Factors Associated With Delay of Diagnosis of Hepatocellular Carcinoma in Patients With Cirrhosis

Clin Gastroenterol Hepatol. 2021 Aug;19(8):1679-1687. doi: 10.1016/j.cgh.2020.07.026. Epub 2020 Jul 18.


Background & aims: We examined the frequency of and factors associated with delays in diagnosis of hepatocellular carcinoma (HCC) in a cohort of patients with cirrhosis in the Veterans Health Administration.

Methods: In a retrospective study, we collected and analyzed data from the Veterans Health Administration's electronic health records. We used a multivariate logistic regression model to identify factors associated with a delay in diagnosis of HCC of more than 60 days following a red flag (defined as the earliest date at which a diagnosis of HCC could have been made, based on American Association for the Study of Liver Disease 2005 guidelines). We used multivariate Cox proportional hazards model to evaluate the effects of delayed diagnosis on survival, adjusting for patient and provider characteristics.

Results: Among 655 patients with cirrhosis and a diagnosis of HCC from 2006 through 2011, 46.9% had a delay in diagnosis of more than 60 days following a red flag for HCC. Delays in diagnosis for more than 60 days were significantly associated with lack of provider adherence to the guidelines (adjusted odds ratio [OR], 4.82; 95% CI, 3.12-7.45), a diagnostic imaging evaluation instead of only measurement of alfa fetoprotein (adjusted OR, 2.63; 95% CI, 1.09-6.24), and diagnosis as an incidental finding during examination for an unrelated medical problem (compared with an HCC-related assessment) (adjusted OR, 2.26; 95% CI, 1.09-4.67). Diagnostic delays of 60 days or more were associated with lower mortality compared to patients without a delay in diagnosis (unadjusted hazard ratio, 0.57; 95% CI, 0.47-0.68 and adjusted hazard ratio, 0.63; 95% CI, 0.50-0.78).

Conclusions: Nearly half of veterans with cirrhosis have delays in diagnosis of HCC of 60 days or more after a red flag, defined by guidelines. Interventions are needed to improve timely follow-up of red flags for HCC and adherence to guidelines, to increase early detection of HCC.

Keywords: Liver Cancer; Surveillance; Testing; VA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma, Hepatocellular* / diagnosis
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis
  • Liver Neoplasms* / diagnosis
  • Proportional Hazards Models
  • Retrospective Studies