Survival In Acute Liver Failure Research Articles

Plasma exchange improves survival in acute liver failure- An updated systematic review and meta-analysis focussed on comparing within single etiology.

Therapeutic plasma exchange (PLEX) is increasingly used in patients with acute liver failure (ALF) as either stand-alone therapy or bridge to liver transplantation. Etiology plays a major role in prognosis of these patients and benefit of PLEX may consequently differ across etiologies. This systematic review and meta-analysis aims to evaluate the efficacy of PLEX in treating ALF, focussing on studies with single etiology. We conducted a systematic literature search and identified studies comparing PLEX vs. standard medical therapy (SMT) for patients with ALF across all age groups. The protocol was registered in theInternational Prospective Register of Systematic Reviews (PROSPERO) (CRD42023442383). Pooled risk-ratios were determined by Mantel-Haenszel method within a random effect model. Primary outcome was mortality at ≤ 60-days and 90days. Secondary outcome was adverse events attributable to PLEX. Eight studies (pooled sample size in PLEX arm:284; randomized trials:2; Comparative cohorts:6) with retrievable data on ALF were included in this systematic review. Analysis showed that PLEX was associated with significant reduction in mortality at ≤ 60-days (RR 0.64; CI, 0.51-0.80; P < 0.001) and at 90-days (RR 0.67; CI, 0.50-0.90; P = 0.008) as compared to SMT. On sub-group analysis, the survival benefit was noted irrespective of the volume of plasma exchanged during PLEX. Three studies (pooled sample size in PLEX arm: 110; all comparative cohorts) were identified, which included patients with a single etiology for ALF. These studies included patients with Wilson's disease, rodenticidal hepatotoxicity and acute fatty liver of pregnancy. Pooled analysis of studies with single etiology ALF showed better reduction in ≤ 90-day mortality with PLEX (RR 0.53; CI, 0.37-0.74; P < 0.001). Studies reported no major side-effects attributable to PLEX. PLEX is safe and improves survival, independent of the volumes utilized, in patients with ALF as compared to standard medical treatment. The survival benefit is especially pronounced in studies restricted to single etiology.

Continuous renal replacement therapy and survival in acute liver failure: A systematic review and meta-analysis

ObjectiveAcute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia. Different therapies for hyperammonemia have been assessed including continuous renal replacement therapy (CRRT). We conducted a systematic review and meta-analysis to determine the efficacy of CRRT in ALF patients. Materials and methodsWe searched MEDLINE, EMBASE, Cochrane Library, and Web of Science. Inclusion criteria included adult patients admitted to an ICU with ALF. Intervention was the use of CRRT for one or more indications with the comparator being standard care without the use of CRRT. Outcomes of interest were overall survival, transplant-free survival (TFS), mortality and changes in serum ammonia levels. ResultsIn total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70–0.99, p-value 0.04, I2 = 50%] and improved TFS (RR 0.65, 95% CI 0.49–0.85, p-value 0.002, I2 = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84–1.81, p-value 0.28, I2 = 37%). Ammonia clearance data was unable to be pooled and was not analyzable. ConclusionUse of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT.

Single-center experience in 127 adult patients, mono or dual artificial liver support therapy, in patients with acute liver failure.

Acute liver failure (ALF) is a serious condition characterized by sudden liver dysfunction, jaundice and hepatic encephalopathy. Its mortality rate of approximately 80% underscores the urgent need for effective treatments. Supportive extracorporeal therapies (SET), which temporarily support liver function and remove toxins, have shown promise in improving outcomes in acute liver failure (ALF). The aim of this study was to compare the outcomes of dual supportive extracorporeal therapy (SET) and mono supportive extracorporeal therapy in patients with acute liver failure. A total of 127 patients with acute liver failure were included in this retrospective, single-center study. Of these, 62 patients received dual supportive extracorporeal therapy and 65 patients received mono supportive extracorporeal therapy. Primary endpoints were survival without the need for liver transplantation and mortality. Secondary endpoints included resolution of encephalopathy and normalization of International Normalized Ratio (INR). In the dual supportive extracorporeal therapy group, 59.6% of patients survived without the need for liver transplantation, while 27.4% achieved recovery with liver transplantation. The mortality rate in this group was 12.9%. Significant regression of encephalopathy grade was observed in 87% of patients, and the 1 year mortality rate for liver transplant recipients was 10.7%. In the mono supportive extracorporeal therapy group, 61.5% of patients experienced a successful recovery without the need for liver transplantation, with a mortality rate of 29.2%. Significant improvement in the grade of encephalopathy was observed in 70.7% of patients. Both dual supportive extracorporeal therapy (CVVHDF and PE) and mono supportive extracorporeal therapy (PE) were associated with significant improvements in renal and hepatic biochemical parameters, blood ammonia levels, and neurological status in patients with acute liver failure associated with grade III-IV hepatic encephalopathy. In particular, dual support was associated with improved hemodynamic stability, lactic acidosis and acid-base balance. Survival in acute liver failure in our retrospective cohort using a protocolized approach to extracorporeal therapies is higher compared to previously published large ALF studies. This protocolized approach warrants further prospective studies.

Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

Etiology, Outcome and Factors Predicting Native Liver Survival In Acute Liver Failure In Children: Experience From A Tertiary Care Centre

Etiology, Outcome and Factors Predicting Native Liver Survival In Acute Liver Failure In Children: Experience From A Tertiary Care Centre

Management of Rodenticide Poisoning

Rodenticide ingestion, a common mode of suicide in Tamil Nadu and other states in southern and western parts of India, can lead to hepatotoxicity and death. Most rodenticide agents contain phosphorus, a potent toxin. The only definitive management in a patient who develops rodenticide induced acute liver failure is urgent liver transplantation. A study conducted across Tamil Nadu in 2019 documented that the majority (&gt;99%) of rodenticide hepatotoxicity patients cannot access urgent liver transplantation. The current guidelines proposed by the Tamil Nadu chapter of the Indian Society of Gastroenterology are focused on improving survival in these patients, especially by nontransplant treatments. The indications for the use of plasma exchange, an emerging treatment which improves survival in acute liver failure, are described. In resource-constrained settings, it is preferable to avoid the use of sedative drugs, in rodenticide hepatotoxicity patients, who do not have encephalopathy. These management guidelines are specifically meant for use by doctors in primary health centers and in secondary hospitals who care for patients with rodenticide ingestion and hepatotoxicity. We hope these guidelines may also help inform health care policy in Tamil Nadu state to improve survival in patients with rodenticide hepatotoxicity by cost-effective interventions.

Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study.

The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy. Propensity score-matched retrospective cohort analysis. Tertiary North American liver transplant centers. Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009-2019) and controls from the U.S. Acute Liver Failure Study Group registry. Molecular adsorbent recirculating system treatment versus standard medical therapy (control). One-hundred four molecular adsorbent recirculating system patients were propensity score-matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King's College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07-3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone ("model 2"; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05-3.31; p = 0.033), and further adjustment of the "main model" for mechanical ventilation, and grade 3/4 hepatic encephalopathy ("model 3"; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07-3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all). Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.

Therapeutic plasma-exchange improves systemic inflammation and survival in acute-on-chronic liver failure: A propensity-score matched study from AARC.

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.

Therapeutic plasma exchange in acute on chronic liver failure.

Acute on chronic liver failure (ACLF) has been identified as a distinct syndrome due to acute decompensation of liver cirrhosis accompanied by extra-hepatic organ failure, primarily caused by an overwhelming systemic immune response. Therapeutic plasma exchange (TPE) has been demonstrated in a randomized controlled trial to improve transplant free survival in acute liver failure. Here we investigated if TPE might have comparable beneficial effects in patients with ACLF. Thirty-one patients with ACLF that were treated with TPE were enrolled into this retrospective analysis and 1:1 matched to an ACLF cohort treated with standard medical therapy (SMT) only. Patients considered for a bridge to recovery (n = 21 each group) approach had a 30-day mortality >90% that was not improved by TPE (P = .185). Deaths occurred in the SMT group at significant earlier time points compared to the patients treated with TPE (mortality at 5 days: 33.3% for TPE and 66.7% for SMT, P = .048). However, patients who received TPE as a bridge to transplant strategy (n = 10) survived in 60% of cases and demonstrated 24 hours after study inclusion a stabilization of organ dysfunction (organ failures at inclusion: 4 (3-5) vs 24 hours after inclusion: 3 (2-4), P = .031 and CLIF-C-ACLF score: 64 (49-76) vs 54 (49-66), P = .043) not seen in SMT patients. Although these retrospective data need to be interpreted with caution, they suggest that TPE in ACLF patients is feasible but not suitable as a bridge to recovery strategy. In selected patients TPE might assist as bridge to transplant.

