Hepatoblastoma: Causes, Symptoms & Treatment

Hepatoblastoma is the name given to a rare malignant (malignant) embryonal tumor on the liver that mainly affects infants and young children. If the tumor is diagnosed early enough before it metastasizes, surgical removal of the tumor offers a good chance of survival.

What is hepatoblastoma?

Hepatoblastoma is an embryonal tumor on the liver, so it arises on liver cells that are not yet fully differentiated. It mostly affects infants and young children, with a maximum incidence between 6 months and 3 years of age. Only in exceptional cases do children over the age of 15 develop hepatoblastoma. Initially, there is hardly any pain, so that the tumor – especially since it is also rare – is usually only noticed during routine examinations. The hepatoblastoma is usually palpable and in some cases there may be visible liver dysfunction due to yellowing of the skin. The embryonal tumor is subject to different physiologic conditions and requires different therapies than a liver tumor of fully differentiated liver cells (hepatocellular carcinoma) and therefore must be distinguished from the latter.

Causes

Hepatoblastoma is causally associated with various genetic defects, including the rare Beckwith-Wiedemann syndrome (hemiplegic asymmetric giant stature) or other hemiplegic growth problems. Similarly, hepatoblastomas have been associated with familial, autosomal dominant inherited, adenomatous polyposis (development of multiple polyps in the colon) and with extreme prematurity. Japanese studies have demonstrated a significant statistical correlation between the incidence of hepatoblastoma and birth weights of less than 1,000 g in preterm births. The extent to which this is a coincidental or causal relationship has not yet been conclusively determined. An equally (as yet) uncertain association exists with Li-Fraumeni syndrome, which is caused by a mutation at a tumor suppressor gene in the germline and can lead to multiple tumors at an early age.

Symptoms, complaints, and signs

Initially, hepatoblastoma is often not noticeable symptomatically. Only a painless swelling of the abdomen in the child is occasionally observed. In most cases, the disease begins before the end of the second year of life. In rare cases, a later or earlier onset of the disease is also possible. Boys are affected more often than girls. After a longer symptom-free period, affected children suffer from nausea, vomiting and weight loss. Before that, in rare cases, abdominal pain and jaundice may occur if the tumor leads to obstruction of the bile ducts at an early stage. Overall, the disease is characterized by increasing general weakness. Developmental delays occur, but only become noticeable after a longer duration of the disease. In boys, puberty may be brought forward (pubertas praecox). Other symptoms do not appear until metastases have formed. These depend on which organs are affected by the metastases. The lungs are most frequently affected. Thus, there are often breathing difficulties, coughing fits and sometimes spitting blood. In rare cases, metastases occur to the bones, bone marrow and brain. This leads to bone pain, frequent bone fractures, severe limitations in movement, seizures, bleeding tendency, anemia and general fatigue. With timely treatment and complete removal of the tumor, there is a good chance of complete recovery.

Diagnosis and course

When hepatoblastoma is first suspected, several diagnostic procedures are available that may complement each other. Initially, a nonspecific laboratory examination is offered, in which platelets and ferritin as well as LDH (lactate dehydrogenase) concentration and liver enzyme levels are determined. An elevated LDH concentration provides evidence of cell or organ damage in the body. A specific laboratory examination should provide information as to whether the tumor marker alpha-fetoprotein (AFP) is significantly elevated, because in 80% – 90% of cases this value is elevated and, conversely, a hepatoblastoma is definitely present with corresponding AFP values. For further clarification, diagnostic imaging procedures are available such as ultrasound of the abdominal cavity, X-ray thorax, chest CT or upper abdominal CT, in each case with contrast media.Histopathological examinations should also be performed to confirm a positive diagnosis. The course of the disease, if left untreated, leads to liver failure and the formation of metastases, predominantly in the lungs, so that a fatal course is predicted.

Complications

Because hepatoblastoma is a tumor, it presents with the usual symptoms and complications of cancer. In the worst case, this can lead to the patient’s death if the tumor spreads to other regions of the body and causes damage there. If hepatoblastoma is diagnosed and removed at an early stage, life expectancy is usually not reduced. Hepatoblastoma primarily causes severe abdominal pain and jaundice. The abdomen swells and appears bloated. Furthermore, affected patients suffer from vomiting and nausea. It is not uncommon for the symptoms to lead to weight loss and deficiency symptoms. The symptoms often also lead to psychological upsets and irritability in the patient. If hepatoblastoma is not treated, metastases usually develop in the lungs and liver, causing both organs to fail. This results in the death of the patient. If diagnosed early, the tumor can be removed. However, the further course of the disease depends on the region and the extent of the tumor. In some cases, transplantation is necessary if the internal organs have been damaged.

When should you go to the doctor?

