King's College Hospital Criteria Research Articles

Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model.

Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. Not applicable as this is a retrospective study.

Developing a mathematical model for early detection of viral hepatitis induced liver dysfunction

Acute liver failure (ALF) is characterized by a sudden loss of hepatic function within a few weeks without pre-existing cirrhosis or prior history of liver disease. ALF can be difficult to identify using non-invasive methods such as coagulation abnormality and encephalopathy alone as alternative causes may confound the ALF diagnostic. This often results in delayed treatment at the onset of the disease, and a liver transplant might be the only option for ALF patients with a limited success rate. Due to these variables, ALF treatment is highly subjective to the clinicians' expertise, with a very high morbidity and mortality rate. Therefore, a prognostic model can help identify patients who can be managed with medical treatments and those who need liver transplants, along with an optimum intervention time window. Currently, only statistical models are available to identify ALF, such as King's College Hospital criteria, Clichy criteria, and End-Stage Liver Disease score. While these models provide much-needed critical support to clinicians, these models have limited specificity and sensitivity toward the cause of ALF and liver disease progression. For example, among all the common causes, the viral hepatitis-induced liver disease remains a major cause of ALF in developing countries such as in India and Bangladesh. Therefore, a dynamic patient-specific model is needed to improve patient care by correlating liver dysfunction with various healthcare variables and interventions. In this work, a new physiological linked data-driven model is formulated that can track the progression of liver disease and failure due to viral hepatitis. The approach relies on integrating the dynamics of healthy hepatocytes with immune system response, which is a vital component in tracking the time-sensitive infectious disease progression. The model uses the patient-specific measured values of alanine transaminase and aspartate transaminase enzymes and the clinically calculated international normalized ratio value to estimate the sensitive model parameter. This patient-specific model is then used to determine the disease progression by predicting the number of damaged hepatocytes and correlating it with the indication criteria for liver transplantation. The model can reproduce the essential dynamics seen in the ALF patient data and can be adapted to incorporate the effect of different therapeutic interventions. Thus, providing a vital bridge between understanding and treating viral hepatitis-induced liver dysfunction. No conflicts of interest, financial or otherwise, are declared by the author. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute Liver Failure Prognostic Criteria: It's Time to Revisit.

Acute liver failure (ALF) is a devastating disease, and patients are at a higher risk of death without liver transplantation. Indicators are needed to identify the risk of death in ALF, which will help in the timely referral of patients to specialized centers. Clichy criteriaand King's College Hospital (KCH) criteria are the most widely used prognostic criteria. Real-life application of Clichy criteria is limited due to the non-availability of factor V level measurement. KCH criteria have good specificity but low sensitivity to predict outcomes. Therefore, we attempted to use the model for end-stage liver disease (MELD) score and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in ALF patients as prognostic indicators and need for liver transplantation. Forty-one patients with ALF were enrolled in the study. On the day of admission, MELD and CLIF-SOFA scores were calculated for each patient. Area under receiver operating characteristics (AUROC) curve, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy (DA) of MELD and CLIF-SOFA score were calculated to predict the outcome of the patients. Out of 41 patients, nine patients left against medical advice. The sensitivity, specificity, PPV, NPV, and DA for the MELD score of enrolled patients in the study were 81.5%, 62.5%, 59.5%, 83.3%, 70.1%, and for the CLIF-SOFA score of enrolled patients in the study were 88.9%, 90.0%, 85.7%, 92.3%, 89.6% respectively. Patients who did not survive had higher INR, MELD, CLIF-SOFA scores, and hepatic encephalopathy (HE) grades. Five patients who had a combination of MELD ≥30 and CLIF-SOFA ≥10, expired. In our study, we used MELD score and CLIF-SOFA as prognostic markers, and we concluded that CLIF-SOFA is a better predictor of mortality than MELD score in terms of sensitivity, specificity, NPV, PPV, and diagnostic accuracy. AUROC for CLIF-SOFA score is higher when compared to the MELD score.

