The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease
J Hepatol. 2021 Jun 11;S0168-8278(21)00402-5.doi: 10.1016/j.jhep.2021.05.029.Online ahead of print.
Carolin Lackner1, Rudolf E Stauber2, Susan Davies3, Helmut Denk4, Hans Peter Dienes5, Viviane Gnemmi6, Maria Guido7, Rosa Miquel8, Valerie Paradis9, Peter Schirmacher10, Luigi Terracciano11, Andrea Berghold12, Gudrun Pregartner12, Lukas Binder2, Philipp Douschan2, Florian Rainer2, Stephan Sygulla4, Marion Jager13, Pierre-Emmanuel Rautou13, Andreea Bumbu14, Adelina Horhat14, Ioana Rusu15, Horia Stefanescu14, Sönke Detlefsen16, Aleksander Krag17, Maja Thiele17, Helena Cortez-Pinto18, Christophe Moreno19, Annette S H Gouw20, Dina G Tiniakos21
Author information
1Institute of Pathology, Medical University of Graz, Austria. Electronic address: karoline.lackner@medunigraz.at.
2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
3Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
4Institute of Pathology, Medical University of Graz, Austria.
5Department of Pathology, Medical University of Vienna, Vienna, Austria.
6Université Lille, Canther, Inserm, UMR-S 1277, CHU Lille, Service de Pathologie, Lille, France.
7Department of Medicine - DIMED, University of Padova, Padova, Italy.
8Liver Histopathology Laboratory, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
9Assistance Publique-Hôpitaux de Paris, Service d'Anatomie et de Cytologie Pathologiques, Hôpital Universitaire Beaujon, France; Université Paris Diderot, CNRS, Centre de Recherche sur l'Inflammation (CRI), Paris; Département Hospitalo-Universitaire (DHU) UNITY, Clichy, France.
10Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
11Anatomic Pathology Institute, Humanitas University Research Hospital, Rozzano, (Milano), Italy.
12Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
13Université de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149, Paris, France.
14Liver Unit, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania; Liver Research Club, Cluj-Napoca, Romania.
15University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
16Department of Pathology, Odense University Hospital, Odense C, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense C, Denmark.
17Department of Gastroenterology and Hepatology and OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense C, Denmark; Department of Clinical Research, University of Southern Denmark, Odense C, Denmark.
18Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Portugal.
19Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.
20Dept. of Pathology and Medical Biology, University Medical Center Groningen, Groningen, Netherlands.
21Transitional and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Department of Pathology, Aretaieio Hospital, Medical School, National & Kapodistrian University of Athens, Athens 11528, Greece.
Abstract
Background & aims: The SALVE Histopathology Group (SHG) developed and validated a grading and staging system for the clinical and full histological spectrum of alcohol-related liver disease (ALD) and evaluated its prognostic utility in a multinational cohort of 445 patients.
Methods: SALVE grade was described by semiquantitative scores for steatosis, activity (hepatocellular injury and lobular neutrophils) and cholestasis. The histological diagnosis of steatohepatitis due to ALD (histological ASH, hASH) was based on the presence of hepatocellular ballooning and lobular neutrophils. Fibrosis staging was adapted from the Clinical Research Network staging system for NAFLD and the Laennec staging system and reflects the pattern and extent of ALD fibrosis. There are 7 SALVE fibrosis stages (SFS) ranging from no fibrosis to severe cirrhosis.
Results: Interobserver κ-value for each grading and staging parameter was >0.6. In the whole study cohort long-term outcome was associated with activity grade and cholestasis, as well as cirrhosis with very broad septa (severe cirrhosis) (p<0.001 for all parameters). In decompensated ALD, adverse short-term outcome was associated with activity grade, hASH and cholestasis (p=0.038, 0.012 and 0.001, respectively), whereas in compensated ALD, hASH and severe fibrosis/cirrhosis were associated with decompensation-free survival (p=0.011 and 0.001, respectively). On multivariable analysis, severe cirrhosis emerged as an independent histological predictor of long-term survival in the whole study cohort. Severe cirrhosis and hASH were identified as independent predictors of short-term survival in decompensated ALD, and also as independent predictors of decompensation-free survival in compensated ALD.
Conclusion: The SALVE grading and staging system is a reproducible and prognostically relevant method for the histological assessment of disease activity and fibrosis in ALD.
Lay summary: Patients with alcohol-related liver disease (ALD) may undergo liver biopsy to assess disease severity. We developed a system to classify ALD under the microscope by grading ALD activity and staging the extent of liver scarring and validated its prognostic performance in 445 patients from four European centers.