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Li ZX, Zeng JH, Zhong HL, Peng B. Liver transplantation improves prognosis across all grades of acute-on-chronic liver failure patients: A systematic review and meta-analysis. World J Gastroenterol 2025; 31:102007. [PMID: 40182592 PMCID: PMC11962855 DOI: 10.3748/wjg.v31.i12.102007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 01/23/2025] [Accepted: 02/26/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Liver transplantation (LT) is recognized as an effective approach that offers survival benefits for patients with acute-on-chronic liver failure (ACLF). However, controversies remain regarding the LT selection criteria, and meta-analyses reporting overall survival outcomes across different ACLF severity grades are lacking. AIM To depict a comprehensive postoperative picture of patients with ACLF of varying severity and contribute to updating LT selection. METHODS Systematic searches in Web of Science, EMBASE, PubMed, and Cochrane databases were performed, from inception to December 26, 2023, for studies exploring post-transplant outcomes among ACLF patients, stratified by severity grades as identified by the European Association for the Study of the Liver-Chronic Liver Failure criteria. The primary outcome of interest was the survival rate within one year, with post-transplant complications as secondary outcomes. Additionally, the subgroup analysis examined region-specific one-year survival rates. RESULTS A total of 17 studies involving 28025 participants were included. Patients with ACLF-1 and ACLF-2 have favorable survival within one year, with survival rates reaching 87% [95% confidence interval (CI): 84%-91%] and 86% (95%CI: 81%-91%), respectively. Despite the relatively lower survival (73%, 95%CI: 66%-80%) and higher incidence of infection (48%, 95%CI: 29%-67%) observed in ACLF-3 patients, their survival exceeds that of those who do not undergo LT. Moreover, post-transplant survival was highest in North America across all ACLF grades. CONCLUSION LT can provide survival advantages for ACLF patients. To optimize the utilization of scarce donor organs and improve prognosis, comprehensive preoperative health evaluations are essential, especially for ACLF-3 patients.
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Affiliation(s)
- Zhi-Xin Li
- Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Clinical Research Center, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Jun-Hao Zeng
- Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Hong-Lin Zhong
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Bo Peng
- The Transplantation Center, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Key Laboratory of Translational Research on Transplantation Medicine, National Health Commission, Changsha 410013, Hunan Province, China
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Goran LG, Liţă (Cofaru) FA, Fierbinţeanu-Braticevici C. Acute-on-Chronic Liver Failure: Steps Towards Consensus. Diagnostics (Basel) 2025; 15:751. [PMID: 40150093 PMCID: PMC11941433 DOI: 10.3390/diagnostics15060751] [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: 02/16/2025] [Revised: 03/09/2025] [Accepted: 03/14/2025] [Indexed: 03/29/2025] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by organ failure and high short-term mortality. Since its first definition in 2013, many international organizations have defined this syndrome and, till now, there has been no agreement regarding definitions and diagnostic criteria. Although the precise mechanism of ACLF is unknown, precipitant factors and the systemic inflammation response play a major role. Specific management of this high-mortality syndrome is still under development, but a general consensus in the diagnosis and management of ACLF is needed.
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Affiliation(s)
- Loredana Gabriela Goran
- Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (F.A.L.); (C.F.-B.)
- Internal Medicine II and Gastroenterology Department, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Florina Alexandra Liţă (Cofaru)
- Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (F.A.L.); (C.F.-B.)
- Emergency Department, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Carmen Fierbinţeanu-Braticevici
- Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (F.A.L.); (C.F.-B.)
- Internal Medicine II and Gastroenterology Department, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
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Tanaka T, Roberts EK, Platt J. Reduced short-term survival following liver transplant in patients with acute-on-chronic liver failure: Reevaluating OPTN data. Hepatol Commun 2025; 9:e0651. [PMID: 39969433 PMCID: PMC11841847 DOI: 10.1097/hc9.0000000000000651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 12/26/2024] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Prior studies show severe acute-on-chronic liver failure (ACLF) at liver transplantation (LT) negatively impacts short-term, but not long-term, post-LT outcomes. However, not accounting for ACLF's time-varying effect on the waitlist may underappreciate its dynamic nature. Moreover, excluding those who died or dropped off the waitlist raises concerns about selection bias. METHODS This US nationwide retrospective cohort study estimated the effect of severe ACLF (grade 3) (ACLF-3) on post-LT outcomes, including adult, first-time deceased donor LT candidates listed from June 2013 to May 2023. A marginal structural model (MSM) to address selection bias and time-varying exposure (ACLF-3) was applied, with extended Cox proportional hazard models using a Heaviside step function to assess the hazard of death after LT. RESULTS Among 31,267 eligible candidates for LT (baseline cohort), 11.3% (n = 3518) had ACLF-3 at listing; 13.6% (n = 4243) died or dropped out while on the LT waitlist. Of the 27,024 patients who received LT (transplanted cohort), 12.3% (n = 3333) had ACLF-3 at LT. ACLF-3 at LT (but not at waitlisting) was associated with a higher hazard of death, with the hazard ratio of 1.80 (95% CI: 1.09-2.97) within 1 year after LT but not thereafter. This marginal structural model effect size was 9% higher than conventional multivariable Cox proportional hazard models. Sensitivity analyses corroborated these findings. CONCLUSIONS Compared to previous studies, ACLF-3 at LT in our marginal structural model was associated with a discernible increase in short-term mortality after transplant, presumably due to our addressing of selection bias, while long-term survival was similar to those without severe ACLF at LT. However, potential vulnerability to posttransplant complications warrants further investigation.
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Affiliation(s)
- Tomohiro Tanaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
- Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, Iowa, USA
| | - Emily K. Roberts
- Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA
| | - Jonathan Platt
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA
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Ballester MP, Elshabrawi A, Jalan R. Extracorporeal liver support and liver transplantation for acute-on-chronic liver failure. Liver Int 2025; 45:e15647. [PMID: 37312660 PMCID: PMC11815617 DOI: 10.1111/liv.15647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/31/2023] [Accepted: 06/04/2023] [Indexed: 06/15/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is defined by acute decompensation, organ failure and a high risk of short-term mortality. This condition is characterized by an overwhelming systemic inflammatory response. Despite treating the precipitating event, intensive monitoring and organ support, clinical deterioration can occur with very poor outcomes. During the last decades, several extracorporeal liver support systems have been developed to try to reduce ongoing liver injury and provide an improved environment for the liver to regenerate or as a bridging therapy until liver transplantation. Several clinical trials have been performed to evaluate the clinical efficacy of extracorporeal liver support systems, but no clear impact on survival has been proven. DIALIVE is a novel extracorporeal liver support device that has been built to specifically address the pathophysiological derangements responsible for the development of ACLF by replacing dysfunctional albumin and removing pathogen and damage-associated molecular patterns (PAMPs and DAMPs). In phase II clinical trial, DIALIVE appears to be safe, and it seems to be associated with a faster time to the resolution of ACLF compared with standard medical treatment. Even in patients with severe ACLF, liver transplantation saves lives and there is clear evidence of transplant benefit. Careful selection of patients is required to attain good results from liver transplantation, but many questions remain unanswered. In this review, we describe the current perspectives on the use of extracorporeal liver support and liver transplantation for ACLF patients.
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Affiliation(s)
- Maria Pilar Ballester
- Digestive Disease DepartmentHospital Clínico Universitario de ValenciaValenciaSpain
- INCLIVA Biomedical Research InstituteHospital Clínico Universitario de ValenciaValenciaSpain
| | - Ahmed Elshabrawi
- Liver Failure Group, Institute for Liver & Digestive HealthUniversity College LondonLondonUK
- Endemic Hepatology and Gastroenterology DepartmentMansoura UniversityMansouraEgypt
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver & Digestive HealthUniversity College LondonLondonUK
- European Foundation for the Study of Chronic Liver Failure (EF Clif)BarcelonaSpain
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Praktiknjo M, Shawcross D, Laleman W. The clinical relevance of acute-on-chronic liver failure in medical procedures: Endoscopy, interventions and surgery. Liver Int 2025; 45:e15749. [PMID: 37753553 PMCID: PMC11815627 DOI: 10.1111/liv.15749] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 08/30/2023] [Accepted: 09/13/2023] [Indexed: 09/28/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a specific, but complex and multifactorial form of acute decompensation (AD) of cirrhosis and is characterized by an extraordinary dynamic natural course, rapidly evolving organ failure and high short-term mortality. In daily clinical practice, patients with liver cirrhosis and decompensation have indications for different medical procedures such as endoscopies, interventional treatments like transjugular intrahepatic portosystemic shunt (TIPS) or even surgical procedures. In these situations, clinicians often need to balance the expected benefits of such procedures with the risks of causing acute decompensation or ACLF. This review summarizes the evidence of medical procedures and their role in precipitating or preventing ACLF and highlights the aspects to consider during patient selection.
