Hepatitis B virus reactivation by immunosuppressive therapy in patients with autoimmune diseases: risk analysis in Hepatitis B surface antigen-negative cases

J Rheumatol. 2011 Oct;38(10):2209-14. doi: 10.3899/jrheum.110289. Epub 2011 Aug 15.

Abstract

Objective: To evaluate the risk of reactivation of resolved hepatitis B virus (HBV) by immunosuppressive therapy in patients with autoimmune diseases.

Methods: Thirty-five patients with autoimmune diseases were included in our study; all were hepatitis B surface antigen (HBsAg)-negative and antibody against hepatitis B core antigen-positive. They were followed for 8-124 weeks and clinical outcomes were analyzed, including serum levels of HBV-DNA and aminotransferase every 4 weeks during their immunosuppressive therapy for underlying autoimmune diseases. If HBV-DNA was detected during the immunosuppressive therapy, HBsAg, antibody against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), and antibody against HBeAg were also monitored every 4 weeks.

Results: HBV-DNA was detected in 6 out of 35 patients. Anti-HBs titer was significantly lower in the patients in whom HBV-DNA was detected compared with the others at baseline: 2.83 (range 0.24-168.50) mIU/ml vs 99.94 (range 0.00-5342.98) mIU/ml, respectively (p = 0.036). Outcomes of the 6 patients with HBV reactivation were as follows: HBV-DNA turned negative in 2 patients without nucleic acid analog (NAA) and 1 with NAA; 2 died due to bacterial sepsis; and 1 died due to autoimmune hemolytic anemia. Significant elevation of aminotransferase was found in only 1 patient, but HBsAg converted to positive in 2 patients and HBeAg converted to positive in 1 patient.

Conclusion: Reactivation of resolved HBV can occur during standard immunosuppressive therapy for autoimmune diseases. The low titer of baseline anti-HBs may carry its risk.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases / drug therapy*
  • DNA, Viral / immunology
  • Female
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / physiology*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Risk Assessment
  • Virus Activation / drug effects*
  • Virus Activation / immunology

Substances

  • DNA, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Immunosuppressive Agents