Brian J. McMahon, MD; Peter Holck, PhD; Lisa Bulkow, MS; Mary Snowball, RN
Grant Support: By the U.S. Public Health Service, Indian Health Service Viral Hepatitis Program for Alaska Natives.
Requests for Single Reprints: Brian J. McMahon, MD, Viral Hepatitis Program, Alaska Native Medical Center, c/o Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Centre Drive, Anchorage, AK 99508-5932.
Current Author Addresses: Dr. McMahon: Viral Hepatitis Program, Alaska Native Medical Center, c/o Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Centre Drive, Anchorage, AK 99508-5932.
Dr. Holck: Alaska Native Health Board, 4201 Tudor Centre Drive, Suite 105, Anchorage, AK, 99508
Ms. Bulkow: Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Centre Drive, Anchorage, AK 99508-5932.
Ms. Snowball: Viral Hepatitis Program, Alaska Native Medical Center, 4315 Diplomacy Drive, Anchorage, AK 99508.
Author Contributions: Conception and design: B.J. McMahon, L. Bulkow.
Analysis and interpretation of the data: B.J. McMahon, P. Holck, L. Bulkow.
Drafting of the article: B.J. McMahon, L. Bulkow.
Critical revision of the article for important intellectual content: B.J. McMahon, L. Bulkow, M. Snowball.
Final approval of the article: B.J. McMahon, P. Holck, L. Bulkow, M. Snowball.
Provision of study materials or patients: B.J. McMahon, M. Snowball.
Statistical expertise: P. Holck, L. Bulkow.
Administrative, technical, or logistic support: B.J. McMahon.
Collection and assembly of data: B.J. McMahon, L. Bulkow, M. Snowball.
Knowledge of the outcome of chronic hepatitis B virus (HBV) infection is limited.
To determine the incidence of and risk factors for adverse events (hepatocellular carcinoma and end-stage liver disease) and clearance of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) in carriers of HBV.
Population-based cohort study of hepatitis B carriers who were observed for a median of 12.3 years as part of an active surveillance program to detect carriers with hepatocellular carcinoma.
126 communities in Alaska.
1536 Alaska Natives with chronic hepatitis B.
Bivariate comparisons, multivariable models, and other statistical methods were used to examine the relationships of risk factors to outcomes and clearance of HBeAg and HBsAg.
1536 chronic HBV carriers were followed up for 19 430 person-years from their first HBsAg-positive test result. At the first serologic test, 641 were HBeAg positive and 893 were anti-HBe positive. Older carriers were more likely than younger carriers to clear HBeAg (P < 0.001). The observed probability of clearing HBeAg within 10 years of diagnosis was 72.5%. Clearance of HBsAg occurred in 106 (7%) of all carriers and was positively associated with older age and positive result on initial anti-HBe test. The incidence of adverse events was 2.3 per 1000 carrier-years, and the incidence of hepatocellular carcinoma was 1.9 per 1000 carrier-years (2.3 in men and 1.2 in women). Risk for hepatocellular carcinoma increased with age, among those of Yupik Eskimo ethnicity, and among carriers who reverted from anti-HBe to HBeAg.
In HBsAg-positive carriers, observed clearance of HBeAg was more than 70% during the first 10 years of follow-up.
Table 1. Hepatitis B e Antigen and anti-HBeAg Serologic Outcome over Time of 1534 HBsAg-Positive Carriers
Time until seroconversion from hepatitis B e antigen (HBeAg) positivity to negativity.
Data shown for carriers of hepatitis B surface antigen who were persistently HBeAg positive throughout follow-up (solid line); those who seroconverted from HBeAg positivity to anti-HBe positivity (dashed line); those who seroconverted from HBeAg to anti-HBe, then had reactivation of HBeAg (dotted line); and those who were initially anti-HBe negative, then had reactivation and tested HBeAg positive (smaller dashed line). Those who were persistently HBeAg negative and anti-HBe positive (group D in Table 1) are not shown.
Estimated survival curve showing time to loss of hepatitis B e antigen (HBeAg) from first HBeAg-positive determination at 10, 20, and 50 years of age.
Table 2. Long-Term Follow-up of 95 HBsAg-Positive Carriers Whose Approximate Date of Infection Was Known
Survival curve showing years to seroconversion to hepatitis B surface antigen (HBsAg) negativity in carriers, by hepatitis B e antigen (HBeAg)/anti-HBe status.
Line patterns represent carriers who seroconverted from HBeAg to anti-HBe; those who seroconverted from HBeAg to anti-HBe, then had reactivation of HBeAg; those who were persistently HBeAg negative and anti-HBe positive; and those who were initially anti-HBe positive, then had reactivation of HBeAg.
Survival curves showing years to seroconversion from hepatitis B surface antigen (HBsAg) positivity to HBsAg negativity in carriers, by age at the start of the study.
The center solid line represents participants 20 years of age or older; the center dotted line represent participants younger than 20 years of age. The lines on either side of the center lines are 95% CIs, which are largely nonoverlapping.
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McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and Clinical Outcomes of 1536 Alaska Natives Chronically Infected with Hepatitis B Virus. Ann Intern Med. 2001;135:759–768. doi: 10.7326/0003-4819-135-9-200111060-00006
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Published: Ann Intern Med. 2001;135(9):759-768.
Gastroenterology/Hepatology, Gastrointestinal Cancer, Hematology/Oncology, Infectious Disease, Liver Cancer.
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