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Affiliation(s)
- Michael Praktiknjo
- Department of Medicine B, Gastroenterology, Hepatology, Endocrinology, Infectious DiseasesUniversitätsklinikum MünsterMünsterGermany
| | - Debbie Shawcross
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College LondonLondonUK
| | - Wim Laleman
- Department of Medicine B, Gastroenterology, Hepatology, Endocrinology, Infectious DiseasesUniversitätsklinikum MünsterMünsterGermany
- Department of Gastroenterology & HepatologyUniversity Hospitals LeuvenLeuvenBelgium
- Department of Chronic Diseases, Metabolism and Aging (CHROMETA)Catholic University of LeuvenLeuvenBelgium
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Kwon HM, Kim JH, Kim SH, Jun IG, Song JG, Moon DB, Hwang GS. Benefits of liver transplant in critically ill patients with acute-on-chronic liver failure: Implementation of an urgent living-donor program. Am J Transplant 2025; 25:150-163. [PMID: 39155023 DOI: 10.1016/j.ajt.2024.08.008] [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: 08/17/2023] [Revised: 08/08/2024] [Accepted: 08/09/2024] [Indexed: 08/20/2024]
Abstract
We evaluated the liver transplantation (LT) criteria in acute-on-chronic liver failure (ACLF), incorporating an urgent living-donor LT (LDLT) program. Critically ill patients with a Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C_ACLF_score) ≥65, previously considered unsuitable for LT, were included to explore the excess mortality threshold of the CLIF-C_ACLF_score (CLIF-C_ACLF_score_threshold). We followed 854 consecutive patients with ACLF (276 ACLF grade 2 and 215 ACLF grade 3) over 10 years among 4432 LT recipients between 2008 and 2019. For advanced ACLF patients without immediate deceased-donor (DD) allocation, an urgent LDLT program was expedited. The CLIF-C_ACLF_score_threshold was determined by the metrics of transplant survival benefit: >60% 1-year and >50% 5-year survival rate. In predicting post-LT mortality, the CLIF-C_ACLF_score outperformed the (model for end-stage liver disease-sodium) MELD-Na and (model for end-stage liver disease) MELD-3.0 scores but was comparable to the Sundaram ACLF-LT-mortality score. A CLIF-C_ACLF_score ≥65 (n = 54) demonstrated posttransplant survival benefits, with 1-year and 5-year survival rates of 66.7% and 50.4% (P < .001), respectively. Novel CLIF-C_ACLF_score_threshold for 1-year and 5-year mortalities was 70 and 69, respectively. A CLIF-C_ACLF_score-based nomogram for predicting survival probabilities, integrating cardiovascular disease, diabetes, and donor type (LDLT vs DDLT), was generated. This study suggests reconsidering the criteria for unsuitable LT with a CLIF-C_ACLF_score ≥65. Implementing a timely salvage LT strategy, and incorporating urgent LDLT, can enhance survival rates.
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Affiliation(s)
- Hye-Mee Kwon
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Hwan Kim
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Hoon Kim
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - In-Gu Jun
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jun-Gol Song
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Deok-Bog Moon
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gyu-Sam Hwang
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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Jin YX, Hu HQ, Zhang JC, Xin XY, Zhu YT, Ye Y, Li D. Mechanism of mesenchymal stem cells in liver regeneration: Insights and future directions. World J Stem Cells 2024; 16:842-845. [PMID: 39351263 PMCID: PMC11438733 DOI: 10.4252/wjsc.v16.i9.842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Revised: 08/08/2024] [Accepted: 08/26/2024] [Indexed: 09/24/2024] Open
Abstract
Mesenchymal stem cells (MSCs) are a prevalent source for stem cell therapy and play a crucial role in modulating both innate and adaptive immune responses. Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in liver cells and involves immune system activation, leading to histological changes, tissue damage, and clinical symptoms. A recent publication by Jiang et al, highlighted the potential of MSCs to mitigate in NAFLD progression by targeting various molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. In this editorial, we comment on their research and discuss the efficacy of MSC therapy in treating NAFLD.
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Affiliation(s)
- Yu-Xin Jin
- Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Hang-Qi Hu
- Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Jia-Cheng Zhang
- Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Xi-Yan Xin
- Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Yu-Tian Zhu
- Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Yang Ye
- Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China.
| | - Dong Li
- Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing 100191, China
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8
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Pollmanns MR, Pajaziti Q, Hohlstein P, Adams JK, Abu Jhaisha S, Kabak E, Hamesch K, Nusser SHA, Weiskirchen R, Wirtz TH, Koch A. Serum Adiponectin Is Elevated in Critically Ill Patients with Liver Disease and Associated with Decreased Overall Survival. Biomedicines 2024; 12:2173. [PMID: 39457486 PMCID: PMC11504267 DOI: 10.3390/biomedicines12102173] [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: 09/05/2024] [Revised: 09/20/2024] [Accepted: 09/22/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Adiponectin, an adipokine with anti-inflammatory properties, has been implicated in various liver diseases. This study aimed to elucidate the prognostic value of serum adiponectin levels in critically ill patients with liver disease. METHODS This observational study included 161 critically ill patients admitted to the medical ICU of RWTH Aachen University Hospital due to acute liver failure or decompensated advanced chronic liver disease. Serum adiponectin levels were measured at ICU admission and after 48 h. Clinical parameters and outcomes, including transplant-free survival, were analyzed. RESULTS Serum adiponectin concentrations were significantly elevated compared to healthy controls (p < 0.001). Levels were particularly high in patients with sepsis compared to those with gastrointestinal bleeding as the precipitating factor of acute decompensation (p = 0.045) and were higher in female patients (p = 0.023). Adiponectin concentrations correlated with the Model of End-Stage Liver Disease (MELD) score and Child-Pugh score. Multivariate analysis confirmed a significant correlation with total bilirubin (r = 0.292, p < 0.001) and serum sodium (r = -0.265, p = 0.028). Higher adiponectin concentrations were associated with a trend towards poorer 30- and 180-day survival. Cox regression analysis identified a significant association between increased adiponectin concentration and reduced transplant-free survival (p = 0.037), supported by a Kaplan-Meier analysis using a cutoff of 119 ng/mL (log-rank 5.145, p = 0.023). CONCLUSIONS Elevated serum adiponectin concentrations are associated with liver dysfunction and poor outcomes in critically ill patients. Higher adiponectin levels at ICU admission may predict poorer transplant-free survival. Further research in larger, multicenter cohorts is warranted to validate these findings and explore the underlying mechanisms.
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Affiliation(s)
- Maike R. Pollmanns
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Qendrim Pajaziti
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Philipp Hohlstein
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Jule K. Adams
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Samira Abu Jhaisha
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Elena Kabak
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Karim Hamesch
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Sophie H. A. Nusser
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany;
| | - Theresa H. Wirtz
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
| | - Alexander Koch
- Department for Gastroenterology, Metabolic Disorders and Intensive Care Medicine, RWTH-University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany; (M.R.P.); (Q.P.); (P.H.); (J.K.A.); (S.A.J.); (E.K.); (K.H.); (S.H.A.N.); (T.H.W.)
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Fernández J, Blasi A, Hidalgo E, Karvellas CJ. Bridging the critically ill patient with acute to chronic liver failure to liver transplantation. Am J Transplant 2024; 24:1348-1361. [PMID: 38548058 DOI: 10.1016/j.ajt.2024.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/16/2024] [Accepted: 03/18/2024] [Indexed: 04/14/2024]
Abstract
Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute-on-chronic liver failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present, adversely impacting the prognosis of these patients. Management of critical care patients with ACLF is complex and requires the participation of different specialties. Once the patient is stabilized, a rapid evaluation for salvage LT should be performed because the time window for LT is often narrow. The development of sepsis and prolonged organ support may preclude LT or diminish its chances of success. The current review describes strategies to bridge severe ACLF patients to LT, highlights the minimal evaluation required for listing and the currently suggested contraindications to proceed with LT, and addresses different aspects of management during the perioperative and early posttransplant period.
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Affiliation(s)
- Javier Fernández
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Spain; EF Clif, EASL-CLIF Consortium, Barcelona, Spain.
| | - Annabel Blasi
- Anesthesiology Department, Hospital Clínic, and University of Barcelona, Spain
| | - Ernest Hidalgo
- Hepatolobiliary Surgery Department, Hospital Vall d'Hebron, Barcelona, Spain
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Canada; Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
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10
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Zhu ZY, Huang XH, Jiang HQ, Liu L. Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit. World J Gastroenterol 2024; 30:2657-2676. [PMID: 38855159 PMCID: PMC11154676 DOI: 10.3748/wjg.v30.i20.2657] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 04/22/2024] [Accepted: 05/09/2024] [Indexed: 05/27/2024] Open
Abstract
BACKGROUND Cirrhotic patients with acute-on-chronic liver failure (ACLF) in the intensive care unit (ICU) have a poor but variable prognoses. Accurate prognosis evaluation can guide the rational management of patients with ACLF. However, existing prognostic scores for ACLF in the ICU environment lack sufficient accuracy. AIM To develop a new prognostic model for patients with ACLF in ICU. METHODS Data from 938 ACLF patients in the Medical Information Mart for Intensive Care (MIMIC) database were used to develop a new prognostic model (MIMIC ACLF) for ACLF. Discrimination, calibration and clinical utility of MIMIC ACLF were assessed by area under receiver operating characteristic curve (AUROC), calibration curve and decision curve analysis (DCA), respectively. MIMIC ACLF was then externally validated in a multiple-center cohort, the Electronic Intensive Care Collaborative Research Database and a single-center cohort from the Second Hospital of Hebei Medical University in China. RESULTS The MIMIC ACLF score was determined using nine variables: ln (age) × 2.2 + ln (white blood cell count) × 0.22 - ln (mean arterial pressure) × 2.7 + respiratory failure × 0.6 + renal failure × 0.51 + cerebral failure × 0.31 + ln (total bilirubin) × 0.44 + ln (internationalized normal ratio) × 0.59 + ln (serum potassium) × 0.59. In MIMIC cohort, the AUROC (0.81/0.79) for MIMIC ACLF for 28/90-day ACLF mortality were significantly greater than those of Chronic Liver Failure Consortium ACLF (0.76/0.74), Model for End-stage Liver Disease (MELD; 0.73/0.71) and MELD-Na (0.72/0.70) (all P < 0.001). The consistency between actual and predicted 28/90-day survival rates of patients according to MIMIC ACLF score was excellent and superior to that of existing scores. The net benefit of MIMIC ACLF was greater than that achieved using existing scores within the 50% threshold probability. The superior predictive accuracy and clinical utility of MIMIC ACLF were validated in the external cohorts. CONCLUSION We developed and validated a new prognostic model with satisfactory accuracy for cirrhotic patients with ACLF hospitalized in the ICU. The model-based risk stratification and online calculator might facilitate the rational management of patients with ACLF.
