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Panackel C, Raja K, Fawas M, Jacob M. Prognostic models in acute liver failure-historic evolution and newer updates "prognostic models in acute liver failure". Best Pract Res Clin Gastroenterol 2024; 73:101957. [PMID: 39709212 DOI: 10.1016/j.bpg.2024.101957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 10/22/2024] [Indexed: 12/23/2024]
Abstract
Acute liver failure (ALF) is a rare and dynamic syndrome occurring as a sequela of severe acute liver injury (ALI). Its mortality ranges from 50% to 75% based on the aetiology, patients age and severity of encephalopathy at admission. With improvement in intensive care techniques, transplant-free survival in ALF has improved over time. Timely recognition of patients who are unlikely to survive with medical intervention alone is crucial since these individuals may rapidly develop multiorgan failure and render liver transplantation futile. Various predictive models, biomarkers and AI-based models are currently used in clinical practice, each with its fallacies. The King's College Hospital criteria (KCH) were initially established in 1989 to identify patients with acute liver failure (ALF) caused by paracetamol overdose or other causes who are unlikely to improve with conventional treatment and would benefit from a liver transplant. Since then, various models have been developed and validated worldwide. Most models include age, aetiology of liver disease, encephalopathy grade, and liver injury markers like INR, lactate, factor V level, factor VIII/V ratio and serum bilirubin. But none of the currently available models are dynamic and lack accuracy in predicting transplant free survival. There is an increasing interest in developing prognostic serum biomarkers that when used alone or in combination with clinical models enhance the accuracy of predicting outcomes in ALF. Genomics, transcriptomics, proteomics, and metabolomics as well as machine learning and artificial intelligence (AI) algorithms are areas of interest for developing higher-precision predictive models. Overall, the future of prognostic models in ALF is promising, with ongoing research paving the way for more accurate, personalized, and dynamic risk assessment tools that can potentially save lives in this challenging condition. This article summarizes the history of prognostic models in ALF and future trends.
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Affiliation(s)
| | | | - Mohammed Fawas
- Aster Integrated Liver Care, Aster Medcity, Kochi, India
| | - Mathew Jacob
- Aster Integrated Liver Care, Aster Medcity, Kochi, India
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2
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Wang X, Zhao M, Ju C, Gao H, Wang W. Protective Mechanisms of Juncus effusus and Carbonized Juncus effusus against D-Galactosamine-Induced Acute Liver Injury in Mice. Chem Pharm Bull (Tokyo) 2024; 72:280-285. [PMID: 38325836 DOI: 10.1248/cpb.c23-00578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.
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Affiliation(s)
- Xiangming Wang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine
| | - Menghui Zhao
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine
| | - Chengguo Ju
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine
| | - Hui Gao
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine
| | - Wei Wang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine
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3
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Agumava LU, Gulyaev VA, Lutsyk KN, Olisov OD, Akhmetshin RB, Magomedov KM, Kazymov BI, Akhmedov AR, Alekberov KF, Yaremin BI, Novruzbekov MS. Issues of intensive care and liver transplantation tactics in fulminant liver failure. BULLETIN OF THE MEDICAL INSTITUTE "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH) 2023. [DOI: 10.20340/vmi-rvz.2023.1.tx.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Fulminant liver failure is usually characterized as severe acute liver injury with encephalopathy and synthetic dysfunction (international normalized ratio [INR] ≥1.5) in a patient without cirrhosis or previous liver disease. Management of patients with acute liver failure includes ensuring that the patient is cared for appropriately, monitoring for worsening liver failure, managing complications, and providing nutritional support. Patients with acute liver failure should be treated at a liver transplant center whenever possible. Serial laboratory tests are used to monitor the course of a patient's liver failure and to monitor for complications. It is necessary to monitor the level of aminotransferases and bilirubin in serum daily. More frequent monitoring (three to four times a day) of blood coagulation parameters, complete blood count, metabolic panels, and arterial blood gases should be performed. For some causes of acute liver failure, such as acetaminophen intoxication, treatment directed at the underlying cause may prevent the need for liver transplantation and reduce mortality. Lactulose has not been shown to improve overall outcomes, and it can lead to intestinal distention, which can lead to technical difficulties during liver transplantation. Early in acute liver failure, signs and symptoms of cerebral edema may be absent or difficult to detect. Complications of cerebral edema include increased intracranial pressure and herniation of the brain stem. General measures to prevent increased intracranial pressure include minimizing stimulation, maintaining an appropriate fluid balance, and elevating the head of the patient's bed. For patients at high risk of developing cerebral edema, we also offer hypertonic saline prophylaxis (3%) with a target serum sodium level of 145 to 155 mEq/L (level 2C). High-risk patients include patients with grade IV encephalopathy, high ammonia levels (>150 µmol/L), or acute renal failure, and patients requiring vasopressor support. Approximately 40 % of patients with acute liver failure recover spontaneously with supportive care. Predictive models have been developed to help identify patients who are unlikely to recover spontaneously, as the decision to undergo liver transplant depends in part on the likelihood of spontaneous recovery of the liver. However, among those who receive a transplant, the one-year survival rate exceeds 80 %, making this treatment the treatment of choice in this difficult patient population.
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Affiliation(s)
- L. U. Agumava
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - V. A. Gulyaev
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. N. Lutsyk
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - O. D. Olisov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - R. B. Akhmetshin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. M. Magomedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Kazymov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - A. R. Akhmedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. F. Alekberov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Yaremin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - M. S. Novruzbekov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
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Kuwano A, Okui T, Kohjima M, Kurokawa M, Goya T, Tanaka M, Aoyagi T, Takahashi M, Imoto K, Tashiro S, Suzuki H, Fujita N, Ushijima Y, Ishigami K, Tokunaga S, Kato M, Ogawa Y. Transcatheter arterial steroid injection therapy improves the prognosis of patients with acute liver failure. Medicine (Baltimore) 2023; 102:e33090. [PMID: 36897684 PMCID: PMC9997803 DOI: 10.1097/md.0000000000033090] [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: 11/11/2022] [Accepted: 02/03/2023] [Indexed: 03/11/2023] Open
Abstract
Acute liver failure (ALF) is a disorder defined by coagulopathy and encephalopathy with a poor prognosis. No effective therapies have been established except for liver transplantation. We previously reported a subgroup of patients with acute liver injury who developed microcirculatory disturbance. We also established and reported transcatheter arterial steroid injection therapy (TASIT) as a new treatment of ALF. Here, we analyze the effectiveness of TASIT in a larger cohort and evaluate the impact on ALF patients with or without microcirculatory disturbance. We conducted a single-center retrospective study to evaluate the effectiveness of TASIT in patients with ALF admitted at Kyushu University Hospital between January 2005 and March 2018. TASIT is performed by injecting methylprednisolone via the proper hepatic artery for 3 days. One hundred ninety-4 patients with ALF were enrolled and analyzed in this study. Of the 87 patients given TASIT, 71 (81.6%) recovered without any complications and 16 (18.4%) died or underwent liver transplantation. Of the 107 patients not administered TASIT, 77 (72.0%) recovered and 30 (28.0%) progressed to irreversible liver failure. In the high-lactate dehydrogenase subgroup, 52 (86.7%) of the 60 patients with TASIT recovered, and the survival rate was significantly higher than that in patients who did not receive TASIT. Multivariate regression analysis revealed that the TASIT procedure was one of the significant prognostic factors in the high-lactate dehydrogenase subgroup and was significantly associated with prothrombin activity percentage improvement. TASIT is an effective treatment for patients with ALF, especially in those with microcirculatory disturbance.
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Affiliation(s)
- Akifumi Kuwano
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Tasuku Okui
- Medical Information Center, Kyushu University Hospital, Higashi-ku, Fukuoka, Japan
| | - Motoyuki Kohjima
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Miho Kurokawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Takeshi Goya
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Masatake Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Tomomi Aoyagi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Motoi Takahashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Koji Imoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Shigeki Tashiro
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Hideo Suzuki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Nobuhiro Fujita
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Yasuhiro Ushijima
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Kousei Ishigami
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
| | - Shoji Tokunaga
- Medical Information Center, Kyushu University Hospital, Higashi-ku, Fukuoka, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
- Graduate School of Nutritional Sciences, Nakamura Gakuen University, Jounan-ku, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
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Higher circulating natural killer cells and lower lactate levels at admission predict spontaneous survival in non-acetaminophen induced acute liver failure. Clin Immunol 2021; 231:108829. [PMID: 34419620 DOI: 10.1016/j.clim.2021.108829] [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: 02/10/2021] [Revised: 08/18/2021] [Accepted: 08/18/2021] [Indexed: 11/20/2022]
Abstract
Massive cellular necrosis in acute liver failure (ALF) is dominantly immune mediated and innate immune cells are major pathophysiological determinants in liver damage. In fifty ALF and fifteen healthy, immune cells phenotyping by flow-cytometry, DAMPs using ELISA were analysed and correlated with clinical and biochemical parameters. ALF patients (aged 27 ± 9 yr, 56% males, 78% viral aetiology) showed no difference in neutrophils and classical monocytes, but significantly increased intermediate monocytes (CD14+CD16+) (p < 0.01), decreased non-classical monocytes (CD14-CD16+) and CD3-veCD16+CD56+ NK cells compared to HC. ALF patients who survived, showed higher NK cells (9.28 vs. 5.1%, p < 0.001) among lymphocytes and lower serum lactate levels (6.1 vs. 28, Odds ratio 2.23, CI 1.27-3.94) than non- survivors had higher. Logistic regression model predicted the combination of lactate levels with NK cell percentage at admission for survival. In conclusion, Combination of NK cell frequency among lymphocytes and lactate levels at admission can reliably predict survival of ALF patients.
