Clin Gastroenterol Hepatol. 2019 Jul 16. pii: S1542-3565(19)30751-7. doi: 10.1016/j.cgh.2019.07.018. [Epub ahead of print]
Durability of Spontaneous and Treatment-related Loss of Hepatitis B s Antigen.
Alawad AS1, Auh S2, Suarez D1, Ghany MG3.
Author information
1
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases.
2
Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
3
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases. Electronic address: [email protected].
Abstract
BACKGROUND & AIMS:
Clearance of hepatitis B surface antigen (HBsAg) from serum is the most desirable endpoint and a proposed definition of functional cure for hepatitis B virus (HBV) infection. However, little is known about the long-term durability of HBsAg loss, and there is controversy over whether the development of antibodies against HBsAg (anti-HBs) is required for maintenance. We aimed to assess the durability of spontaneous or treatment-related (interferon or nucleos(t)ide analogue [NA]) loss of HBsAg.
METHODS:
We performed a retrospective study of patients with chronic HBV infection followed at the National Institutes of Health from February 1980 through November 2017. We identified those with HBsAg loss, confirmed on 2 visits at least 24 weeks apart. Patients with HCV, HDV, HIV, or HTLV-1 co-infection or HBsAg loss after liver transplantation were excluded. Patients were assigned to the following groups: spontaneous clearance (cleared HBsAg without ever receiving treatment or those who received treatment with a NA or interferon and discontinued therapy more than 5 years before HBsAg loss), interferon-treated (cleared HBsAg either during treatment or within 5 years after stopping interferon), and NA-treated (cleared HBsAg either during treatment or within 5 years after stopping NA).
RESULTS:
Among the 787 HBsAg-positive patients, 89 achieved HBsAg loss; 65/89 had confirmed HBsAg loss, which was spontaneous in 19 of the patients (29%), after interferon in 22 (34%), and after NA in 24 (37%). Of the 65 patients with confirmed loss of HBsAg, 62 patients (95%) remained HBsAg negative after a mean time of 9.6 years from first negative HBsAg test result. HBsAg sero-reversion occurred in 3 of the 46 treated patients (7%) (1 interferon and 2 NA), 1 of whom was positive for anti-HBs. At time of HBsAg loss, 33/65 (51%) were anti-HBs positive. At the last follow-up evaluation, anti-HBs was detectable in 50 of the 62 patients (81%) assessed. The rate of development of anti-HBs was proportionally higher among interferon-treated patients (19/21, 90%) than NA-treated patients (17/22, 77%) or patients with spontaneous loss of HBsAg (14/19, 74%).
CONCLUSIONS:
In a retrospective study of 787 HBsAg-positive patients, loss of HBsAg (either spontaneous or after treatment) was confirmed in 8% and was durable. Seroconversion to anti-HBs increased over time and appeared to be more frequent after interferon treatment. HBsAg loss is therefore a robust endpoint for functional cure.