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Affiliation(s)
- Zong-Yi Zhu
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
- Department of Gastroenterology, Weixian People's Hospital, Xingtai 054700, Hebei Province, China
| | - Xiu-Hong Huang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Hui-Qing Jiang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Li Liu
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
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11
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Haselwanter P, Scheiner B, Balcar L, Semmler G, Riedl-Wewalka M, Schmid M, Reiberger T, Zauner C, Schneeweiss-Gleixner M. Use of the CytoSorb adsorber in patients with acute-on-chronic liver failure. Sci Rep 2024; 14:11309. [PMID: 38760460 PMCID: PMC11101465 DOI: 10.1038/s41598-024-61658-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 05/08/2024] [Indexed: 05/19/2024] Open
Abstract
CytoSorb is a hemoadsorptive column used to remove high concentrations of proinflammatory cytokines in septic shock. Data on CytoSorb application in acute-on-chronic liver failure (ACLF) is lacking. This retrospective observational study analyzed 21 ACLF patients admitted to ICUs at the Vienna General Hospital who received CytoSorb adsorber therapy between 2017 and 2023. Median ICU length of stay was 8 days (IQR: 3-13), the ICU survival rate was 23.8% (n = 5). Significant decreases in bilirubin (median peak: 20.7 mg/dL to median post-treatment: 10.8 mg/dL; - 47.8%; p < 0.001), procalcitonin (1.34 to 0.74 pg/mL; - 44.6%; p < 0.001), interleukin-6 (385 to 131 ng/mL; - 66.0%; p = 0.0182)-but also of platelets (72 to 31 G/L; - 56.9%; p = 0.0014) and fibrinogen (230 to 154 mg/dL; - 33.0%; p = 0.0297) were detected. ICU survivors had a trend towards a stronger relative decrease in bilirubin (- 76.1% vs. - 48.2%), procalcitonin (- 90.6% vs. - 23.5%), and IL-6 (- 54.6% vs. - 17.8%) upon CytoSorb treatment. Moreover, no serious CytoSorb-attributed complications were detected. In conclusion, use of CytoSorb adsorber in ACLF patients results in a significant decrease in bilirubin and proinflammatory cytokines, while platelets and fibrinogen were also lowered. Prospective trials are warranted to investigate the impact of CytoSorb on clinical outcomes of ACLF patients with high proinflammatory cytokine levels.
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Affiliation(s)
- Patrick Haselwanter
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Bernhard Scheiner
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Lorenz Balcar
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Georg Semmler
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Marlene Riedl-Wewalka
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Monika Schmid
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Thomas Reiberger
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Christian Zauner
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Mathias Schneeweiss-Gleixner
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
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12
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Choudhury A, Adali G, Kaewdech A, Giri S, Kumar R. Liver Transplantation in Chronic Liver Disease and Acute on Chronic Liver Failure- Indication, Timing and Practices. J Clin Exp Hepatol 2024; 14:101347. [PMID: 38371606 PMCID: PMC10869905 DOI: 10.1016/j.jceh.2024.101347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 01/19/2024] [Indexed: 02/20/2024] Open
Abstract
Liver transplantation (LT) is the second most common solid organ transplantation worldwide. LT is considered the best and most definitive therapeutic option for patients with decompensated chronic liver disease (CLD), hepatocellular carcinoma (HCC), acute liver failure (ALF), and acute-on-chronic liver failure (ACLF). The etiology of CLD shows wide geographical variation, with viral hepatitis being the major etiology in the east and alcohol-related liver disease (ALD) in the west. Non-alcoholic fatty liver disease (NAFLD) is on an increasing trend and is expected to be the most common etiology on a global scale. Since the first successful LT, there have been radical changes in the indications for LT. In many circumstances, not just the liver disease itself but factors such as extra-hepatic organ dysfunction or failures necessitate LT. ACLF is a dynamic syndrome that has extremely high short-term mortality. Currently, there is no single approved therapy for ACLF, and LT seems to be the only feasible therapeutic option for selected patients at high risk of mortality. Early identification of ACLF, stratification of patients according to disease severity, aggressive organ support, and etiology-specific treatment approaches have a significant impact on post-transplant outcomes. This review briefly describes the indications, timing, and referral practices for LT in patients with CLD and ACLF.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology and Liver Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Gupse Adali
- Department of Gastroenterology and Hepatology, University of Health Sciences, Ümraniye, İstanbul, Turkey
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneshwar, India
| | - Rahul Kumar
- Duke-NUS Academic Medical Centre, Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
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Torre A, Cisneros-Garza LE, Castillo-Barradas M, Navarro-Alvarez N, Sandoval-Salas R, González-Huezo MS, Pérez-Hernández JL, Méndez-Guerrero O, Ruiz-Manríquez JA, Trejo-Estrada R, Chavez-Tapia NC, Solís-Gasca LC, Moctezuma-Velázquez C, Aguirre-Valádez J, Flores-Calderón J, Higuera-de-la-Tijera F, García-Juárez I, Canedo-Castillo NA, Malé-Velázquez R, Montalvo-Gordon I, Vilatobá M, Márquez-Guillén E, Córdova-Gallardo J, Flores-García NC, Miranda-Zazueta G, Martínez-Saldívar BI, Páez-Zayas VM, Muñoz-Espinosa LE, Solís-Galindo FA. Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology. Ann Hepatol 2023; 28:101140. [PMID: 37482299 DOI: 10.1016/j.aohep.2023.101140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 07/25/2023]
Abstract
Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - Laura Esthela Cisneros-Garza
- Gastroenterology and Hepatology Department, Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - Nalu Navarro-Alvarez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Osvely Méndez-Guerrero
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Luis Carlos Solís-Gasca
- Gastroenterology Department, Hospital General de Zona #12 Benito Juárez del Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Medicine - Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | | | - Judith Flores-Calderón
- Pediatrics Department, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Iaarah Montalvo-Gordon
- Clinic of Gastrointestinal and Hepatic Specialties, Hospital Faro del Mayab, Mérida, Yucatán, Mexico
| | - Mario Vilatobá
- Transplant Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ernesto Márquez-Guillén
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Ángeles del Pedregal, Mexico City, Mexico
| | - Jacqueline Córdova-Gallardo
- Hepatology Department - General Surgery Service, Hospital General Dr. Manuel Gea González, Mexico City, Mexico
| | - Nayeli Cointa Flores-García
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Linda Elsa Muñoz-Espinosa
- Universidad Autónoma de Nuevo León. Liver Unit, Department of Internal Medicine, University Hospital 'Dr. José E. González', Monterrey, Nuevo León, Mexico
| | - Francisco Alfonso Solís-Galindo
- Gastroenterology Department, Unidad Médica de Alta Especialidad # 71 Instituto Mexicano del Seguro Social, Torreón, Coahuila, Mexico
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14
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Puri P, Malik S. Liver Transplantation: Contraindication and Ineligibility. J Clin Exp Hepatol 2023; 13:1116-1129. [PMID: 37975058 PMCID: PMC10643298 DOI: 10.1016/j.jceh.2023.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/14/2023] [Indexed: 11/19/2023] Open
Abstract
Liver transplantation (LT) is a life-saving therapeutic modality for patients with various advanced liver diseases. It is crucial to identify that the patient's illness is sufficiently advanced and unlikely to improve with medical management to justify the need for transplantation. At the same time, it is crucial to identify patients with comorbidities and far advanced disease that would result in an unacceptable outcome after LT. Specific care also is required before deciding on LT in the elderly, acute on chronic liver disease, patients with comorbidities, and hepatocellular carcinoma. Transplantation needs to be timed appropriately to avoid unnecessary LT and ensure that the decision is not left too late to avoid losing the patient without a transplant. Also, important is the decision as to when not to transplant. The current review explores some of these issues of contraindications and ineligibility for LT.