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Kumar R, Anand U, Priyadarshi RN. Liver transplantation in acute liver failure: Dilemmas and challenges. World J Transplant 2021; 11:187-202. [PMID: 34164294 PMCID: PMC8218344 DOI: 10.5500/wjt.v11.i6.187] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/17/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure (ALF) refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease. ALF has different causes, but the clinical characteristics are strikingly similar. In clinical practice, however, inconsistency in the definition of ALF worldwide and confusion regarding the existence of pre-existing liver disease raise diagnostic dilemmas. ALF mortality rates used to be over 80% in the past; however, survival rates on medical treatment have significantly improved in recent years due to a greater understanding of pathophysiology and advances in critical care management. The survival rates in acetaminophen-associated ALF have become close to the post-transplant survival rates. Given that liver transplantation (LT) is an expensive treatment that involves a major surgical operation in critically ill patients and lifelong immunosuppression, it is very important to select accurate patients who may benefit from it. Still, emergency LT remains a lifesaving procedure for many ALF patients. However, there is a lack of consistency in current prognostic models that hampers the selection of transplant candidates in a timely and precise manner. The other problems associated with LT in ALF are the shortage of graft, development of contraindications on the waiting list, vaguely defined delisting criteria, time constraints for pre-transplant evaluation, ethical concerns, and comparatively poor post-transplant outcomes in ALF. Therefore, there is a desperate need to establish accurate prognostic models and explore the roles of evolving adjunctive and alternative therapies, such as liver support systems, plasma exchange, stem cells, auxiliary LT, and so on, to enhance transplant-free survival and to fill the void created by the graft shortage
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Rajeev Nayan Priyadarshi
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Management of Acute Wilsonian Hepatitis with Severe Hemolysis: A Successful Combination of Chelation and MARS Dialysis. Case Reports Hepatol 2021; 2021:5583654. [PMID: 34055429 PMCID: PMC8131166 DOI: 10.1155/2021/5583654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 05/03/2021] [Indexed: 11/18/2022] Open
Abstract
Wilson's disease is a rare hereditary disorder of copper metabolism leading to progressive accumulation of copper in several organs including the brain and the liver. Acute liver failure is a relatively rare hepatic manifestation of WD which may require urgent liver transplantation if medical treatment fails. We report here the case of a young woman who presented with classic acute Wilsonian hepatitis complicated by liver and renal failure and a severe hemolysis related to massive nonceruloplasmin bound copper accumulation requiring repeated blood transfusions. The early initiation of a combined treatment including conventional chelation therapy and repeated MARS dialysis sessions allowed a rapid control of hemolysis, a progressive decrease of free copper overload, and clinical recompensation without liver transplantation.
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8
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Rovegno M, Vera M, Ruiz A, Benítez C. Current concepts in acute liver failure. Ann Hepatol 2020; 18:543-552. [PMID: 31126880 DOI: 10.1016/j.aohep.2019.04.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 03/29/2019] [Accepted: 04/02/2019] [Indexed: 02/04/2023]
Abstract
Acute liver failure (ALF) is a severe condition secondary to a myriad of causes associated with poor outcomes. The prompt diagnosis and identification of the aetiology allow the administration of specific treatments plus supportive strategies and to define the overall prognosis, the probability of developing complications and the need for liver transplantation. Pivotal issues are adequate monitoring and the institution of prophylactic strategies to reduce the risk of complications, such as progressive liver failure, cerebral oedema, renal failure, coagulopathies or infections. In this article, we review the main aspects of ALF, including the definition, diagnosis and complications. Also, we describe the standard-of-care strategies and recent advances in the treatment of ALF. Finally, we include our experience of care patients with ALF.
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Affiliation(s)
- Maximiliano Rovegno
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile
| | - Magdalena Vera
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile
| | - Alex Ruiz
- Unidad de Gastroenterología, Instituto de Medicina, Escuela de Medicina, Universidad Austral de Chile, Chile
| | - Carlos Benítez
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile.
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Speiser JL, Karvellas CJ, Wolf BJ, Chung D, Koch DG, Durkalski VL. Predicting daily outcomes in acetaminophen-induced acute liver failure patients with machine learning techniques. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2019; 175:111-120. [PMID: 31104700 PMCID: PMC6530588 DOI: 10.1016/j.cmpb.2019.04.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 03/26/2019] [Accepted: 04/10/2019] [Indexed: 05/07/2023]
Abstract
BACKGROUND/OBJECTIVE Assessing prognosis for acetaminophen-induced acute liver failure (APAP-ALF) patients during the first week of hospitalization often presents significant challenges. Current models such as the King's College Criteria (KCC) and the Acute Liver Failure Study Group (ALFSG) Prognostic Index are developed to predict outcome using only a single time point on hospital admission. Models using longitudinal data are not currently available for APAP-ALF patients. We aim to develop and compare performance of prediction models for outcomes during the first week of hospitalization for APAP-ALF patients. METHODS Models are developed for the ALFSG registry data to predict longitudinal outcomes for 1042 APAP-ALF patients enrolled 01/1998-02/2016. The primary outcome is defined as daily low versus high coma grade. Accuracy in prediction of outcome (AC), sensitivity (SN), specificity (SP) and area under the receiver operating curve (AUC) are compared between the following models: classification and regression tree, random forest, frequentist generalized linear mixed model (GLMM), Bayesian GLMM, BiMM tree, and BiMM forest using original and imputed datasets. RESULTS BiMM tree offers predictive (test set) 63% AC, 72% SP and 53% SN for the original dataset, whereas BiMM forest offers predictive (test set) 69% AC, 63% SP and 74% SN for the imputed dataset. BiMM tree has the highest AUC for the original testing dataset (0.697), whereas BiMM forest and standard random forest have the highest AUC for the imputed testing dataset (0.749). The three most important predictors of daily outcome for the BiMM tree are pressor use, bilirubin and creatinine. The BiMM forest model identifies lactate, ammonia and ALT as the three most important predictors of outcome. CONCLUSIONS BiMM tree offers a prognostic tool for APAP-ALF patients, which has good accuracy and simple interpretation of predictors which are consistent with clinical observations. BiMM tree and forest models are developed using the first week of in-patient data and are appropriate for predicting outcome over time. While the BiMM forest has slightly higher predictive AC, the BiMM tree model is simpler to use at the bedside.
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Affiliation(s)
- Jaime Lynn Speiser
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston Salem, NC, United States.
| | | | - Bethany J Wolf
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States
| | - Dongjun Chung
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States
| | - David G Koch
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Valerie L Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States
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Figiel W, Morawski M, Grąt M, Kornasiewicz O, Niewiński G, Raszeja-Wyszomirska J, Krasnodębski M, Kowalczyk A, Hołówko W, Patkowski W, Zieniewicz K. Fulminant liver failure following a marathon: Five case reports and review of literature. World J Clin Cases 2019; 7:1467-1474. [PMID: 31363475 PMCID: PMC6656669 DOI: 10.12998/wjcc.v7.i12.1467] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 04/29/2019] [Accepted: 05/01/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The growing popularity of marathon and half-marathon runs has led to an increased number of patients presenting with exertion-induced heat stroke. Mild hepatic involvement is often observed in these patients; however, fulminant liver failure may occur in approximately 5% of all cases. Liver transplantation is a potentially curative approach for exertion-induced liver failure, although there is a lack of consensus regarding the criteria and optimal timing of this intervention.
CASE SUMMARY This paper describes 5 patients (4 men and 1 woman) who were referred to the department where this study was performed with the diagnosis of exertion-induced acute liver failure. Three patients underwent liver transplantation, 1 recovered spontaneously, and 1 patient died on day 11 following the exertion.
CONCLUSION Exertion-induced heat stroke may present as fulminant liver failure. These patients may recover with conservative treatment, may require liver transplantation, or may die. No definitive criteria are available to determine patient suitability for a conservative vs surgical approach.
