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Liang Zhang
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
| | - Chunmei Pu
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
| | - Shanhong Tang
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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33
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La Mura V, Bitto N, Tripodi A. Rational hemostatic management in cirrhosis: from old paradigms to new clinical challenges. Expert Rev Hematol 2022; 15:1031-1044. [PMID: 36342412 DOI: 10.1080/17474086.2022.2144217] [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: 08/10/2022] [Accepted: 11/01/2022] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Patients with cirrhosis are at risk of both thrombotic and hemorrhagic events. Traditional hemostatic tests are inadequate to assess the complex and fragile balance of hemostasis in this setting, especially in advanced stages of disease such as decompensated cirrhosis or acute on chronic liver failure (ACLF). Furthermore, the indiscriminate use of pro-hemostatic agents for prophylaxis and treatment of bleeding episodes is still debated and often contraindicated. Alongside, splanchnic, and peripheral thrombotic events are frequent in this population and require management that involves a careful balance between risks and benefits of antithrombotic therapy. AREAS COVERED This review aims to address the state of the art on the clinical management of the hemostatic balance of cirrhosis in terms of established knowledge and future challenges. EXPERT OPINION The old paradigm of cirrhosis as a naturally anticoagulated condition has been challenged by more sophisticated global tests of hemostasis. Integrating this information in the clinical decision-making is still challenging for physicians and experts in hemostasis.
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Affiliation(s)
- Vincenzo La Mura
- Fondazione I.R.C.C.S. Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Niccolò Bitto
- Fondazione I.R.C.C.S. Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
- Department of Biomedical Sciences for Health, Università degli studi di Milano, Milan, Italy
| | - Armando Tripodi
- Fondazione I.R.C.C.S. Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
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Little CJ, Leverson GE, Hammel LL, Connor JP, Al‐Adra DP. Blood products and liver transplantation: A strategy to balance optimal preparation with effective blood stewardship. Transfusion 2022; 62:2057-2067. [PMID: 35986654 PMCID: PMC9575510 DOI: 10.1111/trf.17074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 07/28/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Unanticipated transfusion requirements during liver transplantation can delay lifesaving intraoperative resuscitation and strain blood bank resources. Risk-stratified preoperative blood preparation can mitigate these deleterious outcomes. STUDY DESIGN AND METHODS A two-tiered blood preparation protocol for liver transplantation was retrospectively evaluated. Eleven binary variables served as criteria for high-risk (HR) allocation. Primary outcomes included red blood cell (RBC), plasma (FFP), and platelet (Plt) utilization. Secondary outcomes included product under- and overpreparation. Contingency tables for transfusion requirements above the population means were generated using 15 clinical variables. Modified protocols were developed and retrospectively optimized using the study population. RESULTS Of 225 recipients, 102 received HR preoperative orders, which correlated to higher intraoperative transfusion requirements. However, univariate analysis identified only two statistical risk factors per product: Hgb ≤7.8 g/dl (p < .001) and MELD ≥38 (p = .035) for RBCs, Hgb ≤7.8 g/dl (p = .002) and acute alcoholic hepatitis (p = 0.015) for FFP, and Hgb ≤7.8 g/dl (p = .001) and normothermic liver preservation (p = .037) for Plts. Based on these findings, we developed modified protocols for individual products, which were evaluated retrospectively for their effectiveness at reducing under-preparatory events while limiting product overpreparation. Cohort statistics were used to define the preparation strategy for each protocol. Retrospective comparative analysis demonstrated the superiority of the modified protocols by improving the under-preparation rate from 24% to <10% for each product, which required a 1.56-fold and 1.44-fold increase in RBC and FFP overpreparation, respectively. Importantly, there was no difference in Plt overpreparation. DISCUSSION We report translatable data-driven blood bank preparation protocols for liver transplantation.
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Affiliation(s)
- Christopher J. Little
- Division of Transplantation, Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Glen E. Leverson
- Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Laura L. Hammel
- Department of AnesthesiologyUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Joseph P. Connor
- Department of Pathology and Laboratory MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - David P. Al‐Adra
- Division of Transplantation, Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
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35
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Pillai AA, Kriss M, Al‐Adra DP, Chadha RM, Cushing MM, Farsad K, Fortune BE, Hess AS, Lewandowski R, Nadim MK, Nydam T, Sharma P, Karvellas CJ, Intagliata N. Coagulopathy and hemostasis management in patients undergoing liver transplantation: Defining a dynamic spectrum across phases of care. Liver Transpl 2022; 28:1651-1663. [PMID: 35253365 PMCID: PMC9790275 DOI: 10.1002/lt.26451] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 01/10/2023]
Abstract
Patients with acute and chronic liver disease present with a wide range of disease states and severity that may require liver transplantation (LT). Physiologic alterations occur that are dynamic throughout all phases of perioperative care, creating complex management scenarios that necessitate multidisciplinary clinical care. Specifically, alterations in hemostasis in liver disease can be pronounced and evolve with disease progression over time. Recent studies and society guidance address this emerging paradigm and offer recommendations to assist with hemostatic management in patients with liver disease. However, patients undergoing LT are unique and diverse, often with unstable disease that requires specialized approaches. Our aim is to provide a focused review of hemostatic management of the LT patient, distinguish unique aspects of the three main phases of care (before LT, perioperative, and after LT), and identify knowledge gaps and critical areas of future research.
