Heart complications common in children with PFIC, study finds
Nearly half met criteria for cirrhotic cardiomyopathy in single-center study
About half of children with progressive familial intrahepatic cholestasis (PFIC) were found to have cirrhotic cardiomyopathy (CCM), a form of heart disease, in a study from India.
The data also suggest that children with CCM have poorer survival outcomes and are more likely to require a liver transplant.
Similar patterns were seen in children with biliary atresia, another liver disease that affects infants and children.
“While well recognized in adults, CCM remains an under-recognized entity in children,” the researchers wrote. “The present study adds to the limited but rapidly evolving evidence on cirrhotic cardiomyopathy in the pediatric population.”
The study, “Cirrhotic cardiomyopathy in children with biliary atresia and genetic intrahepatic cholestasis: clinical course and outcomes,” was published in Hepatology International.
What PFIC is and how it damages the liver
PFIC refers to a group of rare genetic liver diseases marked by intrahepatic cholestasis, a condition in which the flow of bile through small ducts inside the liver is reduced or blocked.
As bile builds up to toxic levels, it can cause ongoing liver damage that may progress to irreversible liver scarring (cirrhosis) and liver failure, at which point a liver transplant may be the only treatment option.
PFIC usually manifests during infancy or childhood and includes several types, each linked to mutations in a specific gene.
Cholestasis is also the hallmark of biliary atresia, a congenital disorder where the bile ducts are missing or blocked at birth.
CCM is a heart condition involving impaired heart function and abnormal electrical activity that can develop in people with cirrhosis, even without prior heart disease. It is also “associated with a higher risk of poor short-term outcomes after major interventions like liver transplantation,” the researchers wrote.
There have been a few studies reporting high rates of CCM among children with biliary atresia, but no studies to date have looked at CCM rates among children with PFIC, the researchers noted.
To address this gap, researchers in India examined CCM rates in 25 children with PFIC and 64 children with biliary atresia treated at a single center.
Children with PFIC had a median age of 25 months (about 2 years), and 72% were boys. The most common form of the disease was PFIC type 2, followed by type 1 and type 3.
Study finds high rates of hidden heart disease
The researchers found that about half of the children met the diagnostic criteria for CCM — 48% of those with PFIC and 53.13% of those with biliary atresia. However, none of the children showed obvious symptoms of heart disease, underscoring the need for routine screening for this under-recognized complication in pediatric liver disease, the researchers noted.
CCM was associated with significantly higher rates of advanced liver scarring (85.19% vs. 55.56%) and significantly higher blood levels of bile acids, a marker of liver damage (158.4 vs. 141.4 micromoles per liter).
The team then examined the children’s survival rates, as well as liver- and heart-related outcomes. Analyses showed children with CCM had significantly lower one-year survival than those without CCM (78.26% vs. 97.67%).
The rates of native liver survival (that is, being alive without the need for a liver transplant) at one year were also lower among children with CCM (67.39% vs. 86.05%).
“CCM was also associated with significantly higher risk of wait-list mortality among patients who did not undergo LT [liver transplant],” as “all 7 patients who died while on the LT wait-list had CCM,” the team wrote.
Among the 14 children who underwent liver transplant (57.14% with CCM), deaths were more frequent in those with CCM (33.33% vs. 16.67%), though the difference was not statistically significant. Other post-transplant outcomes, including length of stay in the hospital, were generally comparable between those with or without CCM.
Among the 10 children who survived beyond one month after liver transplant, five had CCM, and all but one showed resolution of CCM after transplantation.
While well recognized in adults, CCM remains an under-recognized entity in children. The present study adds to the limited but rapidly evolving evidence on cirrhotic cardiomyopathy in the pediatric population.
The researchers noted the study was limited to a relatively small number of participants and a limited follow-up period, and emphasized further research is needed to confirm these findings.
In a letter to the editor published alongside the study, scientists in China wrote that while “this work provides important insights into the field,” it has some technical limitations.
These included questions about the reliability of the CCM definition used in this study, as well as shortcomings of the statistical analyses of survival outcomes, which did not account for the fact that death and liver transplant are competitive outcomes.
For instance, “those with CCM may have experienced delayed transplantation due to [heart] issues, ultimately dying while on the waiting list, making their true risk difficult to accurately reflect,” the scientists wrote.
“Addressing these aspects would strengthen future research in this vulnerable population,” they concluded.
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