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Affiliation(s)
- Wojciech Figiel
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Marcin Morawski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Michał Grąt
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Oskar Kornasiewicz
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Grzegorz Niewiński
- Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Warsaw 02097, Poland
| | - Joanna Raszeja-Wyszomirska
- Liver and Internal Medicine Unit, Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Maciej Krasnodębski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Arkadiusz Kowalczyk
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Wacław Hołówko
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Waldemar Patkowski
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw 02097, Poland
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Abstract
There is a strong imperative to develop valid and accurate prognostic modeling for acute liver failure (ALF). Despite the numerous clinical models that have been proposed thus far and the use of some such models, that is, King's College Criteria and Model for End-Stage Liver Disease, in clinical practice to aid decision-making, there is a significant need for improvement for determining patients' clinical course, survival, and requirement for liver transplantation. Future prognostic models shall need a stronger statistical foundation and accountability for time and variability in the clinical course of ALF and be applied for pretransplant and posttransplant outcomes.
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12
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Abstract
Acute liver failure (ALF) is an uncommon syndrome with a highly variable and unpredictable clinical course. The initial diagnostic evaluation is typically performed in a non-intensive care unit (ICU) setting, like the emergency department or general hospital ward. Prompt restoration of intravascular volume with intravenous fluids and correction of electrolyte, metabolic, and acid-base disturbances are important initial interventions in the management of ALF and can be safely accomplished in non-ICU settings in many patients. Similarly, therapies such as administration of N-acetylcysteine for acetaminophen-induced ALF and other cause-specific interventions can also be administered in non-ICU settings, thus minimizing delay.
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Affiliation(s)
- Andres F Carrion
- Texas Tech University Health Sciences Center El Paso, 4800 Alberta Avenue, El Paso, TX 79905, USA.
| | - Paul Martin
- Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL 33136, USA
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13
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Pan CW, Yang SX, Pan ZZ, Zheng B, Wang JZ, Lu GR, Xue ZX, Xu CL. Andrographolide ameliorates d-galactosamine/lipopolysaccharide-induced acute liver injury by activating Nrf2 signaling pathway. Oncotarget 2018; 8:41202-41210. [PMID: 28465482 PMCID: PMC5522263 DOI: 10.18632/oncotarget.17149] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 03/28/2017] [Indexed: 12/15/2022] Open
Abstract
Andrographolide (ADH), a diterpenoid lactone extracted from Andrographis paniculata, has been found to have anti-inflammatory and anti-oxidative effects. However, its protective effects and mechanisms on liver injury have not been investigated clearly. This study takes an attempt to reveal the protective effects and mechanism of ADH on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury in mice. The mice liver injury model was induced by LPS (60 mg/kg) and D-GalN (800 mg/kg), and ADH was given 1 h after LPS and D-GalN treatment. Hepatic tissue histology was measured by H&E staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by detection kits. The levels of TNF-α and IL-1β were detected by ELISA. Moreover, malondialdehyde (MDA) and reactive oxygen species (ROS) contents were also detected. Meanwhile, the expression of Nrf2, HO-1, and NF-κB were detected by western blot analysis. The results showed that ADH treatment improved liver histology and decreased the levels of ALT, AST, MPO, IL-1β, TNF-α, as well as MDA and ROS levels of hepatic tissues in a dose-dependent manner. ADH also inhibited LPS/D-GalN-induced NF-κB activation. The expression of Nrf2 and HO-1 were increased by treatment of ADH. In conclusion, ADH protected against LPS/D-GalN-induced liver injury by inhibiting NF-κB and activating Nrf2 signaling pathway.
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Affiliation(s)
- Chen-Wei Pan
- Department of Infectious Disease,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Shou-Xing Yang
- Department of Gastroenterology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Zhen-Zhen Pan
- Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Bo Zheng
- Department of Gastroenterology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Jian-Zhang Wang
- Department of Gastroenterology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Guang-Rong Lu
- Department of Gastroenterology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Zhan-Xiong Xue
- Department of Gastroenterology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Chang-Long Xu
- Department of Gastroenterology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
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De Silvestro G, Marson P, Brandolese R, Pittoni G, Ongaro G. A Single Institution's Experience (1982–1999) with Plasma-Exchange Therapy in Patients with Fulminant Hepatic Failure. Int J Artif Organs 2018. [DOI: 10.1177/039139880002300708] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Fulminant hepatic failure is a rare, but often fatal complication of acute viral hepatitis. This condition, in absence of orthotopic liver transplantation (OLTx) surgery, is associated with a high mortality rate, despite the improvement of general intensive care. Plasma-exchange (PEx) therapy has been long used to treat FHF, in particular by removing toxic substances and correcting the severe coagulopathy. In this study we describe our experience with PEx treatment of FHF, beginning in 1982. Seventy patients affected with FHF due to various causes (HBV=40; cryptogenic/non-A, non-E=15; Amanita phalloides=8; other=7) were treated with PEx (altogether 348 sessions). Overall survival rate, comprising patients undergoing OLTx, was 51%, a little higher than what we observed in patients (N=49) treated solely by PEx, i.e., 41%. The best outcome predictor was FHF aetiology, owing to the good survival rate in patients with Amanita phalloides intoxication and the very poor prognosis of patients suffering from cryptogenic/non-A, non-E FHF. Moreover, the marked increase in prothrombin time and alpha-fetoprotein levels after 48 hours from admission was associated with a good prognosis, whereas the patient's age and coma grade were not clearly predictive of survival. Additionally, lymphocyte subpopulation, resulting in a CD4/CD8 ratio lower than 1.0 along with CD8 activation with HLA-DR strong expression, were associated with a high rate of mortality and morbidity. Our data indicate that PEx therapy can improve survival in patients with sufficient residual capacity of liver regeneration. Moreover, the identification of certain prognostic factors may be useful for the rational planning of therapeutic strategy in FHF.
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Affiliation(s)
- G. De Silvestro
- Apheresis Unit, Blood Transfusion Service, University Hospital of Padova, Padova - Italy
| | - P. Marson
- Apheresis Unit, Blood Transfusion Service, University Hospital of Padova, Padova - Italy
| | - R. Brandolese
- Service of Anaesthesia and Intensive Care, University Hospital of Padova, Padova - Italy
| | - G. Pittoni
- Apheresis Unit, Blood Transfusion Service, University Hospital of Padova, Padova - Italy
| | - G. Ongaro
- Apheresis Unit, Blood Transfusion Service, University Hospital of Padova, Padova - Italy
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15
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Halliday N, Westbrook RH. Liver transplantation: need, indications, patient selection and pre-transplant care. Br J Hosp Med (Lond) 2017; 78:252-259. [PMID: 28489446 DOI: 10.12968/hmed.2017.78.5.252] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic or acute liver failure and primary liver cancers can be effectively managed with liver transplantation. The range of indications for liver transplantation is increasing but there is a mismatch between the numbers of available donations and current needs. Specific criteria for listing patients exist but, at minimum, the predicted mortality without transplantation must exceed that with transplantation, coupled with a 50% predicted 5-year survival following liver transplantation. The risk posed by liver disease must be weighed against the risk of liver transplantation, considering the patient's comorbidities, age, nutritional status and behavioural factors in a complex assessment process. This article reviews current UK practice in the selection and care of patients being assessed for liver transplantation.
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Affiliation(s)
- Neil Halliday
- Wellcome Clinical Research Fellow, Institute of Immunity and Transplantation, University College London, London NW3 2PF
| | - Rachel H Westbrook
- Consultant Hepatologist, Sheila Sherlock Liver Centre, Royal Free Hospital NHS Trust, London
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Jiao J, Zhou F, Kang H, Liu C, Yang M, Hu J. Unexpected extrapyramidal symptoms and pulmonary aspergillosis in exertional heatstroke with fulminant liver failure: a case report. J Med Case Rep 2017; 11:37. [PMID: 28183359 PMCID: PMC5301367 DOI: 10.1186/s13256-016-1184-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 12/25/2016] [Indexed: 03/11/2023] Open
Abstract
Background Exertional heatstroke is a life-threatening condition with high mortality because of the rapid progress of multiple organ dysfunction syndrome even if aggressive treatments are initiated rapidly. Mild to moderate hepatic injury is common in exertional heatstroke, while fulminant liver failure is rare. Extrapyramidal symptoms and pulmonary aspergillosis secondary to liver failure induced by exertional heatstroke have never been reported in prior cases. Case presentation A 25-year-old Han Chinese man presented with exertional heatstroke with fulminant liver failure, subsequent pulmonary aspergillosis, and extrapyramidal symptoms. Moreover, he also presented with coma, rhabdomyolysis, acute kidney injury, and disseminated intravascular coagulation. He recovered under conservative treatment including therapeutic plasma exchange plus continuous veno-venous hemofiltration, fluid resuscitation, antibiotics, and other support therapy. Conclusions Therapeutic plasma exchange plus continuous veno-venous hemofiltration could be effective for patients with heatstroke who suffer liver failure and other organ failure. Patients with liver failure are at high risk for pulmonary aspergillosis. Movement disorder in these patients might be extrapyramidal symptoms induced by consistent low level of cholinesterase resulted from hepatic injury besides brain injury.
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Affiliation(s)
- Jie Jiao
- Critical Care Medicine, Hainan Branch of Chinese PLA General Hospital, Haitangwan District, Sanyan, Hainan Province, 572000, China
| | - Feihu Zhou
- Critical Care Medicine, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China
| | - Hongjun Kang
- Critical Care Medicine, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China
| | - Chao Liu
- Critical Care Medicine, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China
| | - Mengmeng Yang
- Critical Care Medicine, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China
| | - Jie Hu
- Critical Care Medicine, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China.
