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Pediatric Liver Center of Excellence: Clinical Research Fuels Innovative Advancements in Care


The Pediatric Liver Center of Excellence at UCSF Benioff Children’s Hospitals delivers interdisciplinary, coordinated care to children with liver and bile duct disorders. The Center also has specialized programs, such as the Liver Tumor and Hepatoblastoma Clinic which treats children with hepatoblastoma, hepatocellular carcinoma (HCC) and fibrolamellar carcinoma. Clinical research is essential for advancing the management of liver tumors. Pediatric hematologist-oncologist Arun Rangaswami, MD, and pediatric surgeon Amar Nijagal, MD, discuss the groundbreaking research spearheaded by the center’s clinical team.

Q: How is UCSF’s Pediatric Liver Center of Excellence unique?

A: The most important characteristic of our program is that we have excellent interdisciplinary communication. Surgery, oncology, radiology, pathology and interventional radiology all work in concert and frequently see patients together in person or virtually.

Second, our leaders are involved with national and international clinical organizations focused on pediatric liver cancer. For example, several members are active within the Children’s Oncology Group, a National Cancer Institute-supported organization devoted exclusively to childhood and adolescent cancer research. In addition, I, Arun Rangaswami, MD, facilitate an international hepatobiliary tumor board, and Soo-Jin Cho, MD, PhD, serves as one of the pediatric pathologists for the liver tumor committee of the Children’s Oncology Group and the Society for Pediatric Pathology. Our team has expertise in reviewing the pathology for rare and unusual cases, which is paramount.

Third, the UCSF 500 exome sequencing panel is one of the most powerful in the country. It improves our ability to find relevant DNA mutations that can provide prognostic or therapeutic information. If a familial predisposition is uncovered, we can screen the patient and their family members. For example, a recent patient had a resection at another facility but had a rapid recurrence at the resection margin, suggesting that the resection was incomplete. We sequenced the tumor and found it had a mutation that made it resistant to the chemotherapy being administered. Once the chemotherapy was adjusted, the patient responded beautifully.

Lastly, our team is actively conducting innovative research and leading clinical trials. For example, I, Amar Nijagal, MD, and hepatologist Bruce Wang, MD, presented research at the 2023 International Pediatric Liver Tumor Research Meeting in Boston on their work focused on refining the molecular characteristics of hepatoblastoma. As a result of our ongoing work in this area, UCSF will host this research meeting in 2025.

Q: How do clinical trials help physicians treat pediatric liver tumors?

A: Clinical trials are essential tools for continually improving outcomes in pediatric cancer patients. With children’s cancer research, we can study large cohorts of children with the same diagnosis. We can analyze the results of a study and conclude whether a therapy was better, the same or inferior to current protocols to craft the next trial to improve outcomes further.

In general, pediatric oncologists are very invested in enrolling patients in clinical trials, and that commitment has led to immense improvements in outcomes in almost every pediatric cancer diagnosis. For example, in the 1920s, leukemia was fatal in 80% of pediatric cases. Today, only 5% to 10% of children with leukemia succumb to their illness. Those gains were accomplished through systematic enrollment in clinical trials.

Pediatric liver cancer, specifically, is a rare cancer that occurs in less than 2% of patients. The incidence of hepatoblastoma is increasing in the United States and Europe. The reasons for this are unclear, but several potential epidemiological factors have been identified and research continues in this area. The only way to make advancements in diagnosis and treatment is by conducting prospective clinical trials. Otherwise, every institution might treat tumors differently, and we will never learn which treatment works best.

Q: In which clinical trials are UCSF participating?

A: UCSF hosts several pediatric liver cancer trials and is involved with several international studies. For example, we are involved with developing and administering the Pediatric Hepatic International Tumor Trial (PHITT) underway in North America, Europe, Australia, New Zealand, Japan and other sites in Asia. The trial has multiple arms; we helped write the high-risk and hepatocellular carcinoma arms. This is the first time pediatric HCC has been studied in this magnitude.

We recently opened a phase-two trial with the Dana Farber Cancer Institute, Cincinnati Children’s Hospital Medical Center and Texas Children’s Hospital to look at immune checkpoint inhibition using pembrolizumab. In addition, UCSF anticipates enrolling patients in several pilot studies that we are helping develop, including trials studying high-risk hepatoblastoma and fibrolamellar carcinoma. The fibrolamellar carcinoma trial will investigate a novel molecular-targeted therapy along with a chemotherapy backbone. UCSF also is involved with several multi-institutional trials, including an industry-sponsored trial examining a chimeric antigen receptor T-cell (CAR-T) therapy to target alpha-fetoprotein, a molecule secreted by most pediatric liver cancers.

Q: How has the treatment of liver pathologies changed in recent years?

A: Fibrolamellar carcinoma was historically treated as an HCC, but we now know there is a molecular aberration, a chimeric fusion that distinguishes it from HCC. In addition, we are increasingly recognizing that not all hepatoblastomas are the same. A significant subset has genetic or genomic aberrations, causing tumors to behave more aggressively. For example, a 12-year-old patient came to us after being provisionally diagnosed with hepatoblastoma. Through genomic sequencing, we learned that he had a telomerase reverse transcriptase, a promoter mutation. Armed with this information, we treated the patient with high-risk therapy before moving forward with a liver transplant because we felt the risk of recurrence with a conventional resection was very high in this case.

To find innovative ways to treat liver tumors, you need a pathologist who is savvy about histological features and can sequence that patient to identify alterations.

Patients of UCSF’s Pediatric Liver Center of Excellence benefit from interdisciplinary care and innovative treatments. Clinical trials hosted at the center offer new hope for children with liver and bile disorders. View more information about the center and how to refer a patient.