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Abstract Details
Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
Hepatology. 2021 Apr 3. doi: 10.1002/hep.31845. Online ahead of print.
Tracey G Simon123, Bjorn Roelstraete4, Rajani Sharma56, Hamed Khalili123, Hannes Hagström78, Jonas F Ludvigsson491011
Author information
1Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, USA.
2Harvard Medical School, Boston, USA.
3Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, USA.
4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
5Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons.
6Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University Irving Medical Center.
7Division of Hepatology, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden.
8Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
9Department of Pediatrics, Orebro University Hospital, Orebro, Sweden.
10Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
11Department of Medicine, Columbia University College of Physicians and Surgeons.
Abstract
Recent studies link nonalcoholic fatty liver disease (NAFLD) to an increased incidence of hepatocellular carcinoma (HCC) and extrahepatic cancers. However, prior studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity. We conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N=8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic nonalcoholic steatohepatitis (NASH), noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to ≤5 general population controls without NAFLD by age, sex, calendar year, and county (N=39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8/1,000 person-years [PYs]; difference=2.9/1,000 PYs; aHR, 1.27 [95%CI, 1.18-1.36]), driven primarily by HCC (difference=1.1/1,000 PYs; aHR, 17.08 [95%CI, 11.56-25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8/1,000 PYs, 1.2/1,000 PYs, 2.3/1,000 PYs, and 6.2/1,000 PYs, respectively) (Ptrend <0.01) and were further amplified by diabetes (1.2/1,000 PYs, 2.9/1,000 PYs, 7.2/1,000 PYs, and 15.7/1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences=0.2/1,000 PYs, 0.1/1,000 PYs, and 0.2/1,000 PYs, respectively) but no other cancers. Compared with controls, patients with biopsy-proven NAFLD had significantly increased cancer incidence, due primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.