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17
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Cardoso FS, Marcelino P, Bagulho L, Karvellas CJ. Acute liver failure: An up-to-date approach. J Crit Care 2017; 39:25-30. [PMID: 28131021 DOI: 10.1016/j.jcrc.2017.01.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Revised: 01/05/2017] [Accepted: 01/09/2017] [Indexed: 12/14/2022]
Abstract
Acute liver failure is a rare but potentially devastating disease. Throughout the last few decades, acute liver failure outcomes have been improving in the context of the optimized overall management. This positive trend has been associated with the earlier recognition of this condition, the improvement of the intensive care unit management, and the developments in emergent liver transplantation. Accordingly, we aimed to review the current diagnostic and therapeutic approach to this syndrome, especially in the intensive care unit setting.
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Affiliation(s)
- Filipe S Cardoso
- Intensive Care Unit, Curry Cabral Hospital, Central Lisbon Hospital Center, Lisbon, Portugal.
| | - Paulo Marcelino
- Intensive Care Unit, Curry Cabral Hospital, Central Lisbon Hospital Center, Lisbon, Portugal
| | - Luís Bagulho
- Intensive Care Unit, Curry Cabral Hospital, Central Lisbon Hospital Center, Lisbon, Portugal
| | - Constantine J Karvellas
- Divisions of Gastroenterology (Liver Unit) and Critical Care, University of Alberta Hospital, Edmonton, Canada
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McPhail MJW, Farne H, Senvar N, Wendon JA, Bernal W. Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis. Clin Gastroenterol Hepatol 2016; 14:516-525.e5; quiz e43-e45. [PMID: 26499930 DOI: 10.1016/j.cgh.2015.10.007] [Citation(s) in RCA: 99] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 09/22/2015] [Accepted: 10/02/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Several prognostic factors are used to identify patients with acute liver failure (ALF) who require emergency liver transplantation. We performed a meta-analysis to determine the accuracy of King's College criteria (KCC) versus the model for end-stage liver disease (MELD) scores in predicting hospital mortality among patients with ALF. METHODS We performed a systematic search of the literature for articles published from 2001 through 2015 that compared the accuracy of the KCC with MELD scores in predicting hospital mortality in patients with ALF. We identified 23 studies (comprising 2153 patients) and assessed the quality of data, and then performed a meta-analysis of pooled sensitivity and specificity values, diagnostic odds ratios (DORs), and summary receiver operating characteristic curves. Subgroups analyzed included study quality, era, location (Europe vs non-Europe), and size; ALF etiology (acetaminophen-associated ALF [AALF] vs nonassociated [NAALF]); and whether or not the study included patients who underwent liver transplantation and if the study center was also a transplant center. RESULTS The DOR for the KCC was 5.3 (95% confidence interval [CI], 3.7-7.6; 57% heterogeneity) and the DOR for MELD score was 7.0 (95% CI, 5.1-9.7; 48% heterogeneity), so the MELD score and KCC are comparable in overall accuracy. The summary area under the receiver operating characteristic curve values was 0.76 for the KCC and 0.78 for MELD scores. The KCC identified patients with AALF who died with 58% sensitivity (95% CI, 51%-65%) and 89% specificity (95% CI, 85%-93%), whereas MELD scores identified patients with AALF who died with 80% sensitivity (95% CI, 74%-86%) and 53% specificity (95% CI, 47%-59%). The KCC predicted hospital mortality in patients with NAALF with 58% sensitivity (95% CI, 54%-63%) and 74% specificity (95% CI, 69%-78%), whereas MELD scores predicted hospital mortality in patients with NAALF with 76% sensitivity (95% CI, 72%-80%) and 73% specificity (95% CI, 69%-78%). In patients with AALF, the KCC's DOR was 10.4 (95% CI, 4.9-22.1) and the MELD score's DOR was 6.6 (95% CI, 2.1-20.2). In patients with NAALF, the KCC's DOR was 4.16 (95% CI, 2.34-7.40) and the MELD score's DOR was 8.42 (95% CI, 5.98-11.88). CONCLUSIONS Based on a meta-analysis of studies, the KCC more accurately predicts hospital mortality among patients with AALF, whereas MELD scores more accurately predict mortality among patients with NAALF. However, there is significant heterogeneity among studies and neither system is optimal for all patients. Given the importance of specificity in decision making for listing for emergency liver transplantation, MELD scores should not replace the KCC in predicting hospital mortality of patients with AALF, but could have a role for NAALF.
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Affiliation(s)
- Mark J W McPhail
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom; Department of Hepatology, St Mary's Hospital, Imperial College London, London, United Kingdom.
| | - Hugo Farne
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Naz Senvar
- Department of Hepatology, St Mary's Hospital, Imperial College London, London, United Kingdom
| | - Julia A Wendon
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - William Bernal
- Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom
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19
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Speiser JL, Lee WM, Karvellas CJ. Predicting outcome on admission and post-admission for acetaminophen-induced acute liver failure using classification and regression tree models. PLoS One 2015; 10:e0122929. [PMID: 25885260 PMCID: PMC4401567 DOI: 10.1371/journal.pone.0122929] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 02/24/2015] [Indexed: 12/15/2022] Open
Abstract
Background/Aim Assessing prognosis for acetaminophen-induced acute liver failure (APAP-ALF) patients often presents significant challenges. King’s College (KCC) has been validated on hospital admission, but little has been published on later phases of illness. We aimed to improve determinations of prognosis both at the time of and following admission for APAP-ALF using Classification and Regression Tree (CART) models. Methods CART models were applied to US ALFSG registry data to predict 21-day death or liver transplant early (on admission) and post-admission (days 3-7) for 803 APAP-ALF patients enrolled 01/1998–09/2013. Accuracy in prediction of outcome (AC), sensitivity (SN), specificity (SP), and area under receiver-operating curve (AUROC) were compared between 3 models: KCC (INR, creatinine, coma grade, pH), CART analysis using only KCC variables (KCC-CART) and a CART model using new variables (NEW-CART). Results Traditional KCC yielded 69% AC, 90% SP, 27% SN, and 0.58 AUROC on admission, with similar performance post-admission. KCC-CART at admission offered predictive 66% AC, 65% SP, 67% SN, and 0.74 AUROC. Post-admission, KCC-CART had predictive 82% AC, 86% SP, 46% SN and 0.81 AUROC. NEW-CART models using MELD (Model for end stage liver disease), lactate and mechanical ventilation on admission yielded predictive 72% AC, 71% SP, 77% SN and AUROC 0.79. For later stages, NEW-CART (MELD, lactate, coma grade) offered predictive AC 86%, SP 91%, SN 46%, AUROC 0.73. Conclusion CARTs offer simple prognostic models for APAP-ALF patients, which have higher AUROC and SN than KCC, with similar AC and negligibly worse SP. Admission and post-admission predictions were developed. Key Points • Prognostication in acetaminophen-induced acute liver failure (APAP-ALF) is challenging beyond admission • Little has been published regarding the use of King’s College Criteria (KCC) beyond admission and KCC has shown limited sensitivity in subsequent studies • Classification and Regression Tree (CART) methodology allows the development of predictive models using binary splits and offers an intuitive method for predicting outcome, using processes familiar to clinicians • Data from the ALFSG registry suggested that CART prognosis models for the APAP population offer improved sensitivity and model performance over traditional regression-based KCC, while maintaining similar accuracy and negligibly worse specificity • KCC-CART models offered modest improvement over traditional KCC, with NEW-CART models performing better than KCC-CART particularly at late time points
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Affiliation(s)
- Jaime Lynn Speiser
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America
| | - William M. Lee
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
| | - Constantine J. Karvellas
- Divisions of Hepatology and Critical Care Medicine, University of Alberta, Edmonton, Canada
- * E-mail:
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Fikatas P, Lee JE, Sauer IM, Schmidt SC, Seehofer D, Puhl G, Guckelberger O. APACHE III score is superior to King's College Hospital criteria, MELD score and APACHE II score to predict outcomes after liver transplantation for acute liver failure. Transplant Proc 2014; 45:2295-301. [PMID: 23953541 DOI: 10.1016/j.transproceed.2013.02.125] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Revised: 01/13/2013] [Accepted: 02/05/2013] [Indexed: 12/13/2022]
Abstract
OBJECTIVES The Model for End-Stage Liver Disease score and King's College Hospital (KCH) criteria are accepted prognostic models acute liver failure (ALF), while the use of (APACHE) scores predict to outcomes of emergency liver transplantation is rare. MATERIALS AND METHODS The present study included 87 patients with ALF who underwent liver transplantation. We calculated (KCH) criteria, as well as MELD, APACHE II, and APACHE III scores at the listing date for comparison with 3-month outcomes. RESULTS According to the Youden-Index, the best cut-off value for the APACHE II score was 8.5 with 100% sensitivity, 49% specificity, 24% positive predictive value (PPV), and 100% negative predictive value (NPV). Patients with <8.5 points had a significantly higher survival rate (P < .05). The proposed APACHE III cut-off was 80. The APACHE III score demonstrated the highest specificity and PPV (90% specificity, 50% PPV). The NPV was 92%. With a 90-point threshold the specificity increased to 98% with 75% PPV and 89% NPV. Only 1 of 4 patients with a score >90 survived transplantation (P = .001). MELD score and KCH criteria were not significant (P > .05). According to the Hosmer-Lemeshow test, only the APACHE III score adequately describe the data. CONCLUSIONS The APACHE III score was superior to KCH criteria, MELD score, and APACHE II score to predict outcomes after transplantation for ALF. It is a valuable parameter for pretransplantation patient selection.
