Comparing the accuracy of prediction models to detect clinically relevant post-hepatectomy liver failure early after major hepatectomy.

BACKGROUND: Arterial lactate measurements were recently suggested as an early predictor of clinically relevant post-hepatectomy liver failure (PHLF). This needed to be evaluated in the subgroup of major hepatectomies only. METHOD: This observational cohort study included consecutive elective major hepatectomies at Karolinska University Hospital from 2010 to 2018. Clinical risk factors for PHLF, perioperative arterial lactate measurements and routine lab values were included in uni- and multivariable regression analysis. Receiver operating characteristics and risk cut-offs were calculated. RESULTS: In total, 649 patients constituted the study cohort, of which 92 developed PHLF grade B/C according to the International Study Group of Liver Surgery (ISGLS). Lactate reached significantly higher intra- and postoperative levels in PHLF grades B and C compared to grade A or no liver failure (all P < 0.002). Lactate on postoperative day (POD) 1 was superior to earlier measurement time points in predicting PHLF B/C (AUC 0.75), but was outperformed by both clinical risk factors (AUC 0.81, P = 0.031) and bilirubin POD1 (AUC 0.83, P = 0.013). A multivariable logistic regression model including clinical risk factors and bilirubin POD1 had the highest AUC of 0.87 (P = 0.006), with 56.6% sensitivity and 94.7% specificity for PHLF grade B/C (cut-off ≥0.32). The model identified 46.7% of patients with 90-day mortality and had an equally good discriminatory potential for mortality as the established ISGLS criteria for PHLF grade B/C but could be applied already on POD1. CONCLUSION: The potential of lactate to predict PHLF following major hepatectomy was inferior to a prediction model consisting of clinical risk factors and bilirubin on first post-operative day.

Validation of diagnoses of liver disorders in users of systemic azole antifungal medication in Sweden.

BACKGROUND: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment. METHODS: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group. RESULTS: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4-73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4-74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3-99.9%). CONCLUSION: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.

Nationwide Analysis of Adult-Onset Still Disease With and Without Hemophagocytic Lymphohistiocytosis.

INTRODUCTION: Adult-onset Still disease (AOSD) is a rare inflammatory condition with a monophasic, intermittent, or chronic clinical course, and a subset may experience life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH). This study aims to characterize concurrent AOSD and HLH and identify variables independently associated with in-hospital death. METHODS: We performed a medical records review of AOSD with and without HLH from the 2016-2019 National Inpatient Sample database. We performed a multivariable logistic regression analysis for in-hospital death. Results were reported as adjusted odds ratios (OR adj ). RESULTS: There were 5495 hospitalizations with AOSD, of which 340 (6.2%) had HLH. Thirty (9.0%) of the combined AOSD and HLH group died in the hospital compared with 75 (1.5%) of those without HLH. Multivariable analysis in AOSD inpatients showed that disseminated intravascular coagulation (OR adj 6.13), hepatic failure (OR adj 7.16), infection (OR adj 3.72), respiratory failure (OR adj 6.89), and thrombotic microangiopathy (OR adj 14.05) were associated with higher odds of death. However, HLH itself was not an independent predictor of mortality in AOSD population. CONCLUSIONS: HLH occurred in a small minority of inpatients with AOSD. HLH itself was not an independent risk factor for in-hospital death. Disseminated intravascular coagulation, hepatic failure, infection, respiratory failure, and thrombotic microangiopathy were associated with higher odds of in-hospital death in AOSD. Better awareness of these life-threatening complications may improve hospital outcomes.

ALBI score combined with FIB-4 index to predict post-hepatectomy liver failure in patients with hepatocellular carcinoma.

