Incidence and antiviral response of hepatitis C virus reactivation in lupus patients undergoing immunosuppressive therapy

Abstract

Objective

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease and usually requires immunosuppressive therapy, which is a major cause of viral reactivation. The incidence and antiviral response in SLE patients with hepatitis C virus (HCV) reactivation is unclear and needs to be investigated.

Methods

One hundred and sixty-six SLE patients with antibody to HCV (anti-HCV) status were retrospectively reviewed regarding the events of HCV reactivation. Patients with HCV reactivation were treated with pegylated interferon plus ribavirin treatment. The virological response and relapse rate were evaluated.

Results

Twenty-six patients were positive for anti-HCV. During a mean 8.4 years of follow-up, 10 (38.5%) cases developed HCV reactivation. No clear relationship was noted between immunosuppressive therapy and the HCV reactivation. Eight patients underwent antiviral therapy and the rapid virological response (RVR), early virological response, and sustained virological response (SVR) rates were 37.5%, 87.5%, and 75.0%, respectively. However, late relapse (reappearance of HCV RNA in serum after archiving SVR) was found in two (33.3%) of six patients achieving SVR. The two cases were HCV genotype 1 b concurrent with corticosteroid treatment.

Conclusions

HCV reactivation in anti-HCV-positive SLE patients was possibly associated with glucocorticoids. The virological response to interferon plus ribavirin treatment is not inferior to the general population. However, monitoring HCV RNA after SVR is necessary for patients concurrent with corticosteroid treatment due to the risk of late relapse.

Keywords

Systemic lupus erythematosus HCV reactivation immunosuppression interferon virological response late relapse

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References

Santini

Crovatto

Giannini

Bortolin

Mazzaro

Invernizzi

. Hepatitis C virus and immunoglobulin gene rearrangements: an early step in lymphomagenesis? Acta Haematol 1998; 100: 117–122.

Sung

. Prevention of hepatitis B and C virus infection for prevention of cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 1997; 12: S370–S376.

Chuang

Chang

. The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study. Cancer 1992; 69: 2052–2054.

Morgan

Baack

Smith

Yartel

Pitasi

Falck-Ytter

. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013; 158: 329–337.

Alter

. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006; 44: S6–S9.

Mahale

Kontoyiannis

Chemaly

. Acute exacerbation and reactivation of chronic hepatitis C virus infection in cancer patients. J Hepatol 2012; 57: 1177–1185.

Hoofnagle

. Reactivation of hepatitis B. Hepatology 2009; 49: S156–S165.

Huang

Hsiao

Hong

. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol 2013; 31: 2765–2772.

Torres

Davila

. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol 2012; 9: 156–166.

10.

Faggioli

De Paschale

Tocci

. Acute hepatic toxicity during cyclic chemotherapy in non-Hodgkin’s lymphoma. Haematologica 1997; 82: 38–42.

11.

Kawatani

Suou

Tajima

. Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies. Eur J Haematol 2001; 67: 45–50.

12.

Nosotti

D’Andrea

Pitidis

. Hepatitis C virus infection prevalence and liver dysfunction in a cohort of B-cell non-Hodgkin’s lymphoma patients treated with immunochemotherapy. Scand J Infect Dis 2012; 44: 70–73.

13.

Bagavant

Deshmukh

Gaskin

. Lupus glomerulonephritis revisited 2004: autoimmunity and end-organ damage. Scand J Immunol 2004; 60: 52–63.

14.

Bertsias

Ioannidis

Boletis

. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008; 67: 195–205.

15.

Magy

Cribier

Schmitt

. Effects of corticosteroids on HCV infection. Int J Immunopharmacol 1999; 21: 253–261.

16.

Humar

Crotteau

Gruessner

. Steroid minimization in liver transplant recipients: impact on hepatitis C recurrence and post-transplant diabetes. Clin Transplant 2007; 21: 526–531.

17.

Ciesek

Wedemeyer

. Immunosuppression, liver injury and post-transplant HCV recurrence. J Viral Hepat 2012; 19: 1–8.

18.

Hochberg

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

19.

Bombardier

Gladman

Urowitz

Caron

Chang

. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35: 630–640.

20.

Ghany

Strader

Thomas

Seeff

. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49: 1335–1374.

21.

Vento

Cainelli

Mirandola

. Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus. Lancet 1996; 347: 92–93.

22.

Arcaini

Merli

Passamonti

. Impact of treatment-related liver toxicity on the outcome of HCV-positive non-Hodgkin’s lymphomas. Am J Hematol 2010; 85: 46–50.

23.

Fong

Valinluck

Govindarajan

Charboneau

Adkins

Redeker

. Short-term prednisone therapy affects aminotransferase activity and hepatitis C virus RNA levels in chronic hepatitis C. Gastroenterology 1994; 107: 196–199.

24.

Dai

Huang

. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut 2007; 56: 553–559.

25.

Dai

Huang

. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology 2008; 47: 1884–1893.

26.

Maylin

Martinot-Peignoux

Moucari

. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C. Gastroenterology 2008; 135: 821–829.

27.

Swain

Lai

Shiffman

. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010; 139: 1593–1601.

28.

Giannini

Basso

Savarino

Picciotto

. Sustained virological response to pegylated interferon and ribavirin is maintained during long-term follow-up of chronic hepatitis C patients. Aliment Pharmacol Ther 2010; 31: 502–508.

29.

Formann

Steindl-Munda

Hofer

. Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based antiviral therapy. Aliment Pharmacol Ther 2006; 23: 507–511.

30.

Veldt

Saracco

Boyer

. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy. Gut 2004; 53: 1504–1508.

31.

Colson

Bregigeon

Tourres

Solas

Poizot-Martin

Tamalet

. Relapse of hepatitis C virus after 14 months of sustained virological response following pegylated-interferon alpha plus ribavirin therapy in a human immunodeficiency virus type 1 infected patient. J Clin Virol 2013; 58: 309–314.

32.

Hara

Rivera

Koh

. Sequence analysis of hepatitis C virus from patients with relapse after a sustained virological response: relapse or reinfection? J Infect Dis 2014; 209: 38–45.

33.

EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55: 245–264.

34.

Papatheodoridis

GV1

Manolakopoulos

Liaw

Lok

. Follow-up and indications for liver biopsy in HBeAg-negative chronic hepatitis B virus infection with persistently normal ALT: a systematic review. J Hepatol 2012; 57: 196–202.