Risk of hepatitis B surface antigen seroreversion after corticosteroid treatment in patients with previous hepatitis B virus exposure [url=]Grace Lai-Hung Wong[/url]1,2,3
, [url=]Vincent Wai-Sun Wong[/url]1,2,3
, [url=]Becky Wing-Yan Yuen[/url]1,2
, [url=]Yee-Kit Tse[/url]1,2
, [url=]Terry Cheuk-Fung Yip[/url]1,2
, [url=]Hester Wing-Sum Luk[/url]2
, [url=]Grace Chung-Yan Lui[/url]2
, [url=]Henry Lik-Yuen Chan[/url]1,2,3,,[url=]Correspondence information about the author Henry Lik-Yuen Chan[/url]Email the author Henry Lik-Yuen Chan
•HBsAg− patients (anti-HBc+ but anti-HBs−) are at increased risk of HBsAg seroreversion after corticosteroid therapy.
•The peak daily dose of corticosteroid is a more important risk factor for hepatitis flares than treatment duration.
•In contrast, dose and duration of corticosteroid use are not associated with the risk of HBsAg reversion.
Background & AimsSystemic corticosteroids may cause HBV reactivation, but the impact on patients with previous HBV exposure is poorly defined. We aimed to study the risk of HBsAg seroreversion and hepatitis flare in patients with previous HBV exposure.
MethodsPatients who were negative for HBsAg and received corticosteroids between 2001–2010 were included. Patients who were positive for antibody to HBsAg (anti-HBs) and/or to HBcAg (anti-HBc) were defined as having previous HBV exposure. The primary endpoint was HBsAg seroreversion; the secondary endpoint was hepatitis flare (alanine aminotransferase >80 U/L) at 1 year.
ResultsA total of 12,997 patients fulfilled the inclusion criteria: anti-HBs positive only (n = 10,561); anti-HBc positive only (n = 970); anti-HBs & anti-HBc positive (n = 830) and anti-HBs & anti-HBc negative (n = 636). HBsAg seroreversion occurred in 165 patients. Patients who were anti-HBc positive only had a higher risk of HBsAg seroreversion (1-year incidence 1.8%) than those negative for both anti-HBs & anti-HBc (0%; p = 0.014). Patients with previous HBV exposure had a similarly low risk of liver failure as unexposed individuals (1.1% vs. 0.9%). The risk of a hepatitis flare started to increase in those receiving corticosteroids at peak daily doses of 20–40 mg (adjusted hazard ratio [HR] 2.19, p = 0.048) or >40 mg (aHR 2.11, p = 0.015) prednisolone equivalents for <7 days, and was increased at treatment durations of 7–28 days and >28 days (aHR 2.02–3.85; p <0.001–0.012).
ConclusionsIn HBsAg-negative patients who were only anti-HBc positive, high peak daily doses of corticosteroids increased the risk of hepatitis flare, but not seroreversion. The rate of liver failure was low and similar in HBV exposed and unexposed individuals; there were no deaths, nor any requirement for liver transplantation.
Lay summaryIt is important to know the hepatitis B virus (HBV) status before starting corticosteroid therapy. Patients with resolved HBV infection without detectable immunity are at an increased risk of HBV surface antigen seroreversion after corticosteroid therapy. High peak daily doses of corticosteroids (>40 mg prednisolone equivalents) increase the risk of hepatitis flare, but not seroreversion, in patients with previous exposure to HBV, irrespective of the duration of treatment. Interval monitoring of liver biochemistries is essential for the early detection of hepatitis flares in these patients.