Post-hepatectomy liver failure (PHLF) is a potentially life-threatening complication following liver resection. Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease, which increases the risk of PHLF. This study aimed to investigate the ability of the combination of liver function and fibrosis markers (ALBI score and FIB-4 index) to predict PHLF in patients with HCC. Patients who underwent hepatectomy for HCC between August 2012 and September 2022 were considered for inclusion. Multivariable logistic regression analysis was used to identify factors associated with PHLF, and ALBI score and FIB-4 index were combined based on their regression coefficients. The performance of the combined ALBI-FIB4 score in predicting PHLF and postoperative mortality was compared with Child-Pugh score, MELD score, ALBI score, and FIB-4 index. A total of 215 patients were enrolled in this study. PHLF occurred in 35 patients (16.3%). The incidence of severe PHLF (grade B and grade C PHLF) was 9.3%. Postoperative 90-d mortality was 2.8%. ALBI score, FIB-4 index, prothrombin time, and extent of liver resection were identified as independent factors for predicting PHLF. The AUC of the ALBI-FIB4 score in predicting PHLF was 0.783(95%CI: 0.694-0.872), higher than other models. The ALBI-FIB4 score could divide patients into two risk groups based on a cut-off value of - 1.82. High-risk patients had a high incidence of PHLF of 39.1%, while PHLF just occurred in 6.6% of low-risk patients. Similarly, the AUCs of the ALBI-FIB4 score in predicting severe PHLF and postoperative 90-d mortality were also higher than other models. Preoperative ALBI-FIB4 score showed good performance in predicting PHLF and postoperative mortality in patients undergoing hepatectomy for HCC, superior to the currently commonly used liver function and fibrosis scoring systems.

Evolución de los pacientes con enfermedad hepática crítica / Prognosis of patients with critical hepatic disease

INTRODUCTION: The acute liver failure on chronic (ACLF), is an entity, whose recognition is increasing. The ACLF and CLIF OF indexes have been recently presented with the objective of predicting mortality in this kind of patients. MATERIAL AND METHODS: All patients admitted to the Ramón y Cajal University Hospital diagnosed of acute liver failure on chronic during 2016 and 2017 were collected. We collect the scores: SOFA, CLIF, APACHE II, SAPS II and ACLF score in patients admitted to the ICU by comparing them with each other and define which stages have worse prognosis. RESULTS: A total of 46 patients were collected. The study presents an intra ICU mortality of 31% (15/46) and a six-month mortality of 59.6% (28/46). Patients classified as death, present ACLF values ​​at admission (49.5 vs 60 p = 0.001), and at three days (46.66 vs 59.4 p = 0.001) higher than survivors. In the analysis of the ROC curve, the area under the curve in relation to six-month mortality is higher in the ACLF index (0.8) compared to the MELD (0.69) SOFA (0.66) SAPS II (0.69) or APACHE II (0.65). Patients with ACLF indexes above 65 had an intra UCI mortality of 54%, however, mortality at 6 months is 90%. Patients with ACLF values ​​greater than 65 present mean values ​​of lactic acid, leukocytes, INR or bilirubin higher than those under 65 in a statistically significant manner. CONCLUSIONS: The data presented in this study suggest that the ACLF index works as an adequate predictor of intra-ICU mortality and at 6 months.

INTRODUCCIÓN: El fallo hepático agudo sobre crónico es una entidad cuyo reconocimiento va en aumento. Los índices ACLF y CLIF OF, han sido presentados recientemente con el objetivo de predecir la mortalidad en este tipo de enfermos. MATERIAL Y MÉTODOS: Se recogen todos los pacientes ingresados en una unidad de cuidados intensivos (UCI) de un hospital terciario universitario, diagnosticados de fallo hepático agudo sobre crónico durante 2016 y 2017. Recogemos los índices SOFA, CLIF, APACHE II, SAPS II Y ACLF en pacientes ingresados en UCI comparándolos entre sí. Definimos que estadios presentan peor pronóstico. RESULTADOS: Se analizan un total de 46 pacientes. El estudio presenta una mortalidad intra-UCI del 31% (15/46) y una mortalidad a los seis meses de 59,6% (28/46). Los pacientes clasificados como éxitus presentan valores ACLF al ingreso (49,5 vs 60 p = 0,001), a los tres días (46,66 vs 59,4 p = 0,001) superiores a los supervivientes. En el análisis de la curva COR, el área bajo la curva en relación a la mortalidad a los seis meses, es superior en el índice ACLF (0,8) en comparación con el MELD (0,69) SOFA (0,66) SAPS II (0,69) o APACHE II (0,65). Los pacientes con índices ACLF superiores a 65 presentaban una mortalidad intra-UCI del 54% sin embargo, la mortalidad a los 6 meses es del 90%. Los pacientes con valores ACLF superiores a 65 presentan a su vez valores medios de láctico, leucocitos, INR o bilirrubina mayores de forma estadísticamente significativa. CONCLUSIONES: Los datos presentados en este estudio sugieren que el índice ACLF funciona como un adecuado predictor de mortalidad intra-UCI y a los 6 meses.