Changes in platelet levels and prognosis in patients with acute liver failure and late-onset hepatic failure

The therapeutic strategies for acute liver failure (ALF) and late-onset hepatic failure (LOHF) still have room for improvement. Recent studies have reported an association between platelets and the pathophysiology of ALF. In this study, we investigated changes in platelet levels and clinical findings in ALF and LOHF patients. We retrospectively investigated the clinical data of 62 patients with ALF and LOHF. We analyzed the association between changes in platelet levels for 7 days after admission and the prognosis in patients with ALF and LOHF. The factors associated with changes in platelet levels were also analyzed. The platelet levels on days 1, 3, and 7 were significantly lower in the patients who died or underwent liver transplantation than in the spontaneous survivors. Administration of recombinant thrombomodulin was associated with spontaneous survival. The platelet levels in patients who met the King's College Hospital Criteria or the Japanese scoring system (JSS) for ALF ≥ 4 were significantly decreased 7 days after admission. The area under the receiver operating characteristic curve (AUROC) of a JSS score of 3 for predicting low platelet levels on day 7 was 0.903. Decreased platelet levels were associated with poor prognosis in patients with ALF and LOHF. The patients with low platelet levels and JSS scores on admission showed a high AUROC for predicting low platelet levels on day 7. Decreased platelet levels after admission may be a simple prognostic marker in ALF and LOHF patients.

Pediatric acute liver failure: An experience of a pediatric intensive care unit from resource limited settings.

IntroductionPediatric acute liver failure is a rare and serious disease. Though liver transplantation is considered as the established treatment option for patients who are unlikely to recover with medical management, however, with the advancement of medical care there has been an increase in spontaneous regeneration of liver, obviating the need for liver transplantation. We identified the etiologies, outcome and prognostic factors of acute liver failure and the validity of the existing liver transplantation criteria to predict the outcome of pediatric acute liver failure.Materials and methodsThis was a retrospective study done from January 2014 to December 2019 in a tertiary pediatric critical care unit in South India. All children aged between 1 month to 18 years admitted with acute liver failure were enrolled.ResultsOf 125 children with acute liver failure, the main etiologies were infections (32%), indeterminate (23%), paracetamol toxicity (21%), metabolic (13%) and others (11%). Dengue was the most common infection (55%). The median pediatric logistic organ dysfunction score at admission was 12 (4–27). Of 125 patients, 63.2% (n = 79) had spontaneous regeneration which was higher in paracetamol induced (92.3%) compared to non-paracetamol induced acute liver failure (55.5%). Only two patients underwent liver transplantation and 35% died. Peak alanine transaminase and use of inotropes significantly predicted the outcome of disease. Of 38 children meeting King's College Hospital criteria for liver transplantation, 57.9% had spontaneous regeneration and 36.8% died. Of 74 children meeting INR > 4 criteria, 54% (n = 40) had spontaneous regeneration and 43.2% died. INR >4 criteria was more sensitive than King's College Hospital criteria for predicting the need for liver transplantation.ConclusionPediatric acute liver failure is caused by varied etiologies and infections were the commonest cause. Despite having a seriously ill cohort of patients, medical management resulted in spontaneous regeneration in the majority of children with acute liver failure. The use of inotropes, advanced hepatic encephalopathy, and peak alanine transaminase were predictors of poor outcome in children with acute liver failure and these patients could be considered for liver transplantation as available. Therefore, we may need to develop better predictors of pediatric acute liver failure in resource limited settings.

Coagulation Factors as Predictive Markers of Poor Outcomes in Children with Acute Liver Failure.

