No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients With Cirrhosis

Abstract

Background & aims: Screening patients with cirrhosis for hepatocellular carcinoma (HCC) has been recommended. We conducted a matched case-control study within the US Veterans Affairs (VA) health care system to determine whether screening by abdominal ultrasonography (USS) and/or by measuring serum level of α-fetoprotein (AFP) was associated with decreased cancer-related mortality in patients with cirrhosis.

Methods: We defined cases (n = 238) as patients with cirrhosis who died of HCC from January 1, 2013 through August 31, 2015 and had been in VA care with a diagnosis of cirrhosis for at least 4 years before the diagnosis of HCC. We matched each case to 1 control (n = 238), defined as a patient with cirrhosis who did not die of HCC and had been in VA care for at least 4 years before the date of the matched case's HCC diagnosis. Controls were matched to cases by year of cirrhosis diagnosis, race and ethnicity, age, sex, etiology of cirrhosis, Model for End-Stage Liver Disease score, and VA medical center. We identified all USS and serum AFP tests performed within 4 years before the date of HCC diagnosis in cases or the equivalent index date in controls and determined by chart extraction (blinded to case or control status) whether these tests were performed for screening.

Results: There were no significant differences between cases and controls in the proportions of patients who underwent screening USS (52.9% vs 54.2%), screening measurement of serum AFP (74.8% vs 73.5%), screening USS or measurement of serum AFP (81.1% vs 79.4%), or screening USS and measurement of serum AFP (46.6% vs 48.3%) within 4 years before the index date, with or without adjusting for potential confounders. There also was no difference in receipt of these screening tests within 1, 2, or 3 years before the index date.

Conclusions: In a matched case-control study of the VA health care system, we found that screening patients with cirrhosis for HCC by USS, measurement of serum AFP, either test, or both tests was not associated with decreased HCC-related mortality. We encourage additional case-control studies to evaluate the efficacy of screening for HCC in other health care systems, in which available records are sufficiently detailed to enable identification of the indication for USS and AFP tests.

Keywords: Liver Cancer; Liver Transplantation; Surveillance; Survival.

Figure 1.. Schematic representation of the case-control study design, illustrating the criteria used to match cases (fatal HCC) to controls, the index date and detectable preclinical phase (DPP).

The DPP comprised an identical period of calendar years for the case and control within each matched pair (e.g. 2010–2014 in the example below), during which both case and control were in VA care at the same VA facility * Index Date: Date of HCC diagnosis or earliest date that patients showed symptoms, laboratory abnormalities or imaging findings suspicious for HCC. † DPP (detectable preclinical phase), is the time period prior to the index date during which we documented the occurrence of screening ultrasonography or serum AFP ǂ Matching by age, gender, race, etiology of cirrhosis, MELD score at the time of cirrhosis diagnosis, date of cirrhosis diagnosis and VA facility

Figure 2.. Flow chart demonstrating the identification/confirmation of cases, identification/confirmation of controls and matching to cases, and identification of USS and serum AFP tests performed prior to the index date