New research supports potential link between low-level lead exposure and liver injury

Nearly a decade on, the Flint water crisis still looms large in the minds of environmental toxin researchers. It was — and continues to be — evidence that not all communities in the United States are equally affected by environmental pollutants.

“It’s true that they’re sort of ubiquitous, but they aren’t uniformly distributed. And I think that’s part of what’s so disturbing,” said Andrea Branch, a professor of medicine at Mount Sinai’s School of Medicine in New York.

Now, research from Branch’s team suggests a link between Black Americans’ higher exposure to environmental toxins and advanced liver scarring, which can lead to disease and cancer. The work was presented at The Liver Meeting earlier this month.

Branch and Ph.D. student Ning Ma dug into blood samples of nearly 43,000 Americans included in the National Health and Nutrition Evaluation Survey. NHANES data includes information on a variety of toxins, including heavy metals, “forever chemicals,” and polychlorinated biphenyls, powerful carcinogens more often called PCBs.

Branch, Ma, and their team then took those blood levels and compared the results with the pool of people who had metabolic dysfunction-associated steatotic liver disease, or MASLD (previously called nonalcoholic fatty liver disease). While cadmium — a toxin found in cigarette smoke, batteries, pigments, plastics, and other products — was associated with liver injury in all groups studied, the researchers found something specific: African American participants’ liver scarring was associated with their blood level of lead.

Basically, the more lead was detected in a blood sample, the more advanced liver injury and scarring a person had. And once a person reaches advanced liver fibrosis — the severe form of injury Branch was assessing — their risk of liver-related mortality skyrockets.

For decades, lead has been known to be harmful even in small doses. And there have been plenty of reports and studies on how racial and ethnic minorities, as well as low-income communities in the U.S., are burdened by higher levels of pollution. But the link between low-level exposure to toxins, like lead, and liver injury is less understood.

Even more troubling to Branch, the NHANES data suggested that African American participants had higher blood levels of almost all pollutants associated with liver disease.

African Americans are up to 60% more likely to have liver cancer and to die from it than white Americans. Other studies have also found that Black patients were less likely to receive a liver transplant and have a higher risk of liver-related death.

It’s a puzzle that Branch has spent years trying to figure out. Racism and a lack of access to adequate health care surely factor in, she said. But sometimes the disease also looks different depending on the patient, she said. Could there also be “something in their environment that is contributing to this different picture that we see?” she asked. Building on a paper from earlier this year, the researchers decided to study a mix of chemicals instead of individual toxins. That way, their analysis would be more reflective of real life.

While the new study doesn’t prove low-level exposure to environmental toxins causes liver damage, it highlights a growing theory among some researchers: that our chronic disease epidemic might be driven at least in part by the very environments we inhabit.

“Could two things at lower levels act synergistically?” asked Craig McClain, a University of Louisville professor of medicine who has studied the effects of alcohol, acetaminophen, and environmental toxins on the liver. “That may be why drug companies have such a hard time coming up with drugs that work. They may be targeting just one mechanism, and that one mechanism may not be playing a pivotal role in all patients.”

The Branch study also found a link between lead exposure, liver scarring, and shorter telomeres — the caps on the end of chromosomes that, when shortened, can contribute to disease. Telomeres are thought to be affected by oxidative stress, which damages DNA, and then shortens the number of times cells can divide. If participants had shorter telomeres and higher lead exposure, they were more likely to have advanced liver fibrosis, Ma said.

“Their findings may support ours,” said Aaron Hipp, who used NHANES data to study the relationship between exposure to neighborhood green space and telomere length. Hipp is associate director of the Center for Geospatial Analytics at North Carolina State University. But the telomere connection still needs further investigation, other researchers said.

To Wei Perng, an associate professor of epidemiology at Colorado School of Public Health who has studied the effects of toxins on liver function, it was unclear why researchers thought the length of participants’ telomeres influenced the connection between liver scarring and toxin exposure. “What may be more powerful,” she said, is to consider the combination of shorter telomere length and environmental exposures.

Telomeres don’t often come up at liver conferences in relation to fibrosis, said Matt Cave, a professor of medicine, pharmacology and toxicology, biochemistry, and molecular genetics at the University of Louisville School of Medicine. He and McClain co-authored a 2010 study on liver disease among workers with high exposure to vinyl chloride. In that paper, they coined the term toxicant-associated steatohepatitis, or TASH.

And they’ve seen the field take off in the intervening years. In the 2010s, when Cave and McClain would show up to The Liver Meeting or other conferences to talk about TASH, they’d be assigned to a poster board “next to the bathroom at the far end of the hall,” Cave said. Nobody was interested. This year, there were several presentations related to various environmental exposures and their effects on the liver, including Branch’s abstract. And evidence is growing.

Small animal models by Cave and other researchers are showing that chemicals like PCB126, a potent type of polychlorinated biphenyl, causes liver injury, metabolic dysfunction and oxidative stress in mice. Researchers are similarly investigating whether microplastics are harmful to liver function.

But longitudinal studies are necessary to understand whether pollutants like lead are responsible for a share of liver damage and disease. If they are, how exactly do they induce liver injury? And most importantly, how can that information be used to protect people?