In children, acute liver failure (ALF) is a severe condition associated with high mortality if an emergency liver transplantation (LT) is impossible. Clinical laboratory parameters and different scores or criteria are used to predict ALF evolution in children. We aimed to assess the role of coagulation factors as predictive markers of poor outcomes in children with ALF. The prospective study included 40 children with ALF, diagnosed based on the Pediatric ALF study group criteria. Patients with emergency LT or deceased were considered with poor outcomes. For all patients, we analyzed clinical and laboratory parameters (including plasma level of factor V (FV), factor VII (FVII), and INR). We calculated the PELD (Pediatric End-stage Liver Disease) and MELD (Model for End-stage Liver Disease) scores, King's College Hospital (KCH), and Clichy criteria. We analyzed their performance in predicting a poor outcome. FV and FVII levels were significantly lower in children with poor outcomes than survivors (18.92 ± 19.95% vs. 10.72 ± 10.21%, p = 0.00139, respectively 46.51 ± 26.05% vs. 10.72 ± 10.21%, p = 0.00014). These parameters varied with ALF etiology, being the lowest in metabolic and infectious causes. The maximum value of INR (INR-max) was higher in children with poor outcomes than survivors (7.05 ± 3.20 vs. 2.96 ± 1.82, p = 0.000007), as it also was for the PELD/MELD score (30.06 ± 15.55 vs. 15.77 ± 9.64, p = 0.00092). FVII, FV, and INR-max had an excellent performance in predicting the poor outcome with an area under the ROC curve of 0.894, 0.816, and 0.861, respectively. KCH criteria had a higher sensitivity than Clichy criteria (92.86% vs. 50%) but lower specificity (53.85% vs. 95%). Our results support the role of coagulation factors (INR, FV, and FVII) as predictive markers for the fatal evolution of children with ALF and underlined the need for monitoring along with the usual liver function tests in children with ALF.

Predicting mortality from acetaminophen poisoning shortly after hospital presentation.

Early identification of patients likely to die after acetaminophen (APAP) poisoning remains challenging. We sought to compare the sensitivity and time to fulfilment (latency) of established prognostic criteria. Three physician toxicologists independently classified every in-hospital death associated with APAP overdose from eight large Canadian cities over three decades using the Relative Contribution to Fatality scale from the American Association of Poison Control Centres. The sensitivity and latency were calculated for each of the following criteria: King's College Hospital (KCH), Model for End Stage Liver Disease (MELD) ≥33, lactate ≥3.5 mmol/L, phosphate ≥1.2 mmol/L 48+ hours post-ingestion, as well as combinations thereof. A total of 162 in-hospital deaths were classified with respect to APAP as follows: 26 Undoubtedly, 40 Probably, 27 Contributory, 14 Probably not, 25 Clearly not, and 30 Unknown. Cases from the first three classes (combined into n = 93 "APAP deaths") typically presented with supratherapeutic APAP concentrations, hepatotoxicity, acidaemia, coagulopathy and/or encephalopathy, and began antidotal treatment a median of 12 hours (IQR 3.4-30 h) from the end of ingestion. Among all patients deemed "APAP deaths", meeting either KCH or lactate criteria demonstrated the highest sensitivity (94%; 95% CI 86-98%), and the shortest latency from hospital arrival to criterion fulfilment (median 4.2 h; IQR 1.0-16 h). In comparison, the MELD criterion demonstrated a substantially lower sensitivity (55%; 43-66%) and longer latency (52 h; 4.4-∞ h, where "∞" denotes death prior to criterion becoming positive). Meeting either KCH or serum lactate criteria identifies most patients who die from acetaminophen poisoning at or shortly after hospital presentation.

Role of therapeutic plasma exchange in acute liver failure due to yellow phosphorus poisoning.

