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©The Author(s) 2023.
World J Hepatol. Nov 27, 2023; 15(11): 1188-1195
Published online Nov 27, 2023. doi: 10.4254/wjh.v15.i11.1188
Published online Nov 27, 2023. doi: 10.4254/wjh.v15.i11.1188
Immunosuppressive therapies with high risk of HBVr | ||||||||
B-cell depleting therapies (rituximab and ofatumumab) | Anthracycline derivatives (doxorubicin and epirubicin) | Corticosteroids | TNF-α inhibitors (infliximab, adalimumab, certolizumab) | Anti-CD52 monoclonal antibody (alemtuzumab) | ||||
Increased HBVr risk in positive HBsAg and negative HBsAg and anti-HBc subjects by acting against the B-lymphocyte antigen CD20; The Food and Drug Administration has placed a black box warning for rituximab regarding HBVr in rituximab-treated individuals; used to treat CD20+ blood cancers (lymphomas, CLL) and IRD; B cells play a previously underestimated role in HBV immune control by producing neutralizing antibodies; rituximab associated with > 5× increase in HBVr risk (incidence 3%–55%, overall mortality rate 30%–38%) | High-risk for patients with hepatocellular carcinoma and hepatitis B undergoing TACE; used to treat lymphomas and acute leukemias, breast and ovarian cancer, and sarcoma; HBVr rate = 41% in patients with HBsAg positive | Prednisone use > 20 mg p.o. daily > 4 wk | TNF-α can activate the APOBEC antiviral pathway which causes the degradation of cccDNA in HBV-infected cells. HBVr pooled incidence in patients with resolved HBV infection = 3.0% vs 15.4% in HBsAg positive patients | Used for refractory CLL; causes reverse HBsAg seroconversion and reactivation-related hepatitis | ||||
Immunosuppressive agents with moderate risk of HBVr | ||||||||
Less potent TNF-α inhibitors (etanercept) | Cytokine or integrin inhibitors (abatacept, ustekinumab, natalizumab, vedolizumab) | Tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib) | Proteasome inhibitors: (Bortezomib) | Histone deacetylase inhibitors (HDIs) (romidepsin) | Prednisone 10-20 mg p.o. daily > 4 wk | Calcineurin inhibitors (cyclosporine or tacrolimus) | ||
Moderate risk of HBVr in patients with HBsAg positive (1%-5%) and even lower in patients with HBsAg negative | Commonly utilized in the treatment of IBD, IRD and dermatologic conditions; inhibit local inflammatory response associated with immune-mediated diseases by blocking the localization and traffic of activated lymphocytes | Standard of treatment for all phases of CML; also used in the treatment of GIST; inhibit various kinase signaling pathways, essential for immune activation and proliferation of lymphocytes, with an important role in immune control of HBV replication; prophylactic antiviral therapy and regular monitoring of HBV DNA and liver enzymes are essential; reported HBVr rates of 26%–34.8% | Used for the treatment of MM and induction therapy for transplant- eligible patients prior to stem cell harvest; target cellular pathways that interfere with the functions of healthy B cells, which are important in HBV immune control | Used in the treatment of T-cell lymphomas; inhibit histone deacetylase, a histone-modifying enzyme that is important for epigenetic regulation of gene expression with possible deacetylation status of silent cccDNA, resulting in active HBV transcription and then HBVr | The mechanism is two-fold: The HBV genome contains a transcription regulatory element responsive to glucocorticoid that is up-regulated by corticosteroids, resulting in increased viral replication; a directly suppressive effect on cytotoxic T cells that are involved in HBV control; risk of HBVr of 10%-15.8% in HBsAg positive individuals | Suppress T cell function by inhibiting calcineurin required for signal transduction of T cell activation and inhibiting transcription of interleukin required for T cell proliferation | ||
Immunosuppressive agents with low risk of HBVr | ||||||||
Methotrexate, azathioprine or 6-mercaptopurine | Intra-articular steroid injections or prednisone < 10 mg p.o. daily | |||||||
Documented cases of HBVr are rather rare | ||||||||
Novel therapies | ||||||||
Immune checkpoint inhibitors such as anti-PD-L1 (nivolumab) and anti-CTLA4 (ipilimumab) | BTK inhibitor ibrutinib and PI3K delta inhibitor idelalisib | Ruxolitinib | Mogamulizumab | Brentuximab | Obinutuzumab | Hypomethylating agents: Decitabine, azacitidine | Daratumumab | |
HBVr rarely reporter; anti-HBV prophylaxis is recommended | B-cell receptor signaling modulators; approved by the FDA for the treatment of CLL and certain low-grade NHL; HBVr has been rarely been reported; anti-HBV prophylaxis is recommended | A novel inhibitor of JAK1 and JAK2 that has been approved for the treatment of patients with MPNs; There are reported cases of HBVr | Humanized monoclonal antibody targeting the C-C chemokine receptor 4; Used for ATLL; HBVr cases have been reported | Anti-CD30 drug conjugated antibody; used in the treatment of relapsed or refractory HL and CD30 positive T-cell lymphoma; There are reported cases of HBVr | Newer generation anti-CD20 monoclonal antibody, similar to rituximab but with greater efficacy; FDA has mandated a warning of the risk of HBVr with obinutuzumab and HBVr has been reported | Used in the treatment of AML; anti-HBV prophylaxis is recommended | Monoclonal antibody against CD38; used in the treatment of hematologic malignancies of B cells; HBVr cases have been reported |
- Citation: Adesola AA, Cozma MA, Chen YF, Srichawla BS, Găman MA. Risk of hepatitis B reactivation in patients with myeloproliferative neoplasms treated with ruxolitinib. World J Hepatol 2023; 15(11): 1188-1195
- URL: https://www.wjgnet.com/1948-5182/full/v15/i11/1188.htm
- DOI: https://dx.doi.org/10.4254/wjh.v15.i11.1188