Incidence of hepatocellular carcinoma according to hepatitis B virus genotype in Alaska Native people

Abstract

Background & Aims Most regions of the world have <3 co-circulating hepatitis B virus (HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma (HCC) risk among HBV-infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native (AN) persons where 5 HBV genotypes (A, B, C, D, F) have been identified. Methods Our cohort comprised AN persons with chronic HBV infection identified during 1983–2012 who consented to participate in the study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semiannual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region, and HBeAg status. Results Among the 1,235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry, and 43 (3.5%) developed HCC. The HBV genotype was known for 1,142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1,000 person-years of follow-up for genotypes A, B, C, D, and F was 1.3, 0, 5.5, 0.4, and 4.2, respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A (adjusted odds ratio [aOR]: 3.9, 95% CI: 1.14–13.74), C (aOR: 16.3, 95% CI: 5.20–51.11), and F (aOR: 13.9, 95% CI: 5.30–36.69). Conclusion HBV genotype is independently associated with HCC risk. AN persons with genotypes A, C, and F are at higher risk compared with genotypes B or D.

Role of HLA‐DP and HLA‐DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population

“…In North America and the circumpolar Arctic, serologic surveys performed in the 1970s and 1980s have demonstrated that Alaskan Eskimos, Canadian Inuit and Greenland Inuit have very high prevalence rates of HBV . In Alaska, a high incidence of HCC in Eskimos, especially males, has been reported, being HBV genotypes A, D and especially F1b related to higher or faster rates of HCC and fibrosis . A recent report has demonstrated that the combination of Basal Core Promoter, preCore mutations and N51H mutations could enhance the carcinogenic potential of HBV/F1b which may explain the unusually high incidence of HCC development among Alaska Native persons chronically infected with this genotype…”

Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance

“…Studies from Alaska also show that HBeAg seroconversion occurs on average 2 decades later in persons infected with HBV genotype C than in those infected with HBV genotypes A, B, D, or F . In addition, a significantly higher incidence of HCC has been reported in persons infected with genotypes C or F in Alaska compared with the others …”

Hepatocellular Carcinoma Risk in Alaska Native Children and Young Adults with Hepatitis B Virus: Retrospective Cohort Analysis

“…A previous study using data from this cohort of AN people with chronic HBV infection reported an HCC incidence of 0.19%/year (0.23%/year in men and 0.12%/year in women) (6). The HCC risk varies by HBV genotype with the highest risk among persons with HBV genotypes C and F1(7, 8). Additionally, AN persons with HBV genotype F1 developed HCC at younger age (23 years) compared with those infected by one of the other four genotypes (60 years) found in this population (9); infection with HBV genotype F1 was identified in 68% of HBV-infected AN persons with HCC compared with 18% of persons not developing HCC (9).…”

“…Additionally, AN persons with HBV genotype F1 developed HCC at younger age (23 years) compared with those infected by one of the other four genotypes (60 years) found in this population (9); infection with HBV genotype F1 was identified in 68% of HBV-infected AN persons with HCC compared with 18% of persons not developing HCC (9). A recent analysis evaluating the incidence of HCC by genotype among AN persons demonstrated that the regional differences in HCC risk were attributable to the geographic distribution of specific HBV genotypes (8). …”