Recent research efforts at the Liver Transplant Center and Liver Care Center at Cincinnati Children’s have made impressive advancements in liver care—directly affecting clinical efforts. From new treatments for hepatitis C to increasing survival rates for babies with jaundice, our teams continue to lead the way in better liver care. Learn about three recent focus areas.
It now appears possible for liver organoids to support liver function without necessarily growing a full-sized replacement organ.
Based on discoveries in the emerging field of organoid medicine, there may be a way to improve survival for children with jaundice or other liver conditions that are hard to treat. Led by Takanori Takebe, MD, PhD, our researchers at Cincinnati Children’s found that we can augment human liver organoids to improve how they filter out bilirubin. In rodents, injecting a small piece of functioning organ tissue (organoids) into a dysfunctional liver can sharply reduce jaundice symptoms and possibly delay the need for an organ transplant.
“It now appears possible for liver organoids to support liver function without necessarily growing a full-sized replacement organ,” Takebe says. “If we can develop more robust versions of this therapy that also reduce the rejection risks, organoid transplantation might someday provide more time for finding a suitable donor organ.”
Takebe’s lab team continues to conduct research to prepare for human clinical trials and explore if the process applies to other liver conditions.
We noticed that what we thought we were seeing was actually true in infants—Black infants were diagnosed with BA one month later than white infants. As such, they had less access to HPE.
Additional research from the Liver Care Center looked at the effects of racial and socioeconomic disparities on the age at which infants receive a biliary atresia (BA) diagnosis therapy, and liver transplant-free survival. Anna Peters, MD, PhD, along with her research team, published findings that highlight the need to improve screening for jaundice in non-white infants.
“It’s really important that infants with BA have a procedure called hepatoportoenterostomy (HPE) as soon as possible,” explains Peters. “Because in BA, bile can’t drain out of the liver. If this isn’t corrected, an infant gets really rapid cirrhosis and will need a liver transplant, usually before the age of 1. The best outcomes happen if the infant is diagnosed with BA and has HPE within 30 days of life.”
Peters and team noticed that babies with non-white skin were referred to them later. As a result, they missed their window for HPE.
“Based on this clinical observation, we looked at our patients with BA diagnosed over the past 10 years,” says Peters. “We noticed that Black infants were diagnosed with BA one month later than white infants. As such, they had less access to HPE.”
The team took their study a step further, becoming the first researchers to distinguish the differential effects of race from the effects of social determinants of health on BA outcomes. They found that infants living in neighborhoods with higher levels of deprivation were also less likely to receive HPE.
Their findings suggest that there may be implicit bias in evaluating jaundice in infants with non-white skin, as well as a lack of social supports in certain geographic areas. For now, Peters and her team continue their work, which includes promoting the need for universal bilirubin screenings in infants.
Over the past six years, the Liver Care Center at Cincinnati Children’s has participated in multicenter clinical trials, studying the safety and efficacy of new direct-acting antiviral (DAA) agents in children and adolescents with hepatitis C. The trials have shown that these drugs are over 97% successful in curing infection with the hepatitis C virus (HCV). They are also safe and easy to administer.
Based on data the team at Cincinnati Children’s submitted to the FDA, three DAAs have received approval for HCV treatment in children ages 3 and older.
“We have continued to assist and encourage our colleagues in their clinical use of these agents and make efforts to educate practitioners locally and globally,” shares William Balistreri, MD, a research lead for HCV treatments.
For example, through several initiatives—including the Hepatitis Academic Mentorship Program in Kentucky (KHAMP), West Virginia (WVHAMP) and Ohio (OHIO-HAMP)—Balistreri and his team focus on improving the health of people in underserved communities in the Appalachian region by building a primary care workforce. That workforce receives training from experts to screen, diagnose, treat and monitor people with HCV infection.
“Our data clearly shows that curative agents for HCV can be effectively administered by non-specialist providers,” says Balistreri. “To date, over 2,500 consultations have been conducted by KHAMP scholars. They have successfully treated patients with chronic HCV and have achieved an SVR [sustained virologic response] in over 95% of treated subjects. None of these practitioners had previously treated patients with HCV.”
Based on the success of these programs, the next step is working with other states to adopt this model, adapting to their local needs, establishing a large network and using the lessons learned from the basic framework. The initiative—the United States Hepatitis Academic Mentorship Program (US-HAMP)—is a multi-state collaborative learning network with collective impact to eliminate hepatitis C and report outcomes across our nation.
(Published December 2024)
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