Artificial Liver Support System Research Articles

Therapeutic and Safety Promise of Mesenchymal Stem Cells for Liver Failure: From Preclinical Experiment to Clinical Application.

Liver failure (LF) is serious liver damage caused by multiple factors, resulting in severe impairment or decompensation of liver synthesis, detoxification, metabolism, and biotransformation. The general prognosis of LF is poor with high mortality in non-transplant patients. The clinical treatments for LF are mainly internal medicine comprehensive care, artificial liver support system, and liver transplantation. However, none of the above treatment strategies can solve the problems of all liver failure patients and has its own limitations. Mesenchymal stem cells (MSCs) are a kind of stem cells with multidirectional differentiation potential and paracrine function, which play an important role in immune regulation and tissue regeneration. In recent years, MSCs have shown multiple advantages in the treatment of LF in pre-clinical experiments and clinical trials. In this work, we reviewed the biological characteristics of MSCs, the possible molecular mechanisms of MSCs in the treatment of liver failure, animal experiments, and clinical application, and also discussed the existing problems of MSCs in the treatment of liver failure.

Efficacy and safety of artificial liver support system treatment for immune checkpoint inhibitors related liver failure in patients with hepatocellular carcinoma: Protocol for a randomized controlled clinical trial

BackgroundImmune checkpoint inhibitor-induced immune-mediated hepatitis (ICI-IMH) in patients with hepatocellular carcinoma (HCC) has been established to increase the risk of liver failure (LF). Given the accumulating evidence supporting the efficacy of artificial liver support systems (ALSS) in mitigating both IMH and LF, a single-center, non-blinded, randomized controlled clinical trial is proposed to investigate the efficacy and safety of ALSS for HCC patients with ICI-LF. Methodsand analysis: Sixty eligible participants will be enrolled in this trial and randomly assigned to one of two groups in a 1:1 ratio. In addition to standard pharmacological management, patients in the trial group will receive treatment with a double plasma molecular adsorption system (DPMAS) and low-volume plasma exchange (LPE) on three occasions, while patients in the control group will undergo PE three times. Patient assessments, including symptoms and laboratory tests, will be conducted at baseline, before and after the three ALSS treatments, and at 2, 4, 8, and 12 weeks post-enrollment. The primary outcome is the mortality rate at 12-week follow-up. Secondary outcomes include changes in the Model for End-Stage Liver Disease (MELD) score following ALSS treatment and the incidence of adverse events (AEs). DiscussionICI-LF in HCC patients is associated with a high mortality rate and lacks effective treatment options. Our study aims to evaluate the efficacy and safety of ALSS for this patient population, comparing the effectiveness of two ALSS modalities (DPMAS + LPE vs. PE). Trial registrationThis clinical trial has been registered on ClinicalTrials.gov with the identifier NCT05484908 (Release Date: July 30, 2022) (https://clinicaltrials.gov/study/NCT05484908).

Comparing the prognostic impact of 131I and/or artificial liver support system on liver function failure combined with hyperthyroidism.

Hyperthyroidism, a prevalent endocrine disorder, can lead to complications such as liver failure due to the liver's essential role in thyroid hormone metabolism. The study aimed to elucidate the respective contributions of 131I and/or ALSS in managing hyperthyroidism alongside liver failure. A retrospective analysis was carried out on 74 patients diagnosed with severe liver failure in the context of Graves' disease. Patients were categorized into three groups: group A (n = 34) received 131I treatment, group B (n = 17) underwent 131I and ALSS treatment, and group C (n = 24) received artificial liver support system (ALSS) treatment alone. Throughout the treatment period, the liver function indexes in all groups exhibited a declining trend. The thyroid function of group A and group B treated with 131I was significantly improved compared to that before treatment. There was no significant change in thyroid function in group C. After the correction of hyperthyroidism, significant improvements were observed in the liver function of individuals in groups A and B, particularly with more noticeable amelioration compared to group C. After two months of treatment, the efficacy rates for the three groups were 79.41%, 82.35%, and 60.87% respectively. Mortality rates of the three groups were 5.88%, 17.65%, and 36% (P < 0.01). Group B, receiving both 131I and ALSS treatments, exhibited a lower mortality rate than group C. In cases of severe liver failure accompanied by hyperthyroidism, prompt administration of 131I is recommended to alleviate the adverse effects of hyperthyroidism on liver function and facilitate a conducive environment for the recovery of liver functionality.

