eMedicine Specialties > Pediatrics: General Medicine > Oncology

Hepatocellular Carcinoma

Author: Girindra G Raval, MD, Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine
Coauthor(s): Paulette Mehta, MD, MPH, Professor of Hematology/Oncology, Department of Internal Medicine, Co-Director of Fellowship Program, Medical Director of Hematology/Oncology at CAVHS, University Arkansas for Medical Sciences and Central Arkansas Veterans Hospital System
Contributor Information and Disclosures

Updated: Feb 23, 2009

Introduction

Background

Hepatocellular carcinoma (HCC) is an aggressive hepatic neoplasm that most commonly affects adults. Nevertheless, children who are affected with biliary atresia, infantile cholestasis, glycogen-storage diseases, and a wide array of cirrhotic diseases of the liver are predisposed to developing hepatocellular carcinoma. 

The 2 pathological subtypes are classic hepatocellular carcinoma and fibrolamellar carcinoma. Although surgical resection remains the mainstay of curative therapy, adjunctive chemotherapeutic and radiotherapeutic strategies are also helpful. The presenting signs and symptoms, epidemiology, biology, and current therapeutic strategies for hepatocellular carcinoma follow.

Pathophysiology

The pathophysiology of hepatocellular carcinoma is not clearly understood; however, underlying liver dysfunction, especially cirrhosis, is a predisposing condition. In contrast to adults, most pediatric hepatocellular carcinomas arise de-novo, without underlying liver abnormalities.¹ Karyotypic abnormalities are not common. Although children and adolescents are unlikely to have chronic liver disease, congenital liver disorders increase the chance of developing hepatocellular carcinoma. These findings are suggestive of a multihit model of malignant transformation in hepatic tissue.

Frequency

United States

Primary liver tumors are uncommon in children and adolescents, accounting for approximately 0.5-2% of all neoplasms in these age groups. Annual incidence in children is approximately 0.5 cases per million. This is the second most common hepatic malignancy in children after hepatoblastoma.

International

The international incidence is highly associated with endemic hepatitis B exposure such as Southeast Asia and sub-Saharan Africa. In China, aflatoxin exposure has been associated with the development of hepatocellular carcinoma in the fifth, sixth, and seventh decades of life.

Mortality/Morbidity

Morbidity and mortality directly correlate with surgical resectability of the primary tumor. Although chemotherapy and radiation control may improve in the clinical course, in selected patients, the overriding objective of these modalities is to render the tumor completely resectable. (See Surgical Care for details.)

Race

In older adults, race may play a role in the development of hepatocellular carcinoma; however, excluding environmental factors from these determinations is difficult. Because the condition is so rare in adolescents and children (0.5 cases per million population), ethnic data are not readily available for these age groups. Most studies of hepatocellular carcinoma have involved patients of Asian descent.

Sex

Because most congenital forms of liver dysfunction (eg, urea cycle defects, storage diseases, hereditary hemochromatosis) are inherited in an autosomal recessive manner, the female-to-male occurrence ratio in children and adolescents is equal. After congenital Hepatitis B infection the life time risk of developing hepatocellular carcinoma is 50% for men and 20% for women.

Age

The incidence is lower in infants and higher in children and adolescents. The patient is usually an older school-aged child or adolescent, often with no preexisting diagnosis of cirrhotic liver disease. In patients with underlying liver dysfunction, the likelihood of developing the condition increases with age.

Clinical

History

Elements to ascertain include a prior history of hepatitis B or hepatitis C, chronic cirrhosis, or other diseases that tend to induce liver dysfunction. Co-infection with human immunodeficiency virus (HIV) may further enhance a patient's risk for developing hepatocellular carcinoma (HCC). Most patients complain of abdominal pain, weight loss, and diminished appetite. In patients with a history of chronic liver disease, a change in routine symptoms may indicate the presence of a liver tumor.

Most patients with hepatocellular carcinoma present with a slowly enlarging, right upper-quadrant mass that may be found during a routine physical examination, brought to medical attention by the patient, or discovered by the patient's parents. Many children also experience localized pain, nausea, vomiting, and weight loss. Nearly 25% of patients present with jaundice.

In adults, chronic hepatitis secondary to alcohol exposure, infection with hepatitis, and hereditary hemochromatosis are predisposing factors. Aflatoxins and other environmental factors also are likely to play a role in the pathogenesis in adults. In comparison, children are far more likely to have inherited errors of metabolism, such as tyrosinemia or urea cycle enzymopathies. Liver diseases that cause cirrhosis increase risk for developing hepatocellular carcinoma (eg, alpha-1 antitrypsin deficiency).

Children with biliary atresia, chronic cholestasis, or glycogen-storage diseases are at increased risk. Symptoms can be masked in children with preexisting hepatic diseases, and, accordingly, a change in a chronic disease pattern merits careful consideration for the possibility of a new malignancy.

Physical

The physical examination often reveals abnormalities attributable to a hepatic tumor. In advanced cases, or when the primary tumor is large, the liver may be palpable below the right costal margin. In addition, deep palpation often reveals pain, especially over the location of the liver. Scleral icterus and other signs of jaundice are frequent. The patient's history also may indicate weight loss, the extent of which may be observed during the examination. In patients in whom metastatic disease to the lungs is in question, percussion of the lungs may reveal a difference in density, suggesting a pleural effusion. Other painful sites discovered on the examination should lead to radiographic imaging to determine the extent of malignant spread. This is particularly true for bone pain at presentation.

Causes

Although no cause has been clearly elucidated, the risk factors for children and adolescents include a history of hepatitis B or C, alpha-1 antitrypsin deficiency, hereditary tyrosinemia, Gaucher disease, congenital biliary atresia, urea cycle defects, severe iron overload (as occurs with thalassemia or sickle cell disease requiring chronic blood transfusion), or other forms of chronic cirrhosis or liver dysfunction. Acquired hepatitis C from blood product transfusions is an important risk factor because the risk of hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis is highest (2-8% per year).

In areas of the world where hepatitis B or C are endemic, the incidence is likely to be proportionally increased in children and adolescents.

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