A histologic scoring system for prognosis of patients with alcoholic hepatitis.
OBJECTIVE
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.
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
José
J
Altamirano
Pathology Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
Rosa
R
Miquel
Department of Morphology and Molecular Pathology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
Aezam
A
Katoonizadeh
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.
Juan G
JG
Abraldes
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Andrés
A
Duarte-Rojo
Services d'Hepáto-Gastroentérologie, CHRU, Université de Lille, and Faculté de Médecine Pôle Recherche and INSERM Unite 837, Hôpital Huriez, Lille, France.
Alexandre
A
Louvet
Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Salvador
S
Augustin
UCL Institute of Hepatology, Royal Free Hospital, London, England.
Rajeshwar P
RP
Mookerjee
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
Javier
J
Michelena
Department of Pathology, Mayo Clinic, Rochester, Minnesota.
Thomas C
TC
Smyrk
Institut de Pathologie, CHRU, Université de Lille, and Faculté de Médecine Pôle Recherche and INSERM Unite 837, Hôpital Huriez, Lille, France.
David
D
Buob
Institut de Pathologie, CHRU, Université de Lille, and Faculté de Médecine Pôle Recherche and INSERM Unite 837, Hôpital Huriez, Lille, France.
Emmanuelle
E
Leteurtre
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.
Diego
D
Rincón
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
Pablo
P
Ruiz
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.
Juan Carlos
JC
García-Pagán
Pathology Department, Hospital General Universitario Gregorio Marañon, IISGM, School of Medicine, Universidad Complutense, CIBER de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
Carmen
C
Guerrero-Marquez
Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Patricia D
PD
Jones
Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
A Sidney
AS
Barritt
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
Vicente
V
Arroyo
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
Miquel
M
Bruguera
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.
Rafael
R
Bañares
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
Pere
P
Ginès
Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBER de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
Juan
J
Caballería
Department of Morphology and Molecular Pathology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
Tania
T
Roskams
Division of Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
Frederik
F
Nevens
UCL Institute of Hepatology, Royal Free Hospital, London, England.
Rajiv
R
Jalan
Services d'Hepáto-Gastroentérologie, CHRU, Université de Lille, and Faculté de Médecine Pôle Recherche and INSERM Unite 837, Hôpital Huriez, Lille, France.
Philippe
P
Mathurin
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Vijay H
VH
Shah
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.
Ramón
R
Bataller
D000328:Adult; D001663:Bilirubin / Q000032:analysis; D001706:Biopsy; D016009:Chi-Square Distribution; D003661:Decision Support Techniques; D005060:Europe; D005260:Female; D006519:Hepatitis, Alcoholic / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000737:chemistry / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000473:pathology; D053142:Mitochondrial Size; D015999:Multivariate Analysis; D020556:Neutrophil Infiltration; D015588:Observer Variation; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014481:United States
D001663:Bilirubin
Alcoholic Hepatitis; Alcoholic Liver Disease; Histologic Classification; Liver Biopsy