Liver transplantation for acute-on-chronic liver failure

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2024, Volume and Issue: 9(6), P. 564 - 576

Published: Feb. 1, 2024

Language: Английский

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Acute and non‐acute decompensation of liver cirrhosis (47/130)

Liver International, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Abstract In the traditional view, occurrence of cirrhosis‐related complications, such as hepatic encephalopathy, formation ascites or variceal haemorrhage, marks transition to decompensated stage cirrhosis. Although dichotomous stratification into a compensated and state reflects prognostic water‐shed moment remains hold its validity, it represents an oversimplification clinical realities. A broadening understanding pathophysiological mechanisms underpinning decompensation have led identification distinct subgroups, associated with different courses following decompensation. Data provided by PREDICT study uncovered three sub‐phenotypes acute (AD). Moreover, acute‐on‐chronic liver failure (ACLF) has been established entity for many years, which is high short‐term mortality. Recently, non‐acute (NAD) proposed pathway decompensation, complementing current concepts spectrum contrast AD, NAD characterized slow progressive development are often presented at first and/or in patients earlier chronic disease. Successful treatment AD may lead stabilization even concept recompensation. This review aims provide overview on delineate recent advances our understanding.

Language: Английский

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Acute decompensation of cirrhosis versus acute‐on‐chronic liver failure: What are the clinical implications?

United European Gastroenterology Journal, Journal Year: 2024, Volume and Issue: 12(2), P. 194 - 202

Published: Feb. 20, 2024

Abstract It is essential to identify the subgroup of patients who experience poorer outcomes in order adapt clinical management effectively. In context liver disease, earlier identification occurs, greater range therapeutic options that can be offered patients. past, with acute decompensation (AD) chronic disease were treated as a homogeneous group, emphasis on identifying those at highest risk death. last 15 years, differentiation has emerged between acute‐on‐chronic failure syndrome (ACLF) and AD, primarily due indications latter linked less favorable short‐term prognosis. Nevertheless, definition ACLF varies among different knowledge societies, making it challenging assess its true impact compared AD. Therefore, purpose this review provide detailed analysis emphasizing critical importance field advanced disease. We will discuss differences Eastern Western approaches, particularly relation occurrence onset. Common characteristics, such dynamic nature course, highlighted. Finally, we focus two key implications arising from these considerations: prevention before onset strategies once develops, including transplantation withdrawal care.

Language: Английский

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Mechanisms and treatment approaches for ACLF

Liver International, Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 16, 2023

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF frequently triggered intra- and/or extrahepatic insults, such as bacterial infections, alcohol-related hepatitis or flares hepatic viruses. The imbalance between immune tolerance causes failures through the following mechanisms: (i) direct damage cells/mediators; (ii) worsening circulatory dysfunction resulting in hypoperfusion (iii) metabolic alterations with prioritization energetic substrates for peripheral 'energetic crisis'. Currently, management includes support failures, identification treatment precipitating factors expedited assessment transplantation (LT). Early LT should be considered patients grade 3, who are unlikely to recover available treatments have mortality rate > 70% at 28 days. However, selection transplant candidates their on waiting list need standardization. Future challenges field include better understanding pathophysiological mechanisms leading development specific disease personalized approaches. Herein, we reviewed current knowledge future perspectives ACLF.

Language: Английский

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Acute and acute‐on‐chronic liver failure: Pathogenesis, management and perspectives

Liver International, Journal Year: 2025, Volume and Issue: 45(2)