Continuous renal replacement therapy and transplant-free survival in acute liver failure: protocol for a systematic review and meta-analysis

BackgroundAcute liver failure is a rare syndrome with significant morbidity and mortality, particularly in absence of transplantation as a rescue therapy. An important mechanism contributing to mortality is hyperammonemia which drives cerebral edema and raised intracranial pressure. Multiple therapies for managing hyperammonemia have been trialed. Continuous renal replacement therapy is effective in treating hyperammonemia in other disease states (notably inborn errors of metabolism). Its efficacy in acute liver failure has been suggested but further investigation is required to prove this. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival.MethodsMEDLINE, EMBASE, Web of Science, and Cochrane Database will be searched. Identified studies will include all patients with acute liver failure in a critical care unit treated with continuous renal replacement therapy. Primary outcome will be effectiveness of ammonia clearance and mortality. Patients treated with any other modality of ammonia lowering therapy (such as plasma exchange or Molecular Adsorbent Recirculating System) will be excluded. Narrative synthesis of the identified studies will occur and if clinical homogeneity is identified, data will be pooled for meta-analysis using a DerSimonian-Laird random effects model.DiscussionWe present a protocol for a systematic review seeking to establish a link between transplant-free survival in acute liver failure and the use of continuous renal replacement therapy. Given the anticipated paucity of literature on this subject, both narrative and quantitative syntheses are planned.Systematic review registration(PROSPERO) CRD42019122520, registered April 16, 2019.

Admission Factor V Predicts Transplant-Free Survival in Acute Liver Failure.

Traditional laboratory markers are insensitive in distinguishing between patients with acute liver failure (ALF) who will require urgent liver transplantation (LT) from those who will recover spontaneously, particularly within 24h of presentation. Coagulation factor-V (FV) may improve the accuracy of outcome prediction in ALF due to its predominant synthesis in the liver and short half-life in plasma. Patients enrolled in the ALF Study Group Registry from a single site had FV determined within 24h of presentation (Derivation-Cohort). Area under the receiver operating characteristic curves (AUROC) dichotomized by ALF etiology [acetaminophen (APAP) or non-APAP] were constructed to evaluate the diagnostic performance of FV for transplant-free-survival (TFS). Multivariate logistic regression modeling was performed using FV and other clinical variables to predict TFS. Accuracy of FV and multivariable model were performed in a Validation-Cohort from a different site. 90-patients (56% with APAP) were included in the Derivation-Cohort. Median FV was significantly higher in TFS versus those who died/LT (31% vs. 15%, respectively; p = 0.001). When dichotomized by etiology, AUROC for FV was 0.77 for APAP (cutoff, sensitivity, specificity 10.5%, 79%, 69%, respectively) and 0.77 for non-APAP (22%, 85%, 67%, respectively). When the optimal cutoffs for FV in the Derivation-Cohort were applied to the Validation-Cohort (N = 51; 59% with APAP), AUROC for FV was 0.75 for APAP (sensitivity/specificity 81/44) and 0.95 for non-APAP (sensitivity/specificity 90/73). In multivariate analyses, AUROC for FV model was 0.86 in the Derivation-Cohort and 0.90 in the Validation-Cohort. Admission FV may improve selection of patients who are likely to improve without LT.

New Predictive Model of Short-term Survival in Acute Liver Failure by Acute Hepatitis A

New Predictive Model of Short-term Survival in Acute Liver Failure by Acute Hepatitis A

Clinical and Laboratory Determinants of Short-Term Transplant-Free Survival in Acute Liver Failure in India—A Prospective Study

Background and Aim: Acute Liver Failure (ALF) is a serious syndrome with high mortality, caused mainly by viral hepatitis and toxins in India. Though MELD score and KCH criteria are commonly used as indicators of prognosis in ALF, there is a need for determining their prognostic accuracy in this population. The study was done to identify the etiology and the factors associated with the outcome and to evaluate MELD score and KCH criteria, in ALF. Methods: A prospective observational study was conducted between September 2015 to August 2016 including all patients satisfying the criteria for ALF (altered mental status, INR ≥ 1.5, duration of illness <26 weeks), in the department of Medicine and Medical Gastroenterology in JIPMER. Results: A total of 84 patients (mean age 38 ± 14.9, 55males) were included in the study, 56 patients (66.66%) survived with medical therapy and 23 patients (27.38%) died in hospital, while 5 patients discontinued hospital admission before the end of treatment and were excluded from the final analysis. Etiology was ascertained in 61 patients (77.21%); Viral hepatitis in 37 patients (46.83%) and Toxin intake in 24 patients (30.37%). The viral hepatitis was due to isolated infections in 21 patients and co-infections 16 patients. Multivariate logistic regression showed that the presence of at least 3 of the following – Creatinine ≥1.5 mg/dL, Platelet count <175,000/mm3, Na+ < 135 mEq/L and Serum albumin < 3 g/dL, predicted the short-term outcome with an accuracy of 84.81%. MELD score ≥ 33 and KCH criteria had a prognostic accuracy of 62.02% and 65.82% respectively. This criteria (AUC, 0.842) was superior to MELD (AUC, 0.655) and KCH criteria (AUC, 0.631) (P = 0.0037 and P = 0.0019 respectively) (Table 1).Table 1Causes of Viral Hepatitis.No.Viral hepatitisTotalSurvivorsNon survivors1.Total373072.HAV alone8803HBV alone6514.HEV alone7525.HAV + HBV8536.HAV + HEV7707.HBV + HEV101 Open table in a new tab Conclusions: Viral hepatitis constitutes nearly one-half of the cases of ALF. Presence at admission of at least 3 of the 4 variables has more accuracy in predicting 28-day patient mortality irrespective of the cause of ALF (Figure 1). The authors have none to declare.