Hemocromatosis Neonatal: una causa de fallo hepático in utero: presentación de dos casos y revisión de la bibliografía / Neonatal Hemochromatosis: a cause of liver failure in utero: report of two cases and review of the literature

La hemocromatosis neonatal es una entidad clínico patológicaque presenta fallo hepático grave, se inicia in útero, asociada a siderosis intrahepática y extrahepática, que respeta el sistema reticulo endotelial.Su causa se desconoce pero se debería a un manejo anormal del hierro fetoplacentario con enfermedad hepática perinatal, relación genética familiar o sería consecuencia de una enfermedad gestacional aloinmunitaria. Es un síndrome con características comunes más que una simple entidad patológica, con transmisión materna y alta recurrencia en la misma progenie. La muerte se produceen los primeros días o semanas de vida por fallomultiorgánico. Presentamos dos recién nacidos con hemocromatosis neonatal. El primero falleció por fallo multiorgánico y el segundo permitió el trasplante hepático. Desde 1993, se emplea un cocktail antioxidantequelantedel hierro, junto al tratamiento de soporteestándar del fallo hepático, pero su uso es polémico. En 2002, una comunicación preliminar sugiere que el tratamiento con inmunoglobulinas endovenosas en la segunda mitad de la gestación, en mujeres con el antecedente de un hijo con hemocromatosis neonatal probada, previene las formas recurrentes letales de la enfermedad. Este trastorno se debe sospechar en todo fallo hepático grave al nacer, acompañado de valores séricos de ferritina elevados; pero debe confirmarse por un aumento de los depósitos hepáticos de hierro y siderosis extrahepática demostrables por resonancia magnética nuclear, en la biopsia de glándulas salivales o en la autopsia. La hemocromatosis neonatal es la indicación específicamás frecuente de trasplante hepático en los primeros 3 meses de vida, que parecería ser el tratamiento de elección por considerar desde el momentoque el soporte médico, incluida la terapia antioxidante-quelante del hierro, sea inefectivo, antes de que surjan complicaciones neurológicas irreversibles

Neonatal hemochromatosis is a rare clinical pathologic entity, defined by severe neonatal liver failure of intrauterine onset associated with intra-and extra hepatic siderosis that spares reticuloendothelial system. It is the most frequently recognized cause of liver failure in neonates. The cause is unknown but it may develop secondary to abnormal fetoplacental iron handling or perinatal liver disease or be familial or as a consequence of gestational alloimmune disease. It’s a syndrome with a common feature rather than a single pathologic entity, with maternal transmission and a high recurrence in the sibship. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two newborn with neonatal hemochromatosis. The first died for multiorgan failure, despite aggressive support. The second underwent to liver transplantation. Since 1993, an antioxidant-chelator cocktail has been used in addition to standard supportive care, but this remains controversial. By 2002, a preliminary report suggested that treatment with weekly intravenous immunoglobulin during the later half of pregnancy, for woman whose most recent gestation was affected with proven NH. The diagnosis is suspected in the presence of severely impaired hepatic synthetic function accompanied by high serum ferritin levels, but is confirmed only by demonstration of increased hepatic iron stores, and extra-hepatic siderosis shown by autopsy or in vivo, which can be achieved by biopsy of the minor salivary glands or magnetic resonance imaging. Neonatal hemochromatosis is the most common specific indication for liver transplantation in the first three months of life and appears to be the treatment of choice, and must as well be considered as soon as it becomes apparent that medical support, which should include chelation-antioxidant treatment, is ineffective, before irreversible neurological complications appear.