title: Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail?
abstract: OBJECTIVE
  Only 40% of patients with hepatocellular carcinoma (HCC) are diagnosed at an early stage, suggesting breakdowns in the surveillance process. The aim of our study was to assess the reasons behind surveillance process failures among patients in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial (HALT-C), which prospectively collected HCC surveillance data on a large cohort of patients.
  
  
  METHODS
  Binary regression analysis was used to identify predictors of consistent surveillance, which was defined as having an ultrasound and alpha-fetoprotein every 12 months. Surveillance failures among patients who developed HCC were classified into one of three categories: absence of screening, absence of follow-up, or absence of detection.
  
  
  RESULTS
  Over a mean follow-up of 6.1 years, 692 (68.9%) of 1,005 patients had consistent surveillance. Study site was the strongest predictor of consistent surveillance (P<0.001). After adjusting for study site, patient-level predictors of consistent surveillance included platelet count >150,000/mm(3) (hazard ratio (HR) 1.28; 95% confidence interval (CI): 1.05-1.56) and complete clinic visit adherence (HR 1.72, 95% CI: 1.11-2.63). Of 83 patients with HCC, 23 (27.7%) were detected beyond Milan criteria. Three (13%) had late-stage HCC due to the absence of screening, 4 (17%) due to the absence of follow-up, and 16 (70%) due to the absence of detection.
  
  
  CONCLUSIONS
  Surveillance process failures, including absence of screening or follow-up, are common and potentially contribute to late-stage tumors in one-third of cases. However, the most common reason for finding HCC at a late stage was an absence of detection, suggesting better surveillance strategies are needed.
authors: Department of Internal Medicine, UT Southwestern Medical Center, and Parkland Health and Hospital System, Dallas, Texas 75390-8887, USA. amit.singal@utsouthwestern.edu
authors: Amit G
authors: AG
authors: Singal
authors: Mahendra
authors: M
authors: Nehra
authors: Beverley
authors: B
authors: Adams-Huet
authors: Adam C
authors: AC
authors: Yopp
authors: Jasmin A
authors: JA
authors: Tiro
authors: Jorge A
authors: JA
authors: Marrero
authors: Anna S
authors: AS
authors: Lok
authors: William M
authors: WM
authors: Lee
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D055088:Early Detection of Cancer; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a