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, Fortis Escorts Hospital, New Delhi 110025, India
| | - Sarthak Malik
- Department of Gastroenterology, Manipal Hospital, Dwarka, New Delhi 110075, India
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15
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Madigan S, Tashkent Y, Trehan S, Muller K, Wigg A, Woodman R, Ramachandran J. Acute on chronic liver failure: A South Australian experience. JGH Open 2023; 7:717-723. [PMID: 37908287 PMCID: PMC10615173 DOI: 10.1002/jgh3.12974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 04/21/2023] [Accepted: 09/08/2023] [Indexed: 11/02/2023]
Abstract
Background and Aim Acute on chronic liver failure (ACLF) is a clinical syndrome described in patients with acute decompensation (AD) of cirrhosis, characterized by organ failures and high mortality. Intensive management, including liver transplantation (LT), has been shown to improve survival. To address the limited Australian data on ACLF, we describe the prevalence, clinical profile, and outcome of ACLF in an Australian cohort of hospitalized patients. Methods A retrospective review of hepatology admissions in a tertiary hospital from 1 January 2017 to 31 December 2019 identified AD and ACLF cohorts, as defined by the European Association for Study of the Liver definition. Patient characteristics, clinical course, survival at 28- and 90-day survival, and feasibility of LT were analyzed. Results Among the 192 admissions with AD, 74 admissions (39%) met ACLF criteria. A prior diagnosis of alcohol-related cirrhosis was highly prevalent in both cohorts. Grade-1 ACLF was the most frequent (60%), with renal failure being the commonest organ failure; 28-day (23% vs 2%, P = <0.001) and 90-day mortality (36% vs 16%, P = 0.002) were higher in ACLF than AD. Due to ongoing alcohol use disorder (AUD), only six patients underwent LT assessment during ACLF admission. Conclusion ACLF was common in our cohort of cirrhosis with AD and was associated with high mortality. AUD despite prior cirrhosis diagnosis was a barrier to LT. Prioritization of ACLF patients for LT after addressing AUD and relaxation of the 6-month abstinence rule may improve ACLF survival and should be addressed in prospective studies.
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Affiliation(s)
- Shauna Madigan
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Yasmina Tashkent
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Sharad Trehan
- Department of General MedicineFlinders Medical CentreBedford ParkSouth AustraliaAustralia
| | - Kate Muller
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Alan Wigg
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Richard Woodman
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Jeyamani Ramachandran
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
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16
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Benítez C, Arnold J, Cambindo V, Schoenfeldt F, Cancino A, Ibáñez S, Grandy C, Hunfan P, González J, Guerra C, Godoy E, Araneda V, Mollo C, Poniachik J, Urzúa A, Cattaneo M, Roblero JP, Oppenheimer I, Pizarro V. Effect of acute on chronic liver failure over post-transplant survival. Ann Hepatol 2023; 28:101128. [PMID: 37331597 DOI: 10.1016/j.aohep.2023.101128] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/06/2023] [Accepted: 05/26/2023] [Indexed: 06/20/2023]
Abstract
INTRODUCTION AND OBJECTIVES Acute-on-chronic liver failure (ACLF) is associated with reduced short-term survival, and liver transplantation is frequently the only therapeutic option. Nonetheless, the post-transplantation prognosis seems to be worse in ACLF patients. MATERIALS AND METHODS The databases of two university centers were retrospectively evaluated, and adult patients with cirrhosis who underwent transplantation between 2013 and 2020 were included. One-year survival of patients with ACLF was compared to that of patients without ACLF. Variables associated with mortality were identified. RESULTS A total of 428 patients were evaluated, and 303 met the inclusion criteria; 57.1% were male, the mean age was 57.1 ± 10.2 years, 75 patients had ACLF, and 228 did not. The main etiologies of ACLF were NASH (36.6%), alcoholic liver disease (13.9%), primary biliary cholangitis (8.6%) and autoimmune hepatitis (7.9%). Mechanical ventilation, renal replacement therapy, the use of vasopressors and the requirement of blood product transfusion during liver transplantation were significantly more frequent in ACLF patients. Among those recipients without and with ACLF, survival at 1, 3 and 5 years was 91.2% vs. 74.7%, 89.1% vs. 72.6% and 88.3% vs. 72.6%, respectively (p=0.001). Among pre-transplantation variables, only the presence of ACLF was independently associated with survival (HR 3.2, 95% CI: 1.46-7.11). Post-transplantation variables independently associated with survival were renal replacement therapy (HR 2.8, 95% CI: 1.1-6.8) and fungal infections (HR 3.26, 95% CI: 1.07-9.9). CONCLUSIONS ACLF is an independent predictor of one-year post-transplantation survival. Importantly, transplant recipients with ACLF require the use of more resources than patients without ACLF.
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Affiliation(s)
- Carlos Benítez
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile.
| | - Jorge Arnold
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Verónica Cambindo
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | | | - Alejandra Cancino
- Instituto de Trasplante, Hospital Clínico UC Christus, Lira 40, Santiago, Chile
| | - Samuel Ibáñez
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Catalina Grandy
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Paola Hunfan
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Jorge González
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Catalina Guerra
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Esteban Godoy
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Verónica Araneda
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Constanza Mollo
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
| | - Jaime Poniachik
- Departamento de Medicina. Sección Gastroenterología. Hospital Clínico Universidad de Chile, Dr. Carlos Lorca Tobar, Independencia, Chile
| | - Alvaro Urzúa
- Departamento de Medicina. Sección Gastroenterología. Hospital Clínico Universidad de Chile, Dr. Carlos Lorca Tobar, Independencia, Chile
| | - Máximo Cattaneo
- Departamento de Medicina. Sección Gastroenterología. Hospital Clínico Universidad de Chile, Dr. Carlos Lorca Tobar, Independencia, Chile
| | - Juan Pablo Roblero
- Departamento de Medicina. Sección Gastroenterología. Hospital Clínico Universidad de Chile, Dr. Carlos Lorca Tobar, Independencia, Chile
| | - Ilan Oppenheimer
- Escuela de Medicina Universidad de Chile, Avenida Independencia 1077, Independencia, Chile
| | - Vicente Pizarro
- Escuela de Medicina Universidad de Chile, Avenida Independencia 1077, Independencia, Chile
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Swaroop S, Arora U, Biswas S, Vaishnav M, Pathak P, Agarwal A, Golla R, Thakur B, Coshic P, Andriyas V, Gupta K, Elhence A, Nayak B, Kumar R, Shalimar. Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: A propensity score-matched analysis. J Clin Apher 2023; 38:376-389. [PMID: 36408827 DOI: 10.1002/jca.22033] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/20/2022] [Accepted: 11/08/2022] [Indexed: 08/09/2024]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. METHODS ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. RESULTS A total of 1151 patients (ACLF n = 864 [75%], AD [without organ failure] n = 287 [25%]) were included. Of the patients with ACLF (n = 864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P = .008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P = .166); HR, 0.82 (0.44-1.52), P = .549. CONCLUSION TPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.
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Affiliation(s)
- Shekhar Swaroop
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Umang Arora
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Manas Vaishnav
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Piyush Pathak
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Ankit Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Rithvik Golla
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Thakur
- Department of Biostatistics, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Poonam Coshic
- Department of Transfusion Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Vijay Andriyas
- Department of Transfusion Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Kamini Gupta
- Department of Transfusion Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Anshuman Elhence
- Department of Gastroenterology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
| | - Baibaswat Nayak
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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18
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Yoo JJ, Park MY, Kim SG. Acute kidney injury in patients with acute-on-chronic liver failure: clinical significance and management. Kidney Res Clin Pract 2023; 42:286-297. [PMID: 37313610 DOI: 10.23876/j.krcp.22.264] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 02/06/2023] [Indexed: 06/15/2023] Open
Abstract
Acute-on-chronic-liver failure (ACLF) refers to a phenomenon in which patients with chronic liver disease develop multiple organ failure due to acute exacerbation of underlying liver disease. More than 10 definitions of ACLF are extant around the world, and there is lack of consensus on whether extrahepatic organ failure is a main component or a consequence of ACLF. Asian and European consortiums have their own definitions of ACLF. The Asian Pacific Association for the Study of the Liver ACLF Research Consortium does not consider kidney failure as a diagnostic criterion for ACLF. Meanwhile, the European Association for the Study of the Liver Chronic Liver Failure and the North American Consortium for the Study of End-stage Liver Disease do consider kidney failure as an important factor in diagnosing and assessing the severity of ACLF. When kidney failure occurs in ACLF patients, treatment varies depending on the presence and stage of acute kidney injury (AKI). In general, the diagnosis of AKI in cirrhotic patients is based on the International Club of Ascites criteria: an increase of 0.3 mg/dL or more within 48 hours or a serum creatinine increase of 50% or more within one week. This study underscores the importance of kidney failure or AKI in patients with ACLF by reviewing its pathophysiology, prevention methods, and treatment approaches.
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Affiliation(s)
- Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea
| | - Moo Yong Park
- Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea
| | - Sang Gyune Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Republic of Korea
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19
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Wu Y, Xu M, Duan B, Li G, Chen Y. Acute-on-chronic liver failure: clinical course and liver transplantation. Expert Rev Gastroenterol Hepatol 2023; 17:251-262. [PMID: 36779306 DOI: 10.1080/17474124.2023.2180630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/14/2023]
Abstract
INTRODUCTION Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by intense systemic inflammatory response, multiple-organ failures, and high short-term mortality in patients with chronic liver disease. ACLF is dynamic and heterogeneous, and the prognosis is closely related to the clinical course. Currently, liver transplantation (LT) remains the only potential curative treatment that improves survival of ACLF patients. AREAS COVERED In this review, we summarize the dynamic clinical course of ACLF and the relationship between the clinical course and the post-LT prognosis, especially the factors affecting the mortality after LT in severe ACLF patients and explore the optimal choice of LT therapy for ACLF patients, both to benefit patients the most and to avoid futile therapy. EXPERT OPINION ACLF is a dynamic disease with varying clinical phenotypes, and the global burden is high. Early identification of the clinical course is important to assess the prognosis and guide the treatment. The contradiction between shortage of liver donors and the large number of recipients makes it necessary for us to strictly screen out the recipients and identify patients who really need LT to save liver sources.