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Affiliation(s)
- P Fikatas
- General, Visceral and Transplantation Surgery, Charité-Campus Virchow, Universitätsmedizin Berlin, Berlin, Germany.
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Mendizabal M, Marciano S, Videla MG, Anders M, Zerega A, Balderramo DC, Chan D, Barrabino M, Gil O, Mastai R, Yantorno S, Gadano A, Silva MO. Changing etiologies and outcomes of acute liver failure: perspectives from 6 transplant centers in Argentina. Liver Transpl 2014; 20:483-9. [PMID: 24425668 DOI: 10.1002/lt.23823] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 12/23/2013] [Indexed: 02/06/2023]
Abstract
There is significant geographic variation in the etiologies and prognoses of acute liver failure (ALF). The aims of the present study were to determine the causes and short-term outcomes of ALF in Argentina, to evaluate the performance of prognostic criteria, and to identify clinical prognostic factors of death. We performed a retrospective analysis of 154 adult patients with ALF who were admitted to 6 liver transplantation (LT) programs between June 2005 and December 2011. The most frequent causes of ALF were viral hepatitis B (46 patients or 30%), autoimmune hepatitis (AIH; 40 patients or 26%), and indeterminate causes (40 patients or 26%). No acetaminophen (ACM) overdose was reported. One hundred and twenty one patients (78%) were included on the waiting list, and LT was performed for 83 patients (54%). Overall survival rate is now corected to 73%. Multivariate logistic regression identified 2 independent variables associated with adverse outcomes on admission: a Model for End-Stage Liver Disease (MELD) score ≥ 29 and an encephalopathy grade ≥ 3. In a direct comparison using a receiving operating characteristic curve analysis, the MELD score [C statistic = 0.830, 95% confidence interval (CI) = 0.73-0.93] had better prognostic accuracy for predicting outcomes than the Clichy criteria (C statistic = 0.719, 95% CI = 0.58-0.85) or the King's College criteria (C statistic = 0.631, 95% CI = 0.49-0.77). In conclusion, hepatitis B and AIH were the most frequent causes of fulminant hepatic failure in our series, and no cases of ACM overdosing were identified. A MELD score ≥ 29 and an encephalopathy grade ≥ 3 at admission were associated with death. The MELD score at admission showed the highest prognostic accuracy.
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Affiliation(s)
- Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina
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Yang X, Lu Q, Tang T, Liao R, Yang Z. Prediction of the prognosis after liver transplantation in severe hepatitis B–induced liver failure and clinical decision for liver transplantation. J Surg Res 2013; 183:846-51. [DOI: 10.1016/j.jss.2013.01.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Revised: 11/06/2012] [Accepted: 01/17/2013] [Indexed: 12/13/2022]
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Abstract
The author draws attention on the importance surgical risk analysis from patient's safety point of view. Recently the development in quality assurance affected surgical practice as well, hence determination and evaluation of surgical risk are more exactly defined. This resulted in a significant decrease in mortality during surgical interventions on the liver despite a wider indication and increased numbers, recently. Importantly, surgical risk is much higher in patients with liver disease compared to patients with normal liver. The risk of surgical interventions for liver diseases (HCC, tumor) in patients with diffuse liver diseases (cirrhosis, chronic hepatitis, ALD) can be expressed numerically. For many years the Child-Turcotte-Pugh stadium could have been determined by using actual laboratory values. Recently the "50-50 rule" or more frequently the MELD score -- originally used in the practice of liver transplantation -- mean objective expression of surgical risk. Treatment optimalisation can reduce surgical risk, selected on the basis of risk analysis in multidisciplinary settings, which focus on the need of liver surgeons.
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Affiliation(s)
- Ferenc Jakab
- Uzsoki Utcai Kórház, 1145 Budapest, Uzsoki u. 29-41.
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25
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Hemostasis in patients with acute kidney injury secondary to acute liver failure. Kidney Int 2013; 84:158-63. [PMID: 23515053 DOI: 10.1038/ki.2013.92] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2012] [Revised: 01/05/2013] [Accepted: 01/10/2013] [Indexed: 02/07/2023]
Abstract
Acute kidney injury (AKI) occurs in over half of patients with acute liver failure. Despite prolonged prothrombin times and thrombocytopenia, continuous renal replacement therapy circuits frequently develop clots during patient treatment. Here we assessed factors contributing to this by measuring coagulation parameters (standard coagulation tests, pro- and anticoagulant factors, thromboelastography, and thrombin generation) in 20 consecutive patients with acute liver failure; mean age 42 years. Within 48 h, 10 had developed stage 3 AKI and 9 required continuous renal replacement therapy, of whom 2 had frequent circuit clots. The patients with stage 3 AKI were found to have significantly lower platelet counts and levels of factor V and the natural anticoagulants antithrombin, Protein C and Protein S, but increased extrinsic pathway activation and von Willebrand factor levels. Tissue factor levels were greater in those with stage 3 AKI, as was microparticle activity. Although patients with acute liver failure and advanced AKI requiring continuous renal replacement therapy have an even more marked thrombocytopenia and more prolonged extrinsic pathway activation, this was not associated with increased bleeding. Thus, more frequent circuit clots during continuous renal replacement therapy appear to be due to a combination of increased tissue factor and microparticle release, endothelial activation, and reduction in natural anticoagulants.
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Wlodzimirow KA, Eslami S, Chamuleau RAFM, Nieuwoudt M, Abu-Hanna A. Prediction of poor outcome in patients with acute liver failure-systematic review of prediction models. PLoS One 2012; 7:e50952. [PMID: 23272081 PMCID: PMC3522683 DOI: 10.1371/journal.pone.0050952] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Accepted: 10/29/2012] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Acute liver failure is a rare disease with high mortality and liver transplantation is the only life saving therapy. Accurate prognosis of ALF is crucial for proper intervention. AIM To identify and characterize newly developed prognostic models of mortality for ALF patients, assess study quality, identify important variables and provide recommendations for the development of improved models in the future. METHODS The online databases MEDLINE® (1950-2012) and EMBASE® (1980-2012) were searched for English-language articles that reported original data from clinical trials or observational studies on prognostic models in ALF patients. Studies were included if they developed a new model or modified existing prognostic models. The studies were evaluated based on an existing framework for scoring the methodological and reporting quality of prognostic models. RESULTS Twenty studies were included, of which 18 reported on newly developed models, 1 on modification of the Kings College Criteria (KCC) and 1 on the Model for End-Stage Liver Disease (MELD). Ten studies compared the newly developed models to previously existing models (e.g. KCC); they all reported that the new models were superior. In the 12-point methodological quality score, only one study scored full points. On the 38-point reporting score, no study scored full points. There was a general lack of reporting on missing values. In addition, none of the studies used performance measures for calibration and accuracy (e.g. Hosmer-Lemeshow statistics, Brier score), and only 5 studies used the AUC as a measure of discrimination. CONCLUSIONS There are many studies on prognostic models for ALF but they show methodological and reporting limitations. Future studies could be improved by better reporting and handling of missing data, the inclusion of model calibration aspects, use of absolute risk measures, explicit considerations for variable selection, the use of a more extensive set of reference models and more thorough validation.
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Affiliation(s)
- Kama A Wlodzimirow
- Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Sugawara K, Nakayama N, Mochida S. Acute liver failure in Japan: definition, classification, and prediction of the outcome. J Gastroenterol 2012; 47:849-61. [PMID: 22825549 PMCID: PMC3423565 DOI: 10.1007/s00535-012-0624-x] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Accepted: 05/25/2012] [Indexed: 02/08/2023]
Abstract
Acute liver failure is a clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to severe impairment of liver function caused by massive or submassive liver necrosis. Viral hepatitis is the most important and frequent cause of acute liver failure in Japan. The diagnostic criteria for fulminant hepatitis, including that caused by viral infections, autoimmune hepatitis, and drug allergy induced-liver damage, were first established in 1981. Considering the discrepancies between the definition of fulminant hepatitis in Japan and the definitions of acute liver failure in the United States and Europe, the Intractable Hepato-Biliary Disease Study Group established the diagnostic criteria for "acute liver failure" for Japan in 2011, and performed a nationwide survey of patients seen in 2010 to clarify the demographic and clinical features and outcomes of these patients. According to the survey, the survival rates of patients receiving medical treatment alone were low, especially in those with hepatic encephalopathy, despite artificial liver support, consisting of plasma exchange and hemodiafiltration, being provided to almost all patients in Japan. Thus, liver transplantation is inevitable to rescue most patients with hepatic encephalopathy. The indications for liver transplantation had, until recently, been determined according to the guideline published by the Acute Liver Failure Study Group in 1996. Recently, however, the Intractable Hepato-Biliary Disease Study Group established a scoring system to predict the outcomes of acute liver failure patients. Algorithms for outcome prediction have also been developed based on data-mining analyses. These novel guidelines need further evaluation to determine their usefulness.