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Affiliation(s)
- Anjana A. Pillai
- Department of MedicineUniversity of Chicago MedicineChicagoIllinoisUSA
| | - Michael Kriss
- Department of Internal MedicineUniversity of ColoradoAuroraColoradoUSA
| | - David P. Al‐Adra
- Department of SurgerySchool of Medicine and Public HealthUniversity of WisconsinMadisonWisconsinUSA
| | - Ryan M. Chadha
- Department of Anesthesiology and Perioperative MedicineMayo ClinicJacksonvilleFloridaUSA
| | - Melissa M. Cushing
- Department of Pathology and Laboratory MedicineWeill Cornell MedicineNew YorkNew YorkUSA
| | - Khashayar Farsad
- Department of Interventional RadiologyOregon Health & Science UniversityPortlandOregonUSA
| | | | - Aaron S. Hess
- Department of AnesthesiologyUniversity of WisconsinMadisonWisconsinUSA,Department of Pathology & Laboratory MedicineUniversity of WisconsinMadisonWisconsinUSA
| | | | - Mitra K. Nadim
- Department of MedicineUniversity of Southern CaliforniaLos AngelesCaliforniaUSA
| | - Trevor Nydam
- Department of SurgeryUniversity of ColoradoAuroraColoradoUSA
| | - Pratima Sharma
- Department of MedicineUniversity of MichiganAnn ArborMichiganUSA
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36
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Hemorrhagic complications in individuals with liver disease submitted to minor oral surgery. Blood Coagul Fibrinolysis 2022; 33:412-417. [PMID: 35867941 DOI: 10.1097/mbc.0000000000001157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Individuals with chronic liver disease (CLD) have an increased risk of bleeding from thrombocytopenia and changes in hemostasis. The aim of this study was to evaluate the frequency of and the factors associated with the occurrence of bleeding in CLD patients who underwent dental surgical procedures. This was a retrospective study whose data were collected in a hospital dentistry service between 2010 and 2016. The patients were referred from the gastroenterology and liver transplantation services of a university hospital for dental treatment. The study followed the STROBE guidelines. Among the 71 surgical procedures performed, there were 17 (24%) perioperative and postoperative bleeding episodes, 14 of which were in pretransplant patients and 11 received blood transfusion before dental surgery. Individuals with a previous history of bleeding (PR = 2.67, CI = 1.07-6.67, P = 0.035) and those with a platelet count before surgery 50 × 109/l or less (PR = 7.48, CI = 1.70-32.86, P = 0.008) had a higher prevalence of perioperative and postoperative bleeding episodes than their peers without a previous history of bleeding, and those with platelet count greater than 50 × 109/l. The approach to individuals with CLD is complex and represents a challenge to the clinician. A careful anamnesis combined with laboratory screening of coagulation disorders appears to be useful to identify individuals at a major risk of bleeding. Studies identifying the predisposing factors of bleeding in CLD patients support well tolerated protocols for oral surgery in this group.
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37
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Lisman T, Caldwell SH, Intagliata NM. Haemostatic alterations and management of haemostasis in patients with cirrhosis. J Hepatol 2022; 76:1291-1305. [PMID: 35589251 DOI: 10.1016/j.jhep.2021.11.004] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/31/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022]
Abstract
Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic proteins. Although historically patients with cirrhosis were thought to have a haemostasis-related bleeding tendency, it is now widely accepted that the haemostatic system of patients with cirrhosis remains in balance as a result of simultaneous changes in pro- and anti-haemostatic systems. The concept of rebalanced haemostasis has led to changes in clinical management, although firm evidence from well-designed clinical studies is largely lacking. For example, many invasive procedures in patients with cirrhosis and a prolonged prothrombin time are now performed without prophylaxis with fresh frozen plasma. Conversely, clinicians have become more aware of the need for anti-thrombotic therapy, even in those patients with abnormal routine coagulation tests. This paper will outline recent advances in pathogenesis, prevention and treatment of both bleeding and thrombotic complications in patients with cirrhosis. Among other topics, we will discuss the haemostatic status of acutely ill patients with cirrhosis, the various causes of bleeding in patients with cirrhosis, and how best to prevent or treat bleeding. In addition, we will discuss the hypercoagulable features of patients with cirrhosis, new insights into the pathogenesis of portal vein thrombosis, and how best to prevent or treat thromboses.
