Rare liver cancer found in toddler with Alagille syndrome

A toddler boy with cirrhosis, or permanent liver scarring, due to Alagille syndrome developed a hepatoblastoma, a type of liver cancer that typically occurs in children but may be very rare in those with Alagille, according to a report from India.

While Alagille is associated with an increased risk of liver cancer, the researchers said their case is likely the first reported case of hepatoblastoma in that specific patient population.

“Hepatoblastoma should be suspected in any child with AGS [Alagille syndrome] presenting with a right upper quadrant mass even in the setting of chronic liver disease,” the researchers wrote. An early diagnosis of hepatoblastoma may help improve clinical outcomes and guide decisions.

The case report, “Hepatoblastoma in a cirrhotic child with Alagille syndrome,” was published in BMJ Case Reports.

Alagille syndrome is a genetic disease that can cause a range of symptoms, including liver defects, heart issues, and characteristic facial features.

Liver defects may lead to transplant need

Liver problems in Alagille are mostly caused by a reduced number of bile ducts inside the liver. These ducts transport bile, a fluid that helps the body digest fats and fat-soluble vitamins, from the liver to the intestines. These liver defects result in bile accumulation in the liver, which damages the organ, and bile acid leakage into the bloodstream, which leads to symptoms such as jaundice (yellowish skin and whites of the eyes) and itching.

Over time, liver damage can cause cirrhosis and liver failure, and an Alagille patient may eventually require a liver transplant.

Alagille patients are also at a higher risk of developing liver tumors and cancer, including hepatocellular carcinoma, the most common type of liver cancer. There are several reports of hepatocellular carcinoma among Alagille patients as young as 4, with or without cirrhosis, but not of “hepatoblastoma in a cirrhotic child with AGS,” the researchers wrote.

The researchers described the rare case of a toddler with Alagille and cirrhosis who developed a hepatoblastoma.

The boy, with no family history of metabolic or genetic diseases, had had jaundice and pale stools, another common sign of liver problems, since early infancy. Imaging scans showed no signs of biliary atresia or liver mass lesions. Biliary atresia is a rare liver disease affecting infants that is marked absence or blockage of certain bile ducts.

He received treatment with ursodeoxycholic acid, a medication sold as Urso and Actigall that works to improve bile flow, and supplementation of fat-soluble vitamins.

The boy continued to show jaundice and later developed itching, abdominal swelling, and blood clotting problems. A liver biopsy did not suggest biliary atresia or any metabolic or genetic disorder.

As the cause of his worsening symptoms couldn’t be pinpointed, he was referred to another hospital for a liver transplant.

Scans suggest cancer

Doctors there noted that the boy had a broad forehead, widely spaced eyes, and a pointed chin — all characteristic facial features of Alagille. He also showed impaired growth for his age, and both his liver and spleen appeared enlarged. Blood tests showed high levels of bilirubin and certain liver enzymes, common markers of liver damage, and of alpha-fetoprotein, a tumor marker.

Further imaging scans revealed an enlarged liver with abnormal nodules (growths) and blood vessel patterns that suggested hepatocellular carcinoma.

“As our patient had undiagnosed chronic liver disease with liver mass, the possibility of [hepatocellular carcinoma] was high, and we went ahead with the liver transplantation awaiting [results from comprehensive genetic testing],” the researchers wrote.

The boy was prepared for a liver transplant, without undergoing chemotherapy “because of the known poor response of childhood Hepatocellular Carcinoma (HCC) to chemotherapy and side effect profile especially in a decompensated child awaiting liver transplantation,” the team wrote.

Examination of the removed liver showed hepatoblastoma cells.

“A diagnosis of hepatocellular carcinoma was strongly considered,” the researchers wrote, but close examination of liver tissue “later demonstrated the lesion to be [a] hepatoblastoma.”

After the transplant, the boy received three cycles of chemotherapy.

In the meantime, genetic testing confirmed an Alagille diagnosis, and re-examination of the liver biopsy sample showed fewer than normal bile ducts.

After the third cycle of chemotherapy, the boy developed gastroenteritis with fever, leading to septic shock, a serious body-wide reaction to infection that causes organs to shut down. He also developed other complications, and died.

While the boy “was doing well on chemotherapy, unfortunately, he developed sepsis and succumbed to multiorgan dysfunction,” the team wrote.

“Although we lost our kid … we have been very thankful to the doctors involved in the child’s treatment,” the toddler’s parents said. “They had put in their best efforts first to give us a diagnosis [Alagille] which we didn’t have [before] … [and that] may have implications in subsequent pregnancies too.”

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