Hepatitis B prophylaxis in chronic myeloid leukemia patient on Tyrosine kinase inhibitor with previous hepatitis B infection: Case report and literature review

DOI: https://doi.org/10.21203/rs.3.rs-905521/v1

Abstract

Hepatitis B virus reactivation is a well-known risk in cancer patients who are receiving cytotoxic chemotherapy and may result in different forms of liver injury including fulminant liver failure and death. There are increasing concerns regarding the risk of Hepatitis B reactivation among chronic myeloid leukemia patients who are receiving tyrosine kinase inhibitors. Reactivation risk is not limited to chronic carrier patients but also involves people who have previous Hepatitis B virus infection. This report describes the importance of starting hepatitis B prophylaxis in a newly diagnosed chronic myeloid leukemia patient who was found to have positive hepatitis B anticore antibody before starting tyrosine kinase inhibitor.

Introduction

Chronic myeloid Leukemia (CML) is a myeloproliferative disorder resulting from abnormal production and proliferation of granulocytes[1]. It is associated with Philadelphia (Ph) chromosome which is a reciprocal translocation between chromosomes 9 and 22 resulting in BCR-ABL1 tyrosine kinase gene production[2]. This gene is the target of Tyrosine kinase inhibitors (TKIs) such as Imatinib, dasatinib and nilotinib, which are now the standard of CML management[3]. Cancer patients who are receiving cytotoxic chemotherapy are at higher risk for hepatitis B virus (HBV) reactivation (HBVr) which may cause various forms of liver injury including fulminant liver failure and death[4], [5]. This risk is not limited to HBsAg-positive patients but it also includes HBsAg-negative cases with positive hepatitis B core antibody (HBcAb) which means previous HBV infection [6], [7]. There are increasing concerns regarding the risk of HBVr among CML patients who are receiving TKIs, which may necessitate testing liver function and hepatitis B serology and prescribing prophylaxis if indicated before starting TKIs [7]–[9].

Here we are reporting the management of a newly diagnosed CML patient who was found to have positive hepatitis B core antibody before starting TKI.

Case report

A 46-year-old female patient with no past medical history of note. She presented to Emergency department (ED) complaining of headache for 3 days, she denied any other complaint. She was vitally stable and physical examination was unremarkable.

Investigation showed marked leukocytosis. CBC revealed: WBC: 81.3 × 109/L, HG:11.3 gm/dL, platelets: 1751 x 109/L, Neutrophils: 65 × 109/L, lymphocytes: 5.7 × 109/L. monocytes: 1.6 × 109/L, eosinophils: 1.6 × 109/L, basophils:0.81 × 109/L.

Peripheral smear reported marked neutrophil leukocytosis with marked shift to left, eosinophilia, basophilia and scanty circulating blasts. These findings are in keeping with myeloproliferative neoplasm, favoring CML.

Abdomen ultrasounds didn’t show hepatosplenomegaly or lymphadenopathy.

Bone marrow biopsy showed features consistent with CML BCR-ABL1 positive with morphological features of chronic phase.

At the time of diagnosis, patient had normal liver function tests (aspartate

aminotransferase (AST) 26 U/L, alanine aminotransferase

(ALT) 25 U/L, and total bilirubin 5 umol/L.

As part of screening before starting TKI, hepatitis serology was sent and it showed positive hepatitis B core antibody, positive hepatitis B surface antibody, negative HBV surface antigen, undetectable hepatitis B DNA, negative hepatitis C antibody and negative HIV test.

Patient was started on imatinib and entecavir. Follow up over the next 6 months showed good medication tolerance and normal liver function tests.

Discussion

Hepatitis B infection is a global health problem with estimates of about 350 million people have chronic infection with future risks of developing chronic liver disease and hepatocellular carcinoma[10]. Liver injury is a serious complication of HBVr in cancer patients who are receiving chemotherapy [4], [5].

HBVr is an increase in viral replication in patient who has chronic HBV infection or prior HBV infection. As per American Association for the Study of Liver Diseases (AASLD), HBVr is defined as: an elevation of ALT three times above the baseline, Seroconversion to HBsAg positive for HBsAg-negative, HBcAb-positive patients or an elevation in HBV DNA in comparison to baseline [11].

There are multiple risk factors for HBVr which include old age, liver cirrhosis, male sex and underlying disease but being on immunosuppressive and cytotoxic medication carries the highest risk [12]. The American Gastroenterology association has categorized the risk of HBVr during immunosuppressive treatment into 3 groups: high risk (> 10 %), moderate risk (1–10%) and low risk (< 1%) depending on type of immunosuppression. CML Patients on TKIs fall in moderate risk group [13]. The mechanism by which TKIs cause HBVr still unclear. In vitro studies showed that TKIs can inhibit T-cell activation and proliferation which may lead to HBVr [14].

Providing this moderate risk of HBVr after commencing TKIs, and the reported serious consequences including fulminant liver failure and death[8], [9], our patient was screened with sending liver function tests and hepatitis B serology which came positive for hepatitis B core and hepatitis B surface antibodies, negative HBV surface antigen, and undetectable hepatitis B DNA indicating previous HBV exposure.

HBVr risk is not limited to chronic carrier patients but it also involves people who have previous HBV infection and hepatitis B virus DNA should be checked to rule out hidden infection[7], [15]. Antiviral prophylaxis was recommended in moderate and high-risk groups[13].So our patient was started on entecavir with clinical and laboratory follow up.

The next clinical question is for how long we have to keep our patient on antiviral prophylaxis. As per the American Gastroenterology Association guidelines, patients taking TKIs are stratified as moderate risk (1 to10%) for HBVr and they may continue antiviral prophylaxis until at least 6 months after completion of chemotherapy[16].

In conclusion, HBVr in CML patients on TKI carries a substantial risk of morbidity and mortality which highlights the importance of hepatitis B serology screening before commencing TKIs and to start antiviral agent if needed to achieve better outcome.

Declarations

Ethical Disclosure

Case approved by HMC Medical Research center and the patient signed a written informed consent to publish their case (including publication of images).

Acknowledgment

Internal medicine residency program for scientific support 

Funding source:

Qatar national library  

Authors contributions:

Dr. Awni Alshurafa

Dr. Ahmed Abdalhadi

Dr. Deena  Mudawi1

Dr. Mohamed Yassin 

Equally contributed in witting and editing 

On behalf of all authors, the corresponding author states that there is no conflict of

Interest.

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