Published: Jan. 28, 2025

Acute liver failure (ALF) and acute-on-chronic (ACLF) represent critical junctures in the spectrum of diseases, characterized by rapid deterioration function often multi-organ dysfunction. Despite advances medical care, they remain significant challenges clinical practice, necessitating a deeper understanding their pathophysiology development effective therapeutic strategies. This special issue intents to address these topics 15 selected reviews. The first two reviews are ALF pathogenesis therapy focus.1, 2 is rare but life-threatening condition sudden loss individuals with no pre-existing disease. It associated high mortality rate, typically ranging from 50% 80%. aetiology can be diverse, including viral hepatitis, drug-induced injury, autoimmune hepatitis acute ischaemic injury among others (Figure 1). Regardless underlying cause, hallmark massive hepatocyte death, leading impaired synthetic metabolic functions liver. presentation vary widely, common features include jaundice, coagulopathy, hepatic encephalopathy, often, deterioration. management involves intensive supportive measures maintain hemodynamic stability, correct coagulopathy manage complications such as cerebral oedema encephalopathy.1 Liver transplantation remains only definitive treatment option for many patients ALF, offering possibility long-term survival. However, availability donor organs timing crucial factors that significantly impact outcomes. In recent years, there has been growing interest artificial support systems bridge or promote regeneration ALF. These aim remove toxins, imbalances provide temporary while awaiting recovery transplantation. Various modalities, extracorporeal devices bioartificial systems, have investigated, efficacy subject debate.2 ACLF, on other hand, represents distinct syndrome chronic disease, most commonly cirrhosis. Hernaez colleagues summarized comprehensive review definition, diagnosis epidemiology ACLF.3 ACLF develops setting decompensation may also develop stage decompensation, so-called non-acute decompensation.4 For precipitating event, bacterial infection, alcoholic gastrointestinal bleeding, triggers systemic inflammatory response exacerbates injury. But necessary interventions 2) induce precipitate Praktiknjo et al.5 dysregulated immune leads widespread tissue damage organ dysfunction, extra-hepatic failures, driving extreme short-term 30% 50%.6 Alcoholic specific trigger still unaddressed condition.7 Similarly hepatitis,7 complex multifactorial, involving interactions between system, gut microbiota inflammation. progress made, we expect technological (omics) digital (artificial intelligence) improve understanding, potentially design approaches.8 Especially using large cohorts omics data sets will facilitate construction algorithms predict prognosis ACLF. Existing future reviewed Valainathan al.9 Current focuses treating factors, providing care and, some cases, considering life-saving intervention.10 role inflammation dysregulation demonstrated over last this exploration novel targets, interleukin-22 Hwang al.11 Strategies aimed at modulating response, corticosteroids, immunomodulatory agents anti-inflammatory cytokines, shown promise preclinical studies early-phase trials.12 approaches multimodal, indeed, one shape strategy based molecular mechanism supporting clear rationale 3), nicely Morrison al.13 addition pharmacological interventions, increasing use potential support, toxins mediators, regeneration. While early promising results, larger randomized controlled trials needed establish ACLF.14, conclusion, morbidity mortality. need further research better understand conditions more targeted therapies holds improving outcomes validate safety practice. Jonel Trebicka was supported German Research Foundation (DFG) project ID 403224013—SFB 1382 (A09), Federal Ministry Education (BMBF) DEEP-HCC Hessian Higher Education, Arts (HMWK) ENABLE ACLF-I cluster projects. MICROB-PREDICT (project 825694), DECISION 847949), GALAXY 668031), LIVERHOPE 731875) IHMCSA 964590) projects received funding European Union's Horizon 2020 innovation program. manuscript reflects authors' views, Commission not responsible any made information it contains. funders had influence study design, collection analysis, decision publish preparation manuscript. speaking and/or consulting fees Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit CSL Behring. article does contain primary patient nor did involve human animal subjects. As such, ethical approval required production article. data, materials sources. authors writing assistance disclose. editorial present new synthesis existing findings. Therefore, sets, code submission. All included publicly available literature references cited within text.

Language: Английский

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Acute-on-Chronic Liver Failure: Steps Towards Consensus

Diagnostics, Journal Year: 2025, Volume and Issue: 15(6), P. 751 - 751

Published: March 17, 2025

Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by organ and high short-term mortality. Since its first definition in 2013, many international organizations have defined this and, till now, there has been no agreement regarding definitions diagnostic criteria. Although the precise mechanism of ACLF unknown, precipitant factors systemic inflammation response play major role. Specific management high-mortality still under development, but general consensus diagnosis needed.