Polyethylene Terephthalate Fiber Modified with Type I Collagen as a 3D Scaffold Material for Bioartificial Liver

Acute and chronic liver failure are clinically significant conditions, and the artificial liver support system (ALSS) is emerging as a novel and effective approach for the clinical management of liver failure. Within this framework, scaffold materials occupy a pivotal position as integral components of the bioreactor. Elevating the performance capabilities of these scaffolds not only augments the therapeutic efficacy of the artificial liver but also lays the groundwork for refining and selecting large-scale hepatocyte culture models. In this study, we introduced a novel hepatocyte scaffold material designated as PET-COL, crafted by coating polyethylene terephthalate (PET) with collagen. This involved a sequence of modifications, including alkaline hydrolysis, EDC/NHS activation and crosslinking, as well as collagen conjugation. The physicochemical attributes of the scaffold were thoroughly characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), second harmonic generation (SHG), water contact angle measurements, and high-performance liquid chromatography–mass spectrometry (HPLC-MS). Furthermore, an investigation into the material’s biological properties was conducted that encompassed SEM (HepaRG growth), fluorescence staining (assessment of cell viability), staining by trypan blue (HepaRG counting), CCK-8 (proliferation of cells), biochemical testing, and immunosorbent assay. Our findings revealed that collagen was covalently bonded to the PET surface, leading to a substantial enhancement in the material’s hydrophilicity (p &lt; 0.001). The quantity of collagen coating was determined to be precisely 33.30 μg per scaffold. Human liver progenitor HepaRG cells thrived on the PET-COL material. Compared with the untreated group, cell viability, albumin secretion, urea synthesis, and the expression levels of CYP3A4 and CPS1 increased significantly (p &lt; 0.001), demonstrating remarkable biological vitality. The PET-COL scaffold, as developed in this study, holds immense potential for application in bioartificial livers.

Outcome of patients with different stages of acute-on-chronic liver failure treated with artificial liver support system.

Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail. A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality. A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15-8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34-10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52-35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69-1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73-0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3-5 sessions of ALSS treatment was lower than that of patients received 1-2 sessions (aHR (95% CI), 0.34 (0.20-0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3-5 sessions (0.69 (0.43-1.11), p = 0.128). ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3-5 sessions of ALSS treatment might be reasonable.

Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system.

The increased expression of G3BP1 was positively correlated with the prognosis of liver failure. To investigate the effect of G3BP1 on the prognosis of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) after the treatment of artificial liver support system (ALSS). A total of 244 patients with ALF and ACLF were enrolled in this study. The levels of G3BP1 on admission and at discharge were detected. The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis. This study was shown that lactate dehydrogenase (LDH), alpha-fetoprotein (AFP) and prothrombin time were closely related to the prognosis of patients. After the ALSS treatment, the patient' amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission (difG3BP1) < 0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index. The subgroup analysis showed that the difG3BP1 < 0 group had a higher risk of progression, regardless of model for end-stage liver disease high-risk or low-risk group. At the same time, compared with the inflammatory marks [tumor necrosis factor-α, interleukin (IL)-1β and IL-18], G3BP1 had higher discrimination and was more stable in the model analysis and validation set. When combined with AFP and LDH, concordance index was respectively 0.84 and 0.8 in training and validation cohorts. This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS. The combination of G3BP1, AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.