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Affiliation(s)
- Kayoko Sugawara
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0495 Japan
| | - Nobuaki Nakayama
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0495 Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0495 Japan
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Acute hepatic failure as a leading manifestation in exertional heat stroke. Case Rep Crit Care 2012; 2012:295867. [PMID: 24826335 PMCID: PMC4010014 DOI: 10.1155/2012/295867] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Accepted: 04/11/2012] [Indexed: 12/19/2022] Open
Abstract
Background. Acute hepatic failure (AHF) is uncommon as a leading symptom in patients with exertional heat stroke (EHS). Which stage to perform the liver transplantation for severe hepatic failure in EHS is still obscure at clinical setting. The conservative management has been reported to be successful in treating heat-stroke-associated AHF even in the presence of accepted criteria for emergency liver transplantation. Case Presentation. Here, we reported a 35-year-old male who presented with very high transaminases, hyperbilirubinemia, significant prolongation of the prothrombin time, and coma. No other causes for AHF could be identified but physical exhaustion and hyperthermia. Although the current patient fulfilled London criteria for emergency liver transplantation, he spontaneously recovered under conservative treatment including intravenous fluids, cooling, diuretics as mannitol, and hepatocyte growth-promoting factors. Conclusions. Meticulous supportive management could be justified in some selected cases of AHF due to EHS.
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Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RAFM. Systematic review: acute liver failure - one disease, more than 40 definitions. Aliment Pharmacol Ther 2012; 35:1245-56. [PMID: 22506515 DOI: 10.1111/j.1365-2036.2012.05097.x] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2011] [Revised: 01/13/2012] [Accepted: 03/26/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Acute liver failure (ALF) is a clinical syndrome with very high mortality estimates ranging between 60% and 80%. AIM To investigate the explicitness and extent of variability in the used ALF definitions in the ALF prognostic literature. METHODS All studies that pertain to the prognosis of patients with ALF were electronically searched in MEDLINE (1950-2012) and EMBASE (1950-2012). Identified titles and abstracts were independently screened by three reviewers to determine eligibility for additional review. We included English articles that reported original data from clinical trials or observational studies on ALF patients. RESULTS A total of 103 studies were included. Of these studies 87 used 41 different ALF definitions and the remaining 16 studies did not report any explicit ALF definition. Four components underlying ALF definitions accounted for the differences: presence and/or grading of hepatic encephalopathy (HE); the interval between onset of disease and occurrence of HE; presence of coagulopathy and pre-existing liver disease. CONCLUSIONS The diversity in acute liver failure definitions hinders comparability and quantitative analysis among studies. There is room for improvement in the reporting of acute liver failure definitions in prognostic studies. The result of this review may be useful as a starting point to create a uniform acute liver failure definition.
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Affiliation(s)
- K A Wlodzimirow
- Department of Medical Informatics, Academic Medical Center, University of Amsterdam, The Netherlands
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Teufel U, Weitz J, Flechtenmacher C, Prietsch V, Schmidt J, Hoffmann GF, Kölker S, Engelmann G. High urgency liver transplantation in ornithine transcarbamylase deficiency presenting with acute liver failure. Pediatr Transplant 2011; 15:E110-5. [PMID: 21884343 DOI: 10.1111/j.1399-3046.2009.01171.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OTCD can present with ALF at any age. Under adequate therapy symptoms resolve quickly. We report a three-yr-old girl with the manifestation of an OTCD as ALF. Despite adequate pharmacotherapy and protein restriction, the patient deteriorated and developed hepatic encephalopathy. A high urgency liver transplantation was performed and the patient recovered completely. We conclude that in patients with ALF urea cycle defects in general and OTCD in particular should be considered as differential diagnosis. Patients should be managed in a center that has the capacity for an emergency liver transplantation.
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Affiliation(s)
- Ulrike Teufel
- Department of General Pediatrics, University of Heidelberg, Heidelberg, Germany.
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Shankar Hari M, Parsons AK, Burroughs AK, Shaw S, O'Beirne J, Agarwal B. Neurogenic diabetes insipidus presenting in a patient with subacute liver failure: a case report. J Med Case Rep 2010; 4:232. [PMID: 20673320 PMCID: PMC2923168 DOI: 10.1186/1752-1947-4-232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2008] [Accepted: 07/30/2010] [Indexed: 12/02/2022] Open
Abstract
Introduction To the best of our knowledge, this is the first report in the literature of development of neurogenic diabetes insipidus in a patient with subacute liver failure. Case presentation A 25-year-old man presented with subacute liver failure. While awaiting a liver transplant, the patient developed cerebral edema, which resulted in neurogenic diabetes insipidus secondary to cerebral edema. The patient died before the liver transplantation could be carried out. Conclusion Neurogenic diabetes insipidus is well recognized in the neurosurgical population as a consequence of cerebral edema and increased intracranial pressure, both of which occur commonly in patients with subacute liver failure.
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McPhail MJW, Wendon JA, Bernal W. Meta-analysis of performance of Kings's College Hospital Criteria in prediction of outcome in non-paracetamol-induced acute liver failure. J Hepatol 2010; 53:492-9. [PMID: 20580460 DOI: 10.1016/j.jhep.2010.03.023] [Citation(s) in RCA: 97] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2009] [Revised: 03/10/2010] [Accepted: 03/28/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Current techniques for predicting outcome and requirement for emergency liver transplantation (ELT) in acute liver failure (ALF) are imperfect, though The Kings College Criteria (KCC) are the most commonly applied tools for this purpose. Their performance in identification of patients with non-paracetamol-induced ALF (non-POD ALF), who would not survive without ELT, has recently been questioned. Using quantitative techniques, we therefore performed a meta-analysis of outcome data of the KCC for prediction of survival in non-POD ALF. METHODS A systematic database search was performed and retrieved articles graded according to a pre-agreed pro-forma of methodological quality. Collated data was meta-analysed for summary sensitivity, specificity, diagnostic odds ratio (DOR) and ROC curve analysis. Pre-specified sub-group analysis was performed on the basis of methodological quality, the severity of hepatic encephalopathy (HE) of reported patients, timing of KCC application and exclusion of those who underwent ELT. RESULTS Eighteen studies with data on 1105 patients were available for production of 2x2 tables. Summary sensitivity was 68 (95% CI 59-77)%, specificity 82 (75-88)% and DOR 12.6 (6.5-26.1). Heterogeneity was detected in the DOR and related to methodological quality (I(2)=64% for all studies versus 47% for 'good' quality studies) and was lower in studies considering high grade HE or dynamic application of KCC (I(2)=0%). For data where ELT were excluded (13 studies) summary sensitivity was 68 (57-79)%, specificity 81 (72-90)% and DOR 12.2 (4.9-30.1) and a symmetric summary ROC curve was produced. Specificity was highest in studies of patients with high grade HE (93 (80-100)%) and where KCC were applied dynamically through the clinical course (88 (78-97)%). Sensitivity was reduced in studies published post 2005 compared with studies pre 1995 (58 (46-71)% versus 85 (76-82)%). CONCLUSIONS KCC for outcome in non-POD ALF have good specificity and more limited sensitivity. There is significant heterogeneity in the published data partially related to methodological quality. KCC perform best in groups with high grade encephalopathy and in historically earlier studies suggesting modern medical management of ALF may modify performance of KCC.
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Affiliation(s)
- Mark J W McPhail
- Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital, London SE5 9RS, UK
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Acetaminophen dose does not predict outcome in acetaminophen-induced acute liver failure. J Investig Med 2010; 58:707-10. [PMID: 20305573 DOI: 10.231/jim.0b013e3181db8764] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator. METHODS Prospective data from 113 patients with ALF having single-time-point ingestions of acetaminophen were analyzed. Multivariate and chi tests were used to determine the relationship of dose to clinical outcome. We also used the Mann-Whitney U test to compare prognosis and survival in ALF with acetaminophen dose ingested. RESULTS Multivariate and chi analyses failed to show any relationship between acetaminophen dose and spontaneous survival. A separate analysis showed no correlation between acetaminophen dose and clinical prognostic indicators. CONCLUSIONS Dose of acetaminophen ingested did not seem to play a role in prognosis. The most important prognostic factor was coma grade on admission to study. Acetaminophen dosing information is not always obtainable. When it is, it adds little to the clinical assessment. Severity of encephalopathy is a more reliable indicator of prognosis in these critically ill patients.
