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Abstract Details
Hepatocellular carcinoma in primary sclerosing cholangitis and primary biliary cholangitis: a clinical and pathological study in an uncommon but emerging setting
Virchows Arch. 2021 Aug 20. doi: 10.1007/s00428-021-03183-6. Online ahead of print.
Dustin E Bosch12, Yoh Zen3, Sarag A Boukhar2, Yongjun Liu4, Lin Cheng5, Matthew M Yeh67
Author information
1Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, 1959 NE Pacific St., Box 357470, Seattle, WA, 98195, USA.
2Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
3Institute of Liver Studies, King's College Hospital & King's College London, London, UK.
4Department of Pathology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
5Department of Pathology, Rush University, Chicago, IL, USA.
6Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, 1959 NE Pacific St., Box 357470, Seattle, WA, 98195, USA. myeh@uw.edu.
7Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. myeh@uw.edu.
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are biliary tract pathologies with increased risk of HCC, although HCC is more commonly associated with viral hepatitis and steatohepatitis. HCC risk stratification in PBC/PSC populations may help select patients for surveillance. We hypothesized that metabolic syndrome associated diagnoses and co-morbid nonalcoholic fatty liver disease (NAFLD) may be risk factors for HCC in patients with PBC and PSC. We undertook a multi-institutional case control study of PSC (19 cases, 38 controls) and PBC (39 cases and controls) patients with advanced fibrosis, matched for known HCC risk factors of age and sex, who had native liver explant or resection specimens. In the PSC population, HCC risk was significantly associated with multiple metabolic syndrome associated diagnoses (OR 13, p = 0.02), hyperlipidemia (OR 29, p = 0.03), and obesity (OR 6.8, p = 0.01). In the PBC cohort, only type 2 diabetes was a risk factor for HCC (OR 4.7, p = 0.03). In the PSC cohort, thick fibrous septae were associated with HCC risk (OR 3.4, p = 0.04). No other pathologic features of the nonneoplastic liver were significantly associated with HCC, including features of NAFLD such as macrovesicular steatosis, pericellular fibrosis, and steatohepatitis. Metabolic syndrome associated diagnoses, specifically type 2 diabetes among PBC patients, is associated with HCC risk in patients with biliary type cirrhosis. However, we found no evidence that HCC risk is related to co-morbid NAFLD, indicating a likely distinct mechanism of metabolic syndrome-associated carcinogenesis in these populations.