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Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Coagulation in Liver Disease, University of Virginia Medical Center, Charlottesville VA, United States
| | - Nicolas M Intagliata
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Coagulation in Liver Disease, University of Virginia Medical Center, Charlottesville VA, United States
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Sundaram V, Patel S, Shetty K, Lindenmeyer CC, Rahimi RS, Flocco G, Al-Attar A, Karvellas CJ, Challa S, Maddur H, Jou JH, Kriss M, Stein LL, Xiao AH, Vyhmeister RH, Green EW, Campbell B, Cranford W, Mahmud N, Fortune BE, for the Multi-Organ Dysfunction and Evaluation for Liver transplantation (MODEL) consortium. Risk Factors for Posttransplantation Mortality in Recipients With Grade 3 Acute-on-Chronic Liver Failure: Analysis of a North American Consortium. Liver Transpl 2022; 28:1078-1089. [PMID: 35020260 PMCID: PMC9117404 DOI: 10.1002/lt.26408] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 12/13/2021] [Accepted: 12/22/2021] [Indexed: 12/30/2022]
Abstract
Although liver transplantation (LT) yields survival benefit for patients with acute-on-chronic liver failure grade 3 (ACLF-3), knowledge gaps remain regarding risk factors for post-LT mortality. We retrospectively reviewed data from 10 centers in the United States and Canada for patients transplanted between 2018 and 2019 and who required care in the intensive care unit prior to LT. ACLF was identified using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. A total of 318 patients were studied, of whom 106 (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Survival probability 1 year after LT was significantly higher in patients without ACLF (94.3%) compared with patients with ACLF (87.3%; P = 0.02), but similar between ACLF-1 (88.5%), ACLF-2 (87.8%), and ACLF-3 (85.7%; P = 0.26). Recipients with ACLF-3 and circulatory failure (n = 29) had similar 1-year post-LT survival (82.3%) compared with patients with ACLF-3 without circulatory failure (89.6%; P = 0.32), including those requiring multiple vasopressors. For patients transplanted with ACLF-3 including respiratory failure (n = 20), there was a trend toward significantly lower post-LT survival (P = 0.07) among those with respiratory failure (74.1%) compared with those without (91.0%). The presence of portal vein thrombosis (PVT) at LT for patients with ACLF-3 (n = 15), however, yielded significantly lower survival (91.9% versus 57.1%; P < 0.001). Multivariable logistic regression analysis revealed that PVT was significantly associated with post-LT mortality within 1 year (odds ratio, 7.3; 95% confidence interval, 1.9-28.3). No correlation was found between survival after LT and the location or extent of PVT, presence of transjugular intrahepatic portosystemic shunt, or anticoagulation. LT in patients with ACLF-3 requiring vasopressors yields excellent 1-year survival. LT should be approached cautiously among candidates with ACLF-3 and PVT.
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Affiliation(s)
- Vinay Sundaram
- Karsh Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Sarvanand Patel
- Karsh Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Kirti Shetty
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD
| | | | - Robert S. Rahimi
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Baylor Scott and White, Dallas, TX
| | - Gianina Flocco
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD
| | - Atef Al-Attar
- Karsh Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Constantine J. Karvellas
- Department of Critical Care and Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton AB, Canada
| | - Suryanarayana Challa
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland OH
| | - Harapriya Maddur
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Il, USA
| | - Janice H. Jou
- Division of Gastroenterology and Hepatology, Oregon Health and Sciences University, Portland, OR
| | - Michael Kriss
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO
| | - Lance L. Stein
- Piedmont Transplant Institute, Piedmont Healthcare, Atlanta, GA
| | - Alex H. Xiao
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Il, USA
| | - Ross H. Vyhmeister
- Division of Gastroenterology and Hepatology, Oregon Health and Sciences University, Portland, OR
| | - Ellen W. Green
- Division of Gastroenterology and Hepatology, Oregon Health and Sciences University, Portland, OR
| | - Braidie Campbell
- Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO
| | | | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, PA, USA
| | - Brett E. Fortune
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA
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Cao Q, Mei Z. Predictive value of elevated serum D‑dimer for short‑term prognosis in patients with HBV‑related acute‑on‑chronic liver failure. Exp Ther Med 2022; 24:472. [PMID: 35761810 PMCID: PMC9214591 DOI: 10.3892/etm.2022.11399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/06/2022] [Indexed: 11/05/2022] Open
Abstract
To study the predictive value of elevated serum D-dimer on short-term prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and the correlation between serum D-dimer level and the clinical data of these patients, a single center retrospective study was conducted to collect the clinical data and 28 and 90-day survival rates of 201 patients. Logistic regression analysis and receiver operating characteristic curves were used to determine the factors affecting short-term prognosis. A Kaplan-Meier curve was used to compare the difference in survival rate between the two groups with elevated D-dimer and normal D-dimer levels. Correlation analysis was used to determine the correlation between serum D-dimer level and the clinical data of the patients. The results showed that international normalized ratio (INR) >2.3 and age >53 years were independent risk factors affecting the 28-day survival rate of the patients (P<0.05). INR >2.3, serum total bilirubin >358.2 µmol/l, age >49 years and elevated serum D-dimer (>550 ng/ml) were independent risk factors affecting the 90-day survival rate of the patients (P<0.05). There were significant differences in the 90-day survival rate and the survival time between the patients with elevated D-dimer and normal D-dimer levels (P<0.05). Serum D-dimer level was positively associated with age, combined spontaneous peritonitis, albumin, INR and the model for end-stage liver disease sodium (MELD-Na) scores, and negatively associated with male sex, red blood cell count, and serum sodium and fibrinogen levels. It was concluded that elevated serum D-dimer (>550 ng/ml) is an independent risk factor affecting the 90-day survival rate of patients with HBV-ACLF. The 90-day survival rate and the survival time of patients with HBV-ACLF and elevated D-dimer levels are significantly lower than those with normal D-dimer levels. Overall, serum D-dimer is associated the short-term prognosis of patients with HBV-ACLF, and the detection of serum D-dimer level at admission can help predict the short-term prognosis of patients with HBV-ACLF, especially the 90-day prognosis.