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Affiliation(s)
- Yu Wu
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Manman Xu
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Binwei Duan
- Department of General Surgery Center, Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Guangming Li
- Department of General Surgery Center, Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China
| | - Yu Chen
- Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
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20
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Ngu NLY, Flanagan E, Bell S, Le ST. Acute-on-chronic liver failure: Controversies and consensus. World J Gastroenterol 2023; 29:232-240. [PMID: 36687118 PMCID: PMC9846945 DOI: 10.3748/wjg.v29.i2.232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/01/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease. Consequences include high short-term morbidity, mortality, and healthcare resource utilisation. ACLF encompasses a dysregulated, systemic inflammatory response, which can precipitate extra hepatic organ failures. Common precipitants include infection, alcoholic hepatitis, and reactivation of viral hepatitis although frequently no cause is identified. Heterogenous definitions, diagnostic criteria, and treatment guidelines, have been proposed by international hepatology societies. This can result in delayed or missed diagnoses of ACLF, significant variability in clinical management, and under-estimation of disease burden. Liver transplantation may be considered but the mainstay of treatment is organ support, often in the intensive care unit. This review will provide clarity around where are the controversies and consensus in ACLF including: Epidemiology and resource utilisation, key clinical and diagnostic features, strategies for management, and research gaps.
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Affiliation(s)
- Natalie L Y Ngu
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
- Department of Gastroenterology and Hepatology, Alfred Health, Melbourne 3004, Victoria, Australia
| | - Eliza Flanagan
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
- Monash digital Therapeutics and Innovation Laboratory (MoTILa), Monash University, Clayton 3168, Victoria, Australia
| | - Sally Bell
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
| | - Suong T Le
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
- Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton 3800, Victoria, Australia
- Monash digital Therapeutics and Innovation Laboratory (MoTILa), Monash University, Clayton 3168, Victoria, Australia
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21
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Schulz MS, Mengers J, Gu W, Drolz A, Ferstl PG, Amoros A, Uschner FE, Ackermann N, Guttenberg G, Queck A, Brol MJ, Graf C, Stoffers P, de la Vera ALL, Cremonese C, Erasmus HP, Welker MW, Grünewaldt A, Arroyo V, Bojunga J, Fernandez J, Zeuzem S, Kluwe J, Peiffer KH, Welsch C, Fuhrmann V, Rohde G, Trebicka J. Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failure. Liver Int 2023; 43:180-193. [PMID: 35727853 DOI: 10.1111/liv.15343] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 05/26/2022] [Accepted: 06/19/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND & AIMS In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.
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Affiliation(s)
- Martin S Schulz
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany.,Department of Internal Medicine B, University of Münster, Münster, Germany
| | - Jan Mengers
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Wenyi Gu
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany.,Department of Internal Medicine B, University of Münster, Münster, Germany
| | - Andreas Drolz
- 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Philip G Ferstl
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Alex Amoros
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | - Frank E Uschner
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany.,Department of Internal Medicine B, University of Münster, Münster, Germany
| | - Nora Ackermann
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Georg Guttenberg
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Alexander Queck
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Maximilian J Brol
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany.,Department of Internal Medicine B, University of Münster, Münster, Germany
| | - Christiana Graf
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Philipp Stoffers
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | | | - Carla Cremonese
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Hans-Peter Erasmus
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Martin W Welker
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Achim Grünewaldt
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Vincente Arroyo
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | - Jörg Bojunga
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Javier Fernandez
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain.,Hospital Clinic of Barcelona, University of Barcelona, CIBEReHD, IDIBAPS, Barcelona, Spain
| | - Stefan Zeuzem
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Johannes Kluwe
- 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Christoph Welsch
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Valentin Fuhrmann
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gernot Rohde
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Jonel Trebicka
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany.,Department of Internal Medicine B, University of Münster, Münster, Germany.,European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
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22
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Lu W, Tang H, Li S, Bai L, Chen Y. Extracellular vesicles as potential biomarkers and treatment options for liver failure: A systematic review up to March 2022. Front Immunol 2023; 14:1116518. [PMID: 36911706 PMCID: PMC9992400 DOI: 10.3389/fimmu.2023.1116518] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 02/09/2023] [Indexed: 02/25/2023] Open
Abstract
Introduction Extracellular vesicles (EVs) carrying functional cargoes are emerging as biomarkers and treatment strategies in multiple liver diseases. Nevertheless, the potential of EVs in liver failure remains indistinct. In this systematic review, we comprehensively analyzed the potential of EVs as biomarkers of liver failure and the therapeutic effects and possible mechanisms of EVs for liver failure. Methods We conducted a systematic review by comprehensively searching the following electronic databases: PubMed, Web of Science, Embase and Cochrane Central Register of Controlled Trials from inception to March 2022. The used text words (synonyms and word variations) and database-specific subject headings included "Extracellular Vesicles", "Exosomes", "Liver Failure", "Liver Injury", etc. Results A total of 1479 studies were identified. After removing 680 duplicate studies and 742 irrelevant studies, 57 studies were finally retained and analyzed. Fourteen studies revealed EVs with functional cargoes could be used to make the diagnosis of liver failure and provide clues for early warning and prognostic assessment of patients with liver failure. Forty-three studies confirmed the administration of EVs from different sources alleviated hepatic damage and improved survival through inhibiting inflammatory response, oxidative stress as well as apoptosis or promoting hepatocyte regeneration and autophagy. Conclusions EVs and their cargoes can be used not only as superior biomarkers of early warning, early diagnosis and prognostic assessments for liver failure, but also as potentially effective treatment options for liver failure. In the future, large-scale studies are urgently needed to verify the diagnostic, predictive and therapeutic value of EVs for liver failure.
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Affiliation(s)
- Wang Lu
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Huixin Tang
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Shanshan Li
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Li Bai
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
| | - Yu Chen
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China.,Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China
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23
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Li X, Zhang L, Pu C, Tang S. Liver transplantation in Acute-on-Chronic liver failure: Timing of transplantation and selection of patient population. Front Med (Lausanne) 2022; 9:1030336. [PMID: 36569133 PMCID: PMC9773247 DOI: 10.3389/fmed.2022.1030336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 11/21/2022] [Indexed: 12/13/2022] Open
Abstract
Acute-on-Chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality. Alcoholic ACLF is prevalent in European and American countries, while hepatitis B virus (HBV)-related ACLF is more common in the Asia-Pacific region. There is still a lack of a unified definition standard for ACLF, due to various etiologies and pathogeneses in different continents. Currently, liver transplantation (LT) is the most effective treatment for liver failure. However, the shortage of liver sources is still a global problem, which seriously limits the clinical application of an LT. Premature LT aggravates the shortage of liver resources to a certain extent, and too much delay significantly increases the risk of complications and death. Therefore, this study reviews the current literature on LT in the treatment of ACLF and discusses further the challenges for ACLF patients, the timing of LT for ACLF, and the choice of the patient population.
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Affiliation(s)
- Xue Li
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Liang Zhang
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
| | - Chunmei Pu
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
| | - Shanhong Tang
- Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu, China
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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24
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Human stem cells for decompensated cirrhosis in adults. Cochrane Database Syst Rev 2022; 2022:CD015173. [PMCID: PMC9531721 DOI: 10.1002/14651858.cd015173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of stem cell treatment in adults with decompensated cirrhosis, regardless of ethnicity, sex, types of stem cells, route of stem cell injection, and administered dose.
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25
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Xie D, Qian B, Li X. Nucleic acids and proteins carried by exosomes from various sources: Potential role in liver diseases. Front Physiol 2022; 13:957036. [PMID: 36213232 PMCID: PMC9538374 DOI: 10.3389/fphys.2022.957036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 08/17/2022] [Indexed: 12/24/2022] Open
Abstract
Exosomes are extracellular membrane-encapsulated vesicles that are released into the extracellular space or biological fluids by many cell types through exocytosis. As a newly identified form of intercellular signal communication, exosomes mediate various pathological and physiological processes by exchanging various active substances between cells. The incidence and mortality of liver diseases is increasing worldwide. Therefore, we reviewed recent studies evaluating the role of exosomes from various sources in the diagnosis and treatment of liver diseases.
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Affiliation(s)
- Danna Xie
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Baolin Qian
- Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xun Li
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
- Department of General Surgery, the First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, China
- Center for Cancer Prevention and Treatment, School of Medicine, Lanzhou University, Lanzhou, China
- Gansu Provincial Institute of Hepatobiliary and Pancreatic Surgery, Lanzhou, China
- *Correspondence: Xun Li,
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26
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Predictive factors of inhospital mortality for ICU patients with acute-on-chronic liver failure undergoing liver transplantation. Eur J Gastroenterol Hepatol 2022; 34:967-974. [PMID: 35913780 DOI: 10.1097/meg.0000000000002413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
INTRODUCTION Liver transplantation (LT) is the only effective treatment for acute-on-chronic liver failure (ACLF), but it is limited by organ availability. This study aims to identify predictive factors of mortality for LT candidates based on parameters measured at the admission into the ICU. METHODS Sixty-four patients diagnosed with ACLF, admitted consecutively into ICU between 2015 and 2019, were retrospectively enrolled in the study. Data were assessed using univariate and multivariate regression analyses to identify risk factors for inhospital mortality and 1-year mortality. RESULTS A total of 67% of patients were diagnosed with ACLF grade 3, and 25 and 8% with grades 2 and 1. Thirty percent received LT with a 1-year mortality rate of 16%, whereas for nontransplanted patients it reached 90%. Clinical features were compared according to transplant eligibility. In the univariate analysis model, lung failure (HR, 3.01; 95% CI, 1.48-6.09; P = 0.002), high lactate levels (HR, 1.03; 95% CI, 1.02-1.04; P < 0.001) and CLIF-ACLF score (HR, 1.04; 95% CI, 1.01-1.09; P = 0.026) were independently correlated to increased inhospital mortality. LT reduced mortality risk (HR, 0.16; 95% CI, 0.04-0.72; P = 0.016). CONCLUSION Lung failure, CLIF-ACLF score and blood lactate levels at admission were the only statistically significant independent predictors of inhospital mortality, more accurate in determining transplant success than ACLF grade.
