Improving testing for hepatitis B before treatment with rituximab

Jessica K Dyson, Laura Jopson, Sarah Ng, Matthew Lowery, Jayne Harwood, Sheila Waugh, Manoj Valappil, Stuart McPherson, Jessica K Dyson, Laura Jopson, Sarah Ng, Matthew Lowery, Jayne Harwood, Sheila Waugh, Manoj Valappil, Stuart McPherson

Abstract

Aims/objectives/background: Individuals with current or previous infection with the hepatitis B virus (HBV) can experience viral reactivation when treated with immunosuppression. Rituximab, an anti-CD20 antibody used to treat many diseases, has potent immunosuppressant effects with a high risk of causing HBV reactivation. Reactivation can range from elevated liver enzymes to acute severe hepatitis with liver failure and a significant mortality risk. HBV screening and appropriate use of prophylactic antiviral therapy can prevent reactivation. This work describes the introduction of a local policy for HBV testing in patients before rituximab treatment and assesses its impact.

Methods and results: A baseline review (before policy introduction) of 90 patients showed that only 21 (23%) had hepatitis B surface antigen (HBsAg) and 17 (19%) had hepatitis B core antibody (anti-HBcAb) tested before receiving rituximab. Following introduction of the policy (on the basis of international guidelines), improved laboratory reporting protocols and targeted education sessions, two further reviews of HBV testing rates among patients being initiated onto rituximab were performed. There was a marked increase in pre-rituximab testing for HBsAg from 23 to 79% and for anti-HBcAb from 19 to 78%. Throughout the study period, a total of one (0.8%) HBsAg-positive and six (4.7%) anti-HBcAb-positive patients were identified.

Conclusions: This work clearly indicates that simple strategies can markedly improve appropriate HBV screening. In our cohort, 6% (of whom only 43% had recognized HBV risk factors) required antiviral prophylaxis, which emphasizes the importance of universal screening before rituximab. Reinforcement of the guidelines and ongoing education is needed to further increase testing rates.

Figures

Fig. 1
Fig. 1
Algorithm for prevention of HBV reactivation in patients undergoing immunosuppression. BMT, bone marrow transplant; cAb, core antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IBD, inflammatory bowel disease; LFTs, liver function tests; sAg, surface antigen; TNF, tumour necrosis factor.
Fig. 2
Fig. 2
Prescription of rituximab.