Parents who notice signs of jaundice in their child should contact the pediatrician. If the symptoms persist for more than two to three days, a serious illness is suspected. A specialist must clarify the symptoms and initiate treatment if necessary. A diagnosed hepatoblastoma represents a serious disease. Parents should consult regularly with the medical professional in charge and inform the doctor of any unusual symptoms. If metastasis is suspected, the physician will perform a comprehensive ultrasound examination and refer the parent to a specialist for further treatment. Spread of the tumor may be inconspicuous at first, but sometimes causes symptoms. For example, if the child experiences severe pain, is particularly irritable or suffers from breathing difficulties, an immediate visit to the doctor is indicated. Nausea, vomiting or spitting blood should also be clarified, as these symptoms indicate that the tumor has metastasized to the lungs. Hepatoblastoma usually needs to be removed surgically or with chemotherapy or radiation therapy. After treatment is complete, parents must continue to watch for abnormalities and have the child examined by a doctor on a regular basis.

Treatment and therapy

The goal of any therapy is to remove the tumor completely and to monitor the further postoperative course of the disease at initially narrow time intervals of 6 weeks. If hepatoblastoma is deemed inoperable, prior cisplatin-containing chemotherapy may be necessary. Radiation therapy has little effect in this disease and is therefore not an option. After chemotherapy is completed, the tumor is surgically removed, which is only possible if it is confined to specific areas of the liver. If the hepatoblastoma is not (yet) operable after the first chemotherapy, further chemotherapy may well be worthwhile in order to take another chance of having the tumor regress to an operable state. During total resection of the tumor, careful attention is paid to ensure that no residual tissue remains, which can quickly develop into a recurrence. Postoperative chemotherapy follows again, which should include a combination of cytostatic agents if possible, as hepatoblastomas can develop resistance to cisplatin as the sole agent. In children with inoperable tumors who also do not respond to preoperative chemotherapy, the alternative option is to occlude the feeding and draining vessels supplying the tumors to interrupt the tumor supply if possible. Otherwise, the only remaining treatment option is a liver transplant. During follow-up after total resection of the tumor, the development of the AFP tumor marker is crucial. A renewed increase already indicates the development of a new tumor one to two months before a recurrence that can be diagnosed with imaging techniques.

Outlook and prognosis

The prognosis of hepatoblastoma depends on treatment. With therapy, it is good. Without treatment, the disease always leads to death. It is a cancer of the liver characterized by four stages. During the course of the disease, metastases often occur in the lungs. Less frequently, the brain, bones and bone marrow are affected. If therapy is not started until after the first metastases have appeared, the only thing that can be done is to try to increase the life expectancy of the children and to maintain or restore their quality of life. However, whether a complete or at least long-term cure can be achieved under these circumstances depends on the individual case. As a rule, however, a complete cure is no longer possible when metastases occur. Nevertheless, the chances of a cure for hepatoblastoma are very good if the tumor is completely removed before metastases develop. In doing so, no remnants may remain in the body. However, this is very feasible by performing cytostatic therapy prior to surgery. With this therapy, in which certain cytostatic drugs are applied to the hepatic artery, the certainty increases that the primary tumor can be contained and resected without any remnants. This increases the five-year survival rate for hepatoblastoma to about 80 percent. Thus, eight out of 10 children can be completely cured if the tumor is completely resected.

Prevention

Meaningful prophylaxis to prevent hepatoblastoma is not possible because the development of the disease is most likely due to inherited genetic defects or genetic abnormalities. Therefore, a family history is important. If specific cases of the disease are known in the family, close observation of the child and possibly prophylactic regular monitoring of the AFP tumor marker is recommended.

Follow-up

In most cases of hepatoblastoma, the affected person has very few options for follow-up care. In the worst case, the disease can lead to the death of the affected person if it is detected late. Therefore, the early detection of this disease with subsequent treatment is paramount. A doctor should be consulted at the first signs and symptoms to prevent further complications. The tumor is usually removed by surgery. After such an operation, the patient must rest and take care of his or her body. They should refrain from exertion or other stressful or physical activities in order not to put unnecessary strain on the body. Often, patients are also dependent on the support and help of their own family, which can alleviate psychological upsets or depression. Even after the removal of the hepatoblastoma, it is not uncommon for regular examinations of the internal organs by a physician to be necessary. In this context, taking medications is also often useful, and care should be taken to ensure proper dosage with regular use.

What you can do yourself

Heptoblastoma is usually treated with chemotherapy or radiation therapy. Affected people can support the treatment by taking various measures. Until therapy begins, there is time for those affected to gather information and find a way to cope with the disease. Basically, body and psyche have to be prepared for the treatment. Heptoblastoma patients should get enough exercise, take in enough nutrients and drink plenty of fluids shortly before chemotherapy. Many side effects can be alleviated by remedies from complementary medicine, such as bitter substances for loss of appetite and the homeopathic preparation Nux vomica for nausea and vomiting. There are also many ways to support recovery during therapy. For example, moderate endurance sports are recommended – ideally on a regular basis and outdoors – because exercise promotes oxygen supply and improves the cellular environment. A healthy and balanced diet can additionally alleviate the weakening effect of chemotherapy and support the body in its fight against heptoblastoma. The diet should mainly contain foods rich in trace elements and vitamins. In consultation with the doctor, a targeted detoxification can also be carried out to deacidify the body and remove the breeding ground for cancer cells.