Over the past two decades, the incidence of hepatocellular carcinoma (HCC) has been steadily rising and is now a leading cause of cancer-related death in the United States. However, HCC disproportionally affects all US racial/ethnic minority populations, with blacks, Hispanics, and Asians experiencing higher age-specific incidence rates than non-Hispanic whites, according to an editorial in Journal of the National Cancer Institute (JNCI).
While incidence rates for HCC among most racial/ ethnic groups have steadily increased overall, the rates for blacks and Hispanics are projected to be the highest by 2030.
That said, even though the “projected burden of HCC in the United States is alarming, this future is not inevitable,” write authors Amit G. Singal, MD and Caitlin C. Murphy, PhD, both of the University of Texas Southwestern Medical Center in Dallas.
They point to two studies recently published in the JNCI, which reviewed the racial/ethnic differences in incidence and projected future HCC burden. These two papers “paint a roadmap to reduce the increasing incidence and disparities in HCC in the United States,” the editorialists comment.
Increase Projected in Older Population
In the first study, Christopher Pham and colleagues from the University of Southern California used data from the California Cancer Registry. This showed that Southeast Asians (Vietnamese, Cambodians, and Laotians) had overall HCC incidence rates that were eight to nine times higher than non-Hispanic whites and more than twice that of other Asian groups. In addition, there was a statistically significant increasing trend of HCC in non-Hispanic whites and blacks, and Hispanics, especially those above the age of 50 years.
Of note, the authors point out differences in Asian subgroups, notably that the incidence of HCC appears to be declining in Chinese men but rising in others, specifically Japanese and Filipino men and Vietnamese and Laotian women.
This team used four Surveillance, Epidemiology, and End Results Program registries to obtain incidence data for California from 2000 to 2013, along with 14 registries to represent other states. Their data suggest that by 2030, Hispanics and blacks will have the highest HCC incidence rates in California and Asians will have the lowest. The incidence among whites, blacks, and Hispanics in California has continued to increase each year, but has declined for Asians, although consistent declines were not seen among Asians for the rest of the country.
Similar to the Pham study, they also predicted an increased incidence in an older population; in California, 80% of new cases in 2030 will be in patients older than 65 years vs 44.5% in 2014, with this burden especially high among Hispanics (318.3%) and lowest among Asians (53.2%).
Trends in the US
Virtually all cases (>90%) of HCC are diagnosed in patients with cirrhosis, which tends to be the end result from any chronic liver disease, including hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease, and nonalcoholic fatty liver disease (NAFLD).
Thus, aside from differences in Asian subpopulations, the incidence of HCC in the US is primarily related to an aging population with chronic HCV infection as well a growing number of patients with NAFLD, Singal and Murphy note.
HCV infection is more prevalent among the so-called “baby boomers,” the population born between 1945 and 1965, which is consistent with the findings seen in the Han study. These individuals were most likely exposed to HCV infection in the 1970s and 1980s through injection drug use and contaminated blood products before HCV was even identified or screened for.
Recent advances in treatment for HCV have reduced the risk of HCC, although not eliminated it, the editorialists comment. But with increasing access to curative treatment, “it is possible that Han and colleagues’ projections of HCC burden using data from 2000 to 2013 may not account for recent HCV screening and treatment efforts, thereby overestimating future HCC burden,” they note.
In addition, recent studies have suggested that some European nations are now experiencing plateaus and even declines in HCC incidence after rates had been increasing. This also underscores the “importance of incorporating more recent data in projections of HCC burden,” say Singal and Murphy.
Further studies are needed to gain a better understanding of the racial/ethnic disparities in HCC incidence and burden. The editorialists emphasize that just as the Pham study looked at trends among a heterogeneous Asian cohort, similar analyses are needed for Hispanics. As an example, for cancers other than HCC, studies have identified differences in incidence and prognosis among various Hispanic subgroups such as Mexicans, Puerto Ricans, Cubans, and Dominicans.
Another issue is socioeconomic status. While several papers have focused on the racial/ethnic disparities in HCC incidence, for the most part they have ignored the interaction between race/ethnicity and socioeconomic status.
“Ignoring intersectionality may falsely attribute socioeconomic disparities to race/ethnicity and vice versa, and larger studies including both are needed,” write Singal and Murphy.
The incidence trends reported by these two studies will help inform interventions to reduce the HCC burden, the editorialists write. As an example, the declining HCC incidence among some Asian populations is probably due to improvements in global HBV vaccination and treatment programs. In the US, continued efforts to increase HBV vaccination and treatment will help to reduce HBV-related HCC as well as reinforce declines in HCC incidence that have been observed in Asian subgroups, they suggest.
Other interventions include increased HCV screening and treatment, particularly among baby boomers, and this may particularly benefit blacks and non-Hispanic whites, as HCV infection is their most common risk factor for HCC. Many patient subgroups, including incarcerated individuals, those who do not receive routine medical care, active drug users, and Medicaid-eligible individuals, also have a higher prevalence of untreated HCV infection and could benefit from screening interventions.
Finally, a pressing area of need is for improved treatment of NAFLD, as there are no pharmacologic therapies available. “This would reduce the HCC risk as NAFLD becomes the most common cause of cirrhosis and HCC in the United States,” say Singal and Murphy. “While awaiting pharmacological therapy, continued campaigns for lifestyle modifications including healthy diets, increased exercise, and decreased alcohol abuse may help,” they add.
The study was supported by grants from the National Institutes of Health. Singal reports serving on the speakers’ bureau for Gilead and has received grant support from AbbVie. Murphy has disclosed no relevant financial relationships.
JNCI: Journal of the National Cancer Institute. Published online December 13, 2018. Editorial