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27
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Toshima T, Harada N, Itoh S, Morita K, Nagao Y, Kurihara T, Tomino T, Kosai-Fujimoto Y, Morinaga A, Tomiyama T, Yoshizumi T. Outcomes of living-donor liver transplantation for acute-on-chronic liver failure based on newly proposed criteria in Japan. Clin Transplant 2022; 36:e14739. [PMID: 35642940 DOI: 10.1111/ctr.14739] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 05/15/2022] [Accepted: 05/28/2022] [Indexed: 11/29/2022]
Abstract
AIM Recently, new diagnostic criteria for acute-on-chronic liver failure (ACLF) were established in Japan. However, there is little evidence regarding the feasibility of classifying patients undergoing living-donor liver transplantation (LDLT). The aim was to re-evaluate the impact of these new diagnostic criteria on ACLF and the severity classification of patients undergoing LDLT. METHODS We collected data of 82 recipients who underwent LDLT for liver failure between 1997 and 2020 and reviewed it retrospectively. RESULTS Of the 82 patients with liver failure, 31 (37.8%) were diagnosed with ACLF; Grade 0 (n = 6), Grade 1 (n = 7), Grade 2 (n = 9), and Grade 3 (n = 9). There was no substantial difference in overall survival (OS) and the occurrence of postoperative complications between liver failure patients with and without ACLF. The OS after LDLT was significantly different among the four groups of ACLF patients (P = .036). Interestingly, ACLF Grade 3 patients had substantially lower OS compared to other ACLF groups even after LDLT (P = .006; 5-year OS rates, 33.3% vs. 85.9%). CONCLUSION Proper use of the new diagnostic criteria for ACLF in Japan demonstrated that the presence and severity of ACLF, especially the presence of multiple organ failures, leads to morbidity and mortality even in an LDLT setting. Considering that the patients with ACLF Grade 3 do not have the favorable outcomes of LDLT, deceased-donor liver transplantation usage, or LDLT before reaching the severity of Grade 3 may be suitable for further research.
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Affiliation(s)
- Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Department of Surgery, Beppu Hospital, Kyushu University, Beppu, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazutoyo Morita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Nagao
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Kurihara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomino
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yukiko Kosai-Fujimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akinari Morinaga
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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28
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Kotha S, Berry P. The writing was on the wall: Decision making near the end of life in advanced liver disease. PROGRESS IN PALLIATIVE CARE 2022. [DOI: 10.1080/09699260.2022.2067702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Sreelakshmi Kotha
- Department of Gastroenterology, Guy’s and St Thomas’ Foundation Trust, London, UK
| | - Philip Berry
- Department of Gastroenterology, Guy’s and St Thomas’ Foundation Trust, London, UK
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29
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Queck A, Weiler N, Trebicka J. Transplantation in Acute-on-Chronic Liver Failure: Feasibility and Futility. Clin Liver Dis (Hoboken) 2022; 19:191-193. [PMID: 35662867 PMCID: PMC9135149 DOI: 10.1002/cld.1195] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Interview and Audio Recording.
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Affiliation(s)
- Alexander Queck
- Department of Internal Medicine 1University Hospital of Johann Wolfgang Goethe‐University FrankfurtFrankfurtGermany
| | - Nina Weiler
- Department of Internal Medicine 1University Hospital of Johann Wolfgang Goethe‐University FrankfurtFrankfurtGermany
| | - Jonel Trebicka
- Department of Internal Medicine 1University Hospital of Johann Wolfgang Goethe‐University FrankfurtFrankfurtGermany,European Foundation for the Study of Chronic Liver FailureEFCLIFBarcelonaSpain
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30
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Schulz MS, Gu W, Schnitzbauer AA, Trebicka J. Liver Transplantation as a Cornerstone Treatment for Acute-On-Chronic Liver Failure. Transpl Int 2022; 35:10108. [PMID: 35572467 PMCID: PMC9099355 DOI: 10.3389/ti.2022.10108] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 01/27/2022] [Indexed: 11/13/2022]
Abstract
Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome, characterized by acute decompensation (AD) of liver cirrhosis, severe systemic inflammation, intra- and extrahepatic organ failures, and a high short-term mortality. Liver transplantation (LT) is a potentially life-saving treatment for patients with decompensated liver cirrhosis and, due to the high mortality rates, particularly for ACLF patients. In the last decade, a plethora of studies has produced compelling evidence in favor of LT in ACLF, demonstrating high post-LT survival rates and excessive waitlist mortality. The importance of LT in these patients is underscored by the fact that no specific therapy for ACLF is available yet, rendering expeditious life-saving LT to be the only feasible treatment option for some ACLF patients. This review aims to provide an overview on pathophysiology, clinical trajectory, and clinical management of ACLF and to delineate the current literature regarding perspectives and limitations of LT as a life-saving treatment option for ACLF patients.
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Affiliation(s)
- Martin S. Schulz
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Wenyi Gu
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Andreas A. Schnitzbauer
- Department of General and Visceral Surgery, University Hospital, Goethe University, Frankfurt, Germany
| | - Jonel Trebicka
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
- European Foundation for Study of Chronic Liver Failure (EF-Clif), Barcelona, Spain
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31
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Ntamo Y, Ziqubu K, Chellan N, Nkambule BB, Nyambuya TM, Mazibuko-Mbeje SE, Gabuza KB, Orlando P, Tiano L, Dludla PV. Clinical use of N-acetyl cysteine during liver transplantation: Implications of oxidative stress and inflammation as therapeutic targets. Biomed Pharmacother 2022; 147:112638. [DOI: 10.1016/j.biopha.2022.112638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/05/2022] [Accepted: 01/12/2022] [Indexed: 02/09/2023] Open
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32
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Córdova-Gallardo J, Keaveny AP, Qi X, Méndez-Sánchez N. Metabolic associated fatty liver disease and acute-on-chronic liver failure: common themes for common problems. Eur J Gastroenterol Hepatol 2021; 33:e84-e93. [PMID: 34985050 DOI: 10.1097/meg.0000000000002335] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Metabolic associated fatty liver disease (MAFLD) affects 20-30% of the worldwide population and is becoming the most common cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). MAFLD is the hepatic expression of metabolic dysfunction correlated with a variety of metabolic comorbidities including obesity, dyslipidemia, hypertension and type 2 diabetes (T2DM). Obesity, altered gut permeability, chronic inflammation and dysbiosis related to MAFLD might predispose patients with cirrhosis to the development of acute-on-chronic liver failure (ACLF); however, this relationship remains unclear. ACLF is a syndrome with high short-term mortality, presenting with acute hepatic decompensation associated with organ failures in patients with underlying chronic liver disease with or without an identifiable precipitating event. While this syndrome can occur in any patient with cirrhosis, the increasing prevalence of cirrhosis due to MAFLD is of great concern because, in a recent analysis, MAFLD was the fastest rising cause of cirrhosis associated with ACLF among patients listed for LT in the US. In this review, we will discuss the current knowledge on MAFLD and the development of ACLF.
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Affiliation(s)
- Jacqueline Córdova-Gallardo
- Department of Hepatology, Service of Surgery and Obesity Clinic, General Hospital "Dr. Manuel Gea González"
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Andrew P Keaveny
- Department of Transplantation, Mayo Clinic, Jacksonville, Florida, USA
| | - Xingshun Qi
- General Hospital of Northern Theater Command
- Shenyang Pharmaceutical University, Shenyang, China
| | - Nahum Méndez-Sánchez
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
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33
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Acute on Chronic Liver Failure: Factors Associated With Transplantation. Transplant Direct 2021; 7:e788. [PMID: 34805490 PMCID: PMC8601355 DOI: 10.1097/txd.0000000000001245] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 08/16/2021] [Accepted: 08/18/2021] [Indexed: 12/15/2022] Open
Abstract
Acute on chronic liver failure (ACLF) carries a poor prognosis unless liver transplantation is offered. We present risk factors associated with proceeding with liver transplantation in patients with ACLF.