Acetaminophen dose does not predict outcome in acetaminophen-induced acute liver failure.

Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator. Prospective data from 113 patients with ALF having single-time-point ingestions of acetaminophen were analyzed. Multivariate and chi tests were used to determine the relationship of dose to clinical outcome. We also used the Mann-Whitney U test to compare prognosis and survival in ALF with acetaminophen dose ingested. Multivariate and chi analyses failed to show any relationship between acetaminophen dose and spontaneous survival. A separate analysis showed no correlation between acetaminophen dose and clinical prognostic indicators. Dose of acetaminophen ingested did not seem to play a role in prognosis. The most important prognostic factor was coma grade on admission to study. Acetaminophen dosing information is not always obtainable. When it is, it adds little to the clinical assessment. Severity of encephalopathy is a more reliable indicator of prognosis in these critically ill patients.

Update on acute liver failure.

Although advances in critical care management and liver transplantation have improved survival in acute liver failure (ALF), mortality remains significant. An evidence base to support management has been lacking, due to the condition's rarity, severity and heterogeneity. The purpose of this review is to critically appraise the latest evidence, updating clinicians on the current understanding of the best management. Transplant-free survival in acetaminophen-related ALF has improved considerably, such that reconsidering thresholds for transplant is required, perhaps utilizing biomarkers of liver regeneration. Autoimmune hepatitis-related ALF may be too advanced to permit rescue with corticosteroids, which could be deleterious in the sickest patients. Acute kidney injury is commoner in ALF than previously suspected. Intracranial pressure monitoring does not appear to alter mortality. Despite altered traditional indices of coagulation, new thrombin generation assays suggest a rebalanced coagulation in liver failure. Antimicrobial prophylaxis may not be required in all patients. Liver support systems remain controversial and require further evaluation. Traditional dogma in ALF management is questioned: transplant thresholds for acetaminophen overdose, steroid use in autoimmune ALF, routine antimicrobial prophylaxis, the coagulopathy of liver disease, the value of intracranial pressure monitoring and extracorporeal liver support.

Hepatitis E Virus Infection is Associated with Better Survival in Acute Liver Failure

Background and Aims: Acute Liver Failure (ALF) is associated with a high mortality. The difference in outcomes between different etiologies is not clear. We analysed the outcomes of consecutive ALF patients admitted at a single tertiary-care centre over a period of 25 years.

Hepatic encephalopathy: effects of liver failure on brain function

Liver failure affects brain function, leading to neurological and psychiatric alterations; such alterations are referred to as hepatic encephalopathy (HE). Early diagnosis of minimal HE reveals an unexpectedly high incidence of mild cognitive impairment and psychomotor slowing in patients with liver cirrhosis - conditions that have serious health, social and economic consequences. The mechanisms responsible for the neurological alterations in HE are beginning to emerge. New therapeutic strategies acting on specific targets in the brain (phosphodiesterase 5, type A GABA receptors, cyclooxygenase and mitogen-activated protein kinase p38) have been shown to restore cognitive and motor function in animal models of chronic HE, and NMDA receptor antagonists have been shown to increase survival in acute liver failure. This article reviews the latest studies aimed at understanding how liver failure affects brain function and potential ways to ameliorate these effects.