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Affiliation(s)
- Qianmei Cao
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
| | - Zhechuan Mei
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
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40
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Huang Y, Cai J, Ha F, Guo B, Xin S, Duan Z, Han T. Characteristics of acute kidney injury and its impact on outcome in patients with acute-on-chronic liver failure. BMC Gastroenterol 2022; 22:231. [PMID: 35545763 PMCID: PMC9092688 DOI: 10.1186/s12876-022-02316-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 05/03/2022] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE Acute kidney injury (AKI) is a common and life-threatening complication of liver failure. The purpose of this study is to construct a nomogram and online calculator to predict the development of hospital-acquired acute kidney injury (HA-AKI) in patients with acute-on-chronic liver failure (ACLF), which may contribute to the prognosis of ACLF. METHODS 574 ACLF patients were evaluated retrospectively. AKI was defined by criteria proposed by International Club of Ascites (ICA) and divided into community-acquired and hospital-acquired AKI (CA-AKI and HA-AKI). The difference between CA-AKI and HA-AKI, factors associated with development into and recovered from AKI periods. The risk factors were identified and nomograms were developed to predict the morbidity of HA-AKI in patients with ACLF. RESULTS Among 574 patients, 217(37.8%) patients had AKI, CA-AKI and HA-AKI were 56 (25.8%) and 161 (74.2%) respectively. The multivariate logistic regression model (KP-AKI) for predicting the occurrence of HA-AKI were age, gastrointestinal bleeding, bacterial infections, albumin, total bilirubin, blood urea nitrogen and prothrombin time. The AUROC of the KP-AKI in internal and external validations were 0.747 and 0.759, respectively. Among 217 AKI patients, 81(37.3%), 96(44.2%) and 40(18.4%) patients were with ICA-AKI stage progression, regression and fluctuated in-situ, respectively. The 90-day mortality of patients with AKI was 55.3% higher than non-AKI patients 21.6%. The 90-day mortality of patients with progression of AKI was 88.9%, followed by patients with fluctuated in-situ 40% and regression of AKI 33.3%. CONCLUSIONS The nomogram constructed by KP-AKI can be conveniently and accurately in predicting the development of HA-AKI, and AKI can increase the 90-day mortality significantly in ACLF patients. Trial registration Chinese clinical trials registry: ChiCTR1900021539.
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Affiliation(s)
- Yue Huang
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China.,Department of Hepatology and Gastroenterology, Tianjin Union Medical Center affiliated to Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, China
| | - Junjun Cai
- Department of Hepatology and Gastroenterology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin, 300170, China.,Artificial Cell Engineering Technology Research Center, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
| | - Fushuang Ha
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China.,Department of Hepatology and Gastroenterology, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin, 300170, China.,Artificial Cell Engineering Technology Research Center, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
| | - Beichen Guo
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China.,Department of Hepatology and Gastroenterology, Tianjin Union Medical Center affiliated to Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, China
| | - Shaojie Xin
- Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Zhongping Duan
- Liver Disease Center (Difficult and Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Tao Han
- Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China. .,Department of Hepatology and Gastroenterology, Tianjin Union Medical Center affiliated to Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, China.
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Villa E, Bianchini M, Blasi A, Denys A, Giannini EG, de Gottardi A, Lisman T, de Raucourt E, Ripoll C, Rautou PE. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol 2022; 76:1151-1184. [PMID: 35300861 DOI: 10.1016/j.jhep.2021.09.003] [Citation(s) in RCA: 182] [Impact Index Per Article: 60.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 09/13/2021] [Indexed: 12/11/2022]
Abstract
The prevention and management of bleeding and thrombosis in patients with cirrhosis poses several difficult clinical questions. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics, including current views on haemostasis in liver disease, controversy regarding the need to correct thrombocytopenia and abnormalities in the coagulation system in patients undergoing invasive procedures, and the need for thromboprophylaxis in hospitalised patients with haemostatic abnormalities. Multiple recommendations in this document are based on interventions that the panel feels are not useful, even though widely applied in clinical practice.
