Aging is a significant risk factor for drug-induced kidney injury, underscoring the need for advanced preclinical models. The impact of age on the susceptibility of human primary kidney stem cells to drug-induced mitochondrial toxicity remains largely uncharacterized. To address this gap, we employed a well-established in vitro 3D model, utilizing a silk fiber matrix, to culture renal stem cells derived from both young and elderly donors. Tenofovir, a commonly prescribed antiretroviral medication linked to renal adverse effects, was used to investigate age-related drug-induced mitochondrial toxicity. Our findings reveal a pronounced age-dependent increase in tenofovir-induced mitochondrial dysfunction in older renal stem cells compared with their younger counterparts. This was characterized by diminished mitochondrial mass and function, ATP production, elevated oxidative stress, senescence gene expression, and compromised renal cell function. These results highlight the critical role of aging in exacerbating drug-induced renal injury. The 3D silk matrix model utilizing elderly donor-derived renal stem cells offers a promising platform for identifying medications with age-specific renal toxicity potential and for developing targeted therapies to safeguard the aging kidney.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.

Acute-on-chronic liver failure(ACLF)is one of the leading causes of mortality among patients with chronic liver disease.Potentially reversible,ACLF requires precise clinical classification to facilitate accurate diagnosis,targeted treatment,and comprehensive management.Based on the latest research findings and clinical evidence,the Severe Liver Disease and Artificial Liver Group and the Nutrition and Regeneration in End-Stage Liver Disease Group,Chinese Society of Hepatology,Chinese Medical Association,together with multidisciplinary experts,have jointly compiled China's first guideline for the diagnosis and treatment of ACLF.The guideline aims to provide guidance for the diagnosis,treatment,and individualized management of patients with ACLF in clinical practice.

Images obtained by existing low-light image enhancement methods still suffer from poor visibility, low contrast, and loss of spatial details. This paper proposes a depth-wise convolution attention and multi-scale feature fusion network for low-light image enhancement (DAMFFN) to solve these problems. In DAMFFN, firstly, this paper designs a low-light attention block (LLAB) consisting of a low-light multi-head self-attention block (LL-MSAB), a dual-branch equalization block (DBEB), and two layers of normalization composition. The LL-MSAB balances feature weights between different channels by calculating the attention map between channels, thus improving the image's visibility and contrast. Secondly, this paper leverages the DBEB to enhance the image's contrast. Finally, the paper proposes a multi-scale feature compensation block (MSFCB), which is used to reduce the loss of spatial details in the LLAB and downsampling stages. On the other hand, MSFCB can also fuse the deep spatial information of images of different scales. In terms of the loss function, this paper refers to a multi-scale frequency domain loss function (Mult-SFD), which reduces the difference in the frequency domain space between the reference image and the enhanced low-light image. This paper conducts sufficient qualitative and quantitative experiments in 5 public datasets, which are superior to many other low-light image enhancement methods in terms of visual effects and index scores(PSNR: Peak Signal-to-Noise Ratio. SSIM: Structural Similarity Index): PSNR=24.87dB, SSIM=0.856 on LOw-Light(LOL) dataset; PSNR=25.70dB, SSIM=0.912 on MIT-Adobe FiveK dataset.

BackgroundPeripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard-of-care to prevent mother-to-child transmission (MTCT) of chronic hepatitis B (CHB) infection in highly-viremic mothers. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant subjects.MethodsIn this prospective study, treatment-naïve non-cirrhotic highly-viremic (hepatitis B virus [HBV] DNA ≥200,000 IU/mL) CHB mothers were treated with TDF at 24-28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase (ALT) were monitored every 6-8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization and HBV serology were checked at 7-12 months of age.ResultsAmong 330 subjects recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/mL), TDF was stopped at delivery in 66.4% and ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0% vs. 96.9%), clinical relapse (19.5% vs. 14.3%) or retreatment (12.3% vs. 10.2%) (all p>0.05). Similar proportion of patients developed ALT flare 5x (2.1% vs 1.0%, p=0.464) and 10x (0.5% vs 0%, p=0.669) above upper limit of normal respectively, in early withdrawal and late withdrawal group. No infants developed HBsAg-positivity.ConclusionPP-TDF and neonatal immunization were highly effective to prevent MTCT of HBV in highly-viremic mothers. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment.

