Hepatocellular carcinoma (HCC) is one of the most important clinical complications of chronic hepatitis B virus (HBV) infection. It has been suggested that HBV-infected patients should undergo screening for HCC with abdominal ultrasonography and possibly also serum alpha fetoprotein (AFP) testing. However, it is unclear if screening HBV-infected patients with these two tests reduces HCC-related mortality.
Our Specific Aims are to: 1. Determine whether screening for HCC with abdominal ultrasonography is associated with reduced HCC-related mortality among HBV-infected patients in VA care. 2. Determine whether screening for HCC with serum AFP testing is associated with reduced HCC-related mortality among HBV-infected patients in VA care. We will identify all VA patients with diagnosed HBV infection (defined as positive serum HBV surface antigen [HBsAg]) from 2003-2014 using the national VA Corporate Data Warehouse (CDW), excluding patients with HIV or hepatitis C virus (HCV) co-infection and patients for whom HCC screening is not recommended. Among these patients, we will identify those who died of HCC (cases). Each case will be matched to 2 controls who were not diagnosed with HCC as of the date of their case's HCC diagnosis, did not later die from HCC, and who were in VA care at the time their matched case died. Matching will be performed by race, age, gender, presence/absence of cirrhosis and year of diagnosis of HBV. Cases (N?232-348) and controls (N?464-696) will be compared with respect to presence of abdominal ultrasound or serum AFP testing performed for screening purposes within 1, 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, HBV viral load, HBeAg status, serum albumin, bilirubin, platelet count, APRI (AST to platelet ratio index) score, 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 medical chart abstraction 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 VHA represents an ideal (and possibly the only) setting in the United States for the proposed study, due to the presence of a national repository of electronic medical data extending to 1999, the universal use of electronic medical records, the ability to access electronic medical records nationally and the large number of HBV-infected patients who receive care almost exclusively within the VHA healthcare system. The proposed study represents the best methodology short of a randomized controlled trial to determine whether screening for HCC is associated with reduced HCC-related mortality in HBV-infected patients in the United States.
Hepatitis B virus (HBV) has an enormous worldwide reservoir of 350 million infected persons, which far exceeds the worldwide reservoirs of hepatitis C virus (~150 million) and HIV (~34 million). HBV infection is the most important cause of cirrhosis and hepatocellular carcinoma (HCC) in the world. Recent data suggest that the prevalence of chronic HBV infection among Veterans Health Administration (VHA) users is 0.8%, which is 2-3 fold higher than the general US population. There are an estimated ~47,000 patients with chronic HBV infection in VA care. It is unclear whether these Veterans benefit from HCC screening and data suggest that only a minority receive screening. Our results will influence clinical practice and guidelines on screening for HCC in HBV-infected patients both in the VA and at a national level. If HCC screening is found to be effective, then its wider implementation in the VA could prevent many HCC-related deaths.