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La Mura V, Gagliano N, Arnaboldi F, Sartori P, Procacci P, Denti L, Liguori E, Bitto N, Ristagno G, Latini R, Dondossola D, Salerno F, Tripodi A, Colombo M, Peyvandi F. Simvastatin Prevents Liver Microthrombosis and Sepsis Induced Coagulopathy in a Rat Model of Endotoxemia. Cells 2022; 11:1148. [PMID: 35406712 PMCID: PMC8997834 DOI: 10.3390/cells11071148] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/19/2022] [Accepted: 03/22/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Endotoxemia causes endothelial dysfunction and microthrombosis, which are pathogenic mechanisms of coagulopathy and organ failure during sepsis. Simvastatin has potential anti-thrombotic effects on liver endothelial cells. We investigated the hemostatic changes induced by lipopolysaccharide (LPS) and explored the protective effects of simvastatin against liver vascular microthrombosis. Methods and results: We compared male Wistar rats exposed to LPS (5 mg/kg one i.p. dose) or saline in two experimental protocols—placebo (vehicle) and simvastatin (25 mg/kg die, orally, for 3 days before LPS). Morphological studies were performed by light- and electron-microscopy analyses to show intravascular fibrin deposition, vascular endothelial structure and liver damage. Peripheral- and organ-hemostatic profiles were analyzed using whole blood viscoelastometry by ROTEM, liver biopsy and western-blot/immunohistochemistry of thrombomodulin (TM), as well as immunohistochemistry of the von Willebrand factor (VWF). LPS-induced fibrin deposition and liver vascular microthrombosis were combined with a loss of sinusoidal endothelial TM expression and VWF-release. These changes were associated with parenchymal eosinophilia and necrosis. ROTEM analyses displayed hypo-coagulability in the peripheral blood that correlated with the degree of intrahepatic fibrin deposition (p < 0.05). Simvastatin prevented LPS-induced fibrin deposition by preserving TM expression in sinusoidal cells and completely reverted the peripheral hypo-coagulability caused by endotoxemia. These changes were associated with a significant reduction of liver cell necrosis without any effect on eosinophilia. Conclusions: Simvastatin preserves the antithrombotic properties of sinusoidal endothelial cells disrupted by LPS, deserving pharmacological properties to contrast sepsis-associated coagulopathy and hepatic failure elicited by endotoxemia
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Affiliation(s)
- Vincenzo La Mura
- Fondazione I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, U.O.C. Medicina Generale Emostasi e Trombosi, 20122 Milan, Italy; (N.B.); (A.T.); (F.P.)
- CRC “A.M. e A. Migliavacca” per lo Studio e la Cura delle Malattie del Fegato, Università degli Studi di Milano, 20122 Milan, Italy
- Dipartimento di Fisiopatologia dei Trapianti, Università degli Studi di Milano, 20132 Milan, Italy; (E.L.); (G.R.); (D.D.)
| | - Nicoletta Gagliano
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy; (N.G.); (F.A.); (P.S.); (P.P.); (L.D.); (F.S.)
| | - Francesca Arnaboldi
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy; (N.G.); (F.A.); (P.S.); (P.P.); (L.D.); (F.S.)
| | - Patrizia Sartori
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy; (N.G.); (F.A.); (P.S.); (P.P.); (L.D.); (F.S.)
| | - Patrizia Procacci
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy; (N.G.); (F.A.); (P.S.); (P.P.); (L.D.); (F.S.)
| | - Luca Denti
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy; (N.G.); (F.A.); (P.S.); (P.P.); (L.D.); (F.S.)
| | - Eleonora Liguori
- Dipartimento di Fisiopatologia dei Trapianti, Università degli Studi di Milano, 20132 Milan, Italy; (E.L.); (G.R.); (D.D.)
| | - Niccolò Bitto
- Fondazione I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, U.O.C. Medicina Generale Emostasi e Trombosi, 20122 Milan, Italy; (N.B.); (A.T.); (F.P.)
| | - Giuseppe Ristagno
- Dipartimento di Fisiopatologia dei Trapianti, Università degli Studi di Milano, 20132 Milan, Italy; (E.L.); (G.R.); (D.D.)
- Fondazione I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, U.O.C. Anestesia e Rianimazione, 20122 Milan, Italy
| | - Roberto Latini
- Dipartimento di Ricerca Cardiovascolare, Istituto di Ricerche Farmacologiche Mario Negri I.R.C.C.S., 20156 Milan, Italy;
| | - Daniele Dondossola
- Dipartimento di Fisiopatologia dei Trapianti, Università degli Studi di Milano, 20132 Milan, Italy; (E.L.); (G.R.); (D.D.)