Nursing Care of 10 Patients with Vasovagal Reflex Caused by Artificial Liver Support System Treatment

Nursing Care of 10 Patients with Vasovagal Reflex Caused by Artificial Liver Support System Treatment

Characteristics of circulating immune cells in HBV-related acute-on-chronic liver failure following artificial liver treatment

Background and aimLiver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy.MethodsA total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses.ResultsIn total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8+ T (P = 0.003), CD4+ TCM (P = 0.033), CD4+ TEM (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4+ TCM (P = 0.010), CD4+ TEM (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients.ConclusionsChanges in effector CD8+ T cells, effector and memory CD4+ T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.

Nephrologist Involvement in the Multi-Organ Failure Patient with Artificial Liver Support Systems: Experience of the Single-Center Extracorporeal Therapy Program in Mexico

Nephrologist Involvement in the Multi-Organ Failure Patient with Artificial Liver Support Systems: Experience of the Single-Center Extracorporeal Therapy Program in Mexico

Efficacy of Plasma Exchange and a Double-Plasma Molecular Absorption System for Treating Immune Checkpoint Inhibitor-Related Hepatitis

Background: Immune checkpoint inhibitor (ICI)-related hepatitis has been increasing in the past decade. Objectives: This study aimed to investigate the effectiveness of plasma exchange (PE) and a double-plasma molecular absorption system (DPMAS) for ICI-related hepatitis. Methods: A retrospective analysis was conducted on patients with ICI-related hepatitis treated at the Third Affiliated Hospital of Sun Yat-Sen University (China). The collected data included biochemical indices, treatments, the use of an artificial liver support system (ALSS), and outcomes. Results: From June 2021 to January 2023, 16 patients were treated and included in the analysis. Eight patients in group A received general support. The other 8 patients in group B received general support, plus 3 rounds of ALSS every 2 - 4 days (4 patients were treated with PE and the others with DPMAS + PE). There was no significant difference in age and treatment days between the two groups. Before treatment, there was no significant difference in direct bilirubin (DBIL), glutamine transpeptidase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase (ALT), procalcitonin, the international normalized ratio (INR), model for end-stage liver disease scores, albumin, globulin, and hemocyte count between groups A and B (in all cases, P &gt; 0.05). However, the total bilirubin (TBIL) of group B was significantly higher than that of group A (P = 0.029). After treatment, TBIL and DBIL were significantly decreased in group B (both P &lt; 0.05), and group B had a significantly lower GGT (P = 0.028) and higher INR (P = 0.004) than group A. The ALP level of group B was also lower, but the difference was not significant (P = 0.068). No allergic reaction or severe adverse effect was observed. Conclusions: Both PE and DPMAS + PE can effectively improve ICI-related hepatitis within the short term and are more effective for patients with hyperbilirubinemia. Liver function should be monitored continuously during treatment.

Nonalcoholic fatty liver disease: a review of physiology, treatments, and market outlook

The liver is a multifunctional organ with a wide variety of roles in the body; it is highly vascularized, and 25% of cardiac output is directed toward the liver. Non-alcoholic fatty liver disease (NAFLD is diagnosed when liver cells are injured as a result of fat buildup. People with NAFLD are at greater risk of having the disease progress to hepatis, cirrhosis, and liver cancer. The purpose of this review is to discuss the physiology, available treatments, and market for non-alcoholic fatty liver disease (NAFLD). NAFLD has increased in frequency around the world in the last 20 years, and this trend is predicted to continue into the future. The best known treatment for NAFLD is liver transplantation, but only a fifth of the patients who need treatment are provided with a donor liver. One alternative to a liver transplantation is the use of an artificial liver support system, which uses a variety of dialytic techniques to treat the blood plasma outside the body. Researchers are currently in the process of building bioartificial livers and chemically derived drugs to help reduce the effects of NAFLD, which can range from liver cancer to cirrhosis. While the list of treatments for NAFLD is limited, there is great potential for the industry to grow exponentially once additional treatments are approved by the Food and Drug Administration (FDA).

Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases.

Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Considering such plight, stem cell therapeutic strategies deliver hope to the patients. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.