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Abstract
Fulminant hepatic failure is a life-threatening condition that can lead to rapid deterioration and death if timely treatment is not instituted. Many patients recover with supportive care. Patients with deteriorating signs and laboratory parameters require prompt assessment and listing for liver transplantation. Outcome following transplantation is a function of severity of illness before transplantation, timeliness of liver transplantation and graft quality and function. With appropriate immunosuppression and close follow-up most patients can lead near normal lives following liver transplantation.
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Affiliation(s)
- Ajai Khanna
- Abdominal Transplant and Hepatobiliary Surgery, Department of Surgery, University of California San Diego School of Medicine, 200 West Arbor Drive, San Diego, CA 92103-8401, USA.
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Spahr L, Morard I, Mentha G, Hadengue A, Giostra E. Spontaneous Resolution of Brain Edema in Fulminant Hepatic Failure due to Hepatitis E. Case Rep Gastroenterol 2008; 2:424-7. [PMID: 21897793 PMCID: PMC3166805 DOI: 10.1159/000164618] [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] [Indexed: 11/21/2022] Open
Abstract
Fulminant hepatic failure is characterized by the presence of hepatic encephalopathy in the setting of acute liver injury that occurs in a noncirrhotic organ. Brain edema is the ultimate complication of advanced hepatic encephalopathy as it often leads to cerebral herniation and death. Thus, the presence of fulminant hepatic failure indicates the need for urgent liver transplantation to prevent death or irreversible brain damage. We report a very unusual evolution of fulminant hepatic failure complicated by brain edema and hepatic coma in a 45-year-old woman admitted with acute viral hepatitis E infection.
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Affiliation(s)
- Laurent Spahr
- Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland
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Abstract
Acute liver failure (ALF) is a dramatic, highly unpredictable clinical syndrome defined by the sudden onset of coagulopathy and encephalopathy. Acetaminophen overdose, the leading cause of ALF in the United States, has a 66% chance of recovery with early N-acetylcysteine treatment and supportive care. Cerebral edema and infectious complications are difficult to detect and treat in these patients and may cause irreversible brain damage and multiorgan failure. One-year survival after emergency liver transplantation is 70%, but 20% of listed patients die, highlighting the importance of early referral of patients who have ALF with a poor prognosis to a transplant center.
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Affiliation(s)
- Robert J Fontana
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, University of Michigan Medical Center, Ann Arbor, MI 48109-0362, USA.
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Hadem J, Stiefel P, Bahr MJ, Tillmann HL, Rifai K, Klempnauer J, Wedemeyer H, Manns MP, Schneider AS. Prognostic implications of lactate, bilirubin, and etiology in German patients with acute liver failure. Clin Gastroenterol Hepatol 2008; 6:339-45. [PMID: 18328438 DOI: 10.1016/j.cgh.2007.12.039] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Among the potentially helpful indicators of poor prognosis in acute liver failure (ALF) are etiology, encephalopathy grade, blood lactate, and King's College Criteria (KCC). The accuracy of these parameters in predicting transplantation or death shows significant variation in different countries. METHODS We retrospectively analyzed 102 patients with ALF treated at our institution between 1996 and 2005. Baseline parameters, simplified acute physiology score III (SAPS-III), KCC, Model for End-Stage Liver Disease (MELD) score, and a novel score of bilirubin, lactate, and etiology (BiLE score) were compared between transplant-free survivors and patients who required liver transplantation or died, by using multivariate linear regression analysis and receiver operating characteristics (ROC). RESULTS The most common causes of ALF were indeterminate liver failure (21%), acute hepatitis B (18%), acetaminophen ingestion (16%), and Budd-Chiari syndrome (9%). Transplantation-free survival was 38%, 44% of patients underwent liver transplantation, and 18% died without transplantation. Eight-week survival was 77%. The BiLE score was the best predictor of death or need of transplantation, with 79% sensitivity and 84% specificity. ROC analysis revealed a better performance of BiLE score when compared with bilirubin, lactate, MELD score, and SAPS-III (area under the curve: 0.87 +/- 0.04, 0.73 +/- 0.51, 0.73 +/- 0.52, 0.71 +/- 0.05, and 0.68 +/- 0.59, respectively). CONCLUSIONS The simple, combined BiLE score emerged as the best predictor of poor outcome in our patient cohort and should be prospectively evaluated in other populations.
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Affiliation(s)
- Johannes Hadem
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
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40
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Areia M, Romãozinho JM, Ferreira M, Amaro P, Leitão MC. Fulminant hepatic failure: a Portuguese experience. Eur J Gastroenterol Hepatol 2007; 19:665-9. [PMID: 17625436 DOI: 10.1097/meg.0b013e3281ac20da] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Fulminant hepatic failure (FHF) is a rare condition. Several series have been reported either by individual centres or in multicentre studies but, to our knowledge, this is the first report from a Portuguese population and might be a good example of FHF cases in a SouthWestern European population. AIMS To present the experience in FHF of a Portuguese Hepatogastroenterological Intensive Care Unit. MATERIALS AND METHODS Retrospective study of 61 cases of FHF consecutively admitted between February 1992 and October 2006. Definition and classification of FHF were those suggested by Trey and Davidson (1970) and O'Grady et al. (1993), respectively. Criteria and contraindications for hepatic transplantation (HT) were those proposed by Bernuau et al. (1991) and Muñoz (1993), respectively. RESULTS Fifty-seven per cent of patients were women and median age was 37 years (range: 8-73). Most common cause of FHF was indeterminate (26%) followed by viral (23%) and drug-induced (23%), with 51% of cases with a hyperacute evolution. Global HT rate was 54% with criteria for HT present in 87% of the patients resulting in an applicability rate of 62%. Overall survival was 69% and transplant-free survival was 15%; transplanted patients had survival rates of 70 and 68% at 6 and 12 months, respectively. CONCLUSIONS Drug-induced and viral agents were responsible for almost half of FHF cases with a clear predominance of hyperacute presentation. The HT rate was 54% and the applicability rate was 62%. The overall 1 year survival of 69% might reflect the adequacy of the HT criteria used.
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Affiliation(s)
- Miguel Areia
- Department of Gastroenterology, Coimbra University Hospital, Coimbra, Portugal.
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Yantorno SE, Kremers WK, Ruf AE, Trentadue JJ, Podestá LG, Villamil FG. MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure. Liver Transpl 2007; 13:822-8. [PMID: 17539002 DOI: 10.1002/lt.21104] [Citation(s) in RCA: 134] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Assessment of prognosis in fulminant hepatic failure (FHF) is essential for the need and appropriate timing of orthotopic liver transplantation (OLT). In this study we investigated the prognostic efficacy of King's College criteria, Clichy's criteria, Model for End-Stage Liver Disease (MELD), and Pediatric End-Stage Liver Disease (PELD) in 120 consecutive patients with FHF. Survival with medical therapy (18%), death without OLT (15%), and receipt of a liver transplant were similar in adults (n = 64) and children (n = 56). MELD scores were significantly higher in patients who died compared to those who survived without OLT, both in adults (38 +/- 7 vs. 26 +/- 7, P = 0.0003) and children (39 +/- 7 vs. 23 +/- 6, P = 0.0004). Using logistic regression analysis in this cohort of patients, concordance statistics were significantly higher for MELD (0.95) and PELD (0.99) when compared to King's College (0.74) and Clichy's criteria (0.68). When data was analyzed in a Cox model including patients receiving transplants and censoring the time from admission, the concordance statistic for MELD (0.77) and PELD (0.79) remained significantly higher than that of King's College criteria but not higher than that of Clichy's criteria. In conclusion, this study is the first to show that MELD and PELD are superior to King's College and Clichy's criteria to assess prognosis in FHF. However, because data was generated from a single center and included a rather low number of patients who survived or died without OLT, further confirmation of our findings is required.
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Choi WC, Arnaout WC, Villamil FG, Demetriou AA, Vierling JM. Comparison of the applicability of two prognostic scoring systems in patients with fulminant hepatic failure. Korean J Intern Med 2007; 22:93-100. [PMID: 17616024 PMCID: PMC2687618 DOI: 10.3904/kjim.2007.22.2.93] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Distinguishing those patients with fulminant hepatic failure (FHF) and who require transplantation from those FHF patients who will survive with receiving only intensive medical care remains problematic, and this distinction is important because of the chronic shortage of donor livers. METHODS To assess the applicability of two prognostic scoring systems, referred to as the London and Clichy criteria, we compared using both systems, at the time of admission, for 43 FHF patients (15 M/28 F; age: 3716 yrs). Acetaminophen (ACM) was the etiology for 16 patients, while the remaining 27 had other etiologies. All the patients received intensive care, and 18 (8 ACM/10 non-ACM) had investigational BAL support. RESULTS For the ACM toxicity, neither the London nor the Clichy criteria exhibited acceptable sensitivity (71 vs 86%, respectively), specificity (78 vs 56%, respectively), a positive predictive value (71 vs 60%, respectively), a negative predictive value (78 vs 83%, respectively) or predictive accuracy (75 vs 69%, respectively) to predict patient survival without transplantation. In contrast, applying the London and Clichy criteria to the FHF patients with non-ACM etiologies showed a sensitivity of 96 vs 80%, respectively, a specificity of 100 vs 100%, respectively, a positive predictive value of 100 vs 100%, respectively a negative predictive value of 67 vs 29%, respectively and a predictive accuracy of 96% vs 82%, respectively. CONCLUSIONS Overall, the London criteria more accurately predicted the need for transplantation, and neither the London criteria nor the Clichy prognostic criteria accurately predicted the outcome of those patients who suffered with FHF due to ACM. BAL support may have contributed to the survival of the patients with ACM toxicity and who didn't undergo transplantation, and this survival exceeded the predictions of both prognostic systems. Additional multicenter studies should be conducted to refine these prognostic scoring systems, and this will help physicians rapidly identify those FHF patients who can survive without undergoing liver transplantation.