- U.O. Chirurgia Generale e dei Trapianti di Fegato, Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Francesco Salerno
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy; (N.G.); (F.A.); (P.S.); (P.P.); (L.D.); (F.S.)
| | - Armando Tripodi
- Fondazione I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, U.O.C. Medicina Generale Emostasi e Trombosi, 20122 Milan, Italy; (N.B.); (A.T.); (F.P.)
| | - Massimo Colombo
- Liver Center IRCCS San Raffaele Hospital, 20132 Milan, Italy;
| | - Flora Peyvandi
- Fondazione I.R.C.C.S. Ca’ Granda, Ospedale Maggiore Policlinico, U.O.C. Medicina Generale Emostasi e Trombosi, 20122 Milan, Italy; (N.B.); (A.T.); (F.P.)
- Dipartimento di Fisiopatologia dei Trapianti, Università degli Studi di Milano, 20132 Milan, Italy; (E.L.); (G.R.); (D.D.)
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Premkumar M, Kulkarni AV, Kajal K, Divyaveer S. Principles, Interpretation, and Evidence-Based Role of Viscoelastic Point-of-Care Coagulation Assays in Cirrhosis and Liver Failure. J Clin Exp Hepatol 2022; 12:533-543. [PMID: 35535095 PMCID: PMC9077199 DOI: 10.1016/j.jceh.2021.05.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/02/2021] [Indexed: 12/12/2022] Open
Abstract
Background and Aims Standard coagulation tests such as prothrombin time, activated partial thromboplastin time, and international normalized ratio are determined by liver-synthesized coagulation factors. Despite an increased international normalized ratio, patients with cirrhosis are in a "rebalanced" state of hemostasis as the concomitant effect of reduced protein C, protein S, and thrombomodulin is not evaluated in standard coagulation tests. The cell-based model of hemostasis indicates additional mechanisms such as systemic inflammation, sepsis, and organ failures tip the delicate coagulation balance to an anticoagulant type in acute-on-chronic liver failure. In acute liver failure, thrombin generation and platelet function remain intact despite a marked prolongation in prothrombin time. We aimed to explain the principles, application, and utility of viscoelastic tests such as thromboelastography, rotational thromboelastometry, and Sonoclot. Methods We reviewed the available literature from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trial with the search terms 'coagulation', 'cirrhosis', 'acute-on-chronic liver failure', 'thromboelastography', 'thromboelastometry' and 'sonoclot' for cross sectional studies, cohort studies and randomized trials. Results The point-of-care viscoelastic tests provide actionable targets for correcting the coagulation defect in a patient with bleeding and provide evidence-based algorithms for use in liver disease. A limitation of these tests is the inability to assess vessel injury and endothelial elements. Conclusion Global coagulation tests provide a comprehensive estimate of coagulation in vitro; however, their use has only been validated in the setting of liver transplantation. Newer guidelines for hemostatic resuscitation are now accepting these POC tests, but additional data are required to validate their use as standard of care.
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Key Words
- ACLF, acute-on-chronic liver failure
- ACT, activated clotting time
- ALF, acute liver failure
- CR, clot rate
- INR, international normalized ratio
- MA, maximum amplitude
- R, reaction time
- ROTEM
- ROTEM, rotational thromboelastometry
- SCT, standard coagulation tests
- TEG, thromboelastography
- VWF, von Willebrand factor
- aPTT, activated partial thromboplastin time
- cirrhosis
- coagulation
- sonoclot
- thromboelastography
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Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Anand V. Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Kamal Kajal
- Department of Anesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Smita Divyaveer
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
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Zhang X, Han J, Qi X, Zhang Y, Zhou P, Liu X, Ying Y, Zhang W, Zhang J, Huang Y. DIC Score Combined With CLIF-C OF Score Is More Effective in Predicting Prognosis in Patients With Hepatitis B Virus Acute-on-Chronic Liver Failure. Front Med (Lausanne) 2022; 9:815580. [PMID: 35223914 PMCID: PMC8878906 DOI: 10.3389/fmed.2022.815580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 01/18/2022] [Indexed: 11/13/2022] Open
Abstract
Coagulation and fibrinolysis disorders are major prognostic factors in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Here, we aimed to clarify the role of disseminated intravascular coagulation (DIC) scores in predicting HBV-ACLF patient prognosis. We assessed the DIC score from HBV-ACLF patients at Huashan Hospital in Shanghai, China from June 2013 to May 2021 and evaluated it in relation to short-term mortality, clinical course, and infection. A novel prognostic scoring model was proposed based on DIC scores. A total of 163 transplant-free HBV-ACLF patients were enrolled. DIC scores were higher in non-survivors than survivors (6 vs. 4, P = 0.000) and were independently associated with short-term mortality [hazard ratio (HR): 1.397, 95% confidence interval (95% CI): 1.040–1.875, P = 0.026]. DIC scores were associated with ACLF grade, clinical course, and infection. Moreover, they were correlated with model for end-stage liver disease (MELD) scores (r = 0.521, P < 0.001). The area under the receiver operating curve (auROC) of CLIF-C OF-DICs [a novel prognostic score based on age, DIC score, and Chronic liver failure-consortium organ function score (CLIF-C OFs)] for 90-day mortality was 0.936, which was higher than six other generic prognostic scoring models. These results were confirmed in a validation cohort (n = 82). In conclusion, elevated DIC score is associated with poor prognosis in HBV-ACLF patients, and can be used jointly with CLIF-C OFs to improve the accuracy of prognosis prediction.