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

Background Thermal therapy induces an immune response in patients with hepatocellular carcinoma (HCC), but the dynamic characteristics of the natural killer (NK) cell immune response post-thermal ablation remain unclear. We conducted a prospective longitudinal cohort study to observe the dynamic changes of phenotype and function of NK cells in peripheral blood before and after thermal ablation of hepatitis B-associated HCC and their correlation with tumor recurrence. Methods Fifty-six patients clinically and pathologically confirmed with hepatitis B-associated HCC were selected for thermal ablation. Peripheral blood was collected on day 0, day 7, and month 1. NK cell subsets, receptors, and killing function were detected by flow cytometry, and the LDH levels were examined. Overall recurrence and associated variables were estimated using Kaplan–Meier, log-rank, and Cox proportional-hazards analyses. Results The frequency of CD3 − CD56 + cells was increased on day 7 ( P < 0.01) without significant differences between D0 and M1. NKG2D, NKp44, NKp30, CD159a, and CD158a expression was increased on M1 (all P < 0.05). The granzyme B and IFN-γ expression in NK cells were higher on M1 vs. D0 ( P < 0.05). On day 7, the NK cell lysis activity of the target K562 cells was increased ( P < 0.01) but decreased on M1 ( P < 0.05). Survival analysis showed that CD158a expression and IFN-γ and perforin release on day 0 were associated with the risk of HCC recurrence. Cox regression analysis showed that the expression changes in CD56, NKp46, granzyme B, and perforin (D7-D0) induced by thermal ablation were associated with recurrence-free survival (RFS) of patients with HCC. Conclusion Thermal ablation increased the frequency and function of CD3 − CD56 + NK cells in the peripheral blood of patients with HCC. These cells tended to be more differentiated and activated. Notably, expression levels of NK cell receptors NKp46, perforin, and granzyme B were associated with RFS.

Background:Topical therapy has been shown to induce an immune response in patients with hepatocellular carcinoma (HCC). In this study, a prospective parallel group control experiment was conducted to compare the differences between radiofrequency ablation and microwave ablation in inducing the immune regulation of NK cells.Methods:Sixty patients with clinically and pathologically confirmed hepatitis B-associated hepatocellular carcinoma (HCC) were selected for thermal ablation. Patients were randomly assigned into the MWA group (n = 30) and the RFA group (n = 30). Patient's peripheral blood was isolated on days D0, D7, and month M1. NK cell subsets, receptors, and killing function were detected by flow cytometry and LDH. Student t test and rank sum test were used to compare the statistical differences between the RFA (radio frequency) and MWA (microwave) groups. The Kaplan-Meier curve and log-rank test were used to calculate the difference between the two survival curves.Results:Comparison of the frequency of CD3-CD56+ and CD3-CD56+CD16+ in NK cells between the RFA and WMA groups showed that there was no difference in the D0, D7, M1, D7-D0, M1-D0, and M1-D7 groups. The changes of the inhibitory NK cell receptor CD159A were significantly different at D7 (P<0.05). CD107a were compared between the RFA and WMA groups, indicating that CD107a changes induced by NK cells were significantly different at D7-D0 (P<0.05). Comparison of NK cell lysis activity of target K562 cells between the RFA and WMA groups showed that there was no difference at D0, D7, D7-D0. There was no difference in recurrence-free survival (RFS) between the RFA and WMA groups (P=0.11).Conclusions:The difference between MWA and RFA-induced NK cell changes was mainly manifested in the inhibitory receptors CD159a and CD107a 1 week after surgery, with microwave-induced changes being more severe. Comparison of the NK cell lysis activity of the target K562 cells between the RFA and WMA groups showed that there was no difference in D0, D7, D7- D0. Survival analysis showed that these differences did not affect the recurrence-free survival (RFS) in the two groups.

Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury. Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry. Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy. Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.

Background:Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients. Methods:Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT. Findings:In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated. Interpretation:COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT. Funding:This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).

Notwithstanding their numerous advantages, biological treatments have many limitations when treating patients with psoriasis (PsO) and hepatitis B (HB). Clinicians need to pay careful attention to the issue of hepatitis B virus (HBV) reactivation. In accordance with the PRISMA guidelines, we systematically searched Pubmed, Scopus, Embase, Cochrane Library, and Web of Science databases for observational studies on the topic of HBV reactivation among patients with PsO and HB treated with biologics. The random-effects model was used to pool the reactivation rate by the Freeman–Tukey double arcsine transformation method. We selected Fisher’s exact test to compare multiple rates. To determine the sources of heterogeneity, sensitivity analysis and meta-regression were performed. Ten studies with a total of 238 subjects that met the inclusion criteria were included. The pooled reactivation rate was 1.8% [95% confidence interval (CI) 0.0–5.6%] in patients with PsO and HB. Among them, the viral reactivation rates of HBsAg-positive and HBsAg-negative patients were 4.1% (95% CI 0.0–17.9%) and 0.2% (95% CI 0.0–2.8%). The difference between HBsAg-positive and HBsAg-negative patients was statistically significant (p = 0.002). The viral reactivation rate of individuals who needed antiviral prophylaxis but did not receive it was 26.6% (95% CI 5.8–53.5%), while it decreased to 0.0% (95% CI 0.0–6.6%) after accepting antiviral treatment. The two-sided Fisher’s test exact values between different durations of biological therapy showed no statistical significance (p = 0.104). Without antiviral prophylaxis, HBsAg-positive patients with psoriasis are at high risk of virus reactivation when treated with biological agents. Early and sufficient antiviral prophylaxis will effectively reduce the risk of HBV reactivation and serious complications in HBsAg-positive patients. Prolonging the duration of biological treatment will not increase the risk of reactivation.

