Recommendations for screening, diagnosis, prophylaxis and treatment of hepatitis in haemato-oncological patients – CELL recommendations

Czech version

Authors: Ľ. Soják ¹; Z. Ráčil ²; T. Kabut ³; B. Weinbergerová ³; J. Mayer ³; J. Haber ⁴; P. Žák ⁵; J. Radocha ⁵; M. Navrátil ⁶; R. Hájek ⁶; T. Kozák ⁷; P. Sedláček ⁸; P. Múdrý ⁹; R. Szotkowská ¹⁰; T. Papajík ¹⁰; T. Szotkowski ¹⁰; P. Cetkovský ²; D. Teiserová ¹¹; N. Mallátová ¹¹; J. Lukáš ¹²; L. Drgoňa ¹³
Authors‘ workplace: Klinika infektológie a geografickej medicíny SZU, LFUK a UN, Bratislava ¹; Ústav hematologie a krevní transfuze, Praha ²; Interní hematologická a onkologická klinika FN, Brno ³; I. interní klinika – klinika hematologie 1. LF a VFN, Praha ⁴; IV. Interní hematologická klinika FN, Hradec Králové ⁵; Klinika hematoonkologie FN, Ostrava ⁶; Interní hematologická klinika FN Královské Vinohrady, Praha ⁷; Klinika dětské hematologie a onkologie 2. LF UK a FN Motol, Praha ⁸; Klinika dětské onkologie FN, Brno ⁹; Hemato-onkologická klinika FN a LF UP, Olomouc ¹⁰; Centrální laboratoře, Nemocnice České Budějovice ¹¹; Klinika hematológie a transfuziológie SZU, LFUK a UN, Bratislava ¹²; Klinika onkohematológie LFUK a NOÚ, Bratislava ¹³
Published in: Transfuze Hematol. dnes,26, 2020, No. 4, p. 333-342.
Category: Best Practices

Overview

Viral hepatitis affects millions of people worldwide, with host immunity deciding on the outcome of infection. In patients with haematological malignancies or recipients of haematopoietic stem cells the virus may cause life-threatening complications either due to the virus itself or to the need to interrupt or reduce the chemotherapy. The infected haematopoietic stem cell donor can also transmit viral hepatitis. Knowing complete HBV (hepatitis B virus) serostatus is essential for the right choice of treatment, prophylaxis or pre-emptive approach. Recent recommendations favour treatment using molecules with a high barrier to resistance. In HCV infection, administration of new, direct-acting antiviral agents (DAA), is safe in haematological patients. The use of DAAs in first line is recommended, either as a single treatment for indolent lymphomas or in combination with chemotherapy for aggressive lymphomas. Due to the existing risk of chronic hepatitis E in immunocompromised patients, marker screening should be performed if there are signs and symptoms of hepatitis. In the case of HEV infection, reduction in immunosuppression is recommended and if not possible or unsuccessful, treatment with ribavirin may be considered. Hepatitis A does not progress to chronicity but may be more severe in elderly and immunocompromised patients with risk of hepatic failure. The CELL (Czech Leukaemia Study Group – for Life) Working Group for the Treatment of Opportunistic Infections recommends that all patients undergo screening for hepatotropic viruses before haematological treatment and that patients or donors of haematopoietic stem cells with markers of previous or current viral hepatitis should be consulted with specialists (infectious disease specialist/hepatologists). The screening, vaccination and treatment guidelines outlined here were presented and discussed at the CELL workshop in Brno in May 2018.

Sources

WHO. Global hepatitis report. Geneva: 2017.
Versluis J, Pas SD, Agteresch HJ, et al. Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation. Blood. 2013;122(6):1079–1086.
Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010;7(1):31–40.
Kamar N, Dalton HR, Abravanel F, et al. Hepatitis E virus infection. Clin Microbiol Rev. 2014;27(1):116–138.
Fujiwara S, Yokokawa Y, Morino K, et al. Chronic hepatitis E: a review of the literature. J Viral Hepat. 2014;21(2):78–89.
Dalia S, Chavez J, Castillo JJ, et al. Hepatitis B infection increases the risk of non-Hodgkin lymphoma: a meta-analysis of observational studies. Leuk Res. 2013;37(9):1107–1115.
Dal Maso L, Franceschi S. Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: a meta-analysis of epidemiologic studies. Cancer Epidemiol Prev Biomark. 2006;15(11):2078–2085.
Salah-Eldin MA, Ebrahim MA, El-Sadda W. Clinical outcome of HCV--positive patients with diffuse large B-cell lymphoma treated with rituximab-based chemotherapy. Ann Hematol. 2014;93(11):1903–1911.
Raimondo G, Allain JP, Brunetto MR, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008;49(4):652–657.
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology (Baltimore, MD). 2007;45(2):507–539.
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261–83.
Chu CM, Liaw YF. HBsAg seroclearance in asymptomatic carriers of high endemic areas: appreciably high rates during a long-term follow-up. Hepatology. 2007;45:1187–1192.
Raimondo G, Allain JP, Brunetto MR, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008;49:652–657.
Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology. 2001;120(4):1009–1022.
Mallet V, Van Bommel F, Doerig C, et al. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). Lancet Infect Dis. 2016;16(5):606–617.
Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol. 2012;9(3):156–166.
Hwang JP, Lok AS. Management of patients with hepatitis B who require immunosuppressive therapy. Nat Rev Gastroenterol Hepatol. 2014;11(4):209–219.
McIvor C, Morton J, Bryant A, et al. Fatal reactivation of precore mutant hepatitis B virus associated with fi brosing cholestatic hepatitis after bone marrow transplantation. Ann Intern Med. 1994;121:274–275.
Lenci I, Marcuccilli F, Tisone G, et al. Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis. Dig Liver Dis. 2010; 42(8):578–584.
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–662.
Sarmati L, Andreoni M, Antonelli G, et al. Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper. Clin Microbiol Infection. 2017;23(12):935–940.
Awerkiew S, Daumer M, Reiser M, et al. Reactivation of an occult hepatitis B virus escape mutant in an anti-HBs positive, anti-HBc negative lymphoma patient. J Clinic Virol. 2007;38(1):83–86.
Gärtner BC, Jung W, Welsch C, et al. Permanent loss of anti-HBc after reactivation of hepatitis B virus infection in an anti-HBs and anti-HBc-positive patient after allogeneic stem cell transplantation. J Clin Virol. 2007;38(2):146–148.
Benwell N, Boan P, Raby E, et al. False positive hepatitis B virus core and surface antibodies due to intravenous immunoglobulin. Intern Med J. 2017;47(1):119–120.
Yeo W, Chan TC, Leung NW, 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.
Knöll A, Boehm S, Hahn J, et al. Long-term surveillance of haematopoietic stem cell recipients with resolved hepatitis B: high risk of viral reactivation even in a recipient with a vaccinated donor. J Viral Hepat. 2007;14:478–483.
Hammond SP, Borchelt AM, Ukomadu C, et al. Hepatitis B 9virus reactivation following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:1049–1059.
Seto WK, Chan TS, Hwang YY, 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.
Evens AM, Jovanovic BD, Su YC, 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.
Pyrpasopoulou A, Douma S, Vassiliadis T, et al. Reactivation of chronic hepatitis B virus infection following rituximab administration for rheumatoid arthritis. Rheumatol Int. 2011;31:403–404.
Mitka M. FDA: Increased HBV reactivation risk with ofatumumab or rituximab. JAMA. 2013;310:1664.
EASL. Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–398.
Lee J-H, Cho Y, Lee DH, et al. Prior exposure to lamivudine increases entecavir resistance risk in chronic hepatitis B Patients without detectable lamivudine resistance. Antimicrob Agents Chemother. 2014;58(3):1730–1737.
Baran B, Soyer OM, Ormeci AC, et al. Efficacy of tenofovir in patients with Lamivudine failure is not different from that in nucleoside/nucleotide analogue-naive patients with chronic hepatitis B. Antimicrob Agents Chemother. 2013;57(4):1790–1796.
European, Medicines, Agency. Tenofovir disoproxil fumarate – Drug monograph.
European, Medicines, Agency. Tenofovir alafenamide – Drug monograph.
Ray AS, Fordyce MW, Hitchcock MJ. Tenofovir alafenamide: a novel prodrug of tenofovir for the treatment of human immunodeficiency virus. Antiviral Res. 2016;125:63–70.
Dervite I, Hober D, Morel P. Acute hepatitis B in a patient with antibodies to hepatitis B surface antigen who was receiving rituximab. N Engl J Med. 2001;344:68–69.
Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215–219.
Seto WK, Chan TS, Hwang YY, 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.
Mikulska M, Nicolini L, Signori A, et al. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome. Clin Microbiol Infect. 2014;20:O694–O701.
Hsu C, Tsou HH, Lin SJ, et al. Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: a prospective study. Hepatology (Baltimore, MD). 2014;59(6):2092–2100.
