Clearance of Hepatitis B Surface Antigen and Risk of... : Hepatology (original) (raw)
Viral Hepatitis
Clearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma in A Cohort Chronically Infected With Hepatitis B Virus
Simonetti, Josephine1; Bulkow, Lisa2; McMahon, Brian J.1,2,*; Homan, Chriss1; Snowball, Mary1; Negus, Susan1; Williams, James1; Livingston, Stephen E.1
1_Liver Disease & Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK_
2_Arctic Investigations Program, National Center for Preparedness, Detection and Control of Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, AK_
*Address reprint requests to: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, 4315 Diplomacy Drive, Anchorage, AK 99508. Email:[email protected]; fax: 907-729-3429.
Received 1 June 2009; Accepted 24 October 2009
Published online 30 November 2009 in Wiley InterScience (www.interscience.wiley.com).
Supported by Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, and Native American Research Centers for Health (grant 1 U26 94 00005).
Potential conflict of interest: Nothing to report.
Abstract
Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated. We performed a prospective population-based cohort study in 1,271 Alaska Native persons with chronic HBV infection followed for an average of 19.6 years to determine factors associated with loss of HBsAg and risk of developing HCC thereafter. HBsAg loss occurred in 158 persons for a rate of HBsAg clearance of 0.7%/year. Older age, but not sex, was associated with clearance of HBsAg, and loss of HBsAg was not associated with any particular HBV genotypes (A, B, C, D, and F) found in this population. Participants were followed for an average of 108.9 months after HBsAg loss. Six patients, two with cirrhosis and four without, developed HCC a mean of 7.3 years after HBsAg clearance (range, 2.0–15.5 years). The incidence of HCC after clearance of HBsAg was 36.8 per 100,000 per year (95% CI 13.5–80.0) which was significantly lower than the rate in those who remained HBsAg-positive (195.7 cases per 100,000 person-years of follow-up [95% CI 141.1–264.5; P < 0.001]). After loss of HBsAg, HBV DNA was detected in the sera of 28 (18%) of those who cleared a median of 3.6 years after clearance. Conclusion: HCC can occur in persons with chronic hepatitis B who have lost HBsAg, even in the absence of cirrhosis. These persons should still be followed with periodic liver ultrasound to detect HCC early. (Hepatology 2010.)
Erratum
In the May 2010 issue of Hepatology, the article titled “Clearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma in a Cohort Chronically Infected With Hepatitis B Virus” (volume 51, pages 1531‐1537; doi: <10.1002/hep.23464>), by Josephine Simonetti, Lisa Bulkow, Brian J. McMahon, Chriss Homan, Mary Snowball, Susan Negus, James Williams and Stephen E. Livingston, described the factors associated with hepatitis B surface antigen (HBsAg) seroclearance in a cohort of Alaska Native persons with chronic hepatitis B virus (HBV) infection followed for 20 years. A secondary objective of that article was to evaluate the risk for hepatocellular carcinoma (HCC) among persons after HBsAg seroclearance. For the subanalysis on the development of HCC after HBsAg loss, the authors reported that the HCC incidence for persons with HBsAg seroclearance was 36.8 in 100,000 person‐years (95% confidence interval [CI]: 13.5‐80.0) and for persons without HBsAg seroclearance was 195.7 in 100,000 person‐years (95% CI: 141.1‐264.5). The authors concluded that HBsAg seroclearance was associated with a significant reduction in risk for developing HCC.
It was recently brought to the authors' attention that the HCC incidence for persons with HBsAg seroclearance was miscalculated. The HCC incidence for persons with HBsAg seroclearance was reported in terms of person‐months, not person‐years, whereas the incidence for persons without HBsAg seroclearance was reported in terms of person‐years. The corrected HCC incidence for persons with HBsAg seroclearance is 441.6 in 100,000 person‐years (95% CI: 162.0‐958.0). Based on the corrected HCC incidence, there is no significant difference in HCC risk between persons with and without HBsAg seroclearance (P = 0.09).
The authors are grateful to the readers who brought the error in the previous HCC incidence calculation to their attention. The revised HCC incidence represents one of the few published population‐based estimates of HCC risk in persons with and without HBsAg seroclearance. The results indicate that persons with HBsAg seroclearance remain at increased risk for HCC and can benefit from continued HCC surveillance.
Hepatology. 62(4):1330, October 2015.
Copyright © 2010 American Association for the Study of Liver Diseases.