Routine Screening for HCC in the Inactive Hepatitis B Carrier?
Routine Screening for HCC in the Inactive Hepatitis B Carrier?
Is routine screening for hepatocellular carcinoma (HCC) recommended for the hepatitis B patient in the inactive carrier state? If the viral load is 24,000 copies/mL (as a measure of the rate of viral replication in determining whether the patient is indeed in the inactive carrier state), would this change your recommendation regarding screening?
This first question that arises related to the issue of screening for HCC is whether there is a randomized controlled trial that has shown a survival benefit in screened individuals. It is unlikely that trials with sufficient size and sufficiently long follow-up will ever be conducted to demonstrate conclusively whether screening is beneficial in prolonging survival. However, evidence that HCC can be detected early with periodic screening is based on 1 large randomized trial from China, 1 population-based study from Alaska, several clinic-based studies, as well as meta-analyses. In addition, prolonged survival of patients with small tumors undergoing specific treatment has been demonstrated in several cohort studies and case series.
A second question is whether the disease burden of HCC warrants screening. According to the SEER (Surveillance, Epidemiology, and End Results) database, the incidence of HCC in the United States between 1980 and 1995 increased by 70%, associated with a 41% increase in mortality. In cirrhotic patients, an annual HCC incidence rate of 2% to 9% has been observed.
Another question that is relevant to the initial question posed (regarding screening) is, who warrants screening? Risk factors for HCC include: cirrhosis of any cause (the most dominant risk factor), increasing age (which may be a surrogate for advanced liver disease), male sex, chronic hepatitis B, and a positive family history of HCC (specific genetic factors yet to be determined). Screening is generally recommended in all individuals with chronic hepatitis B over 40 years of age. Although the risk of HCC is highest in hepatitis B patients with cirrhosis (2%-3% per year), particularly those with high levels of viral replication (positive hepatitis B e antigen [HBeAg] or levels of serum hepatitis B virus [HBV] DNA > 10 copies/mL), there remains a risk (0.5% per year) in those patients who are inactive carriers without cirrhosis (with negative HBeAg and serum HBV DNA levels < 10 copies/mL), and even in the unusual patient who clears hepatitis B surface antigen later in life.
The next question regarding screening for HCC is whether there are good screening tests. The ability to detect HCC is highly dependent on the test used (ie, test performance characteristics of sensitivity and specificity), the experience of the center, the size of the lesion, and "biological behavior" of the tumor. Alpha-fetoprotein (AFP) has a sensitivity of about 50% to 60% (using a cut-off value of 20 ng/mL, but at a loss of specificity). More data are needed to determine the value of other tumor markers, such as glypican-3 protein induced by vitamin K (PIVKA) or fractions of AFP. Ultrasound has a sensitivity of approximately 60% to 80% (for lesions 1-2 cm), whereas computed tomography (CT) and magnetic resonance imaging (MRI) have a sensitivity of about 60% to 90% (for lesions 1-2 cm).
Screening is based on the issue of whether there are good treatment options for HCC. Candidates for liver transplantation include those patients with a single lesion < 5 cm in diameter or 2-3 lesions, each < 3 cm in diameter. Surgical resection is reserved for HCC in noncirrhotic patients or selected Child's class A patients. Palliative options in nonsurgical candidates, or as a bridge to transplantation, include percutaneous ethanol injection, radiofrequency ablation, or chemoembolization.
A final question to be considered is whether screening for HCC is acceptable, affordable, and accessible. Screening should be performed with the idea of offering some form of therapy. A general principle of screening, which also applies to screening for other malignancies, is that screening should only be undertaken in individuals who would be treated if diagnosed with the disease. Screening for HCC may be cost-effective in some settings (ie, high incidence areas). There may be medicolegal ramifications of not offering screening. The most common screening strategy for HCC, which has become a standard of care in patients with chronic hepatitis B and in all patients with cirrhosis, is serum AFP and ultrasound performed every 6 months, with CT or MRI as an alternative to ultrasound.