Abstract Background Patients with HBV-related acute-on-chronic liver failure (HBV–ACLF) have a high 90-day mortality rate, so early prognostic evaluation is important. Aim We aimed to explore the correlation between dynamic changes in free triiodothyronine (FT3) levels and 90-day prognosis of patients with HBV–ACLF. Methods A prospective cohort study investigated 122 inpatients with HBV–ACLF. Patients were divided into three groups based on the dynamic change in FT3 level, as follows: continuous normal FT3; continuous decreased FT3; and FT3 U-shaped change groups, and patients were divided into survival group and non-survival group according to whether they were alive or not. The correlation between the change in FT3 level and 90-day prognosis was explored. Three factors that affected the prognosis most significantly were used to form an FT3 correlation formula to compare the difference in predicting prognosis between the formula score and the conventional score. Results There were 98 patients with decreased FT3 level (80.33%), and the lowest FT3 level was at 8.52 ± 6.38 days after admission, which lasted for 16 days. There were no significant differences in FT3 levels at admission and at the lowest point between the survival and non-survival groups. Cox regression analysis showed that the FT3 level, FT3 change type, and hepatic encephalopathy (HE) grading were important factors related to prognosis. The area under the receiver operating characteristics curve for the FT3 correlation formula score was 0.892, which was significantly higher than that of the CTP, MELD, MELD–Na, CLIF–SOFA, CLIF–C OF, and AARC scores (P < 0.001). Conclusions The FT3 level and its dynamic change type together with the HE grading can facilitate prediction of 90-day prognosis for patients with HBV–ACLF.

BACKGROUND:Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients. METHODS:Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-R2, relative prediction errors, and odds ratios. RESULTS:Thirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p < 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, R2 0.609 and lower prediction errors by 10-50%. Day-7 NACSELD-ACLF-binary was the simple model (minimum AIC/BIC 12/17) with the highest odds (8.859) and sensitivity (100%) but with a lower PPV (70%) for mortality. Patients with day-7 AARC score > 12 had the lowest 30-day survival (5.7%). CONCLUSIONS:APASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score > 12 may be used as a futility criterion in APASL-ACLF patients.

Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT). Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant. The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01). ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. ‘Emergent LT’ should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.

BACKGROUND:Critical illness-related corticosteroid insufficiency (CIRCI) is known to be a common complication in patients with acute-on-chronic liver failure (ACLF). However, factors that predict the survival rate of ACLF patients remain unclear. The present study aims to determine the prognostic factors that impinge on the survival rate of ACLF patients.METHODS:A total of 90 patients with ACLF at different stages, with or without CIRCI, were prospectively evaluated.RESULTS:Various clinical factors were found to be significantly different among patients at early, mid and late stages of ACLF, as well as between the same population of patients with and without CIRCI. Specifically, patients at later stages of ACLF and patients with CIRCI had significantly higher Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) and ACLF Research Consortium (AARC)-ACLF scores. CIRCI was observed in 20% of the enrolled patients (18 out of 90). In addition, the 90-day mortality rate was higher in mid- and late-stage ACLF patients, as well as patients with CIRCI.CONCLUSION:ACLF stage and CIRCI predict early mortality in patients with ACLF and could be actively monitored in these patients for prioritized liver transplantation.

BACKGROUND:Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF).METHODOLOGY:One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively.RESULTS:Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores.CONCLUSION:Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

Plasma-exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients. Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE. ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS-matched cohort (n = 208, [ALS-119; PE-94, FPSA-25)], SMT-89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42-24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5-11.1), and lower liver-failure-related deaths as compared to FPSA and SMT ( P  < .05). PE cleared inflammatory cytokines, damage-associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) compared to non-responders. PE was associated with lesser adverse effects as compared to FPSA. PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma-exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.