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Hou W, Hao Y, Yang W, Tian T, Fang P, Du Y, Gao L, Gao Y, Zhang Q. The Jieduan-Niwan (JDNW) Formula Ameliorates Hepatocyte Apoptosis: A Study of the Inhibition of E2F1-Mediated Apoptosis Signaling Pathways in Acute-on-Chronic Liver Failure (ACLF) Using Rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:3845-3862. [PMID: 34526765 PMCID: PMC8436178 DOI: 10.2147/dddt.s308713] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 08/04/2021] [Indexed: 12/29/2022]
Abstract
Background Acute-on-chronic liver failure (ACLF) is a severe, complicated human disease. E2F1-mediated apoptosis plays an important role in ACLF development. Jieduan-Niwan (JDNW) formula, a traditional Chinese medicine (TCM), has shown remarkable clinical efficacy in ACLF treatment. However, the hepatoprotective mechanisms of the formula are barely understood. Purpose This study aimed to investigate the mechanisms of JDNW formula in ACLF treatment by specifically regulating E2F1-mediated apoptotic signaling pathways in rats. Methods The JDNW components were determined by high-performance liquid chromatography (HPLC) analysis. The ACLF rat model was established using human serum albumin immune-induced liver cirrhosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. The ACLF rat was treated with JDNW formula. Prothrombin time activity was measured to investigate the coagulation function. Liver pathological injury was observed by hematoxylin-eosin (HE) and reticular fiber staining. The hepatocyte apoptosis index and apoptosis rate were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry, respectively. Additionally, the expression of key genes and proteins that regulate E2F1-mediated apoptosis was analyzed by quantitative real-time PCR and Western blot. Results Seven major components of JDNW formula were detected. The formula ameliorated the coagulation function, decreased the hepatocyte apoptosis index and apoptosis rate, and alleviated liver pathological damage in ACLF rats. The down-regulation of the expression of genes and proteins from p53-dependent and non-p53-dependent apoptosis pathways and the up-regulation of the expression of genes from blocking anti-apoptotic signaling pathways indicated that JDNW formula inhibited excessive hepatocyte apoptosis in ACLF rats via E2F1-mediated apoptosis signaling pathways. Conclusion The findings indicate that JDNW formula protects livers of ACLF rats by inhibiting E2F1-mediated apoptotic signaling pathways, implying that these pathways might be a potential therapeutic target for ACLF treatment.
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Affiliation(s)
- Weixin Hou
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China.,Department of Endocrinology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Endocrinology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Yulin Hao
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Wenlong Yang
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Tian Tian
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Peng Fang
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Yuqiong Du
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Lianyin Gao
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Yanbin Gao
- Department of Endocrinology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Endocrinology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
| | - Qiuyun Zhang
- Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.,Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People's Republic of China
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35
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Zanetto A, Shalaby S, Gambato M, Germani G, Senzolo M, Bizzaro D, Russo FP, Burra P. New Indications for Liver Transplantation. J Clin Med 2021; 10:3867. [PMID: 34501314 PMCID: PMC8432035 DOI: 10.3390/jcm10173867] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/20/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) is an important therapeutic option for the treatment of several liver diseases. Modern LT is characterized by remarkable improvements in post-transplant patient survival, graft survival, and quality of life. Thanks to these great improvements, indications for LT are expanding. Nowadays, clinical conditions historically considered exclusion criteria for LT, have been considered new indications for LT, showing survival advantages for patients. In this review, we provide an updated overview of the principal newer indications for LT, with particular attention to alcoholic hepatitis, acute-on-chronic liver failure (ACLF), cholangiocarcinoma and colorectal cancer metastases.
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Affiliation(s)
| | | | | | | | | | | | | | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (M.S.); (D.B.); (F.P.R.)
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36
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Herrick-Reynolds KM, Punchhi G, Greenberg RS, Strauss AT, Boyarsky BJ, Weeks-Groh SR, Krach MR, Anders RA, Gurakar A, Chen PH, Segev DL, King EA, Philosophe B, Ottman SE, Wesson RN, Garonzik-Wang JM, Cameron AM. Evaluation of Early vs Standard Liver Transplant for Alcohol-Associated Liver Disease. JAMA Surg 2021; 156:1026-1034. [PMID: 34379106 DOI: 10.1001/jamasurg.2021.3748] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance Traditionally, liver transplant (LT) for alcohol-associated liver disease (ALD) requires 6 months of abstinence. Although early LT before 6 months of abstinence has been associated with decreased mortality for decompensated ALD, this practice remains controversial and concentrated at a few centers. Objective To define patient, allograft, and relapse-free survival in early LT for ALD, and to investigate the association between these survival outcomes and early vs standard LT. Design, Setting, and Participants This cohort study analyzed all patients with ALD who underwent their first LT at a single academic referral center between October 1, 2012, and November 13, 2020. Patients with known pretransplant hepatocellular carcinoma, hepatitis B or C, or an alternative cause of liver failure were excluded. Follow-up period was defined as the time from LT to the most recent encounter with a transplant center or death. Exposures The exposure of interest was early LT, which was defined as less than 180 days of pre-LT abstinence. Standard LT was defined as 180 days or more of pre-LT abstinence. Patients were separated into early LT and standard LT by time from abstinence to LT. Main Outcomes and Measures The outcomes were patient, allograft, relapse-free, and hazardous relapse-free survival for patients who underwent early LT or standard LT. These groups were compared by log-rank testing of Kaplan-Meier estimates. Hazardous relapse was defined as binge, at-risk, or frequent drinking. Abstinence was reassessed at the most recent follow-up visit for all patients. Results Of the 163 patients with ALD included in this study, 88 (54%) underwent early LT and 75 (46%) underwent standard LT. This cohort had a mean (SD) age at transplant of 52 (10) years and was predominantly composed of 108 male patients (66%). Recipients of early LT vs standard LT were younger (median [interquartile range (IQR)] age, 49.7 [39.0-54.2] years vs 54.6 [48.7-60.0] years; P < .001) and had a higher median (IQR) Model for End-stage Liver Disease score at listing (35.0 [29.0-39.0] vs 20.0 [13.0-26.0]; P < .001). Both recipients of early LT and standard LT had similar 1-year patient survival (94.1% [95% CI, 86.3%-97.5%] vs 95.9% [95% CI, 87.8%-98.7%]; P = .60), allograft survival (92.7% [95% CI, 84.4%-96.7%] vs 90.5% [95% CI, 81.0%-95.3%]; P = .42), relapse-free survival (80.4% [95% CI, 69.1%-88.0%] vs 83.5% [95% CI, 72.2%-90.6%]; P = .41), and hazardous relapse-free survival (85.8% [95% CI, 75.1%-92.2%] vs 89.6% [95% CI, 79.5%-94.9%]; P = .41). Conclusions and Relevance Adherence to the 6-month rule was not associated with superior patient survival, allograft survival, or relapse-free survival among selected patients. This finding suggests that patients with ALD should not be categorically excluded from LT solely on the basis of 6 months of abstinence, but rather alternative selection criteria should be identified that are based on need and posttransplant outcomes.
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Affiliation(s)
- Kayleigh M Herrick-Reynolds
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Gopika Punchhi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ross S Greenberg
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Alexandra T Strauss
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brian J Boyarsky
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sharon R Weeks-Groh
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Michelle R Krach
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Robert A Anders
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Elizabeth A King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Benjamin Philosophe
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shane E Ottman
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Russell N Wesson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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37
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Balcar L, Semmler G, Pomej K, Simbrunner B, Bauer D, Hartl L, Jachs M, Paternostro R, Bucsics T, Pinter M, Trauner M, Mandorfer M, Reiberger T, Scheiner B. Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute-on-chronic liver failure. United European Gastroenterol J 2021; 9:427-437. [PMID: 34050619 PMCID: PMC8259248 DOI: 10.1002/ueg2.12089] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 03/22/2021] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Recently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on-chronic liver failure (pre-ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real-life cohort of hospitalized patients with cirrhosis. METHODS Patients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis. RESULTS Two hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre-ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1-year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90-day mortality: pre-ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C-reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre-ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre-ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis. DISCUSSION The recently proposed pathophysiological/prognostic EF-CLIF subgroups are also reproduceable in a real-life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre-ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.
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Affiliation(s)
- Lorenz Balcar
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Georg Semmler
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Katharina Pomej
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
- Christian‐Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
- Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - David Bauer
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Lukas Hartl
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Mathias Jachs
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Rafael Paternostro
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Theresa Bucsics
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Matthias Pinter
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
| | - Michael Trauner
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
- Christian‐Doppler Laboratory for Portal Hypertension and Liver FibrosisMedical University of ViennaViennaAustria
- Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Bernhard Scheiner
- Department of Internal Medicine IIIDivision of Gastroenterology and HepatologyMedical University of ViennaViennaAustria
- Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
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38
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Yu M, Zhou C, Tian D, Jia HM, Li ZQ, Yang C, Ba YM, Wu HK, Zou ZM. Molecular classification and clinical diagnosis of acute-on-chronic liver failure patients by serum metabolomics. J Pharm Biomed Anal 2021; 198:114004. [PMID: 33721610 DOI: 10.1016/j.jpba.2021.114004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023]
Abstract
Prevalence of acute-on-chronic liver failure (ACLF) patients is growing worldwide, associating with multi-organ failure and high short-term mortality rates. ACLF can be of varying entity manifestation, whereas it remains poorly defined. Traditional Chinese medicine (TCM) stratifies ACLF into two types, damp hot (DH) and cold damp (CD), by seasoned TCM practitioners, for specific treatment with different TCMs. The biggest challenge for the outcome of TCM therapy is the accuracy of diagnosis. However, it is difficult to guarantee it due to lack of the molecule classification of ACLF. Herein, we recruited 58 subjects including 34 ACLF patients (18 DH and 16 CD) and 24 healthy controls, and analyzed serum metabolic profiles using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics approach. A total of 10 serum metabolites were found as potential biomarkers for diagnosis of ACLF. Among them, taurochenodesoxycholic acid (N3), glycyldeoxycholic acid (N5) and 12-HETE-GABA (N7), varied between two types of ACLF and can be merged as a combination marker to differentiate CD from DH patients with area under the receiver operating curve (AUC) of 0.928 (95 % CI 0.8-1). CD patients possessed comparatively higher bile acid metabolism and lower arachidonic acid metabolism compared with DH patients. The results provide not only serum molecules for early accurate diagnosis of ACLF patients, but also potential clinical biomarkers for classification of CD and DH types. The findings clarify that molecular markers will be objective criteria for diagnosis of clinical types in TCM practice.
