Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis B virus (HBV) reactivation is a known risk in cancer patients receiving cytotoxic or immunosuppressive therapy; however, the risk associated with newer molecularly-targeted agents has not been well-quantified. Imatinib, a small molecule inhibitor directed against BCR-ABL, CKIT, and other tyrosine kinases, has been associated with HBV reactivation primarily in patients treated for chronic myelogenous leukemia. Herein we present the first reported case of a patient who developed HBV reactivation while receiving imatinib therapy for a gastrointestinal stromal tumor (GIST) in the adjuvant setting. This eventually resulted in fulminant liver failure and was effectively treated with living-related donor liver transplant and anti-viral medication. Currently, no guidelines exist for HBV screening prior to imatinib therapy. This report emphasizes the need for such guidelines and supports the idea that viral reactivation is a risk in all imatinib-treated patients, regardless of the underlying disease.
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PMID:Hepatitis B viral reactivation secondary to imatinib treatment in a patient with gastrointestinal stromal tumor. 2498 79

Reactivation of hepatitis B virus (HBV) following immunosuppressive therapy or hematopoietic stem cell transplantation is a potentially fatal complication that may occur even in patients with prior resolution of HBV infection. Dasatinib is a small-molecule inhibitor of the tyrosine kinases SRC and ABL that has been approved for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. Here, we report the first case of reactivation of resolved infection with the HBV immune escape mutant G145R in a CML patient receiving dasatinib. Although dasatinib is not recognized as an immunosuppressant, our observations suggest that dasatinib may enhance HBV replication and induce its reactivation in immunocompetent patients, that HBV escape mutants may contribute to the pathogenesis of HBV reactivation, and that close monitoring of HBV status is advisable in patients with current or resolved HBV infection.
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PMID:Reactivation of resolved infection with the hepatitis B virus immune escape mutant G145R during dasatinib treatment for chronic myeloid leukemia. 2584 92

Sanger sequencing or DNA hybridization have been the primary modalities for hepatitis B (HBV) resistance testing and genotyping; however, there are limitations, such as low sensitivity and the inability to detect novel mutations. Next-generation sequencing (NGS) for HBV can overcome these limitations, but there is limited guidance for clinical microbiology laboratories to validate this novel technology. In this study, we describe an approach to implementing deep pyrosequencing for HBV resistance testing and genotyping in a clinical virology laboratory. A nested PCR targeting the pol region of HBV (codons 143 to 281) was developed, and the PCR product was sequenced by the 454 Junior (Roche). Interpretation was performed by ABL TherapyEdge based on European Association for the Study of the Liver (EASL) guidelines. Previously characterized HBV samples by INNO-LiPA (LiPA) were compared to NGS with discordant results arbitrated by Sanger sequencing. Genotyping of 105 distinct samples revealed a concordance of 95.2% (100/105), with Sanger sequencing confirming the NGS result. Resistance testing by NGS was concordant with LiPA in 85% (68/80) of previously characterized samples. Additional mutations were found in 8 samples, which related to the identification of low-level mutant subpopulations present at <10% (6/8). To balance the costs of testing for the validation study, reproducibility of the NGS was investigated through an analysis of sequence variants at loci not associated with resistance in a single patient sample. Our validation approach attempts to balance costs with efficient data acquisition.
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PMID:Implementation of Next-Generation Sequencing for Hepatitis B Virus Resistance Testing and Genotyping in a Clinical Microbiology Laboratory. 2653 48

The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis.
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PMID:Infections in patients on BCR-ABL tyrosine kinase inhibitor therapy: cases and review of the literature. 2938 66

Patients undergoing cytotoxic or immunosuppressive therapy for cancer have an established predilection for hepatitis B virus reactivation; however, the risk associated with newer molecularly targeted agents has not been well investigated. Imatinib, a small molecule tyrosine kinase inhibitor, induces rapid and sustained clinical benefit by inhibiting a number of signaling pathways, including BCR-ABL and c-KIT. We report the case of a patient who developed hepatitis B virus reactivation while receiving imatinib therapy for gastrointestinal stromal tumor. Furthermore, a structured literature search of the medical databases consisting of MEDLINE and PubMed was performed using the terms "hepatitis B", "reactivation", and "imatinib". The search identified nine case reports only. The data on patients' characteristics, epidemiology, clinical features, comorbid conditions, diagnosis, and management are summarized. Imatinib-associated hepatitis B virus reactivation was reported in seven patients with chronic myeloid leukemia, one with desmoid tumor, and one with gastrointestinal stromal tumor. This review serves to outline our current understanding of the epidemiology, risk factors, and pathophysiology of chronic hepatitis B virus reactivation secondary to imatinib therapy as well as the current approaches to diagnosis and management of this condition. We aim to increase awareness about this possible association and advocate for hepatitis B virus screening prior to imatinib therapy, especially in patients who are at increased risk for chronic hepatitis B virus infection.
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PMID:Hepatitis B virus reactivation following imatinib therapy: A comparative review of 9 cases. 3007 2

Molecular targeted therapy is medical treatment targeting specific molecules, which are essential in the pathology of diseases. Most agents used are monoclonal antibodies ("biologics") and low-molecular-weight compounds. Molecular targeted therapy is widely utilized against malignancies, such as imatinib for chronic myelogenous leukemia blocking BCR-ABL tyrosine kinase, gefitinib for non-small cell lung cancer interrupt- ing signal transduction through EGFR, and trastuzumab for HER2-positive breast cancer. It is a companion diagnostic used as a companion to a molecular targeted drug to determine its applicability for a specific patient, showing the importance of laboratory tests for cancer treatment. While the pathogeneses of connective tissue diseases are still unknown, recent progress in understanding the pathophysiology enables us to use molecular targeted drugs for effective treatment. Rheumatoid arthri- tis (RA) is the most common connective tissue disease, and inflammatory cytokines such as TNFa and IL-6 play a pivotal role in the pathogenesis of RA. In Japan, successful treatment of RA with a chimeric antibody to TNFa(infliximab) is followed by a number of anti-cytokine drugs, such as humanized anti-TNFa, anti- TNF receptor, and anti-IL-6 receptor antibodies. A fusion protein (abatacept), an inhibitor of activated T- cells, composed of the extracellular domain of CTLA-4 and the Fc region of IgG1, and more recently Janus kinase inhibitor (tofacitinib), have also been demonstrated to be highly effective. Since molecular targeted therapy suppresses the immune function, patients receiving the therapy become susceptible to infection. Thus, clinical laboratory tests are of great importance, not only to classify potentially high-risk patients (especially in the case of the so-called post-infectious state of tuberculosis and hepatitis B to avoid reactivation) before treatment but also for the early detection of infections during treatment. [Review].
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PMID:[Molecular Targeted Therapy and Laboratory Tests]. 3069 30