Hepatocellular Carcinoma in the Elderly
Morris Sherman, MB BCh, PhD, FRCP(C)
University of Toronto and,
University Health Network,
Toronto, ON.
Introduction
Although hepatocellular carcinoma (HCC) is not a common cancer in North America, it is the fifth most common cancer in the world.1 Age standardized incidence rates vary from three per 100,000 in North American men to 80 per 100,000 in China.1,2 HCC affects people of all ages. However, as with many cancers, the incidence of this disease increases with age, so that the peak incidence is at about age 67-70, (M Sherman, submitted) regardless of the underlying etiology. In Canada, the incidence of HCC is largely driven by three chronic liver diseases: chronic hepatitis B, chronic hepatitis C and alcoholic cirrhosis. In Toronto, hepatitis B is the single most common cause of HCC, accounting for nearly half of all cases, while elsewhere in Ontario hepatitis C and alcohol are the major causes. (M Sherman, submitted)
Prognosis
HCC causes substantial morbidity and mortality. In the absence of early detection programs, most HCC present late, with advanced incurable disease. The reported survival rates for untreated symptomatic HCC varies from 0% at four months to 1% at two years.3-5 The prognosis for small, untreated HCC--lesions that are the target of surveillance--is not well described. However, two-year survival in excess of 50% is not unusual.6,7
Etiology
Hepatitis B
Many prospective and retrospective studies have confirmed the causal relationship between chronic hepatitis B (HBV) infections and the subsequent development of HCC. For example, a prospective study of hepatitis, reported by Beasley et al.,8,9 included 3,454 male hepatitis B carriers and 19,253 uninfected male controls. In this study, the relative risk that HBV carriers would develop HCC was about 100.9 The overall yearly incidence of HCC in the HBsAg-positive group was 0.5%, and was 1% at age 70. In cirrhotic HBV carriers, the relative risk was much higher at 961. The incidence of HCC in cirrhotics was 2.5%/yr.
Hepatitis C
There are many retrospective and prospective cohort analyses of hepatitis C carriers. Almost all of the studies come to the same conclusion--namely, that there is a considerably increased risk of developing HCC--although there is considerable variability in the reported odds ratios.12-14 Cirrhosis is almost a necessary precondition for the development of HCC. There are no prospective studies comparing the incidence of HCC in a population of hepatitis C cirrhosis vs. non-infected individuals, so calculation of relative risk is not possible. However, retrospective studies suggest that HCC is between 20-200 times more common in patients with hepatitis C cirrhosis than in the non-infected. The incidence in these populations ranges from 1.3%/year to about 5%/year.11-13 It should be noted that these are all clinic-based studies. There are no population-based data on the incidence of HCC in hepatitis C carriers.
Within these larger categories are sub-categories in which the risk differs from that of the groups as a whole. In the presence of cirrhosis, increasing age and male sex are independent risk factors for HCC.14,15 The increased incidence of HCC with increasing age in HBsAg carriers, shown by Beasley8,9 (Table 1), has also been confirmed in several surveillance studies of HBV-positive individuals.16-18 In the Alaska study,16 surveillance detected HCC at a rate of 0.2%/year in asymptomatic HBsAg positive male carriers who were less than 20 years of age, increasing to 1.1% in males aged over 50 years at the start of screening (Table 1). Similarly, the detection rate of HCC also increases with age in patients with HBV chronic hepatitis18 and HBV cirrhosis.17