Two adolescent cases of early use of Molecular Adsorbent Recirculating System&lt;sup&gt;®&lt;/sup&gt; for drug-induced fulminant hepatic failure

Fulminant hepatic failure (FHF) is a rare but fatal disease with a 40%-80% mortality, often requiring liver transplantation, which is hard to perform in children. A therapeutic intervention alternative to liver transplantation is an extracorporeal artificial liver support system. Molecular Adsorbent Recirculation Systems® (MARS) has emerged as a bridge therapy for adult FHF, whereas in pediatric FHF, there have been a small number of cases of implementing MARS. Recently, we witnessed the recovery of 2 teenagers with FHFs caused by acetaminophen and a diet aid. Both patients were treated uneventfully, with early use of MARS. These cases suggest that early use of MARS may be a promising therapeutic intervention in pediatric drug-induced FHF.

Research progress of non-biological artificial liver support system therapy for paitents with liver failure

Liver failure progresses quickly with high mortality. Non-biological artificial liver support system therapy is one of the important treatments for patients with liver failure. The basic techniques of non-biological artificial liver support system therapy include plasma exchange, plasma adsorption and continuous renal replacement therapy. In this paper, the effect and choice of these basic techniques, the treatment timing, the possible patients who may benefit, and the existing problems are summarized and discussed. We hope to provide a reference for the rational use of non-biological artificial liver support system therapy in clinical practice.

WITHDRAWN: Comparing the prognostic impact of 131I or/and Artificial Liver Support System on liver function failure combined with hyperthyroidism

WITHDRAWN: Comparing the prognostic impact of 131I or/and Artificial Liver Support System on liver function failure combined with hyperthyroidism

Effect of Artificial Liver Support Systems on Gut Microbiota in Patients with HBV-Related Acute-on-Chronic Liver Failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rare and severe form of end-stage liver disease with high mortality; gut microbes are strongly associated with the development of this severe liver disease but the exact association is unclear. Artificial liver support systems (ALSS) are clinically important in prolonging the waiting time for liver transplantation and in aiding drug therapy to achieve remission. The aim of this study was to investigate the effect of ALSS on the abundance and diversity of microorganisms in the gut of HBV-ACLF patients. In this study, 109 stool samples were collected from patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) for 16S rRNA sequencing. Among them, 44 samples were from patients treated with ALSS therapy as an adjunct to standard medical treatment (SMT) and 65 were from patients receiving SMT only. Analysis of the sequencing results suggested that there were significant differences in the abundance and diversity of gut microbiota between the with-ALSS and without-ALSS groups (p < 0.05). The operational taxonomic units and Shannon indexes indicated that the diversity and abundance of the gut microbiome, while decreasing after the first ALSS treatment, gradually increased after an increase in the number of ALSS therapies. The overall proportion of HBV-ACLF patients with coinfection was 27.59%; the coinfection can reduce the abundance of the Bacteroidetes phylum in the microbiome significantly whereas Proteobacteria were highly enriched. After ALSS therapy, HBV-ACLF patients had a decrease in potentially harmful bacteria, an increase in potentially beneficial bacteria, an increase in the diversity of the intestinal microbiota, and the intestinal microecological disorders were corrected to a certain extent. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels, as well as the international normalized ratio (INR), showed a decreasing trend whereas plasminogen activity (PTA) increased and the condition of patients with HBV-ACLF progressed in a favorable direction. In addition, the abundance of Blautia and Coprococcus was negatively correlated with TBIL and INR, positively correlated with PTA, and positively correlated with disease recovery. Our study shows that ALSS can alter the composition of the gut microbiota and have an ameliorating effect on the gut microecological imbalance in HBV-ACLF patients. It is worth mentioning that Blautia and Coprococcus may have great potential as biomarkers.