Albumin Dialysis With a Noncell Artificial Liver Support Device in Patients With Acute Liver Failure

Albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be beneficial in acute liver failure (ALF). To determine whether MARS improves survival in ALF. Randomized, controlled trial. (ClinicalTrials.gov: NCT00224705). 16 French liver transplantation centers. 102 patients with ALF. Conventional treatment (n = 49) or MARS with conventional treatment (n = 53), stratified according to whether paracetamol caused ALF. 6-month survival and secondary end points, including adverse events. 102 patients (mean age, 40.4 years [SD, 13]) were in the modified intention-to-treat (mITT) population. The per-protocol analysis (49 conventional, 39 MARS) included patients with at least 1 session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8% to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol population. In patients with paracetamol-related ALF, the 6-month survival rate was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1% to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non-paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ between groups. The short delay from randomization to liver transplantation (median, 16.2 hours) precludes definitive efficacy or safety evaluations. This randomized trial of MARS in patients with ALF was unable to provide definitive efficacy or safety conclusions because many patients had transplantation before administration of the intervention. Acute liver failure not caused by paracetamol was associated with greater 6-month patient survival. Assistance Publique-Hôpitaux de Paris.

Asialoglycoprotein Receptor Scintigraphy with 99mTc-Galactosyl Human Serum Albumin (99mTc-GSA) as an Early Predictor of Survival in Acute Liver Failure

This study evaluated the usefulness of asialoglycoprotein receptor scintigraphy with 99mTc-galactosyl human serum albumin (99mTc-GSA scintigraphy) as an early predictor for prognosis of acute liver failure. Forty-eight patients with acute liver failure and without a past history of chronic liver disease were enrolled. Patients were divided into survival and non-survival groups by 28-day mortality. 99mTc-GSA scintigraphy to detect uptake ratio of the heart at 15 minutes to that at three minutes (HH15) and uptake ratio of the liver at 15 minutes to the liver plus the heart at 15 minutes (LHL15), and measurements of serum total bilirubin, hepatocyte growth factor and prothrombin time were performed immediately after the diagnosis of acute liver failure. Areas under the receiver operating characteristic curves were used to compare the prognostic ability of total bilirubin, hepatocyte growth factor, prothrombin time, HH15 ratio, LHL15 ratio and the model for end-stage liver disease score. Clinical characteristics of patients in the survival group (n=20) and in the non-survival group (n=28) were not significantly different. HH15 and LHL15 uptake ratios in the survival group were 0.670 and 0.875, and they were significantly lower and higher than those in the non-survival group, respectively. All patients with LHL15 <0.760 died, and the area under the receiver operating characteristic curve for LHL15 were significantly larger than the areas under the receiver operating characteristic curves of serum variables and model for end-stage liver disease score. In summary, in patients with acute liver failure without chronic liver disease, HH15 and LHL15 of 99mTc-GSA scintigraphy are more useful variables in predicting prognosis than serum variables and model for end-stage liver disease score.

Effects of N‐acetylcysteine on cytokines in non‐acetaminophen acute liver failure: potential mechanism of improvement in transplant‐free survival

N-Acetylcysteine (NAC) improves transplant-free survival in patients with non-acetaminophen acute liver failure (ALF) when administered in early stages of hepatic encephalopathy. The mechanisms of this benefit are unknown. To determine whether NAC improves transplant-free survival in ALF by ameliorating the surge of pro-inflammatory cytokines. Serum samples were obtained from 78 participants of the randomized, ALF Study Group NAC Trial with grade 1 or 2 hepatic encephalopathy on randomization. Concentrations of ten cytokines, chosen to represent a wide array of inflammatory responses, were determined by multiplex enzyme-linked immunosorbent assay ELISA. In univariate analysis, predictors of transplant-free survival included NAC administration (P=0.012), admission bilirubin (P=0.003), international normalized ratio INR (P=0.0002), grade 1 vs. grade 2 encephalopathy (P=0.006) and lower admission interleukin (IL)-17 concentrations (P=0.011). IL-17 levels were higher in patients with grade 2 vs. grade 1 encephalopathy on randomization (P=0.007) and in those who progressed to grade 3 or grade 4 encephalopathy over the following 7days (P≤0.01). Stepwise multivariate logistic regression analysis identified only NAC administration and lower IL-17 concentrations as independent predictors of transplant-free survival. In patients with detectable IL-17 concentrations on admission, 78% of those who received NAC vs. 44% of those who received placebo had undetectable levels by day 3-5 (P=0.042), and the mean decrease in IL-17 concentrations between admission and late samples was significantly greater in patients who received NAC vs. placebo (P=0.045). N-acetylcysteine (NAC) may improve transplant-free survival in patients with non-acetaminophen ALF by ameliorating the production of IL-17, which is associated with progression of hepatic encephalopathy and poor outcome.