BackgroundTherapeutic plasma exchange (TPE) has been utilized in various liver disorders. There is limited data on the efficacy of TPE in patients with acute liver failure (ALF).MethodsStudy group consisted of patients who underwent TPE for ALF due to yellow phosphorous poisoning (YPP) between 2015 and 2019. Demographic data and biochemical parameters were recorded before and after TPE. Overall survival and transplant-free survival (based on King’s College Hospital Criteria [KCHC]) were analyzed.ResultsForty-three patients underwent TPE for ALF due to YPP. Most of them were young males. Overall survival was 34 (79.06%). In our study population, 20 patients fulfilled KCHC (Group A) and 23 did not fulfill KCHC (Group B). Both the groups showed significant improvement in alanine aminotransferase, aspartate aminotransferase, and international normalized ratio (INR) after TPE (p < 0.05). In Group B, there was significant improvement in ammonia after TPE (p < 0.05) and all 23 patients (100%) survived after TPE. In Group A, 4 underwent liver transplantation (LT), 7 survived without LT, and the remaining 9 died without LT. Mean survival after completing TPE was 41.2 ± 44.5 days in Group A and 90 days in Group B. This difference was statistically significant (p = 0.001). There was statistically significant difference in post-TPE values of INR (p = 0.012) and ammonia (p = 0.011) between non-survivors and survivors. Adverse events such as hypotension (11.62%) and minor allergic reaction (4.65%) were managed conservatively.ConclusionTPE is an effective procedure in ALF due to YPP, not fulfilling KCHC for LT. In KCHC fulfilled group, though it shows LT-free survival benefit, there is requirement of prospective, large volume, multi-center study to assess its efficacy.

Liver Transplant in Acute Liver Failure – Looking Back Over 10 Years

Acute liver failure (ALF) is the leading cause for emergency liver transplantation (LT) all over the world. We looked at the profile of cases who required LT for ALF from a single centre to identify the possible predictors of poor outcomes. During the 10-year period starting from 2007, 320 cases of ALF were treated at our institution, of which 70 (median age 24 years, Male:Female 1:2) underwent LT. Retrospective analyses of these 70 patients were performed. Etiology was identifiable in 73% (n=51) of cases (yellow phosphorous [YP] poisoning [n= 16], Hepatitis A virus [HAV] [n= 15], Hepatitis B virus [HBV] [n= 5], Hepatitis E virus [HEV] [n= 1], anti-tubercular therapy [ATT] induced [n=6], acute Wilson's [n= 3], and autoimmune [n= 5]]. Upon meeting King's College Hospital criteria, 69 had live donor LT (61 right lobe grafts, three left lobe grafts, five leftlateral segment grafts) and one had deceased donor LT. Among these, there were five auxiliary partial orthotopic grafts and four ABO-incompatible transplants. Overall, 90-day mortality was 35.7% (n= 25), predominantly due to sepsis. Significant risk factors for mortality on multivariate analysis included indeterminate etiology, pre-op renal dysfunction, and Grade IV hepatic encephalopathy (HE). Cumulative 10-year survival of the remaining survivors was 95.6% (n= 45). LT for ALF carries high perioperative mortality (35.7%) in those presenting with indeterminate etiology, pre-op renal dysfunction, and Grade IV HE. Nevertheless, if they survive the perioperative period, long-term survival is excellent.

Outcome of Acetaminophen-Induced Acute Liver Failure Managed Without Intracranial Pressure Monitoring or Transplantation.

Acetaminophen-induced acute liver failure (ALF) may require emergency liver transplantation (LT) in the presence of specific criteria, and its management may also include intracranial pressure (ICP) monitoring in selected patients at high risk of cerebral edema. We aimed to test the hypothesis that management of such patients without ICP monitoring or LT would yield outcomes similar to those reported with conventional management. We interrogated a database of all patients treated in an intensive care unit for acetaminophen-induced ALF between November 2010 and October 2016 and obtained relevant information from electronic medical records. We studied 64 patients (58 females) with a median age of 38 years. Such patients had a high prevalence of depression, substance abuse, or other psychiatric disorders and had ingested a median acetaminophen dose of 25 g. No patient received ICP monitoring or LT. Overall, 51 (79.7%) patients survived. Of the 42 patients who met King's College Hospital (KCH) criteria, 29 (69.0%) survived without transplantation. There were 45 patients who developed severe hepatic encephalopathy, and 32 (71.1%) of these survived. Finally, compared with the KCH criteria, the current UK Registration Criteria for Super-Urgent Liver Transplantation (UKRC) for super-urgent LT had better sensitivity (92.3%) and specificity (80.4%) for hospital mortality. In conclusion, in a center applying a no ICP monitoring and no LT approach to the management of acetaminophen-induced ALF, during a 6-year period, overall survival was 79.7%, and for patients fulfilling KCH criteria, it was 69.0%, which were both higher than for equivalent patients treated with conventional management as reported in the literature. Finally, the current UKRC may be a better predictor of hospital mortality in this patient population.

Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

IntroductionKing’s College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation.MethodsWe analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility.Results152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%).ConclusionALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation.

Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines on the Prediction of Liver Transplantation.

Determining the indications for and timing of liver transplantation (LT) for acute liver failure (ALF) is essential. The King's College Hospital (KCH) guidelines and Japanese guidelines are used to predict the need for LT and the outcomes in ALF. These guidelines' accuracy when applied to ALF in different regional and etiological backgrounds may differ. Here we compared the accuracy of new (2010) Japanese guidelines that use a simple scoring system with the 1996 Japanese guidelines and the KCH criteria for living donor liver transplantation (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub-acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the accuracies of the 3 guidelines' criteria for ALF. The overall 1-year survival rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new Japanese guidelines could identify 13 acute-type ALF patients for LT, based on the timing of encephalopathy onset. Using the previous Japanese guidelines, although the same 13 acute-type ALF patients (72%) had indications for LT, only 4 patients were indicated at the 1st step, and it took an additional 5 days to decide the indication at the 2nd step in the other 9 cases. Our findings showed that the new Japanese guidelines can predict the indications for LT and provide a reliable alternative to the previous Japanese and KCH guidelines.

Acute Liver Failure Due to Hepatitis E Virus Infection Is Associated with Better Survival than Other Etiologies in Indian Patients.

Hepatitis E virus (HEV) is a global disease and an important cause of acute liver failure (ALF) in the Indian subcontinent. The aim of this study was to assess the differences in the course of HEV-ALF as compared to other etiologies of ALF. We compared the clinical course, complications, and outcomes of HEV-ALF with other etiologies. We assessed the prognostic factors and compared existing prognostic scores in HEV-ALF patients. One thousand four hundred and sixty-two ALF patients were evaluated between January 1986 and December 2015. HEV was the etiology of ALF in 419 (28.7%) cases, whereas non-A non-E hepatitis, HBV and anti-tuberculosis therapy (ATT) were the etiologies in 527 (36.0%), 128 (8.8%), and 103 (7.0%) cases, respectively. The frequency of cerebral edema in HEV-ALF (41.3%) was lower than that in non-A non-E ALF (52.9%; P<0.001) and HBV-ALF (52.8%; P=0.024). Infection and seizures were significantly less in patients with HEV-ALF compared to non-A non-E and HBV-ALF (P=0.038 and 0.022, respectively). The survival of HEV-ALF patients was significantly better (55.1%, P<0.001) than patients of other etiologies-including ATT (30.0%), non-A non-E (38.1%) and HBV (35.9%). In HEV-ALF patients, age, female sex, cerebral edema, prothrombin time >60s, infection, and total bilirubin were observed as independent predictors of outcome on multivariate logistic regression analysis. Model for end-stage liver disease, acute liver failure study group model and King's College Hospital criteria had poor discriminative accuracy for outcome (area under receiver operator characteristic curve 0.63-0.64) in HEV-ALF. Hepatitis E virus-associated ALF has a better outcome than ALF of other etiologies.

