Hepatitis B vaccine is effective in preventing infection with hepatitis B virus (HBV), but its duration of protection is unknown. To examine the effect of exposure to HBV on an immunized population, data were analyzed from a cohort of Alaska Natives who were immunized and then followed up annually for 10 years. A boost in antibody to hepatitis B surface antigen (anti-HBs) was defined as a fourfold rise in levels to > or = 20 mIU/mL that was not accompanied by the presence of antibody to hepatitis B core antigen or attributable to interim vaccination. During 10 years of follow-up, 8.2% of 1,595 vaccines had boosts in anti-HBs. Persons with boosts did not differ significantly from those without boosts in terms of age, gender, village, initial level of anti-HBs, or level of anti-HBs before the boost. These results underscore the continued exposure to HBV among vaccinees and the continued protection against disease that the vaccine provides.

A program of twice yearly testing of Alaska Native carriers of hepatitis-B surface antigen (HBsAg), for alpha-fetoprotein elevations as an indicator of early hepatocellular carcinoma has been established in Alaska. Because many HBsAg carriers live in remote regions of Alaska, logistical and cost considerations complicate the efficiency of this program. We evaluated the feasibility of using blood spotted onto mail-in cards as a system of blood collection and commercial assays for alpha-fetoprotein and HBsAg testing. We compared alpha-fetoprotein levels and the detection of HBsAg in both plasma and blood spots from HBsAg-positive carriers, normal volunteers, and pregnant females. There was good correlation between serum and blood spot AFP levels (r = 0.94, p < 0.001) over a wide range of serum alpha-fetoprotein levels. alpha-fetoprotein and HBsAg remained detectable in blood spots stored at room temperature for more than 8 weeks. The sensitivity of detection of HBsAg in blood spots was not as great in blood spots when compared to plasma levels. This system has been incorporated into the hepatocellular carcinoma screening program in Alaska. It should also prove feasible and economical for such screening to be undertaken in developed countries and possibly make alpha-fetoprotein screening affordable in those developing countries where the prevalence of hepatitis-B virus infection is high.

Alaska Natives have a high incidence of hepatocellular carcinoma (HCC), with regional, ethnic, village, and familial clustering. During 1969-1988, 15 of the 45 incident cases of HCC in Alaska Natives occurred in 5 families. This report presents epidemiologic, virologic, and immunogenetic data on these 5 families. The results of hepatitis B virus (HBV) serologic testing indicates that HBV infection was an important factor in 4 of the 5 families. Human lymphocyte antigen (HLA) testing was performed in 3 families. The HLA results are reviewed in relationship to the familial clustering of HCC.

Enzyme immunoassay (EIA) and radioimmunoassay (RIA) for the detection of antibody to hepatitis B core antigen (anti‐HBc) were compared using serum specimens from Alaska Natives screened during a hepatitis B control program that were initially positive by EIA for only anti‐HBc. Of 36 specimens from persons previously HBsAg positive but who were now only anti‐HBc positive by EIA, 94.4% were anti‐HBc positive by both assays, with anti‐HBc levels exceeding 93% inhibition. Low‐level antibody to hepatitis B surface antigen (anti‐HBs) (<10 SRU) and antibody to hepatitis Be (anti‐HBe) were also present in 50% and 48% of specimens positive for anti‐HBc, respectively. Of 148 specimens from persons initially positive for only anti‐HBc by EIA who had no previous documentation of any hepatitis B virus (HBV) infection, 64.5% were positive by repeat testing for anti‐HBc by both assays, and anti‐HBc levels in this sample exceeded 70% in 91.6% and 80.2% of specimens by EIA and RIA, respectively. Low‐level anti‐HBs and anti‐HBe were present in 45.8% and 15.6%, respectively. EIA detection of anti‐HBc was found to be less specific than RIA. Of specimens positive for anti‐HBc by EIA, 14.8% were negative by RIA. The specificity of the EIA could be improved with respect to RIA by increasing the cut‐off from 48% to 68%. In samples with lowlevel anti‐HBc (≧70% inhibition) as measured by either method, the anti‐HBc results was less likely to persist upon retesting, whereas sample with anti‐HBc levels of >70% inhibition the anti‐HBc was a reproducible finding frequently accompanied by either low‐level anti‐HBs or anti‐HBe.

Hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection in Yupik Eskimos in southwestern Alaska, detected in early stages as a result of screening, appears to be more frequently associated with variants of chronic portal inflammation in the noninvolved liver than with fully developed cirrhosis, otherwise common in HBV-associated HCC from other geographic areas. Of 38 patients diagnosed with HCC since 1969, adequate tissue was available from both the tumor and nontumorous liver in 17. Of the 17 specimens, 14 had chronic portal inflammation and three had advanced cirrhosis; 12 of the 14 were from hepatitis B surface antigen carriers. These 12 cases were studied in detail to examine the features accompanying the development of HCC unobscured by cirrhotic transformation. In the noninvolved parenchyma they included hepatocytic nodules as apparent precursors to HCC and, as markers of phenotypic alterations, dysplastic hepatocytes and hepatitis B surface antigen-laden ground-glass hepatocytes. The latter were observed in eight instances and often accumulated in nodules. Parenchyma within 1 mm of the HCC exhibited increased confluent hyperplasia and frequently conspicuous necroinflammation associated with pericellular and periductular fibrosis, which contributed, in addition to fibrous connections between displaced and heavily inflamed portal tracts, to the capsule that was forming in all cases to varying degrees in the pericarcinomatous region. The HCC was uniformly trabecular and in a few specimens, a continuous transition from hyperplasia and dysplasia near the periphery of the tumor to increasing anaplasia in the center could be made out in addition to pressure effects of the HCC. The pericarcinomatous changes, including hyperplasia progressing to neoplasia and necroinflammation, are also observed in experimental models, particularly the woodchuck HCC induced by a hepadna virus related to HBV. Coordinated morphologic and molecular biologic studies on such animal models and on human HCC detected by screening, as for instance in Eskimos, neither complicated by cirrhosis, should elucidate the direction of the evolution of the HCC and the postulated promoting role of the inflammation.

One hundred fifty asymptomatic patients who were carriers of hepatitis B surface antigen (HBsAg) were studied serologically for up to 11.3 years (mean, 6.1 years). Only 9 (6.0%) lost HBsAg during the study period, for a mean annual clearance rate of 1.0%. We found no difference in the clearance of HBsAg by age, but a higher percentage of females lost HBsAg than did males (P less than .02). Hepatitis B e antigen (HBeAg) was found in 102 (68.5%) of the 149 carriers of HBsAg who were tested. Carriers of HBsAg who were seropositive for HBeAg were younger than those who were seronegative for HBeAg (P less than .01). The prevalence of HBeAg was not affected by the patients' sex. The clearance of HBeAg was gradual; 9.6% of the HBsAg carriers lost HBeAg each year. Females were more likely to clear HBeAg than were males (P less than .01), and those who cleared HBeAg were older than those who did not (P less than .01). Three (2.0%) of the HBsAg carriers developed primary hepatocellular carcinoma during the study period.

Yupik Eskimos of southwestern Alaska have the highest known prevalence of hepatitis B virus infection of any general population in the United States. Prospective serological surveys of 1,280 seronegative Yupik Eskimos, performed between 1971 and 1976, identified 189 (14.8%) who developed serological evidence of hepatitis B virus infection. Twenty-six (13.8%) developed clinical hepatitis during the interval when seroconversion occurred. The proportion of patients with clinically apparent hepatitis increased with age (P less than .01), ranging from 9.5% of infections in patients who were four years of age or less to 33.3% of infections in patients who were 30 years of age or older. Twenty-five (13.3%) of the 188 individuals who were studied became chronic carriers of hepatitis B surface antigen. The risk of becoming a carrier was inversely related to the age of the patient at the time of infection (P = .02). Among patients who were four years of age or less when infected, 28.8% became chronic carriers of hepatitis B, as compared with 7.7% of those who were 30 years of age or older.

The records of 20 Alaskan Native patients with primary hepatocellular carcinoma (PHC) diagnosed in the II‐year period 1969–1979 were reviewed. The annual incidence of PHC was found to be high among Alaskan Native males and especially high among Alaskan Eskimo males (7.6 and 11.2 per 100,000, respectively) in comparison to Greenland and Canadian Eskimos and US white males. Familial and geographic clustering of PHC patients was noted in areas known to be hyperendemic for hepatitis B virus (HBV) infection. A bimodal age distribution among PHC patients occurred with peaks at 15–25 years and 40–65 years. A high prevalence of hepatitis B surface antigen (HBsAg) in serum of patients in the younger age group suggests that HBV infection might be a factor associated with the development of PHC in young Eskimos. PHC in Alaskan Natives is apparently not closely associated with alcoholic cirrhosis.