Health disparities in diagnosis and treatment of hepatocellular carcinoma

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Abbreviations

HBV

hepatitis B virus

HCC

hepatocellular carcinoma

HCV

hepatitis C virus

SES

socioeconomic status

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide and the leading cause of death in patients with cirrhosis. Most cases of HCC occur in Africa and Eastern Asia, although the incidence of HCC is decreasing in these parts of the world due to higher rates of hepatitis B virus (HBV) vaccination and treatment1. Although HCC has an intermediate incidence in Europe and the United States, its incidence has been rapidly increasing over the past two decades given the high number of advanced hepatitis C virus (HCV) and non‐alcoholic fatty liver disease (NAFLD) cases1.

HCC disproportionately affects disadvantaged populations, with the highest age‐specific rates among racial/ethnic minorities. HCC rates are two times higher in Asian Americans than African Americans, whose rates are two times higher than those in Caucasians2. Similarly, HCC cases are often clustered in areas of low socioeconomic status (SES) (e.g. high poverty, high unemployment, and low education areas) compared to the general population3.

Elderly patients, African Americans and those of low SES also have poorer survival rates than their counterparts4. The reasons for these differences in survival are likely multi‐factorial, involving medical, financial, and social factors. Some studies have hypothesized this difference is largely related to biologic differences in tumor behavior, such as African Americans presenting with more advanced tumor stage; however, other studies have highlighted socio‐demographic inequalities across the HCC cancer care continuum as a potential etiology for health disparities in HCC5, 6, 7, 8. The continuum of HCC care extends from risk assessment and primary prevention to early detection and diagnosis to treatment and survivorship services9. In this review, we will highlight health disparities in several steps along the continuum: prevention, early detection, and treatment.

Disparities in HCC Prevention

The primary risk factors for HCC are HBV worldwide and HCV in developed countries1. Accordingly, most data for prevention has focused on HBV vaccination and/or HBV/HCV anti‐viral therapy. Successful anti‐viral therapy for HBV and HCV can significantly reduce HCC risk by over 50%10 ^, 11. However, prior studies from the National Veterans Administration (VA) database found only 12% of HCV‐infected patients underwent treatment12. The authors found significantly lower treatment rates among elderly patients and racial/ethnic minorities (Black and Hispanic patients), even after adjusting for the presence of comorbid illnesses. Further, genetic variability, such as IL28B allele frequency, results in lower response rates to interferon‐based therapy in racial minorities who undergo treatment13.

Disparities in HCC Early Detection

Guidelines from the American Association for the Study of Liver Diseases (AASLD) recommend HCC surveillance in patients with cirrhosis and/or chronic HBV using ultrasound every 6 months14. Surveillance is efficacious for early stage detection and is associated with higher rates of curative treatment and improved survival in at‐risk patients15 ^, 16. However, despite a strong evidence base and guideline recommendations, less than 20% of patients with cirrhosis currently receive surveillance7. Underuse of surveillance may be mediated by patient‐level factors (e.g. non‐adherence), provider‐level factors (e.g. lack of knowledge or disbelief regarding benefits of HCC surveillance), and/or system‐level factors (e.g. lack of access to medical care)17, 18, 19, 20.

Several socio‐demographic factors are associated with HCC surveillance utilization, with lower surveillance rates observed in patients older than 65 years, non‐Caucasians, and those of low SES7 ^, 21. For example in the Surveillance Epidemiology and End Results (SEER)‐Medicare database, the lowest surveillance rates were seen in Black (12%) patients, intermediate rates in non‐Hispanic Caucasian (15%) and Hispanic (17%) patients, and the highest rates among Asian (28%) patients (p<0.001)22. Similarly, patients who lived in zip codes with higher median income and/or education levels were significantly more likely to receive HCC surveillance22.

Disparities in HCC Treatment Rates

Prognosis for HCC depends on tumor stage at diagnosis and the receipt of curative treatment. Patients with early stage HCC can achieve 5‐year survival rates approaching 70% with surgical resection, radiofrequency ablation, or liver transplantation, whereas those diagnosed at advanced stages are only amenable to palliative treatments and have median survival rates below one year14. A recent systematic review reported pooled treatment and curative treatment rates of 52.8% (95%CI 52.2‐53.4%) and 21.8% (95%CI 21.4‐22.1%) respectively8. Even among those diagnosed at an early stage, more than 40% failed to undergo curative treatment. Underuse of curative treatment may be related to patient‐level factors (e.g., poor liver function, comorbid conditions, or patient choice), provider‐level factors (e.g. lack of knowledge or expertise), and/or technical factors (e.g. tumor location or limited organ availability)23 ^, 24.

Similar to HCC surveillance, socio‐demographic disparities in treatment utilization are evident, with lower treatment rates among elderly patients, African Americans, and those of low SES8. For example, in the California Cancer Registry, Hispanic patients were less likely to receive curative treatment, largely related to lower rates of surgical resection (p<0.01). African Americans were also 58% and 36% less likely to undergo liver transplantation (p=0.02) or resection (p=0.05) respectively23. Similarly, insurance status was associated with receipt of curative treatment (p<0.01), with patients with private insurance being 3‐fold more likely to undergo liver resection than those without insurance23. For liver transplantation, geographic variation in organ availability has contributed to health disparities. Median MELD scores at transplant can differ by up to 10 points between regions, leading to differences in wait times and drop‐out risk for those with HCC25. Furthermore, the possibility of multiple listings within different regions favors patients of higher SES25.

Future Directions

It is clear that significant socio‐demographic inequalities in HCC prevention, early detection and treatment rates exist. Despite the availability of potentially efficacious interventions, these inequalities can lead to low effectiveness rates in subgroups of patients. For example, the effectiveness of HCC prevention through HCV treatment may still be limited, despite the introduction of new efficacious anti‐viral agents, if treatment penetration is not increased among racial/ethnic minority groups and those of low SES26.

Studies are needed to characterize reasons behind health disparities in HCC care. Cancer care occurs in a complex multi‐level environment with influences at the patient, provider, organization, community, and policy levels24 (Figure 1). Therefore, health disparities can relate to several factors including but not limited to differential access to care, patient attitudes and adherence rates, provider knowledge and cultural competency, state or national policies, or a combination of these factors. Studies evaluating reasons behind surveillance and treatment underutilization are needed to help inform appropriate intervention strategies that can increase early detection and treatment rates and thereby reduce health disparities in the future.

Figure 1.

Multi‐level Influences on Cancer Care. Adapted with permission from Taplin et al. JNCI Monographs 2012; 44: 2‐10