José Altamirano1, Rosa Miquel2, Aezam Katoonizadeh3, Juan G Abraldes4, Andrés Duarte-Rojo5, Alexandre Louvet6, Salvador Augustin7, Rajeshwar P Mookerjee8, Javier Michelena1, Thomas C Smyrk9, David Buob10, Emmanuelle Leteurtre10, Diego Rincón11, Pablo Ruiz1, Juan Carlos García-Pagán12, Carmen Guerrero-Marquez13, Patricia D Jones14, A Sidney Barritt14, Vicente Arroyo1, Miquel Bruguera1, Rafael Bañares11, Pere Ginès1, Juan Caballería1, Tania Roskams3, Frederik Nevens15, Rajiv Jalan8, Philippe Mathurin6, Vijay H Shah16, Ramón Bataller17. 1. Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. 2. Pathology Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. 3. Department of Morphology and Molecular Pathology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium. 4. Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Hepatic Hemodynamic Laboratory, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. 5. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas. 6. Services d'Hepáto-Gastroentérologie, CHRU, Université de Lille, and Faculté de Médecine Pôle Recherche and INSERM Unite 837, Hôpital Huriez, Lille, France. 7. Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 8. UCL Institute of Hepatology, Royal Free Hospital, London, England. 9. Department of Pathology, Mayo Clinic, Rochester, Minnesota. 10. Institut de Pathologie, CHRU, Université de Lille, and Faculté de Médecine Pôle Recherche and INSERM Unite 837, Hôpital Huriez, Lille, France. 11. Liver Unit, Gastroenterology and Hepatology Division, Hospital General Universitario Gregorio Marañon, IISGM, School of Medicine, Universidad Complutense, CIBER de Enfermedades Hepáticas y Digestivas, Madrid, Spain. 12. Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Hepatic Hemodynamic Laboratory, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. 13. Pathology Department, Hospital General Universitario Gregorio Marañon, IISGM, School of Medicine, Universidad Complutense, CIBER de Enfermedades Hepáticas y Digestivas, Madrid, Spain. 14. Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 15. Division of Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium. 16. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. 17. Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain; Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: bataller@med.unc.edu.
Abstract
BACKGROUND & AIMS: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality. METHODS: We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. RESULTS: The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0-3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. CONCLUSIONS: We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making.
BACKGROUND & AIMS: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality. METHODS: We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. RESULTS: The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0-3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. CONCLUSIONS: We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making.
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