Journal Article Ahead of print
PubMed: 42467969 DOI: 10.14309/ajg.0000000000004116
Characteristics and outcomes of patients with imaging-defined MASLD and histological steatosis grade S0.
Am J Gastroenterol
Authors: Wen-Yue Liu, Li-You Lian, Seung Up Kim, Terry Cheuk-Fung Yip, Salvatore Petta, Atsushi Nakajima, Emmanuel Tsochatzis, Junping Shi, Wah-Kheong Chan, Jérôme Boursier, Elisabetta Bugianesi, Yusuf Yilmaz, Hannes Hagström, Manuel Romero-Gomez, Khalid Alswat, José Luis Calleja, Hirokazu Takahashi, Victor de Lédinghen, Shalimar, Laurent Castéra, Arun J Sanyal, George Boon-Bee Goh, Philip N Newsome, Jian-Gao Fan, Michelle Lai, Sandeep Aggarwal, Stergios Kechagias, Yoichi Hiasa, Bheesham Dayal, Zhongtao Zhang, Jacob George, Mohamed El-Kassas, Jinjun Chen, Hong You, Barham K Abu Dayyeh, Huiping Sheng, Leon A Adams, Jing Wang, Fangping He, Huiqing Liang, Yong-Feng Yang, Xiaoling Chi, Bihui Zhong, Yan Bi, Yuqiang Mi, Yongfen Zhu, Rixing Bai, Jing Zhang, Bingyuan Wang, Jinghai Song … and 49 other authors
Affiliations
- Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
- Section of Gastroenterology, PROMISE, University of Palermo, Italy.
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
- University College London (UCL) Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK.
- Department of Hepatology, Hangzhou Normal University Affiliated Hospital, Hangzhou, China.
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaysia.
- Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France.
- Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey.
- Department of Medicine, Huddinge, Karolinska Institute, Sweden.
- Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.
- Digestive Diseases Unit and CIBERehd, Virgen Del Rocío University Hospital, Seville, Spain.
- Liver Disease Research Center, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
- Liver Center, Saga University Hospital, Saga, Japan.
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
- Echosens, Paris, France.
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Delhi, India.
- Université Paris Cité, UMR1149 (CRI), INSERM, Paris, France.
- Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris (AP-HP), Clichy, France.
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.
- Institute of Hepatology, Faculty of Life Sciences & Medicine, King's College London and King's College Hospital, London, UK.
- Department of Gastroenterology and Hepatology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
- Institute of Minimal Access, Bariatric, GI and Robotic Surgery, Manipal Hospitals, Dwarka, New Delhi, India.
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden.
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
- Department of Medicine, North Shore University Hospital/Northwell Health, Manhasset, NY, USA.
- Northwell Health Center for Liver Diseases & Transplantation, Manhasset, NY, USA.
- Donald and Barbara Zucker School of Medicine at Hofstra, Hempstead Tpke, Hempstead, NY, USA.
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases & State Key Lab of Digestive Health, Beijing, China.
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, NSW, Australia.
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt.
- Applied Science Research Center. Applied Science Private University, Amman, Jordan.
- Steatotic Liver Disease Study Foundation in Middle East and North Africa (SLMENA), Cairo, Egypt.
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Hepatology, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangzhou, China; Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangzhou, China.
- Liver Research Center, Beijing Friendship Hospital, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Capital Medical University, Beijing, China.
- Division of Gastroenterology and Hepatology, Cedar Sinai Medical Center, Los Angeles, USA.
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Ningxia, China.
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia.
- Medical School, The University of Western Australia, Perth, Australia.
- Department of Hepatobiliary Disease, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.
- Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, China.
- Department of Liver Disease, the Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
- Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.
- Department of Hepatology, Clinical School of the Second People's Hospital, Tianjin Institute of Hepatology, Tianjin Medical University, Tianjin, China.
- Department of Hepatology and Infection, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, China.
- Department of General Surgery, Beijing TianTan Hospital, Capital Medical University, Beijing, China.
- Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
- Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, China.
- Department of General Surgery, Beijing Hospital, National Center of Gerontology, Beijing, China.
Abstract
BACKGROUND AND AIMS
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease, and liver biopsy remains the gold standard for diagnosis. However, a subset of patients diagnosed with MASLD by imaging paradoxically exhibit steatosis grade S0 upon liver biopsy, posing a diagnostic challenge. This study investigates the outcomes and causes of "steatosis 0".
METHODS
"Steatosis 0" was defined as imaging-detected MASLD with a biopsy-defined steatosis grade S0. We used global cohorts to evaluate outcomes, histologic progression via paired biopsies, and possible causes. The cause analysis included MRI-PDFF for fat distribution, pathologist consistency testing, and comparison of serial biopsy sections.
RESULTS
In a follow-up cohort of 3,273 biopsy individuals from 16 centers, 123 (3.8%) exhibited "steatosis 0". Of these, 29.3% of them had advanced fibrosis ("burnt-out" MASLD) and demonstrated a risk of liver-related events, while those without advanced fibrosis had no such events. In the paired-biopsy cohort of 1,865 patients, 74 (4.0%) individuals initially showed steatosis grade S0; among them, 93.2% retained no or mild steatosis on follow-up biopsy. MRI-PDFF assessments in 42 MASLD patients revealed heterogeneous hepatic fat distribution, with some segments showing steatosis grade S0 despite elevated average liver fat. Inter-pathologist variability and discrepancies across consecutive biopsy sections contributed to misclassification of steatosis grade.
CONCLUSION
"Steatosis 0" represents a potential diagnostic gray zone in MASLD. It may be caused by "burnt-out" MASLD, uneven liver fat distribution, or variability in pathological assessment. Understanding the causes and implications of "steatosis 0" is critical for diagnosis and management.
MeSH
Liver Diseases, Gastroenterology, Fibrosis, Pathologists, Biopsy, Liver, Diagnosis