References

    1. WHO. Hepatitis B factsheet. Available at: . [Accessed 8 November 2015].
    1. Cooke GS, Main J, Thursz MR. Treatment for hepatitis B. BMJ 2010; 340:b5429.
    1. Centers for Disease Control and Prevention. Travelers’ health; yellow book. Atlanta, GA: Services UDoHaH; 2008.
    1. Uddin G, Shoeb D, Solaiman S, Marley R, Gore C, Ramsay M, et al. Prevalence of chronic viral hepatitis in people of south Asian ethnicity living in England: the prevalence cannot necessarily be predicted from the prevalence in the country of origin. J Viral Hepat 2010; 17:327–335.
    1. McPherson S, Valappil M, Moses SE, Eltringham G, Miller C, Baxter K, et al. Targeted case finding for hepatitis B using dry blood spot testing in the British-Chinese and South Asian populations of the North-East of England. J Viral Hepat 2013; 20:638–644.
    1. National Institute for Health and Care Clinical Excellence (NICE). Hepatitis B (chronic): diagnosis and management of chronic hepatitis B in children, young people and adults; 2013. Available at: . [Accessed 8 November 2015].
    1. European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57:167–185.
    1. Centers for Disease Control and Prevention. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR [online serial]. 2008; 57:RR-8. Available at: . [Accessed 8 November 2015].
    1. Lee R, Vu K, Bell CM, Hicks LK. Screening for hepatitis B surface antigen before chemotherapy: current practice and opportunities for improvement. Curr Oncol 2010; 17:32–38.
    1. Wi CI, Loo NM, Larson JJ, Moynihan TJ, Madde NR, Grendahl DC, et al. Low level of hepatitis B virus screening among patients receiving chemotherapy. Clin Gastroenterol Hepatol 2015; 13:970–975. quiz e51.
    1. Hwang JP, Fisch MJ, Lok AS, Zhang H, Vierling JM, Suarez-Almazor ME. Trends in hepatitis B virus screening at the onset of chemotherapy in a large US cancer center. BMC Cancer 2013; 13:534.
    1. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American Gastroenterological Association Institute. 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 e16–e17.
    1. Lee GW, Ryu MH, Lee JL, Oh S, Kim E, Lee JH, et al. The prophylactic use of lamivudine can maintain dose-intensity of adriamycin in hepatitis-B surface antigen (HBs Ag)-positive patients with non-Hodgkin’s lymphoma who receive cytotoxic chemotherapy. J Korean Med Sci 2003; 18:849–854.
    1. Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology 1991; 100:182–188.
    1. Chen KL, Chen J, Rao HL, Guo Y, Huang HQ, Zhang L, et al. Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival. Chin J Cancer 2015; 34:225–234.
    1. Seto WK, Chan TS, Hwang YY, Wong DK, Fung J, Liu KS, et al. Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. J Clin Oncol 2014; 32:3736–3743.
    1. Kumagai K, Takagi T, Nakamura S, Sawada U, Kura Y, Kodama F, et al. Hepatitis B virus carriers in the treatment of malignant lymphoma: an epidemiological study in Japan. Ann Oncol 1997; 8 (Suppl 1):107–109.
    1. Markovic S, Drozina G, Vovk M, Fidler-Jenko M. Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology 1999; 46:2925–2930.
    1. FDA Prescribing Information. Label information for rituximab. Available at: . [Accessed 8 November 2015].
    1. Huang YH, Hsiao LT, Hong YC, Chiou TJ, Yu YB, Gau JP, et al. 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.
    1. Ho EY, Yau T, Rousseau F, Heathcote EJ, Lau GK. Preemptive adefovir versus lamivudine for prevention of hepatitis B reactivation in chronic hepatitis B patients undergoing chemotherapy. Hepatol Int 2015; 9:224–230.
    1. Huang H, Li X, Zhu J, Ye S, Zhang H, Wang W, 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.
    1. Dyson JK, Hudson M, McPherson S. Lesson of the month 2: severe reactivation of hepatitis B after immunosuppressive chemotherapy. Clin Med (Lond) 2014; 14:551–555.
    1. Standards for microbiology investigations. Available at: . [Accessed 14 February 2016].
    1. Liang R. How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hematopoietic stem cell transplantation. Blood 2009; 113:3147–3153.
    1. Hoofnagle JH, Dusheiko GM, Schafer DF, Jones EA, Micetich KC, Young RC, Costa J. Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Intern Med 1982; 96:447–449.
    1. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, 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.
    1. Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, Csako G. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008; 148:519–528.
    1. Neuss MN, Desch CE, McNiff KK, Eisenberg PD, Gesme DH, Jacobson JO, et al. A process for measuring the quality of cancer care: the Quality Oncology Practice Initiative. J Clin Oncol 2005; 23:6233–6239.
    1. Sun WC, Hsu PI, Yu HC, Lin KH, Tsay FW, Wang HM, et al. The compliance of doctors with viral hepatitis B screening and antiviral prophylaxis in cancer patients receiving cytotoxic chemotherapy using a hospital-based screening reminder system. PLoS One 2015; 10:e0116978.
    1. National Comprehensive Cancer Network. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw 2012; 10:1412–1415.
    1. Zurawska U, Hicks LK, Woo G, Bell CM, Krahn M, Chan KK, Feld JJ. Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectiveness analysis. J Clin Oncol 2012; 30:3167–3173.
    1. Uhm JE, Kim K, Lim TK, Park BB, Park S, Hong YS, et al. Changes in serologic markers of hepatitis B following autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13:463–468.
    1. Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY, et al. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 2006; 131:59–68.
    1. Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients’ recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 1996; 2:1104–1108.
    1. Li JM, Wang L, Shen Y, Xia ZG, Chen Y, Chen QS, et al. Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in Chinese patients. Ann Hematol 2007; 86:639–645.
    1. Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol 2009; 27:605–611.
    1. Kusumoto S, Tanaka Y, Mizokami M, Ueda R. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. Int J Hematol 2009; 90:13–23.
    1. Evens AM, Jovanovic BD, Su YC, Raisch DW, Ganger D, Belknap SM, et al. Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol 2011; 22:1170–1180.
    1. Stasi R, Del Poeta G, Stipa E, Evangelista ML, Trawinska MM, Cooper N, Amadori S. Response to B-cell depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. Blood 2007; 110:2924–2930.
    1. Tsutsumi Y, Tanaka J, Kawamura T, Miura T, Kanamori H, Obara S, et al. Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin’s lymphoma. Ann Hematol 2004; 83:58–60.
    1. European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC). PRAC recommendations on signals. EMAPRAC (PRAC); 2016. Available at: . [Accessed 14 February 2015].
    1. Keam B, Lee JH, Im SA, Yoon JH. Why, when, and how to prevent hepatitis B virus reactivation in cancer patients undergoing chemotherapy. J Natl Compr Canc Netw 2011; 9:465–477.

Source: PubMed

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