Hepatoblastoma: A Parent Guide

Hepatoblastoma is a cancer that forms in the tissues of the liver. It is the most common type of childhood liver cancer. It usually affects children younger than 3 years of age.

It is rare. Only about 100 to 125 cases are diagnosed in North America each year. Among children aged 4 and under with a malignant liver tumor, about 90% have hepatoblastoma.

The number of cases has risen. In the United States, the yearly rate went from 0.8 cases per 1 million children aged 19 and under in 1975 to 1983, up to 2.3 per 1 million in 2020. Nobody is certain why.

Most children with hepatoblastoma have no known cause. But the National Cancer Institute lists these risk factors:

• Aicardi syndrome.
• Beckwith-Wiedemann syndrome.
• Hemihyperplasia, in which one side of the body grows larger than the other.
• Familial adenomatous polyposis (FAP), an inherited condition caused by a change in the APC gene.
• Glycogen storage disease.
• Premature birth with very low birth weight.
• Simpson-Golabi-Behmel syndrome.
• Certain genetic changes, such as trisomy 18.

Two of these deserve extra explanation.

Beckwith-Wiedemann syndrome. Tumors develop in about 10% of people with this condition, and they almost always appear in childhood. Hepatoblastoma and Wilms tumor, a kidney cancer, are the two main ones.

Very low birth weight. The link is strong. In Japanese data, premature infants weighing under 1,000 grams had a 15-fold higher risk of hepatoblastoma.

If your child has hepatoblastoma, ask whether genetic testing or a genetics referral is needed. A diagnosis of FAP in a child changes screening for the whole family.

The National Cancer Institute lists these:

• A lump in the abdomen.
• Swelling in the abdomen.
• Pain in the abdomen.
• Weight loss for no known reason.
• Loss of appetite.
• Nausea and vomiting.

Many parents first notice a firm lump on the right side of the belly while bathing or dressing the child. The child may seem well otherwise. That is common and it is not a sign anyone missed something.

Alpha-fetoprotein (AFP) is a protein found in blood. Many liver tumors make it, so children with liver cancer often have raised AFP levels.

AFP is not a yes-or-no cancer test. Other cancers, benign liver tumors, and some noncancer conditions can also raise it. Newborns normally have high AFP that falls over the first months of life.

AFP still matters a lot. A falling AFP during chemotherapy is one sign the treatment is working, and the National Cancer Institute lists the drop in AFP after treatment among the factors that affect outlook.

The National Cancer Institute lists these tests for childhood liver cancer:

• Serum tumor marker test, which measures AFP.
• SMARCB1 gene testing.
• Complete blood count (CBC).
• Liver function tests.
• Blood chemistry studies.
• MRI with gadolinium, a contrast dye.
• CT scan.
• Ultrasound exam.
• Chest x-ray, to look for spread to the lungs.
• Biopsy.
• Immunohistochemistry, a lab test that stains the tumor cells to identify the type.

The SMARCB1 test is not a formality. Small cell undifferentiated hepatoblastoma is SMARCB1 positive. Rhabdoid tumor of the liver is SMARCB1 negative. They can look alike under a microscope, and they are treated differently.

PRETEXT describes how much of the liver the tumor involves. The liver is divided into four sections. The group is set before any treatment starts.

• Group I. Cancer is in one section. Three sections next to it are free of cancer.
• Group II. Cancer is in one or two sections. Two sections next to each other are free of cancer.
• Group III. Cancer is in three sections and one is free, or in two sections that are not next to each other.
• Group IV. Cancer is in all four sections.

This grouping drives the surgical plan. It answers the key question: can a surgeon remove the tumor and leave enough working liver behind?

Surgery. Removing the tumor is the goal. A partial hepatectomy removes the part of the liver with cancer. If the tumor has spread, surgery may also remove those deposits.

Chemotherapy. Cisplatin is the backbone drug. Chemotherapy is often given first, to shrink a tumor that cannot be removed at diagnosis. Many tumors that start out unresectable become resectable after it.

Liver transplant. When the tumor cannot be removed and enough liver cannot be spared, transplant is an option. Post-transplant survival is about 70% to 80% in children with liver tumors that cannot be removed.

Other options. Radiofrequency ablation, chemoembolization, radioembolization, radiation therapy, and clinical trials may be used in specific situations.

Ask early whether your child should be seen at a center that does pediatric liver transplants. That referral is easier before an operation than after one.

Cisplatin works, but it causes permanent hearing loss in up to 75% of children who receive it. Hearing loss in a toddler affects speech and school for life, so this is not a small side effect.

There is a drug that reduces it. Sodium thiosulfate (Pedmark) is approved by the FDA for patients aged 1 month through 18 years with localized tumors that have not spread. It is given as a 15-minute infusion after the cisplatin infusion.

In a Children's Oncology Group trial, 44% of children who got sodium thiosulfate had hearing loss, compared with 58% who did not. In a UK-led trial, the figures were 39% versus 68%.

Ask directly: is my child eligible for sodium thiosulfate, and will hearing be tested before, during, and after treatment?

Cisplatin needs close watching, and so does the tumor itself.

• Call 911 or go to an emergency department if your child goes floppy, grey or hard to wake, or if the belly swells fast and turns hard and very painful. A tumor that bleeds inside can do both.
• Ring the oncology line the moment your child spikes a fever during chemotherapy, whatever the hour, and expect to be sent in. A fever on chemotherapy is an emergency, not a same-day call. Follow your center's fever rule exactly, and if no one picks up quickly, take your child to the emergency department and say they are on cancer treatment.
• Call your care team the same day if your child passes much less urine than usual, or the face, hands or legs puff up, or the tiredness is out of proportion to the week. MedlinePlus lists these among the cisplatin effects to report immediately, because they can mean kidney injury.
• Call your care team within a day or two if hearing seems to drop, ears ring, or your child complains of dizziness. Say it plainly to the team, since cisplatin hearing loss does not come back.
• Call your care team within a day or two if hands or feet start burning, tingling or hurting, or muscle cramps become a regular thing.

Outlook depends on many things: how far the cancer has spread, tumor size, the histology type, whether there is spread to other organs, the number of tumors, whether the tumor has an intact capsule, how it responds to chemotherapy, whether it can be removed, whether transplant is possible, how AFP falls after treatment, the child's age, and whether the cancer has come back.

The overall picture has improved a great deal. In a Children's Oncology Group phase 3 trial in children with hepatoblastoma, the 5-year overall survival rate was 91%, and more than 90% had no symptoms of liver cancer or recurrence. That trial also showed some children could receive two cycles of cisplatin, fluorouracil, and vincristine instead of four.

Ask your child's oncologist what your child's own risk group is, and what the numbers are for that group. General figures do not answer the question you are actually asking.

• Hepatoblastoma — National Cancer Institute
• Childhood Liver Cancer Treatment (PDQ) Health Professional Version — National Cancer Institute
• Childhood Liver Cancer — National Cancer Institute
• Less Chemo for Some Children with Liver Cancer — National Cancer Institute
• Sodium Thiosulfate Reduces Hearing Loss in Kids with Cancer — National Cancer Institute
• Cisplatin Injection — MedlinePlus, National Library of Medicine
• Beckwith-Wiedemann Syndrome — MedlinePlus Genetics, National Library of Medicine