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Affiliation(s)
- Won-Choong Choi
- Department of Internal Medicine, Sanggye-Paik Hospital, Inje University, College of Medicine Seoul, Korea.
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Dhiman RK, Jain S, Maheshwari U, Bhalla A, Sharma N, Ahluwalia J, Duseja A, Chawla Y. Early indicators of prognosis in fulminant hepatic failure: an assessment of the Model for End-Stage Liver Disease (MELD) and King's College Hospital criteria. Liver Transpl 2007; 13:814-21. [PMID: 17370333 DOI: 10.1002/lt.21050] [Citation(s) in RCA: 103] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
While King's Hospital Criteria (KCH) criteria are used worldwide, the Model for End-Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 +/- 14.7 yr; range 12-82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice-encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age >or=50 yr, JEI >7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time >or=35 seconds, and creatinine >or=1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of >or=33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. Any 3 CPI were superior to MELD and KCH criteria in predicting the outcome (c-statistic [95% confidence interval]: CPI 0.802 [0.726-0.878], MELD 0.717 [0.636-0.789], and KCH criteria 0.676 (0.588-0.764); P values: CPI vs. MELD 0.045, CPI vs. KCH criteria 0.019, and MELD vs. KCH criteria 0.472). In conclusion, MELD and KCH criteria are not as useful as a combination of other early CPI in predicting adverse outcome in patients with FHF due to acute viral hepatitis.
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Affiliation(s)
- Radha K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Renner EL. How to decide when to list a patient with acute liver failure for liver transplantation? Clichy or King's College criteria, or something else? J Hepatol 2007; 46:554-7. [PMID: 17316872 DOI: 10.1016/j.jhep.2007.01.009] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- Eberhard L Renner
- Section of Hepatology/Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada R3E 3P4.
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Katoonizadeh A, Decaestecker J, Wilmer A, Aerts R, Verslype C, Vansteenbergen W, Yap P, Fevery J, Roskams T, Pirenne J, Nevens F. MELD score to predict outcome in adult patients with non-acetaminophen-induced acute liver failure. Liver Int 2007; 27:329-34. [PMID: 17355453 DOI: 10.1111/j.1478-3231.2006.01429.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIMS/BACKGROUND A model for end stage liver disease (MELD) score >30 was proposed as an excellent predictor of mortality in patients with non-acetaminophen-induced acute liver failure (ALF). We analyzed the prognostic value of MELD score in our patients with ALF who were prospectively registered in our database since 1990. METHODS Overall, 106 patients met the criteria of ALF. Excluding seven patients with acetaminophen etiology, 99 patients (42+/-15 years, 40M/59F) were studied. RESULTS Causes were cryptogenic (n=38), viral (n=29), drugs (n=20) and miscellaneous (n=12). Of these, 37% (n=37) survived with medical management alone (group I), 16% (n=16) died (group II) and 46% (n=46) underwent liver transplantation (group III). The strongest predictors of poor outcome were advanced encephalopathy, cryptogenic/drug-induced/hepatitis B etiology and a high MELD score. At the time of diagnosis, King's College Hospital criteria and MELD score >30 had similar high negative predictive value (92% and 91%, respectively) and low positive predictive value (52% and 56%, respectively). The predictive values improved only slightly during follow-up. The best cut-off point for MELD score to discriminate between survivors and nonsurvivors was >35, with a sensitivity and specificity of 86% and 75%, respectively. CONCLUSIONS MELD score, which mostly takes into consideration the degree of liver impairment, has a similar prognostic value as King's College Hospital criteria to predict outcome in adult patients with nonacetaminophen-induced ALF. Overall, all current scores miss accuracy and therefore there is a clear need for factors that can better predict the regeneration of the liver in this setting.
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Affiliation(s)
- Aezam Katoonizadeh
- Department of Hepatology, University Hospital Gasthuisberg, KU Leuven, Belgium
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Schmidt LE, Larsen FS. MELD score as a predictor of liver failure and death in patients with acetaminophen-induced liver injury. Hepatology 2007; 45:789-96. [PMID: 17326205 DOI: 10.1002/hep.21503] [Citation(s) in RCA: 113] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
UNLABELLED The Model for End-Stage Liver Disease (MELD) scoring system has been established as a reliable measure of short-term mortality risk in patients with end-stage chronic liver disease. The aim of this study was to evaluate the prognostic value of the MELD scoring as a predictor of fulminant hepatic failure (FHF) and death in patients with acetaminophen poisoning. Prospectively, serial measurements of the 3 MELD components--INR, bilirubin, and creatinine--were performed in 460 patients with acetaminophen-induced liver injury. Starting on the first day after the day of overdose, MELD score was significantly higher in patients who eventually developed hepatic encephalopathy (HE) than in those who did not. HE developed in 63 of 142 patients with a MELD score above 18 at 48-72 hours after the overdose (positive predictive value 44%) compared with 2 of 182 patients with a MELD score of 18 or below (negative predictive value 99%). Among 124 patients with FHF, a threshold MELD score of 33 on the day after the onset of HE had sensitivity of 60%, specificity of 69%, positive predictive value of 65%, and negative predictive value of 63%. However, the discriminative power of MELD score was not superior to that of INR alone or of the King's College Hospital criteria. CONCLUSION MELD score may be useful as a predictor of FHF in patients admitted with acetaminophen toxicity. However, as a predictor of death from FHF, MELD score did not provide more information than the King's College Hospital criteria or INR alone.
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Affiliation(s)
- Lars E Schmidt
- Department of Hepatology A, Rigshospitalet, Copenhagen, Denmark.
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Senzolo M, Burra P, Cholongitas E, Burroughs AK. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol 2006; 12:7725-36. [PMID: 17203512 PMCID: PMC4087534 DOI: 10.3748/wjg.v12.i48.7725] [Citation(s) in RCA: 111] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.
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Affiliation(s)
- M Senzolo
- Department of Surgical and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy.
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48
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Affiliation(s)
- William T Merritt
- Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medicine Center for Information Services, Johns Hopkins Hospital, Baltimore, MD 21287, USA
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Peláez-Luna M, Martinez-Salgado J, Olivera-Martinez MA. Utility of the MAYO End-Stage Liver Disease score, King's College Criteria, and a new in-hospital mortality score in the prognosis of in-hospital mortality in acute liver failure. Transplant Proc 2006; 38:927-9. [PMID: 16647512 DOI: 10.1016/j.transproceed.2006.02.034] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Several prognostic scores attempt to aid in the selection of patients with acute liver failure (ALF) to be treated either medically or by liver transplantation; however, their lack of fulfillment does not predict spontaneous survival in ALF and refined prognostic criteria are needed to improve such selection. Our aim was to evaluate and compare a new ALF in-hospital mortality prediction score versus King's College Criteria (KCC) and model for End-Stage Disease (MELD) score. METHODS First-time ALF-diagnosed individuals admitted to our institution (n = 58) were grouped according their final outcome as "alive" or "death," and those significantly different variables between groups entered into a logistic regression and lineal regression models. An ALF in-hospital mortality score (ALFIHMS) was produced and its sensitivity, specificity, and area under receiver operator characteristics were compared with those of KCC and MELD scores. RESULTS Since no significant differences (P = .81) in mortality rates between fulminant and subfulminant hepatic failure were found, no further analysis according to ALF's classification was performed. After obtaining and comparing ALFIHMS with KCC and MELD, we found that ALFIHMS prediction accuracy is higher than that of KCC and MELD score and that an ALFIHMS cutoff point >15 points is associated with an in-hospital mortality probability >50%. CONCLUSIONS ALFIHMS has higher prognostic accuracy than KCC and MELD scores in ALF.
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Affiliation(s)
- M Peláez-Luna
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Abstract
Since publication of the first descriptions of acute liver failure (ALF) as a distinct clinical entity in the 1950's, the understanding of the pathophysiologic mechanisms involved and the management options have increased substantially. ALF still represents a major challenge for todays hepatologists, because it can rapidly lead to multiorgan failure and death that may be preventable with appropriate intervention. This article summarizes the basic patho-physiology underlying ALF, compares epidemiologic trends in the United States, the United Kingdom, and the Far East, and reviews prognostic markers and treatment options for ALF.
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Affiliation(s)
- Shahid A Khan
- Liver Failure Group, Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK
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