Is routine screening for hepatocellular carcinoma (HCC) recommended for the hepatitis B patient in the inactive carrier state? If the viral load is 24,000 copies/mL (as a measure of the rate of viral replication in determining whether the patient is indeed in the inactive carrier state), would this change your recommendation regarding screening?
This first question that arises related to the issue of screening for HCC is whether there is a randomized controlled trial that has shown a survival benefit in screened individuals. It is unlikely that trials with sufficient size and sufficiently long follow-up will ever be conducted to demonstrate conclusively whether screening is beneficial in prolonging survival. However, evidence that HCC can be detected early with periodic screening is based on 1 large randomized trial from China, 1 population-based study from Alaska, several clinic-based studies, as well as meta-analyses. In addition, prolonged survival of patients with small tumors undergoing specific treatment has been demonstrated in several cohort studies and case series.
A second question is whether the disease burden of HCC warrants screening. According to the SEER (Surveillance, Epidemiology, and End Results) database, the incidence of HCC in the United States between 1980 and 1995 increased by 70%, associated with a 41% increase in mortality. In cirrhotic patients, an annual HCC incidence rate of 2% to 9% has been observed.
Another question that is relevant to the initial question posed (regarding screening) is, who warrants screening? Risk factors for HCC include: cirrhosis of any cause (the most dominant risk factor), increasing age (which may be a surrogate for advanced liver disease), male sex, chronic hepatitis B, and a positive family history of HCC (specific genetic factors yet to be determined). Screening is generally recommended in all individuals with chronic hepatitis B over 40 years of age. Although the risk of HCC is highest in hepatitis B patients with cirrhosis (2%-3% per year), particularly those with high levels of viral replication (positive hepatitis B e antigen [HBeAg] or levels of serum hepatitis B virus [HBV] DNA > 10 copies/mL), there remains a risk (0.5% per year) in those patients who are inactive carriers without cirrhosis (with negative HBeAg and serum HBV DNA levels < 10 copies/mL), and even in the unusual patient who clears hepatitis B surface antigen later in life.
The next question regarding screening for HCC is whether there are good screening tests. The ability to detect HCC is highly dependent on the test used (ie, test performance characteristics of sensitivity and specificity), the experience of the center, the size of the lesion, and "biological behavior" of the tumor. Alpha-fetoprotein (AFP) has a sensitivity of about 50% to 60% (using a cut-off value of 20 ng/mL, but at a loss of specificity). More data are needed to determine the value of other tumor markers, such as glypican-3 protein induced by vitamin K (PIVKA) or fractions of AFP. Ultrasound has a sensitivity of approximately 60% to 80% (for lesions 1-2 cm), whereas computed tomography (CT) and magnetic resonance imaging (MRI) have a sensitivity of about 60% to 90% (for lesions 1-2 cm).
Screening is based on the issue of whether there are good treatment options for HCC. Candidates for liver transplantation include those patients with a single lesion < 5 cm in diameter or 2-3 lesions, each < 3 cm in diameter. Surgical resection is reserved for HCC in noncirrhotic patients or selected Child's class A patients. Palliative options in nonsurgical candidates, or as a bridge to transplantation, include percutaneous ethanol injection, radiofrequency ablation, or chemoembolization.
A final question to be considered is whether screening for HCC is acceptable, affordable, and accessible. Screening should be performed with the idea of offering some form of therapy. A general principle of screening, which also applies to screening for other malignancies, is that screening should only be undertaken in individuals who would be treated if diagnosed with the disease. Screening for HCC may be cost-effective in some settings (ie, high incidence areas). There may be medicolegal ramifications of not offering screening. The most common screening strategy for HCC, which has become a standard of care in patients with chronic hepatitis B and in all patients with cirrhosis, is serum AFP and ultrasound performed every 6 months, with CT or MRI as an alternative to ultrasound.