Hepatocellular carcinoma (HCC) is one of the most important clinical complications of cirrhosis. Screening for HCC in cirrhotic patients has been adopted by many providers using ultrasonography and/or serum alpha fetoprotein testing every 6 months. However, high quality data to support this practice are lacking and it is extremely unlikely that randomized trials of screening for HCC could ever be feasible in the West. We propose a case-control study to evaluate whether screening for HCC with USS or serum AFP is associated with reduced HCC-related mortality among cirrhotic patients.
Our Specific Aims are to: 1. Determine the extent to which screening for HCC with abdominal USS is associated with reduced HCC- related mortality among cirrhotic patients. 2. Determine the extent to which screening for HCC with serum AFP testing is associated with reduced HCC-related mortality among cirrhotic patients. We will identify all Veterans Affairs (VA) patients with cirrhosis who received care in calendar year 2013 (n=60,553) in any VA facility in the country using the national VA Corporate Data Warehouse (CDW), excluding patients for whom HCC screening is not recommended. Among these patients, we will identify those who died of HCC in 2013 and randomly select 450 cases. Each case will be matched to one control who was not diagnosed with HCC as of the date of his case's HCC diagnosis, did not later die from HCC, and who was in VA care at the time his matched case died. Matching will be performed by race, age, gender, etiology of cirrhosis and year of diagnosis of cirrhosis. Cases (N=450) and controls (N=450) will be compared with respect to presence of abdominal ultrasound or serum AFP testing performed for screening purposes within 2, 3, or 4 years prior to the diagnosis of HCC (in the cases) or the equivalent index date in their matched controls. Conditional multivariate logistic regression will be performed to adjust for additional potential confounders that may be associated with both mortality from HCC and screening for HCC including antiviral treatment for HBV or HCV, serum albumin, bilirubin, platelet count, diabetes, obesity, alcohol abuse or dependence, Charlson- Deyo comorbidity index, treatment by subspecialists and complexity level of medical facility. Electronic data obtained from the CDW will be supplemented by review of abstracted medical records performed by the investigators blinded as to case/control status to confirm whether USS or serum AFP testing during the period of interest was performed for screening or not and to confirm that deaths were caused by HCC in the cases. The study is powered to detect a reduction in HCC-related mortality associated with screening greater than 30% (odds ratio <0.70) if one truly exists.
HCC is the fastest growing cause of cancer related death in the USA. The proposed study represents the best methodology short of a randomized controlled trial to determine whether screening for HCC in cirrhotic patients is associated with reduced HCC-related mortality in the United States. If 'positive' our results may lead to improved screening uptake, which is now low, and reduced HCC-related mortality, while if 'negative', our results may reduce the costs and potential harms of screening that is of limited utility.
| Ioannou, George N; Green, Pamela K; Beste, Lauren A et al. (2018) Development of models estimating the risk of hepatocellular carcinoma after antiviral treatment for hepatitis C. J Hepatol 69:1088-1098 |
| Moon, Andrew M; Weiss, Noel S; Beste, Lauren A et al. (2018) No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients With Cirrhosis. Gastroenterology 155:1128-1139.e6 |
| Ioannou, George N; Green, Pamela K; Berry, Kristin (2017) HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol : |
