Acute-on-chronic liver failure: Controversies and consensus

Ngu, Natalie L. Y.; Flanagan, Eliza; Bell, Sally; Le, Suong

doi:10.3748/wjg.v29.i2.232

Cited by 6 publications

(2 citation statements)

References 57 publications

(114 reference statements)

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“…[1][2][3] Patients with ACLF commonly manifest functional failures in the liver, kidneys, brain, coagulation, circulation, respiratory system and other systems, with 90-day mortality rate reaching up to 58%. [4][5][6] Currently, effective treatments for ACLF are lacking. [7][8][9][10] Liver transplantation stands as the definitive treatment, significantly improving long-term survival.…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial

Wang,

Li,

Yang

et al. 2024

BMJ Open

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IntroductionAcute-on-chronic liver failure (ACLF) is a prevalent and life-threatening liver disease with high short-term mortality. Although recent clinical trials on the use of mesenchymal stem cells (MSCs) for ACLF treatment have shown promising results, multicentre randomised controlled phase II clinical trials remain uncommon. The primary aim of this trial is to assess the safety and efficacy of different MSCs treatment courses for ACLF.Methods and analysisThis is a multicentre, double-blind, two-stage, randomised and placebo-controlled clinical trial. In the first stage, 150 patients with ACLF will be enrolled and randomly assigned to either a control group (50 cases) or an MSCs treatment group (100 cases). They will receive either a placebo or umbilical cord-derived MSCs (UC-MSCs) treatment three times (at weeks 0, 1 and 2). In the second stage, 28 days after the first UC-MSCs infusion, surviving patients in the MSCs treatment group will be further randomly divided into MSCs-short and MSCs-prolonged groups at a 1:1 ratio. They will receive two additional rounds of placebo or UC-MSCs treatment at weeks 4 and 5. The primary endpoints are the transplant-free survival rate and the incidence of treatment-related adverse events. Secondary endpoints include international normalised ratio, total bilirubin, serum albumin, blood urea nitrogen, model for end-stage liver disease score and Child-Turcotte-Pugh score.Ethics and disseminationEthical approval of this study has been obtained from the Fifth Medical Center of the Chinese PLA General Hospital (KY-2023-3-19-1). All results of the study will be submitted to international journals and international conferences for publication on completion of the study.Trial registration numberNCT05985863.

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Section: Introductionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial

Wang,

Li,

Yang

et al. 2024

BMJ Open

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“…For various reasons, some cases will progress to liver failure, among which acute-on-chronic liver failure (ACLF) is more common. The features of ACLF are rapid progression and high incidence of short- and medium-term mortality, ranging from 50% to 90%, caused by multi-organ failure[ 2 , 3 ]. In this case, orthotopic liver transplantation remains the most effective treatment.…”

Section: Introductionmentioning

confidence: 99%

Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure

Zhang,

Wang,

Zhao

et al. 2024

World J Clin Cases

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BACKGROUND Stromal cell derived factor-1 (SDF-1) plays a pivotal role in the recruitment of stem cells to injured livers. However, the changes of SDF-l in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) have yet to be elucidated. AIM To study the SDF-1 changes in patients with HBV-related ACLF. METHODS 30 patients with HBV-related ACLF, 27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study. The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction. Immunohistochemical staining was performed to illustrate the expression of SDF-l, CXC receptor 4 (CXCR4) and Ki67. The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays. RESULTS The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients (both P < 0.05). The expression of SDF-l, CXCR4 and Ki67 from ACLF were the highest among the three groups (all P < 0.01). The serum SDF-l levels in ACLF patients were significantly lower than that in other patients (both P < 0.01). Moreover, in ACLF patients, the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio. In addition, the serum SDF-l levels in survival were significantly lower compared with the non-survivals (P < 0.05). The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722 (P < 0.05). CONCLUSION This study provides the SDF-1 changes in patients with HBV-related ACLF. The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.

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Early Prediction of Acute-on-Chronic Liver Failure Development in patients with diverse chronic liver diseases

Shen,

Xu,

Chen

et al. 2024

Preprint

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Background & aims: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, leading to organ failures and high short-term mortality. The course of ACLF is dynamic and reversible in a considerable proportion of patients during hospital admission. Early detection and accurate assessment of ACLF are crucial, yet ideal methods remain lacking. Therefore, this study is aimed to develop a new score for predicting the onset of ACLF in patients with diverse chronic liver diseases. Methods: A total of 6188 patients with diverse chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. Lasso-cox regression was utilized to establish prediction models for the development of ACLF at 7, 14, and 28 days. Findings: Among 5221 patients without ACLF, 477 patients progressed to ACLF within 28 days. Seven predictors were found to be significantly associated with the occurrence of ACLF at 7, 14, and 28 days. The new score had the best discrimination with the c-index of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores(CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score, all P<0 .001). The new score also showed improvements in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluation, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value (9.6) differentiated high and low-risk patients of ACLF onset. These findings were further validated in a separate group of patients. Conclusion: A new progressive score, based on seven predictors, has been developed to accurately predict the occurrence of ACLF within 7, 14, and 28 days in patients with diverse chronic liver diseases and might be used to identify high-risk patients, customize follow-up management, and guide escalation of care, prognostication, and transplant evaluation.

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Acute-on-chronic liver failure: Controversies and consensus

Cited by 6 publications

References 57 publications

Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial

Human umbilical cord mesenchymal stem cell transplantation for the treatment of acute-on-chronic liver failure: protocol for a multicentre random double-blind placebo-controlled trial

Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure

Early Prediction of Acute-on-Chronic Liver Failure Development in patients with diverse chronic liver diseases

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