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Affiliation(s)
- Meng Yu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China
| | - Chao Zhou
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China
| | - Dong Tian
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China
| | - Hong-Mei Jia
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China
| | - Zhi-Qing Li
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Chen Yang
- The Fifth Hospital of Wuhan, Wuhan, 430050, China
| | - Yuan-Ming Ba
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Hui-Kun Wu
- Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China.
| | - Zhong-Mei Zou
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China.
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39
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Crespo G. Long-term outcomes after liver transplantation for ACLF - Don't forget quality of life! Liver Int 2021; 41:430-431. [PMID: 34542226 DOI: 10.1111/liv.14789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 01/09/2021] [Indexed: 02/13/2023]
Affiliation(s)
- Gonzalo Crespo
- Liver Transplant Unit, Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
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40
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Chiriac S, Stanciu C, Cojocariu C, Singeap AM, Sfarti C, Cuciureanu T, Girleanu I, Igna RA, Trifan A. Role of ammonia in predicting the outcome of patients with acute-on-chronic liver failure. World J Clin Cases 2021; 9:552-564. [PMID: 33553393 PMCID: PMC7829715 DOI: 10.12998/wjcc.v9.i3.552] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 12/02/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND High venous ammonia (VA) values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis (LC) as well as acute hepatitis. Moreover, VA has been associated with poor prognosis and high mortality in these clinical settings. However, the role of ammonia in acute-on-chronic liver failure (ACLF) has not yet been clearly established.
AIM To assess the role of VA in predicting the outcome of cirrhotic patients with ACLF in a tertiary care center.
METHODS We performed a retrospective observational study including consecutive patients with LC hospitalized for acute non-elective indications such as ascites, hepatic encephalopathy (HE), upper gastrointestinal bleeding, or bacterial infections that fulfilled the Asian Pacific Association for the Study of the Liver (APASL) criteria for ACLF. The study was conducted in “St. Spiridon” University Hospital, Iasi, Romania, a tertiary care center, between January 2017 and January 2019. The APASL ACLF Research Consortium (AARC) score was calculated and ACLF grade was established accordingly. West-haven classification was used for HE. Statistical analysis was performed using IBM SPSS version 22.0.
RESULTS Four hundred and forty-six patients were included, aged 59 (50-65) years, 57.4% men. Child-Pugh, model for end-stage liver disease (MELD) and AARC scores were 11 (10-12), 19.13 ± 6.79, and 7 (6-8), respectively. 66.4% had ACLF grade I, 31.2% ACLF grade II, and 2.5% ACLF grade III. HE was diagnosed in 83.9%, 34% grade I, 37.2% grade II, 23.5% grade III, and 5.3% grade IV. Overall mortality was 7.8%. VA was 103 (78-148) μmol/L. Receiver operating characteristic analysis showed good accuracy for the prediction of in-hospital mortality for the AARC score [Area under the curve (AUC) = 0.886], MELD score (AUC = 0.816), VA (AUC = 0.812) and a fair accuracy for the Child-Pugh score (AUC = 0.799). Subsequently, a cut-off value for the prediction of mortality was identified for VA (152.5 μmol/L, sensitivity = 0.706, 1-specificity = 0.190). Univariate analysis found acute kidney injury, severe HE (grade III or IV), VA ≥ 152.5 μmol/L, MELD score ≥ 22.5, Child-Pugh score ≥ 12.5, and AARC score ≥ 8.5 to be associated with in-hospital mortality. Multivariate analysis identified AARC score ≥ 8.5 and venous ammonia ≥ 152 μmol/L to be independent predictors of in-hospital mortality.
CONCLUSION VA could be used as an inexpensive predictor of in-hospital mortality in patients with ACLF. Patients with both ACLF and VA > 152.5 μmol/L have a high risk for a poor outcome.
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Affiliation(s)
- Stefan Chiriac
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Carol Stanciu
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Irina Girleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Razvan Alexandru Igna
- Intensive Care, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
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Ferrarese A, Cattelan A, Cillo U, Gringeri E, Russo FP, Germani G, Gambato M, Burra P, Senzolo M. Invasive fungal infection before and after liver transplantation. World J Gastroenterol 2020; 26:7485-7496. [PMID: 33384549 PMCID: PMC7754548 DOI: 10.3748/wjg.v26.i47.7485] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/15/2020] [Accepted: 11/29/2020] [Indexed: 02/06/2023] Open
Abstract
Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Annamaria Cattelan
- Tropical and Infectious Disease Unit, Padua University Hospital, Padua 35128, Italy
| | - Umberto Cillo
- Padua University Hospital, Hepatobiliary Surgery and Liver Transplant Center, Padua 35128, Italy
| | - Enrico Gringeri
- Padua University Hospital, Hepatobiliary Surgery and Liver Transplant Center, Padua 35128, Italy
| | | | - Giacomo Germani
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
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Trebicka J, Belli LS. Liver Transplantation in Acute-on-Chronic Liver Failure Is a Wise Longterm Investment. Liver Transpl 2020; 26:1566-1567. [PMID: 33048445 DOI: 10.1002/lt.25922] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 10/08/2020] [Indexed: 01/13/2023]
Affiliation(s)
- Jonel Trebicka
- Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Luca S Belli
- Department of Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
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Lu CY, Chen CL, Ho CM, Hsiao CY, Wu YM, Ho MC, Lee PH, Hu RH. Dynamic Prognostication in Transplant Candidates with Acute-on-Chronic Liver Failure. J Pers Med 2020; 10:230. [PMID: 33203142 PMCID: PMC7711531 DOI: 10.3390/jpm10040230] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 11/09/2020] [Accepted: 11/11/2020] [Indexed: 12/16/2022] Open
Abstract
We aimed to extensively investigate clinical markers that are sufficiently dynamic for prognosis of acute-on-chronic liver failure (ACLF). Defined by the Asian Pacific Association for the Study of the Liver (APASL) criteria, patients with ACLF on the liver transplant waitlist in a tertiary center were retrospectively reviewed. Laboratory results and severity scores at three time points (days 1, 7, and 14 after admission) were analyzed. From 2015 to 2019, 64 patients with ACLF were enrolled, of which 24 received a liver transplant from 22 live donors. The hospital mortality rate was 31% (8% for transplant; 45% for nontransplant groups), and the 3-month survival was crucial for determining long-term outcomes. The number of significant variables for mortality, and, specifically, the hazards of international normalized ratio of prothrombin time (INR) and APASL ACLF Research Consortium (AARC) score were increased within two weeks. In multivariable analysis, INR and AARC score (D-14) were associated with poor survival and liver transplant was a protective factor in all patients, while AARC score (D-14) was significant in the nontransplant group. AARC score at day 14 is an independent risk factor for mortality in ACLF. Liver transplant from live donors reversed poor outcomes in patients with ACLF in a timely manner.
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Affiliation(s)
- Cheng-Yueh Lu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan; (C.-Y.L.); (C.-Y.H.); (Y.-M.W.); (M.-C.H.); (P.-H.L.); (R.-H.H.)
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University, Taipei 100, Taiwan;
| | - Cheng-Maw Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan; (C.-Y.L.); (C.-Y.H.); (Y.-M.W.); (M.-C.H.); (P.-H.L.); (R.-H.H.)
| | - Chih-Yang Hsiao
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan; (C.-Y.L.); (C.-Y.H.); (Y.-M.W.); (M.-C.H.); (P.-H.L.); (R.-H.H.)
- Graduate Institute of Clinical Medicine, National Taiwan University, Taipei 100, Taiwan;
- Department of Traumatology, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Yao-Ming Wu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan; (C.-Y.L.); (C.-Y.H.); (Y.-M.W.); (M.-C.H.); (P.-H.L.); (R.-H.H.)
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan; (C.-Y.L.); (C.-Y.H.); (Y.-M.W.); (M.-C.H.); (P.-H.L.); (R.-H.H.)
| | - Po-Huang Lee
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan; (C.-Y.L.); (C.-Y.H.); (Y.-M.W.); (M.-C.H.); (P.-H.L.); (R.-H.H.)
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung 886, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan; (C.-Y.L.); (C.-Y.H.); (Y.-M.W.); (M.-C.H.); (P.-H.L.); (R.-H.H.)
- Department of Traumatology, National Taiwan University Hospital, Taipei 100, Taiwan
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Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease. Int J Mol Sci 2020; 21:ijms21176384. [PMID: 32887515 PMCID: PMC7504211 DOI: 10.3390/ijms21176384] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 08/23/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis A virus (HAV) infection occasionally leads to a critical condition in patients with or without chronic liver diseases. Acute-on-chronic liver disease includes acute-on-chronic liver failure (ACLF) and non-ACLF. In this review, we searched the literature concerning the association between HAV infection and chronic liver diseases in PubMed. Chronic liver diseases, such as metabolic associated fatty liver disease and alcoholic liver disease, coinfection with other viruses, and host genetic factors may be associated with severe hepatitis A. It is important to understand these conditions and mechanisms. There may be no etiological correlation between liver failure and HAV infection, but there is an association between the level of chronic liver damage and the severity of acute-on-chronic liver disease. While the application of an HAV vaccination is important for preventing HAV infection, the development of antivirals against HAV may be important for preventing the development of ACLF with HAV infection as an acute insult. The latter is all the more urgent given that the lives of patients with HAV infection and a chronic liver disease of another etiology may be at immediate risk.
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