Acute liver failure caused by mushroom poisoning: still a fork in the road

See Article on Page 1043

Indocyanine green clearance test combined with MELD score in predicting the short-term prognosis of patients with acute liver failure

Acute liver failure (ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease (MELD) scores and King's College Hospital (KCH) criteria are well-accepted as predictive tools, their accuracy is unsatisfactory. The indocyanine green (ICG) clearance test (ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH criteria. Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of diagnosis. In addition, the MELD scores and KCH criteria were calculated. The three-month mortality of all patients was 47.83%. Age, serum total bilirubin and creatinine concentrations, international normalized ratio for prothrombin time, ICGR15, MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores (r=0.328, P=0.006). The ICGR15-MELD model, Logit(P)=0.096XICGR15+0.174XMELD score-9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to -0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model (0.855) was significantly higher than that of the ICGR15 (0.793), MELD scores (0.776) and KCH criteria (0.659). Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group (ICGR15-MELD≥-0.4686) and 13.33% in the second group (ICGR15-MELD<-0.4686), with a significant difference between the two groups (X(2)=25.307, P=0.000). The ICGR15-MELD model is superior to the ICGR15, MELD scores, and KCH criteria in predicting the short-term prognosis of patients with ALF.

Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure

BackgroundAn acetominophen overdose (AOD) is the leading cause of acute liver failure (ALF) in the UK and USA. For patients who meet the King's College Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver transplantation (OLT) is conventionally performed with subsequent life-long immunosuppression. A new technique was developed in 1998 for AOD-induced ALF where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft auxiliary liver transplant (WGALT) was performed with complete withdrawal of immunosupression during the first year post-operatively. ResultsDuring 1998–2010, 68 patients were listed for an emergency transplantation for AOD ALF at our institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5 years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off immunosuppression. Poor prognostic factors in the WGALT group included higher donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54kg, P = 0.036). ConclusionAlthough OLT remains standard practice for AOD-induced ALF, life-long immunosuppression is required. A favourable survival rate using a subtotal hepatectomy and WGALT has been demonstrated, and importantly, all successful patients have undergone complete immunosuppression withdrawal. This technique is advocated for patients who have acetominophen hepatotoxicity requiring liver transplantation.

Prognostic indicators for acute liver failure development and mortality in patients with hepatitis A: consecutive case analysis.

PurposeDue to the seroepidemiological shift in hepatitis A (HA), its severity, mortality, and complications have increased in recent years. Thus, the aim of this study was to identify predictive factors associated with poor prognosis among patients with HA.Materials and MethodsA total of 304 patients with HA admitted to our institution between July 2009 and June 2011 were enrolled consecutively. Patients with complications defined as acute liver failure (ALF) were evaluated, and mortality was defined as death or liver transplantation.ResultsThe mean age of patients (204 males, 100 females) was 32 years. Eighteen (5.9%) patients had progressed to ALF. Of the patients with ALF, 10 patients (3.3%) showed spontaneous survival while 8 (2.6%) died or underwent liver transplantation. Multivariate regression analysis showed that Model for End-Stage Liver Disease (MELD) and systemic inflammatory response syndrome (SIRS) scores were significant predictive factors of ALF. Based on receiver operating characteristics (ROC) analysis, a MELD ≥23.5 was significantly more predictive than a SIRS score ≥3 (area under the ROC: 0.940 vs. 0.742, respectively). In addition, of patients with a MELD score ≥23.5, King's College Hospital criteria (KCC) and SIRS scores were predictive factors associated with death/transplantation in multivariate analysis.ConclusionMELD and SIRS scores ≥23.5 and ≥3, respectively, appeared to be related to ALF development. In addition, KCC and SIRS scores ≥3 were valuable in predicting mortality of patients with a MELD ≥23.5.