Language: Английский

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S100A9/RAGE pathway regulation of mitophagy and the effect of JianPi LiShi YangGan formula in acute-on-chronic liver failure

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119887 - 119887

Published: April 1, 2025

Language: Английский

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IGF2BP3/HIF1A/YAP signaling plays a role in driving acute-on-chronic liver failure through activating hepatocyte reprogramming

Cellular Signalling, Journal Year: 2023, Volume and Issue: 108, P. 110727 - 110727

Published: May 29, 2023

Language: Английский

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Hepatoprotective efficacy and interventional mechanism of JianPi LiShi YangGan formula in acute-on-chronic liver failure

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 318, P. 116880 - 116880

Published: July 6, 2023

Language: Английский

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Predicting the development of acute‐on‐chronic liver failure

United European Gastroenterology Journal, Journal Year: 2023, Volume and Issue: 11(9), P. 813 - 814

Published: Nov. 1, 2023

Acute-on-chronic liver failure (ACLF), as per the European Association for Study of Liver (EASL), is a syndrome that develops in patients with acute decompensation cirrhosis (AD) which characterised by severe systemic inflammation, immune dysfunction, organ failures and high short-term mortality. According to number defined specific thresholds each system (liver, coagulation, brain, renal, respiration circulation), are categorised into distinct ACLF grades increasing severity. Hence, grade 1 corresponds patient single kidney or non-kidney brain dysfunction), 2 two 3 marked three more. In course ACLF, belonging 3, 3-month mortality escalates range 70% more than 90%.1 Over past decade, significant efforts have been made understand natural history pathogenesis syndrome, standardise clinical management access transplantation these patients.1 While critical, it recently researchers tried identify individuals AD showing higher risk developing ACLF. The PREDICT study identified could follow different courses over subsequent months; 'pre-ACLF' group develop an unstable decompensated requiring further hospital admission stable compensated no admission.2 It demonstrates highest rates levels inflammation. also bacterial infection alcohol-related hepatitis main precipitants correlating severity inflammation.3 this issue United Gastroenterology Journal, Zanetto et al. introduced Padua model 2.0 identifies at ACLF.4 This expands on authors' previous work original model, combined C-reactive protein (CRP), Chronic Failure Consortium score (CLIF-C AD) Child Pugh predict AD, accurately development Model End-Stage Disease (MELD), CLIF-C scores alone.5 differs CRP replaced presepsin (PSP), soluble fragment CD14, authors found PSP AD. PSP's superiority predicting likely stems from its specificity infection. released CD14 during inflammatory responses, where co-receptor toll-like receptor 4 (TLR4) macrophages monocytes recognise endotoxin. probably makes accurate predictor compared hepatically produced acute-phase protein, CRP. results monocyte-related interesting latter has investigated potential novel therapy Indeed, interplay between lipid metabolism circulating immunity, dysregulation lysophosphatidylcholine lysophosphatidic acid leads proinflammatory monocyte phenotype participates dysfunction syndrome.6 pathway therefore proposed therapeutically reprogramme monocytes, future research should elucidate impact CD14-related inflammation development. aim who will there would be earlier implementation interventions improve survival. study, median time onset was 66 days leaving enough treat prevent any infections other but also, promising field therapeutical approaches refer trials investigating disease-modifying therapies.7 clearly highlights need preventative therapies help define inclusion criteria trials. These certainly referred transplant assessment without they not receive priority under current listing policies due MELD reaching threshold transplant. However, placing such waiting lists before occurrence one best ways secure LT A multi-centre indeed demonstrated 100% listed were finally transplanted opposed 71% episode.8 summary, both models predictive identifying validated external cohorts, their critical benefits include referral centres recruitment trials, focus patients. declare conflicts interest related work. NIHR; EASL Joan Rodes Fellowship. Data sharing applicable article datasets generated analysed study.

Language: Английский

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