Strategies to Improve Hepatocellular Carcinoma Surveillance in Veterans With Hepatitis B Infection

The incidence of hepatocellular carcinoma (HCC) is rising in the U.S., with an estimated 8,500 to 11,500 new cases occurring annually, representing the ninth leading cause of U.S. cancer deaths.^1,2 An important risk factor for HCC is infection with hepatitis B virus (HBV), an oncogenic virus. Patients with HBV infection have an associated 5- to 15-fold increased risk of HCC, compared with that of the general population.³ Despite clinician awareness of major risk factors for HCC, the disease is often diagnosed at an advanced stage when patients have developed a high tumor burden or metastatic disease and have few treatment options.⁴

It is well recognized that U.S. veterans are disproportionately affected by hepatitis C virus (HCV) infection, which also places them at risk for HCC. In contrast, the prevalence of HBV infection, which has shared routes of transmission with HCV, and its associated complications among U.S. veterans has not been fully characterized. A recent national study showed that 1% of > 2 million veterans tested for HBV infection had a positive hepatitis B surface antigen (HBsAg), indicating active HBV infection.⁵

Routine surveillance for HCC among high-risk patients, such as those with chronic HBV infection, can lead to HCC detection at earlier stages, allowing curative treatments to be pursued more successfully.^6-9 Furthermore, HBV infection can promote development of HCC even in the absence of cirrhosis.^10,11 Therefore, according to the American Association for the Study of Liver Diseases (AASLD) guidelines, HCC screening with abdominal ultrasound is recommended every 6 to 12 months for patients with chronic HBV infection who have additional risk factors for HCC, including those aged ≥ 40 years, and patients with cirrhosis or elevated alanine aminotransferase levels (ALTs).¹⁰

Overall adherence to HCC screening recommendations in the U.S. has been low, although rates have varied depending on the underlying risk factor for HCC, provider type, patient characteristics, and practice setting.^12-20 In a 2012 systematic review, the pooled HCC surveillance rate was 18.4%, but nonwhite race, low socioeconomic status, and follow-up in primary care (rather than in subspecialty clinics) were all associated with lower surveillance rates.¹⁸ Low rates of HCC screening also have been seen among veterans with cirrhosis and chronic HCV infection, and a national survey of VHA providers suggested that provider- and facility-specific factors likely contribute to variation in HCC surveillance rates.¹⁴

There are few data on HCC incidence and surveillance practices specifically among veterans with chronic HBV infection. Furthermore, the reasons for low HCC surveillance rates or potential interventions to improve adherence have not been previously explored, although recent research using national VA data showed that HCC surveillance rates did not differ significantly between patients with HBV infection and patients with HCV infection.¹⁴

Considering that veterans may be at increased risk for chronic HBV infection and subsequently for HCC and that early HCC detection can improve survival, there is a need to assess adherence to HCC screening in VA settings and to identify modifiable factors associated with the failure to pursue HCC surveillance. Understanding barriers to HCC surveillance at the patient, provider, and facility level can enable VA health care providers (HCPs) to develop strategies to improve HCC screening rates in the veteran population.

Methods

The authors conducted a mixed-methods study at the Corporal Michael J. Crescenz VAMC (CMCVAMC) in Philadelphia, Pennsylvania. Both quantitative and qualitative data were collected to evaluate current HCC screening practices for patients with HBV infection and to identify barriers to adherence to nationally recommended screening guidelines. The CMCVAMC Institutional Review Board approved all study activities.

Inclusion Criteria

Patients were included in the quantitative study if they had ≥ 1 positive HBsAg test documented between September 1, 2003 and August 31, 2008; and ≥ 2 visits to a CMCVAMC provider within 6 months during the study period. Patients who had negative results on repeat HBsAg testing in the absence of antiviral therapy were excluded. From September 1, 2003 to December 31, 2014, the authors reviewed the Computerized Patient Record System (CPRS) medical records of eligible patients. Patients were assigned to a HCP group (ie, infectious disease [ID], gastroenterology [GI], or primary care) identified as being primarily responsible for management of their HBV infection.

Focus Group Implementation

Separate focus group discussions were held for primary care (2 focus groups), ID (1 focus group), and GI (1 focus group) providers, for a total of 4 focus groups. The focus group discussions were facilitated by 1 study team member (who previously had worked but had no affiliation with CMCVAMC at the time of the study). All CMCVAMC HCPs involved in the care of patients with chronic HBV infection were sent a letter that outlined the study goals and requested interested HCPs to contact the study team. The authors developed a focus group interview guide that was used to prompt discussion on specific topics, including awareness of HCC screening guidelines, self-reported practice, reasons behind nonadherence to screening, and potential interventions to improve adherence. No incentives were given to HCPs for their participation.

HCC Screening Guidelines

The main study endpoint was adherence to HCC screening guidelines for patients with HBV infection, as recommended by the AASLD.⁹ Specifically, AASLD guidelines recommend that patients with HBV infection at high risk for HCC should be screened using abdominal or liver ultrasound examination every 6 to 12 months. High risk for HCC was defined as: (1) presence of cirrhosis; (2) aged > 40 years and ALT elevation and/or high HBV DNA level > 2,000 IU/mL; (3) family history of HCC; (4) African Americans aged > 20 years; or (5) Asian men aged > 40 years and Asian women aged > 50 years.¹⁰

Cirrhosis was defined by documented cirrhosis diagnosis on liver biopsy or by aspartate aminotransferase-to-platelet ratio index (APRI) ≥ 2, which accurately identifies cirrhosis (METAVIR stage F4) in patients with chronic HBV.²¹ For each patient qualifying for HCC screening, the annual number of abdominal ultrasounds performed during the study period was determined, and adherence was defined as having an annual testing frequency of ≥ 1 ultrasound per year.