Fukushima N, Mizuta T, Tanaka M, et al. Retrospective and prospective studies of hepatitis B virus reactivation in malignant lymphoma with occult HBV carrier. Ann Oncol. 2009;20(12):2013–2017.
Law MF, Ho R, Cheung CK, et al. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy. World J Gastroenterol. 2016;22(28):6484–6500.
Buti M, Manzano ML, Morillas RM, et al. Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: the Preblin study. PloS One. 2017;12(9):e0184550.
Nakamoto S, Kanda T, Nakaseko C, et al. Reactivation of hepatitis B virus in hematopoietic stem cell transplant recipients in Japan: efficacy of nucleos(t)ide analogues for prevention and treatment. Int J Mol Sci. 2014;15(11):21455–21467.
Chen PM, Fan S, Liu CJ, et al. Changing of hepatitis B virus markers in patients with bone marrow transplantation. Transplantation. 1990;49:708–713.
Reed EC, Myerson D, Corey L, Meyers JD. Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen. Blood. 1991;77:195–200.
Onozawa M, Hashino S, Izumiyama K, et al. Progressive disappearance of anti-hepatitis B surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection. Transplantation. 2005;79:616–619.
Viganò M, Vener C, Lampertico P, et al. Risk of hepatitis B surface antigen seroreversion after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011;46:125–131.
Chakvetadze C, Bani-Sadr F, Le Pendeven C, et al. Serologic response to hepatitis B vaccination in HIV-Infected patients with isolated positivity for antibodies to hepatitis B core antigen. Clin Infect Dis. 2010;50:1184–1186.
Locasciulli A, Alberti A, Bandini G, et al. Allogeneic bone marrow transplantation from HBsAg+ donors: a multicenter study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood. 1995;86:3236–3240.
Lau GKK, Lie AKW, Kwong YL, et al. A case-controlled study on the use of HBsAg-positive donors for allogeneic hematopoietic cell transplantation. Blood. 2000;96:452–458.
Hui CK, Sun J, Au WY, et al. Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol. 2005;42:813–819.
Lindemann M, Barsegian V, Runde V, et al. Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation. Transplantation. 2003;75:833–838.
Lau GK, Suri D, Liang R, et al. Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. Gastroenterology. 2002;122:614–624.
Mahale P, Thomas SK, Kyvernitakis A, et al., Management of multiple myeloma complicated by hepatitis c virus reactivation: The role of new antiviral therapy. Open Forum Infect Dis. 2016;3(1):ofv211.
Mahale P, Kontoyiannis DP, Chemaly RF, et al. Acute exacerbation and reactivation of chronic hepatitis C virus infection in cancer patients. J Hepatol. 2012;57(6):1177–1185.
Besson C, Canioni D, Lepage E, et al. Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d’Etude des Lymphomes de l’Adulte programs. J Clin Oncol. 2006;24(6):953–960.
Coppola N, Pisaturo M, Guastaﬁ E, et al. Increased hepatitis C viral load and reactivation of liver disease in HCV RNA-positive patients with onco-haematological disease undergoing chemotherapy. Dig Liver Dis. 2012;44:49–54.
Watanabe T, Tanaka Y. Reactivation of hepatitis viruses following immunomodulating systemic chemotherapy. Hepatol Res. 2013;43:113–121.
De Rosa G, Gobbo ML, De Renzo A, et al. High prevalence of hepatitis C virus infection in patients with B-cell lymphoproliferative disorders in Italy. Am J Hematol. 1997;55(2):77–82.
Kyvernitakis A, Mahale P, Popat UR, et al. Hepatitis C virus infection in patients undergoing hematopoietic cell transplantation in the era of direct-acting antiviral agents. Biol Blood Marrow Transpl. 2016;22(4):717–722.
Asselah T, Boyer N, Saadoun D, et al. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current INF-free treatment and future perspectives. Liver Int. 2016;36(S1):47–57.
Ende AR, Kim NH, Yeh MM, et al. Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep. 2015;9(1):164.
Burgess S, Partovi N, Yoshida EM, et al. Drug interactions with direct-acting antivirals for hepatitis C: implications for HIV and transplant patients. Ann Pharmacother. 2015;49(6):674–687.
Peveling-Oberhag J, Arcaini L, Bankov K, et al. The anti-lymphoma activity of antiviral therapy in HCV-associated B-cell non-Hodgkin lymphomas: a meta-analysis. J Viral Hepat. 2016;23(7):536–544.
Arcaini L, Vallisa D, Rattotti S, et al. Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi. Ann Oncol. 2014;25(7):1404–1410.
Galati G, Rampa L, Vespasiani-Gentilucci U, et al. Hepatitis C and double-hit B cell lymphoma successfully treated by antiviral therapy. World J Hepatol. 2016;8(29):1244–1250.
Persico M, Aglitti A, Caruso R, et al. Efficacy and safety of new direct antiviral agents in HCV infected patients with diffuse large B cell nonhodgkin lymphoma. Hepatology (Baltimore, MD). 2017;67(1):48–55.
Piñana J, Serra M, Hernández-Boluda J, et al. Successful treatment of hepatitis C virus infection with sofosbuvir and simeprevir in the early phase of an allogeneic stem cell transplant. Transpl Infect Dis. 2016;18(1):89–92.
Versluis J, Pas SD, Agteresch HJ, et al. Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation. Blood. 2013;122(6):1079–1086.
Tavitian S, Péron J-M, Huynh A, et al. Hepatitis E virus excretion can be prolonged in patients with hematological malignancies. J Clin Virol. 2010;49(2):141–144.
DebingY, Emerson SU, Wang Y, et al. Ribavirin inhibits in vitro hepatitis E virus replication through depletion of cellular GTP pools and is moderately synergistic with alpha interferon. Antimicrob Agents Chemother. 2014;58(1):267–273.
Le Coutre P, Meisel H, Hofmann J, et al. Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukaemia after allogeneic stem cell transplantation. Gut. 2009;58(5):699–702.