Prognostic Value of Model for End-Stage Liver Disease Scores in Patients with Fulminant Hepatic Failure

BackgroundThis study was undertaken to investigate risk factors of mortality in patients with fulminant hepatic failure (FHF). MethodsFifty-three patients with FHF treated from January 2006 to April 2011 were allocated to a spontaneous survival group (group 1), a death without liver transplantation (LT) group (group 2), and an LT group (group 3). To analyze risk factors associated with mortality in FHF, we excluded group 3 patients. Clinical features, Model for End-Stage Liver Disease (MELD) scores, and King's College Hospital criteria at the time of hepatic encephalopathy in group 2 were compared with those of group 1. ResultsThe causes of FHF were acute viral infection (n = 29, hepatitis A:B, 28:1), drugs (n = 18; including 4 acetaminophen and 14 herbal medication), autoimmune (n = 4), and miscellaneous (n = 2). Of the 53 patients, 19 were allocated to group 1, 18 to group 2, and 16 to group 3. According to univariate analysis, risk factors for mortality in group 2 were acute renal failure requiring renal replacement therapy and a MELD score ≥30 at the time of hepatic encephalopathy. However, by multivariate analysis, a MELD score ≥30 was the only independent risk factor for mortality in group 2 (P = .042; hazard ratio, 4.500). ConclusionsA MELD score ≥30 was found to be the only independent risk factor of mortality in FHF patients without LT. Therefore, the findings of this study suggest that these patients may need emergent LT for survival.

APACHE III Score Is Superior to King's College Hospital Criteria, MELD score and APACHE II Score to Predict Outcomes After Liver Transplantation for Acute Liver Failure

ObjectivesThe Model for End–Stage Liver Disease score and king's College Hospital (KCH) criteria are accepted prognostic models acute liver failure (ALF), while the use of (APACHE) scores predict to outcomes of emergency liver transplantation is rare. Materials and MethodsThe present study included 87 patients with ALF who underwent liver transplantation. We calculated (KCH) criteria, as well as MELD, APACHE II, and APACHE III scores at the listing date for comparison with 3-month outcomes. ResultsAccording to the Youden-Index, the best cut-off value for the APACHE II score was 8.5 with 100% sensitivity, 49% specificity, 24% positive predictive value (PPV), and 100% negative predictive value (NPV). Patients with <8.5 points had a significantly higher survival rate (P < .05). The proposed APACHE III cut-off was 80. The APACHE III score demonstrated the highest specificity and PPV (90% specificity, 50% PPV). The NPV was 92%. With a 90-point threshold the specificity increased to 98% with 75% PPV and 89% NPV. Only 1 of 4 patients with a score >90 survived transplantation (P = .001). MELD score and KCH criteria were not significant (P > .05). According to the Hosmer-Lemeshow test, only the APACHE III score adequately describe the data. ConclusionsThe APACHE III score was superior to KCH criteria, MELD score, and APACHE II score to predict outcomes after transplantation for ALF. It is a valuable parameter for pretransplantation patient selection.

King's College Hospital Criteria for Non-Acetaminophen Induced Acute Liver Failure in an International Cohort of Children

To validate King's College Hospital criteria (KCHC) in children with non-acetaminophen induced pediatric acute liver failure (PALF) and to determine whether re-optimizing the KCHC would improve predictive accuracy. We used the PALF study group database. Primary outcomes were survival without liver transplantation vs death at 21 days following enrollment. Classification and regression tree analysis was used to determine if modification of KCHC parameters would improve classification of death vs survival. Among 163 patients who met KCHC, 54 patients (33.1%) died within 21 days. Sensitivity of KCHC in this cohort was significantly lower than in the original study (61% vs 91%, P = .002), and specificity did not differ significantly. The positive predictive value (PPV) and negative predictive value (NPV) of KCHC for this cohort was 33% and 88% respectively. Classification and regression tree analysis yielded the following optimized parameters to predict death: grade 2-4 encephalopathy, international normalized ratio >4.02, and total bilirubin >2.02 mg/dL. These parameters did not improve PPV, but NPV was significantly better (88% vs 92%, P < .0001). KCHC does not reliably predict death in PALF. With a PPV of 33%, twice as many participants who met KCHC recovered spontaneously than died, indicating that using KCHC may cause over utilization of liver transplantation. Re-optimized cutpoints for KCHC parameters improved NPV, but not PPV. Parameters beyond the KCHC should be evaluated to create a predictive model for PALF.