Increased risk of hepatitis B virus reactivation in systemic lupus erythematosus patients receiving immunosuppressants: a retrospective cohort study

Abstract

Objective

We aimed to investigate risk of hepatitis B virus reactivation in systemic lupus erythematosus patients with different hepatitis B virus infection statuses receiving immunosuppressive therapy.

Methods

We retrospectively analyzed systemic lupus erythematosus patients with positive hepatitis B surface antigen or anti-hepatitis B core IgG antibody who underwent immunosuppressive therapies from January 2001 to December 2012 at a medical center in Taiwan for evidence of hepatitis B virus reactivation.

Results

During this period, 906 out of 3125 patients who were diagnosed with systemic lupus erythematosus received screening tests for hepatitis B virus. Thirty-eight patients were identified as hepatitis B surface antigen-positive. Fifteen of 38 (39.5%) hepatitis B surface antigen-positive patients developed hepatitis B virus reactivation, and 53.3% of these patients experienced severe hepatitis flare. Three of 157 hepatitis B surface antigen-negative/anti-hepatitis B core IgG antibody-positive patients (1.9%) experienced hepatitis B surface antigen seroreversion after immunosuppressive therapy. Five patients received prophylactic or preemptive antiviral therapy and none of them developed hepatitis B virus flares. A daily dose of prednisolone greater than 5 mg was a risk factor for hepatitis B reactivation by multivariate logistic analysis.

Conclusions

The risk of hepatitis B virus reactivation is high in lupus patients receiving immunosuppressive therapy. Antiviral prophylaxis or preemption can effectively reduce the incidence of hepatitis B virus reactivation in lupus patients.

Keywords

Systemic lupus erythematosus hepatitis B virus reactivation immunosuppressant antiviral agents prophylaxis

Get full access to this article

View all access options for this article.

References

Lok

McMahon

. Chronic hepatitis B: update 2009. Hepatology 2009; 50: 661–662.

Chung

Chen

et al.

Seroepidemiological studies on hepatitis B and D viruses infection among five ethnic groups in southern Taiwan. J Med Virol 1988; 26: 411–418.

Chung

Chen

et al.

[Epidemiological study on hepatitis B virus infection among five ethnic groups in Pingtung County, Taiwan]. Taiwan Yi Xue Hui Za Zhi 1987; 86: 497–504.

Tsokos

. Systemic lupus erythematosus. N Engl J Med 2011; 365: 2110–2121.

Mok

. Current role of rituximab in systemic lupus erythematosus. Int J Rheum Dis 2015; 18: 154–163.

Lee

Bae

Song

. Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs. Int J Rheum Dis 2013; 16: 527–531.

Tamori

Koike

Goto

et al.

Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts. J Gastroenterol 2011; 46: 556–564.

Lan

Chen

Hsieh

et al.

Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy. Ann Rheum Dis 2011; 70: 1719–1725.

Hui

Cheung

Zhang

et al.

Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 2006; 131: 59–68.

10.

Yeo

Chan

Zhong

et al.

Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol 2000; 62: 299–307.

11.

Huang

Zhu

et al.

Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA 2014; 312: 2521–2530.

12.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

13.

Chang

Liaw

. Hepatitis B flares in chronic hepatitis B: Pathogenesis, natural course, and management. J Hepatol 2014; 61: 1407–1417.

14.

Wong

Yiu

et al.

Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B. J Hepatol 2011; 54: 236–242.

15.

Chien

Lin

Liaw

. The effect of lamivudine therapy in hepatic decompensation during acute exacerbation of chronic hepatitis B. J Hepatol 2003; 38: 322–327.

16.

Gladman

Ibanez

Urowitz

. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29: 288–291.

17.

Tan

Zhou

Zhao

et al.

Prospective study of HBV reactivation risk in rheumatoid arthritis patients who received conventional disease-modifying antirheumatic drugs. Clin Rheumatol 2012; 31: 1169–1175.

18.

Tunnicliffe

Singh-Grewal

Kim

et al.

Diagnosis, monitoring, and treatment of systemic lupus erythematosus: a systematic review of clinical practice guidelines. Arthritis Care Res 2015; 67: 1440–1452.

19.

Singh

Saag

Bridges

Jr et al.

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res 2016; 68: 1–25.

20.

Conn

. The use of low-dose oral glucocorticoids was minimized in the 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis: Comment on the article by Singh et al. Arthritis Rheumatol (Hoboken, NJ) 2016; 68: 1314–1314.

21.

Yeo

Johnson

. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology (Baltimore, MD) 2006; 43: 209–220.

22.

Yeo

Zee

Zhong

et al.

Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer 2004; 90: 1306–1311.

23.

Cheng

Hsiung

et al.

Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology (Baltimore, MD) 2003; 37: 1320–1328.

24.

Kim

Kwon

et al.

Risk of hepatitis B virus reactivation in patients with asthma or chronic obstructive pulmonary disease treated with corticosteroids. Respirology (Carlton, Vic) 2010; 15: 1092–1097.

25.

Reddy

Beavers

Hammond

et al.

American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015; 148: 215–219; quiz e216–e217.

26.

Steinberg

. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 1991; 34: 945–950.

27.

Levey

Lan

Corwin

et al.

Progression and remission of renal disease in the Lupus Nephritis Collaborative Study. Results of treatment with prednisone and short-term oral cyclophosphamide. Ann Intern Med 1992; 116: 114–123.

28.

Hsu

Hsiung

et al.

A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin’s lymphoma: a randomized trial. Hepatology 2008; 47: 844–853.

29.

Sarin

Kumar

Lau

et al.

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10: 1–98.