Focusing on timing selection and whole-course management of liver transplantation treatment for patients with acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is a clinical syndrome of acute decompensation accompanied by organ failure that occurs on the basis of chronic liver disease and has a high short-term mortality rate. Currently, there are still differences in relation to the definition of ACLF; thus, baseline characteristics and dynamic changes are important bases for clinical decision-making in patients with liver transplantation and others. The basic strategies for treating ACLF currently include internal medicine treatment, artificial liver support systems, and liver transplantation. Multidisciplinary active collaborative management throughout the whole course is of great significance for further improving the survival rate in patients with ACLF.

#4431 PREPARATION OF IMIDAZOLE QUATERNARY AMMONIUM SALT MICROSPHERES WITH HIGH BILIRUBIN ADSORPTION PERFORMANCE AND SELF-ANTICOAGULATION ABILITY

Abstract Background and Aims Bilirubin is a crucial toxin in liver metabolism. Increase of bilirubin is one of common manifestations in patients with abnormal liver function, and large accumulation of bilirubin in the blood can lead to more severe hepatic dysfunction and even death. Due to the poor therapy effect and the shortage of available donor organs, the artificial liver support system has been introduced to maintain the liver function and bridge patients to transplantation. Previous studies have found that imidazole quaternary ammonium salts have great potential to adsorb bilirubin. This work is to develop a novel bilirubin adsorption column by simple and general method, and evaluate the removal efficiency, anticoagulant property and biocompatibility of the bilirubin adsorption column. Method Multifunctional microspheres were fabricated by in situ co-polymerization of 1-vinylimidazole and divinylbenzene. Nuclear magnetic resonance (NMR), thermo-gravimetric analysis and X-ray photoelectron spectroscopy (XPS) etc. were performed to characterize the chemical compositions of the microspheres. Meanwhile, hemolysis test, blood routine test and clotting time test etc. were leveraged to evaluate the biocompatibility of the microspheres. Both static adsorption test and dynamic adsorption test were performed in vitro to evaluate adsorption performance. Results A variety of methods had proved successful synthesis of the adsorption performance. The hemolysis ratios of microspheres were less than 5%. Compared with BS330 microspheres and PES microspheres, the activated partial thromboplastin time (APTT) and thrombin time (TT) were longer in this work. Moreover, the microspheres showed a high adsorption clearance. In PBS solution of bilirubin, the adsorbent could decrease bilirubin from 200 mg/L to 45-55 mg/L. Conclusion The results suggested that the multifunctional microspheres can significantly reduce bilirubin concentration without obvious adverse interactions and could exhibit anticoagulation activity.

Case Report: Complete Remission of a Patient with Acute-on-chronic Liver Failure with Rare Hepatic Encephalopathy and Fever of Unknown Origin Treated with Anti-infective Therapy Combined with Psychotherapy After Artificial Liver Support System

The theme of this report is incredible psychological therapy's inspiration for fever of unknown origin (FUO). We analyzed this incredible phenomenon through psychological immunity, liver immunity, inflammation, etiology, diagnostic methods, and treatment strategies. A man, 44 years old, was dyed for more than 40 days due to abdominal distension with skin and scleral yellow, and feathers accompanied him for four days to enter the hospital. Hepatitis virus test shows HBV infection. HBV DNA detection shows negative. The detection of the respiratory tract nine-fold, tuberculosis, anemia, and gut-to-club ratio all show negative. Due to the weakness of the patient's body, we cannot cooperate with more examinations. We use blood specimens to monitor and analyze for 25 days. In short, this is a case of chronic-acute liver failure, manic, and fever, likely to be an FUO cause in terms of the treatment plan, general treatment, artificial liver treatment, surgical treatment, anti-infection therapy, and psychotherapy. The patient reached the common treatment goal after 25 days of treatment. This report aims to provide psychotherapy programs and clinical characteristics for patients with chronic-acute liver failure, manic, and FUO and provide inspirational thinking strategies for long-term blood specimen examination. The potential mechanism of psychological fever is immune disorders, and the decline in the concentration of immunoglobulin A and E may be a direct factor.

Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study

BackgroundThere is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF.MethodsPatients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients.ResultsRegarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients).ConclusionsBased on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.