Occult hepatitis B reactivation following rituksimab treatment in a patient with Waldenström macroglobulinemia

Abstract

The anti-CD20 monoclonal antibody rituximab has been used extensively in the treatment of B-cell lymphoma. Several studies reported hepatitis B virus (HBV) reactivation after rituximab. The majority of these cases have been described in chronic carriers of HBV, whereas reactivation in occult hepatitis B virus (OHBV) carriers may occur. The presented case with the diagnosis of Waldenström\'s macroglobulinemia was HBsAg negative and anti HBcIgG positive before chemotherapy. The patient was started on CVP (cyclophosphamide, vincristine, prednisolone) chemotherapy. However, no clinical or laboratory response was obtained and the patient was considered unresponsive to three cycles of CVP therapy. Therefore R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine and prednisolone) was planned as the second therapy. Laboratory work-up after the first cycle of R-CHOP therapy revealed an aspartate aminotransferase (AST) level of 267 U/L and alanine aminotransferase (ALT) level of 318 U/L. HBsAg and anti HBcIgG were positive and HBV DNA was 56400 IU/ml. Lamivudin 100 mg/day was started. Four weeks after the initiation of lamivudin therapy, ALT and AST levels returned to normal. Currently, the patient has received the fourth cycle of R-CHOP therapy. ALT and AST levels continue to be in normal range. This condition was considered to be the reactivation of OHBV following rituximab. The aim of this case presentation is to call attention to HBV reactivation possibility in cases taking immunosupressive medications like Rituximab.

Keywords

• Waldenström\'s macroglobulinemia, rituximab, occult HBV infection

Waldenström makroglobulinemili hastada rituksimab tedavisi sonrası gelişen gizli hepatit B reaktivasyonu

Öz

Anti CD 20 monoklonal antikor olan rituksimab B hücreli lenfomaların tedavisinde yaygın olarak kullanılmaktadır. Bir çok çalışmada rituksimab tedavisi sonrası hepatit B virüs (HBV) reaktivasyonu gösterilmiştir. Bu vakaların büyük bir kısmı kronik HBV taşıyıcılarında tanımlanmış olmakla birlikte, gizli hepatit B virüs taşıyıcılarında reaktivasyon gelişebilir. Waldenström Makroglobulinemisi tanısı konulan olgumuzda kemoterapi öncesi bakılan HBsAg (-) ve Anti HBc IgG (+) idi. Hastaya CVP (siklofosfamid, vinkristin, prednizolon) kemoterapisi başlandı. Ancak klinik ve laboratuar olarak yanıt alınamadı ve hasta 3 kürlük CVP tedavisine yanıtsız kabul edildi. Hastaya ikinci basamak tedavi olarak R-CHOP (rituksimab, siklofosfamid, adriamisin, vinkristin ve prednizolon) verilmesi planlandı. 1. kür R-CHOP tedavisi sonrası yapılan tetkiklerde aspartat aminotransferaz (AST) değeri: 267 U/L ve alanin aminotransferaz (ALT) değeri: 318 U/L olarak bulundu. Bakılan HBs Ag (+), HBV DNA: 56400 İU/ml ve Anti HBcIgG (+) olarak saptandı. Lamuvidin 100 mg/gün başlandı. Lamuvidin tedavisinin başlanmasından 4 hafta sonra AST ve ALT değerleri normale döndü. Hasta en son olarak 4. kür R-CHOP tedavisini aldı. AST ve ALT değerleri normal aralıkta olarak takip ediliyor. Bu durum Rituksimab sonrası gelişen gizli hepatit B reaktivasyonu olarak kabul edildi. Bu vakayı sunmamızdaki amaç; Rituksimab gibi immünsüpressif tedavi alan olgularda HBV reaktivasyonu olabileceğine dikkat çekmektir.

Anahtar Kelimeler

• Waldenström makroglobulinemisi, rituksimab, gizli hepatit B enfeksiyonu.

References

1. Iannitto E, Minardi V, Calvaruso G, et al. Hepatitis B virus reactivation and alemtuzumab therapy. Eur J Haematol 2005;74 (3): 254-8.
2. Viganò M, Vener C, Lampertico P, et al. Risk of hepa- titis B surface antigen seroreversion after allogeneic hematopoietic SCT. Bone Marrow Transplant 2011; 46 (1):125-31.
3. Matsue K, Kimura S, Takanashi Y, et al. Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-positive B-cell lymphoma. Can- cer 2010; 116 (20):4769-76.
4. 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(4): 605-11.
5. Zhang B, Wang J, Xu W, Wang L, Ni W. Fatal reactiva- tion of occult hepatitis B virus infection after rituximab and chemotherapy in lymphoma: necessity of antiviral prophylaxis. Onkologie 2010; 33 (10):537-9.
6. Armitage JO. How I treat patients with diffuse large B- cell lymphoma. Blood 2007; 110 (1):29-36.
7. Fukushima N, Mizuta T, Tanaka M, et al. Retrospective and prospective studies of hepatitis B virus reactiva- tion in malignant lymphoma with occult HBV carrier. Ann Oncol 2009; 20 (12):2013-7.
8. European Association for The Study of The Liver: EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009; 50 (2): 227-42.

9. Yeo W, Chan PK, Chan HL, Mo FK, Johnson PJ. Hepa- titis B virus reactivation during cytotoxic chemothera- py-enhanced viral replication precedes overt hepati- tis. J Med Virol 2001; 65(3): 473-7.
10. Khaled Y, Hanbali A. Hepatitis B virus reactivation in a case of Waldenstrom’s macroglobulinemia treated with chemotherapy and rituximab despite adefovir prophylaxis. Am J Hematol 2007; 82 (7):688.
11. Gutfreund KS, Williams M, George R, et al. Genotypic succession of mutations of the hepatitis B virus poly- merase associated with lamivudine resistance. Hepa- tology 2000; 33 (3):469-75.
12. Lalazar G, Rund D, Shoouval D. Screening, preven- tion and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Hae- matol 2007; 136 (5): 699-712.