One Factor Contributing to Increase in US Liver Cancer Deaths?

Kristin Jenkins

May 15, 2020

Although cancer mortality in the United States has declined among both men and women, the number of deaths due to liver cancer is rising faster than for any other malignancy. The most vulnerable appear to be men, those born between 1945 and 1968, and people of Hispanic and African race/ethnicity.

A new analysis suggests that one reason for this could be racial disparities in access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. These drugs have been shown to reduce the risk for death and liver cancer among patients with chronic HCV infection, a major risk factor for hepatocellulcar carcinoma (HCC).

"Such drugs are lifesaving but prohibitively expensive for some," said Charles H. Hennekens, MD, PhD, of Charles E. Schmidt College of Medicine at Florida Atlantic University, in Boca Raton, and Baylor College of Medicine, in Houston, Texas, and colleagues.

Hennekes is senior author of the new report on US mortality data for HCC, the most common histologic subtype of liver cancer.

In their analysis, the investigators found that just 1 year after the approval of DAA therapy for HCV infection, steady declines in rates of HCC-associated deaths in older African-Americans did an abrupt reversal. From 1998 until 2016, disproportionate increases in HCC mortality rates were observed among black Americans aged 55 to 64 years compared to white Americans of the same age (77.7% vs 43.1%).

Widening racial disparities in liver cancer mortality rates following licensure of lifesaving drugs "may have resulted, at least in part, from unintended social side effects such as unequal accessibility, acceptability and/or utilization," the authors conclude.

The report was published online April 30 in EClinical Medicine.

The authors emphasize that the descriptive data used for the analysis can help formulate but not test hypotheses. Nevertheless, these findings echo results from previous analyses in which Hennekens and colleagues observed similar racial disparities in mortality rates following the introduction of active retroviral drug therapy for HIV infection and of surfactant for respiratory distress syndrome in newborns.

"The totality of evidence suggests that these findings are more broadly generalizable to all black Americans regardless of age and gender," Hennekens told Medscape Medical News.

Decreasing racial inequalities in mortality following the introduction of lifesaving drugs in the United States and worldwide should be "a major clinical and public health priority," Hennekes said in a statement.

Liver Mortality Rates Rising

The current study focused on Americans aged 55 years or older "because they account for 83% of all deaths from liver cancer in the US," he added.

"Liver cancer mortality rates are rising faster among men 55 to 64 years of age than in other ages, regardless of race/ethnicity," said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern VA Medical School, in Norfolk, Virginia, who was approached for comment.

Although the current study findings are consistent with those of other epidemiologic studies, Johnson said he found it surprising that the study focused only on Americans of either African or white race/ethnicity.

"The disproportionate increase in the incidence of HCC is seen in those born during the peak period of hepatitis C infection [1945 to 1968] and in certain Hispanics, African Americans, as well as Caucasians," he told Medscape Medical News. Johnson was not affiliated with the study.

DAA therapy has "a dramatic effect in risk reduction if effective viral eradication [is achieved] before advanced fibrosis or cirrhosis develops," Johnson said. In patients with advanced fibrosis or cirrhosis, appropriate surveillance with screening for HCC is key, he emphasized.

Another expert who was approached for comment also emphasized the benefits of DAA therapy. Harry A. Torres, MD, associate professor in the Department of Infectious Diseases at the University of Texas MD Anderson Cancer Center, in Houston, pointed out that in studies of DAA drugs in more than 30,000 HCV patients from several countries, overall eradication of HCV and a sustained virologic response reduced HCC risk by approximately 70%.

Some of the early studies raised concerns about a potential hepatocarcinogenic effect with DAA drugs, Torres noted. However, more recent data "showed that successful HCV eradication reduced HCC incidence in DAA-treated patients," he continued.

Even more promising, a multicenter cohort study in the United States and Canada demonstrated that DAA therapy "was associated with a significant reduction in risk of death among patients with complete response to HCC treatment," he told Medscape Medical News.

Details of Latest Analysis

For their study, Hennekes and colleagues analyzed 1979–2016 mortality data from the US Centers for Disease Control and Prevention and the Wide-Ranging Online Data for Epidemiologic Research (WONDER). The results showed that compared to white Americans, rates of excess death among black Americans aged 55 years and older were on the decline between 1979 and 1997 but rose from 27.8% to 45.4% between 1998 and 2016.

Similarly, HCC mortality rates among African Americans increased by 1.7% per year from 1979 to 1997 and then by 4.2% annually from 2000 to 2016. Among same-age white Americans, mortality rates increased by 3.5% annually from 1979 to 1990 and by 2% per year from 1990 to 2016.

This trend toward increasing racial disparity in HCC mortality rates was especially pronounced in men, the researchers found. In addition, they observed that racial inequalities in mortality during the same period decreased for other major liver cancer risk factors, including use of alcohol, obesity, and diabetes.

Improved product safety and health licensing programs could increase access to lifesaving innovations for African Americans, Hennekes suggested in a statement. "Of much greater importance is the recognition, acceptance, and incorporation of multifactorial, culturally tailored interventions that target the different and multifactorial causes of racial inequalities which have been observed in the US for many decades," he added.

Hennekens has financial relationships with Amgen, Cadila, Dalcor, Regeneron, Pfizer, and the US Food and Drug Administration. The study's coauthors and Johnson have disclosed no relevant financial relationships. Torres has financial relationships with Gilead Sciences, Merck & Co, AbbVie, and Dynavax Technologies.

EClinicalMedicine. Published online on April 30, 2020.Full text

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