In a new study, researchers at New York's Mount Sinai are calling for revised screening guidelines to reduce the number of African Americans with hepatitis C who are dying from liver cancer at rates higher than people from other racial groups, and they are seeing similarly disconcerting patterns in ongoing research into other subsets of Black patients with liver cancer.
The study, published in Cancer on Thursday, confirmed that the livers of Black patients with hepatitis C — a type of liver infection that is known to be the strongest driver of liver cancer in the U.S. — deteriorate less quickly and so may not trigger a screening. It documented the surprising finding that one-third of these patients did not qualify for a screening under current guidelines.
To arrive at their findings, the researchers conducted a retrospective study of 1,195 patients with hepatocellular carcinoma, the most common type of primary liver cancer, 390 of whom identified as African American.
The team found that the tumors in Black patients carry worse prognostic features that also contribute to racial disparities in prognoses. They were more likely to metastasize and had a higher grade of inflammation compared to other racial groups. They were larger and more aggressive, numerous and invasive, said Umut Sarpel, an associate professor of surgery and medical education at the Icahn School of Medicine at Mount Sinai.
Sarpel told The Academic Times that the hepatitis C work was just an initial focus for the team. A data set that the colleagues have been building over the past half-year, which is set to be published in the coming months, replicates the findings for all other causes of liver cancer, including hepatitis B, alcohol use, nonalcoholic steatohepatitis, diabetes and others, she said.
"We have recently completed a study in patients with non-HCV liver cancer and see similar findings," she said.
A 2016 study led by Sarpel had shown that Black patients with liver cancer are "significantly less likely" to undergo liver transplantation, the most effective treatment for hepatocellular carcinoma, compared with other racial groups. Previous research also shows that Black patients have a more advanced tumor stage by the time they are diagnosed with hepatocellular carcinoma, as well as lower rates of surgical intervention and survival.
The incidence of this type of cancer — and the mortality rates — are also higher in Black patients. One study last year reported 16,770 deaths from liver cancer among Black Americans between 1998 and 2016. It found that the rate of death increased by 77.7% among this population, whereas the rate among white Americans grew by 43.1%.
Sarpel set out to conduct the new study with the goal of identifying reasons behind such disparities.
Mount Sinai researchers retrospectively reviewed the records of patients with hepatitis C and hepatocellular carcinoma who were treated at their institution between 2003 and 2018. The team compared imaging, laboratory and pathological features between Black and non-Black cohorts, which included patients who had self-identified as white, Hispanic or Asian/Pacific Islander.
Pointing to a 2018 study that similarly found triple-negative breast cancer — in which the receptors typically found in breast cancer are lacking — to be more common in Black patients, Sarpel noted that she was already considering the tumors might be worse in these individuals, which they were. But the finding that surprised her was that one-third of Black patients fell outside the current screening guidelines.
This means that Black patients with hepatitis C and liver cancer are "getting hit at both ends of the spectrum," Sarpel said. "Not only are the tumors that are developing worse players," but also, these patients are "not even having the opportunity to have their tumors detected at an early enough stage, because a third of the patients aren't even meeting the criteria for screening that we currently use as nationally accepted guidelines."
The research follows a smaller pilot study from 2018 of 42 Black patients that was conducted by coauthor Andrea Branch, a hepatologist who has been studying cirrhosis, a form of chronic liver damage that is often caused by hepatitis. Currently, the development of cirrhosis is what triggers a medical recommendation for liver cancer screening.
Sarpel, who is also a surgical oncologist, reached out to Branch in hopes of expanding on her study. The larger study confirms what the pilot study demonstrated: The livers of Black patients with hepatitis C progress to cirrhosis more slowly, so they have better liver function at diagnosis of liver cancer than other patients.
That's what led the researchers to advocate for revising screening guidelines, to reflect that tumors tend to progress less quickly in Black patients with liver cancer before reaching the point of cirrhosis.
There are at least two ways to do this, Sarpel said, noting in an example of race-specific caveats that age-based triggers exist in the screening guidelines for Asian patients with hepatitis B. Guidelines could be similarly revised to address the disparity seen in Black patients with liver cancer, she argues.
“We know that liver cancer is more common the older you get, but in some groups, clearly, liver cancer occurs in early ages," Sarpel said. Another potential way to revise the guidelines relates to lowering the score of the FIB-4 index, which helps estimate the amount of scarring in the liver, to an earlier stage.
Committees of thought leaders and experts in the field of cancer, such as the American Joint Committee on Cancer, are responsible for considering all the evidence available to refine screening guidelines.
The next step for the research team is to compare patients with liver cancer whose tumors developed the traditional way in the setting of cirrhosis with the one-third of patients whose tumors developed before cirrhosis set in to identify differences in the cancers between these two groups. Ultimately, Sarpel envisions additional research leading to screening based on a particular gene.
"We won't be screening by whether you're Black, white or Asian," she said. "We will be screening you by whether you have this particular gene," and honing in on what makes a gene more common in a particular community.
The study, “Hepatitis C-Positive Black Patients Develop Hepatocellular Carcinoma at Earlier Stages of Liver Disease and Present With a More Aggressive Phenotype,” was published in Cancer on Feb. 25. The authors of the study are Tali Shaltiel, Serena Zheng, Cleo Siderides, Elizabeth M. Gleeson, Jacquelyn Carr, Eric R. Pletcher, Noah A. Cohen, Benjamin J. Golas, Deepa R. Magge, Daniel M. Labow, Andrea D. Branch and Umut Sarpel; Icahn School of Medicine at Mount Sinai.