Attention A T users. To access the menus on this page please perform the following steps. 1. Please switch auto forms mode to off. 2. Hit enter to expand a main menu option (Health, Benefits, etc). 3. To enter and activate the submenu links, hit the down arrow. You will now be able to tab or arrow up or down through the submenu options to access/activate the submenu links.

Locator

Contact

Ask a Question

Toll Free Numbers

Locator

Hospitals and Clinics

Vet Centers

Regional Benefits Offices

Regional Loan Centers

Cemetery Locations

VA » Health Care » Viral Hepatitis and Liver Disease » Liver Cancer » What's New » Background and Epidemiology

Viral Hepatitis and Liver Disease

Background and Epidemiology

for Health Care Providers

Background and Epidemiology - Liver Cancer

Introduction
Risk Factors
Diagnosis
Prevention
Related pages
References

Introduction

Hepatocellular carcinoma (HCC) is a cancer that is becoming increasingly common in the United States.(1) Its effects on the health of Americans, and particularly Veterans, are likely to grow substantially over the coming decades as the later health consequences of the hepatitis C epidemic continue to play out.(2)

HCC is the fifth most common cancer in the world and the most common type of liver cancer. The incidence of HCC in the United States is approximately 2.4 per 100,000 persons per year, and rising.(3) Chronic infection with hepatitis C virus (HCV) is now a major risk factor for the development of HCC in developed countries. Patients with advanced liver disease, particularly cirrhosis, are those at risk for HCC and should be screened every 6 months for its development. The risk of developing HCC for a patient with HCV-related cirrhosis is approximately 2 to 6% per year.(4)

Risk Factors

Chronic hepatitis B virus (HBV) infection, chronic HCV-related cirrhosis, and cirrhosis of any etiology are the major risk factors for the development of HCC. Patients with HBV are known to be at risk for HCC even without cirrhosis, so all patients with chronic HBV (those who are hepatitis B surface antigen positive) should be considered for HCC screening.(5) Individuals with chronic HBV who are at increased risk for HCC include men, anyone over age 45, and those with cirrhosis or a family history of HCC.(6)

In patients with HCV, only those with advanced liver disease (particularly cirrhosis) have been shown to be at high risk for HCC, so screening should be applied only to these patients.(7) Other risk factors include inherited metabolic diseases such as hemochromatosis and tyrosinemia. Additional risk factors for HCC development include older age, alcohol use, and exposure to aflatoxin, particularly in developing countries.

Diagnosis

Clinical Presentation

Clinical signs and symptoms present in the later stages of HCC. They may include:

right upper quadrant pain or fullness
weight loss
elevated liver function tests, particularly an elevated alkaline phosphatase
increases in AFP levels
infrequently: polycythemia, hypoglycemia, hypercalcemia, dysfibrinogenemia, or intraperitoneal bleeding due to tumor rupture

Histological Evaluation

Because the clinical presentation of HCC is not entirely specific, histological evaluation with a percutaneous biopsy is sometimes performed to aid in the diagnosis. This often is not done, however, in patients with known cirrhosis who are found to have a new mass lesion concerning for HCC during screening. In particular, a nodule greater than 2 cm in diameter in this setting has a greater than 95% likelihood of being an HCC.(16) According to European Association for the Study of the Liver guidelines, confirmation of arterial hypervascularity of the lesion by 2 additional imaging techniques (CT, MRI, or angiography), or 1 additional imaging technique if the AFP is greater than 400 ng/mL, is sufficient for a diagnosis of HCC without a biopsy.(17) Smaller lesions in a cirrhotic patient also often represent early HCCs. If a patient with a concerning lesion is being considered for referral for liver transplantation, consultation with the referring center can be undertaken before proceeding with a percutaneous biopsy of the lesion.

Prevention

Primary and secondary prevention of HCC

Prevention efforts have been directed at prevention of the underlying liver disease. Primary prevention of HCV infection includes thorough screening of the blood supply and risk-reduction interventions in people who inject drugs. Secondary prevention of the progression from HCV-related cirrhosis to HCC has been shown following interferon-alfa treatment of cirrhosis.(46, 47) Limiting alcohol intake and reducing obesity in patients with HCV may also lead, through decreased liver disease progression, to a reduction in HCC.

HBV immunization programs have successfully reduced the incidence of HBV-associated HCC. In Taiwan, the rate of HCC in children aged 6 to 9 decreased from 5.2 per million before a neonatal HBV vaccination program began in 1984 to 1.3 per million in the first vaccinated cohort.(48)

Prevention of recurrence after resection

Kubo and colleagues randomized 30 HCV-positive men after HCC resection to either 2 years of interferon-alfa or no postoperative therapy.(49) The rate of tumor recurrence was significantly lower in the interferon-alfa group than in the control group, and the authors concluded that postoperative interferon-alfa therapy had a role in decreasing recurrence after resection of HCV-related HCC. Agents such as polyprenoic acid and acyclic retinoids are also being investigated in the hope of preventing second primaries following resection of HCC.(50)