@article{d73b4afa2d7c4e70b48b7079d0b7577d,
title = "Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis",
abstract = "Background: Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC). Aims: To identify risk factors for new-onset HCC in patients cured of hepatitis C. Methods: Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post-SVR were analyzed. Histology of 20 nontumor tissues was analyzed in a blinded manner using the Knodel/Ishak/HAI system for necroinflammation and fibrosis/cirrhosis stage and the Brunt system for steatosis/steatohepatitis. Factors associated with post-SVR HCC were identified by comparison with HALT-C participants who did not develop post-SVR HCC. Results: Hepatocellular carcinoma was diagnosed in 54 patients (45 M/9F), a median of 6 years of post-SVR [interquartile range (IQR) =1.4-10y] at a median age of 61 years (IQR, 59–67). Approximately one-third lacked cirrhosis, and only 11% had steatosis on imaging. The majority (60%) had no steatosis/steatohepatitis in histopathology. The median HAI score was 3 (1.25–4), indicating mild necroinflammation. In a multivariable logistic regression model, post-SVR HCC was positively associated with non-Caucasian race (p = 0.03), smoking (p = 0.03), age > 60 years at HCC diagnosis (p = 0.03), albumin<3.5 g/dL (p = 0.02), AST/ALT>1 (p = 0.05), and platelets <100 × 103 cells/μL (p < 0.001). Alpha fetoprotein ≥4.75 ng/mL had 90% specificity and 71% sensitivity for HCC occurrence. Noncirrhotic patients had larger tumors (p = 0.002) and a higher prevalence of vascular invasion (p = 0.016) than cirrhotic patients. Conclusions: One-third of patients with post-SVR HCC did not have liver cirrhosis; most had no steatosis/steatohepatitis. Hepatocellular carcinomas were more advanced in noncirrhotic patients. Results support AFP as a promising marker of post-SVR HCC risk.",
keywords = "alpha-fetoprotein, hepatitis C virus, hepatocellular carcinoma, sustained virological response",
author = "Chiara Rocha and Doyle, {Erin H.} and Bowman, {Chip A.} and Fiel, {M. Isabel} and Stueck, {Ashley E.} and Nicolas Goossens and Kian Bichoupan and Neal Patel and Crismale, {James F.} and Jasnit Makkar and Sara Lewis and Perumalswami, {Ponni V.} and Schiano, {Thomas D.} and Yujin Hoshida and Myron Schwartz and Branch, {Andrea D.}",
note = "Funding Information: This study was supported by the Prevent Cancer Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, the FLAGS foundation, the Nuovo‐Soldati Cancer Research Foundation, CA233794, European Commission ERC‐2014‐AdG‐671231, US Department of Defense W81XWH‐16‐1‐0363, Cancer Prevention and Research Institute of Texas RR180016, and the Irma T. Hirschl Trust. Nicolas Goosens was supported by an advanced training grant from Geneva University Hospital and Erin Doyle was supported by a National Institute of Health training grant. Funding Information: This study was supported by the Prevent Cancer Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse, the FLAGS foundation, the Nuovo-Soldati Cancer Research Foundation, CA233794, European Commission ERC-2014-AdG-671231, US Department of Defense W81XWH-16-1-0363, Cancer Prevention and Research Institute of Texas RR180016, and the Irma T. Hirschl Trust. Nicolas Goosens was supported by an advanced training grant from Geneva University Hospital and Erin Doyle was supported by a National Institute of Health training grant. Funding Information: Supported by NIH (ADB & YH), NIDDK (ADB & YH), NIDA (ADB), FLAGS foundation (YH), Nuovo‐Soldati Cancer Research Foundation (YH), and Irma T. Hirschl Trust (YH). DA031095 and DK090317 (ADB). Advanced training grant from Geneva University Hospital (NG). DK099558 (YH). Virus–host interactions training grant from Icahn School of Medicine at Mount Sinai (EHD). Publisher Copyright: {\textcopyright} 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2023",
month = may,
doi = "10.1002/cam4.5711",
language = "English",
volume = "12",
pages = "10175--10186",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "9",
}