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. 2013 Mar;108(3):425-32.
doi: 10.1038/ajg.2012.449. Epub 2013 Jan 22.

Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail?

Amit G Singal  1 , Mahendra Nehra, Beverley Adams-Huet, Adam C Yopp, Jasmin A Tiro, Jorge A Marrero, Anna S Lok, William M Lee
Affiliations

Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail?

Amit G Singal et al. Am J Gastroenterol. 2013 Mar.

Abstract

Objectives: 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.

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Conflict of interest statement

CONFLICT OF INTEREST

Guarantor of the article: Amit G. Singal, MD, MS.

Specific author contributions: Amit Singal was involved in planning and conducting the study, collecting the data, analyzing and interpreting the data, drafting the manuscript, and revising the manuscript for important intellectual content. Dr Singal approved the final draft submitted. Mahendra Nehra was involved in analyzing and interpreting the data. He approved the final draft submitted. Beverley Adams-Huet was involved in analyzing and interpreting the data and revising the manuscript for important intellectual content. Dr Adams-Huet approved the final draft submitted.

Adam Yopp was involved in interpreting the data and revising the manuscript for important intellectual content. Dr Yopp approved the final draft submitted. Jasmin Tiro was involved in planning and conducting the study, interpreting the data, and revising the manuscript for important intellectual content. Dr Tiro approved the final draft submitted. Jorge Marrero was involved in interpreting the data and revising the manuscript for important intellectual content. Dr Marrero approved the final draft submitted. Anna Lok was involved in planning and conducting the study, collecting the data, interpreting the data, and revising the manuscript for important intellectual content. Dr Lok approved the final draft submitted. William Lee was involved in planning and conducting the study, collecting the data, interpreting the data, and revising the manuscript for important intellectual content. Dr Lee approved the final draft submitted.

Financial disclosures: This work was conducted with support from UT-STAR, NIH/NCATS Grant Number KL2 TR000453, NIH/NCATS Grant UL1-TR000451, and the ACG Junior Faculty Development Award awarded to Dr Singal. The content is solely the responsibility of the authors and does not necessarily represent the official views of UT-STAR, the University of Texas Southwestern Medical Center and its affiliated academic and health care centers, the National Center for Advancing Translational Sciences, or the National Institutes of Health.

Potential competing interests: None.

Figures

Figure 1
Figure 1
Hepatocellular carcinoma (HCC) surveillance rates by study site.
Figure 2
Figure 2
Hepatocellular carcinoma (HCC) surveillance outcome failures for patients beyond Milan criteria.
Figure 3
Figure 3
Hepatocellular carcinoma (HCC) surveillance outcome failures for patients beyond tumor, node, and metastases (TNM) stage T1.
See this image and copyright information in PMC

Comment in

  • Surveillance for hepatocellular carcinoma: just do it!
    Giannini EG, Trevisani F. Giannini EG, et al. Am J Gastroenterol. 2013 Jun;108(6):1013-4. doi: 10.1038/ajg.2013.98. Am J Gastroenterol. 2013. PMID: 23735924 No abstract available.
  • Reply to Giannini and Trevisani.
    Singal AG, Marrero JA, Lok AS, Lee WM. Singal AG, et al. Am J Gastroenterol. 2013 Jun;108(6):1014. doi: 10.1038/ajg.2013.100. Am J Gastroenterol. 2013. PMID: 23735925 No abstract available.

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