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Affiliation(s)
- Xueyun Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiajia Han
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yao Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Pu Zhou
- Huashan Worldwide Medical Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiaoqin Liu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yue Ying
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
- Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Infectious Diseases, Jing'an Branch of Huashan Hospital, Fudan University, Shanghai, China
- Jiming Zhang
| | - Yuxian Huang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- *Correspondence: Yuxian Huang
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45
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Driever EG, Lisman T. Effects of Inflammation on Hemostasis in Acutely Ill Patients with Liver Disease. Semin Thromb Hemost 2022; 48:596-606. [PMID: 35135033 DOI: 10.1055/s-0042-1742438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Patients with liver diseases are in a rebalanced state of hemostasis, due to simultaneous decline in pro- and anticoagulant factors. This balance seems to remain even in the sickest patients, but is less stable and might destabilize when patients develop disease complications. Patients with acute decompensation of cirrhosis, acute-on-chronic liver failure, or acute liver failure often develop complications associated with changes in the hemostatic system, such as systemic inflammation. Systemic inflammation causes hemostatic alterations by adhesion and aggregation of platelets, release of von Willebrand factor (VWF), enhanced expression of tissue factor, inhibition of natural anticoagulant pathways, and inhibition of fibrinolysis. Laboratory tests of hemostasis in acutely-ill liver patients may indicate a hypocoagulable state (decreased platelet count, prolongations in prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels) due to decreased synthetic liver capacity or consumption, or a hypercoagulable state (increased VWF levels, hypofibrinolysis in global tests). Whether these changes are clinically relevant and should be corrected with antithrombotic drugs or blood products is incompletely understood. Inflammation and activation of coagulation may cause local ischemia, progression of liver disease, and multiorgan failure. Anti-inflammatory treatment in acutely-ill liver patients may be of potential interest to prevent thrombotic or bleeding complications and halt progression of liver disease.
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Affiliation(s)
- Ellen G Driever
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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46
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Passi NN, McPhail MJW. The patient with cirrhosis in the intensive care unit and the management of acute-on-chronic liver failure. J Intensive Care Soc 2022; 23:78-86. [PMID: 37593538 PMCID: PMC10427846 DOI: 10.1177/1751143720978849] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2023] Open
Abstract
Acute on chronic liver failure (ACLF) is a clinical syndrome characterised by acute hepatic decompensation, multi-organ failure and high mortality, in patients with cirrhosis. Organ dysfunction in ACLF is often reversible and when necessary these patients should be considered appropriate candidates for admission to an intensive care unit (ICU). The yearly increase in numbers of patients with ACLF admitted to ICU has been matched with an improvement in survival. ACLF has only been recently defined. In the absence of evidence-based guidelines we outline a systems-based approach to care which encompasses accepted ICU practice and evidence from trials in this cohort. We advocate for timely referral to specialist liver centres and consider the complexities of proceeding with liver transplantation. Equally, in a proportion of patients who continue to deteriorate, appropriate ceilings of care should be established. Future clinical trials may change treatment paradigms but care of patients with ACLF is undoubtedly becoming an integral part of an intensivist's practice. We hope that this review is a welcome starting point when managing this complex clinical syndrome.
