ABSTRACT
BACKGROUND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence (AI) in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled AH patients per NIAAA criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day post-admission mortality, three AI algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined via Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce post-test probabilities. The ALCoholic Hepatitis Artificial INtelligence (ALCHAIN) Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30-day) and 27.9% (90-day) in the derivation cohort, versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779 - 0.844) and 0.799 (0.769 - 0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, MELD variations, ABIC, Glasgow, and modified Glasgow Scores (p<0.001). ALCHAIN Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCHAIN Ensemble score>0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing AI within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/.
ABSTRACT
BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).
Subject(s)
Alcohol Drinking/adverse effects , Hepatitis/drug therapy , Steroids/administration & dosage , Time Factors , Adult , Alcohol Drinking/drug therapy , Alcohol Drinking/physiopathology , Cohort Studies , Female , Hepatitis/etiology , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Steroids/therapeutic useABSTRACT
Resumen El objetivo de este trabajo es de estudiar y determinar retrospectivamente las causas y la frecuencia de presentación de la hemorragia digestiva baja , en pacientes del I.G.B.J, demostrado por endoscopía en un periodo de tiempo de 25 años. Se estudiaron 3591 pacientes (1275 mujeres y 1245 hombres), con diagnóstico de hemorragia digestiva baja, diagnóstico que se hizo en base a datos que fueron recolectados de la historia clínica y hallazgos endoscópicos. Se revisaron un total de 8314 procedimientos endoscópicos bajos, en un período de tiempo comprendido entre enero de 1979 a diciembre de 2005 realizados en el I.G.B.J, de Cochabamba, correspondientes a estudios endoscópicos de pacientes internados u ambulatorios, de diferente edad, sexo y patología. De estos 3591 (43,2%) presentan diagnóstico de HDB, de los cuales 2520 procedimientos (70,2%) son patológicos y 1071 procedimientos (29,8%) fueron normales. De los 2520 pacientes de nuestro estudio, el 49.4% son varones (1245 pacientes), y el 50,6% son mujeres (1275 pacientes). Las lesiones vasculares de tubo digestivo bajo como son las hemorroides, lesiones vasculares y proctitis actínica constituyen el mayor porcentaje causante de HDB, 975 pacientes (38,6%), cuya etiología difiere según frecuencia y según grupo etéreo de lo reportado en la literatura. El índice de mortalidad encontrado es del orden de 0.2 % significativamente menor al de la literatura que es del 5 % , esto probablemente a que en nuestro medio la casuística es menor. Se espera que el presente estudio sea el punto de partida para elaborar nuestro propio protocolo de manejo en nuestro hospital.
Abstract This work is a retrospective study and determine the causes and frequency of lower gastrointestinal bleeding in patients I.G.B.J demonstrated by endoscopy in a period of 25 years. We studied 3591 patients (1275 women and 1245 men), diagnosed with lower gastrointestinal bleeding, that diagnosis was based on data that were collected on clinical history and endoscopio findings. We reviewed a total of8314 low endoscopio procedures, in a period oftime from January 1979 to December 2005 in the I.G.B.J Cochabamba, endoscopio studies for inpatient or outpatient, in a different age, sex and pathology. Ofthese 3591 (43.2%) present diagnosis of HDB, ofwhich 2520 procedures (70.2%) are pathological and 1071 procedures (29.8%) were normal. Ofthe 2520 patients in our study, 49.4% are male (1245 patients) and 50.6% are women (1275 patients). The vascular lesions alimentary canal are as low as hemorrhoids, vascular lesions and ra diation proctitis constitute the largest cause of HDB, 975 patients (38.6%), whose etiology differs according to age group and as often as reported in the literature. The mortality rate isfound in the orderofO.2% significantly lower than in the literature that is 5%, this probably because in our case mix is lower. It is hoped that this study is the starting point for developing our own management protocol in our hospital.