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Affiliation(s)
- Neha N Passi
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - Mark JW McPhail
- Institute of Liver Studies, Kings College Hospital, London, UK
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47
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Abstract
In patients with cirrhosis and chronic liver disease, acute-on-chronic liver failure is emerging as a major cause of mortality. These guidelines indicate the preferred approach to the management of patients with acute-on-chronic liver failure and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
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48
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Hemostatic parameters predict 90-day mortality in hospitalized cirrhotic patients with acute decompensation: a prospective cohort study. Blood Coagul Fibrinolysis 2022; 33:176-183. [PMID: 35026788 DOI: 10.1097/mbc.0000000000001124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Hemostatic disturbances are common in patients with cirrhosis. Few studies have evaluated the prognostic role of hemostatic parameters in cirrhosis with acute decompensation. This study aims to determine the prognostic ability of standard hemostatic parameters in hospitalized cirrhotic patients with acute decompensation. Cirrhotic patients admitted with acute decompensation were prospectively enrolled. Hemostatic parameters were determined within 24 h, and the DIC (disseminated intravascular coagulation) score was calculated based on platelet count, prothrombin time (PT), fibrinogen, and D-dimer. New onset of in-hospital major bleeding and 90-day mortality were assessed. Eighty-nine patients were included (MELD 13.6 ± 5.7). The indications of admission were infection (38.2%), and portal hypertension-related bleeding (31.5%). 14.6% developed in-hospital major bleeding, and 90-day mortality rate was 21.3%. Major bleeding group and 90-day nonsurvivors had significantly higher activated partial thromboplastin time (aPTT), PT, and DIC score. The 90-day mortality rate was higher in major bleeding group (46.2 vs. 17.1%, P = 0.029). By multivariate logistic regression analysis, DIC score was associated with 90-day mortality. The AUROC of DIC score for 90-day mortality prediction was significantly higher than of MELD score (0.78 vs. 0.59, P = 0.04). DIC score at least 4 predicted 90-day mortality with a sensitivity of 88.9%. The cumulative 90-day survival was significantly lower in patients with DIC score at least 4 (57.2 vs. 93.6%, P = 0.0003). The development of in-hospital major bleeding significantly increases mortality in cirrhotic patients with acute decompensation. The DIC score within 24 h can be used as a simple and reliable predictor for 90-day mortality in these patients.
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49
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Mezzano G, Juanola A, Cardenas A, Mezey E, Hamilton JP, Pose E, Graupera I, Ginès P, Solà E, Hernaez R. Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis. Gut 2022; 71:148-155. [PMID: 33436495 DOI: 10.1136/gutjnl-2020-322161] [Citation(s) in RCA: 133] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 12/22/2020] [Accepted: 12/23/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures. METHODS We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses. RESULTS We identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates. CONCLUSIONS The global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.
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Affiliation(s)
- Gabriel Mezzano
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.,Gastroenterología - Hepatología, Hospital del Salvador. Universidad de Chile, Santiago, Chile
| | - Adria Juanola
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Madrid, Spain
| | - Andres Cardenas
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Madrid, Spain.,Institute of Digestive Disease and Metabolism, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain
| | - Esteban Mezey
- Division of Gastroenterology and Hepatology. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - James P Hamilton
- Division of Gastroenterology and Hepatology. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elisa Pose
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Madrid, Spain
| | - Isabel Graupera
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Madrid, Spain.,Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Madrid, Spain.,Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain
| | - Elsa Solà
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Madrid, Spain.,Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain
| | - Ruben Hernaez
- Gastroenterology and Hepatology, Depatment of Medicine, Baylor College of Medicine, Houston, Texas, USA .,Section of Gastroenterology, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.,Center for Innovation in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
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50
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Abstract
The liver comprises both parenchymal and non-parenchymal cells with varying functions. Cirrhosis is often complicated by the development of portal hypertension and its associated complications. Hence, assessment of liver in cirrhosis should include assessment of its structural, function of both hepatic and non-hepatic tissue and haemodynamic assessment of portal hypertension. There is no single test that can evaluate all functions of liver and assess prevalence and severity of portal hypertension. Commonly available tests like serum bilirubin, liver enzymes (alanine [ALT] and aspartate aminotransferase [AST], serum alkaline phosphatase [ALP], gamma glutamyl transpeptidase [GGT]), serum albumin and prothrombin time for assessment of liver functions partly assess liver functions. quantitative liver functions like indocyanine clearance tests [ICG-K], methacetin breath test [MBT] were developed to assess dynamic status of liver but has its own limitation and availability. Imaging based assessment of liver by transient elastography, MRI based 99 mTc-coupled asialoglycoprotein mebrofenin scan help the clinician to assess liver function, functional volume of liver left after surgery and portal hypertension [PH]. Hepatic venous pressure gradient still remains the gold standard for the assessment of portal hypertension but is invasive and not available in all centres. Combinations of blood parameters in form of various indices like fibrosis score of 4 [FIB-4], Lok index, scores like model for end stage liver disease (MELD) and Child-Turcotte Pugh score are commonly used for assessing liver function in clinical practice.
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Key Words
- 99mTc-GSA, technetium-99m galactosyl human serum albumin
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- ARFI, Acoustic Radiation Force Impulse
- AST, aspartate aminotransferase
- BUN, blood urea nitrogen
- CLD, chronic liver disease
- ESLD, end-stage liver disease
- FIB-4, fibrosis score of 4
- GGT, gamma glutamyl transpeptidase
- HVPG, Hepatic venous pressure gradient
- ICG-K, indocyanine clearance tests
- INR, International normalised ratio
- LFTs, liver function tests
- MBT, methacetin breath test
- NAFLD, non-alcoholic fatty liver disease
- PBS, primary biliary cholangitis
- PHT, portal hypertension
- PSC, primary Sclerosing cholangitis
- cirrhosis
- liver function tests
- portal hypertension
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Affiliation(s)
- Praveen Sharma
- Address for correspondence: Praveen Sharma, Associate Professor, Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India.
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