A Rare Case of Pembrolizumab-Induced Reactivation of Hepatitis B

Pandey, Anita; Ezemenari, Susan; Liaukovich, Maksim; Richard, Ivan N.; Avezbakiyev, Boris

doi:10.1155/2018/5985131

Cited by 41 publications

(52 citation statements)

References 17 publications

(20 reference statements)

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“…61 Hepatitis related to exacerbation of HBV infection has also been reported in patients who were subsequently found to be HBsAg positive. 62,63 The risk of reactivation in those who are only anti-HBc positive is thought to be low. 9 Interestingly, checkpoint inhibitors are also being investigated in the treatment of chronic hepatitis B by potentially overcoming the T-cell exhaustion that is observed.…”

Section: Specific Immunosuppressive Treatmentsmentioning

confidence: 99%

Reactivation of hepatitis B virus infection in patients with hematologic disorders

Wang¹,

Mufti

Agarwal³

2019

Haematologica

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Hepatitis B reactivation is the reappearance or rise of hepatitis B virus (HBV) DNA in patients with past or chronic HBV infection, usually occurring in the context of immunosuppression. HBV reactivation has been most commonly reported in patients with hematologic disorders, with potentially serious and life-threatening consequences. In this review, we discuss the basis and presentation of HBV reactivation, and risk factors in terms of the host, the virus and the immunosuppression regimen, including newer agents used to manage hematologic malignancies. We overview the management of HBV reactivation, highlighting an up-dated recommendation on the use of newer nucleoside and nucleotide analogs, such as tenofovir and entecavir, for antiviral prophylaxis.

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Section: Specific Immunosuppressive Treatmentsmentioning

confidence: 99%

Reactivation of hepatitis B virus infection in patients with hematologic disorders

Wang¹,

Mufti

Agarwal³

2019

Haematologica

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“…Unfortunately, there are limited published data describing the safety of anti-PD-(L)1 antibody for patients with advanced cancers and HBV infection. Several case reports have demonstrated that HBV reactivation does occur in some patients with resolved HBV infection during anti-PD-1 therapy [7–9]. However, the rate of HBV reactivation and potential risk factors are not defined.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition

Zhang¹,

Zhou²,

Chen³

et al. 2019

j. immunotherapy cancer

137

142

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BackgroundHepatitis B virus (HBV) reactivation is a serious complication in patients with cancers and HBV infection undergoing immunosuppressant treatment or chemotherapy. However, the safety of anti-programmed cell death (PD) -1 and anti-programmed cell death-ligand 1 (PD-L1) therapy in these patients is unknown because they were excluded from clinical trials of immunotherapy.MethodsThis retrospective cohort study involved consecutive hepatitis B surface antigen (HBsAg) -positive cancer patients who were referred to Sun Yat-sen University Cancer Center and received an anti-PD-1/PD-L1 antibody between January 1, 2015 and July 31, 2018. The primary end point was the rate of the occurrence of HBV reactivation.ResultsIn total, 114 eligible patients were included, among whom 90 (79%) were male, and the median (range) age was 46 (16–76) years. Six patients (5.3%) developed HBV reactivation, occurring at a median of 18 weeks (range, 3–35 weeks) from the commencement of immunotherapy. Among these patients, all of them had undetectable baseline HBV DNA; one had prophylactic antiviral therapy while five did not; four were positive for Hepatitis B e antigen while the other two were negative. At reactivation, the median HBV DNA level was 3.89 × 104 IU/mL (range, 1.80 × 103–6.00 × 107 IU/mL); five had HBV-related hepatitis and one exhibited increasing HBV DNA level without alanine transaminase elevation. No HBV-related fatal events occurred. The lack of antiviral prophylaxis was the only significant risk factor for HBV reactivation (odds ratio, 17.50 [95% CI, 1.95–157.07], P = .004).ConclusionsHBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication.

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“…34,35 However, most immune-mediated hepatitis B reactivation cases have been reported in patients with severe immunodeficiency (after immunosuppressive chemotherapy or bone marrow transplantation). 10,35,36 In addition, in the rare cases where immunemediated reactivation of hepatitis B was not associated with profound immunosuppression, the episode was easily resolved after HBV antiviral treatment. 36,37 Thus, while the possibility of HBV reactivation should be considered, the risk of fatal hepatitis in immune-competent chronic HBV infection is low according to current available data.…”

Section: Discussionmentioning

confidence: 99%

HBeAg seroconversion is associated with a more effective PD-L1 blockade during chronic hepatitis B infection

et al. 2019

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Background & Aims: Current therapies for chronic hepatitis B virus (HBV) infection control viral replication but do not eliminate the risk of progression to hepatocellular carcinoma. HBV-specific CD8 T cells are necessary for viral control, but they are rare and exhausted during chronic infection. Preclinical studies have shown that blockade of the PD-1:PD-L1 axis can restore HBV-specific T cell functionality. The aim of this study was to analyze how the clinical and treatment status of patients impacts the ability of HBV-specific T cells to respond to PD-L1 blockade. Methods: Expression patterns of the PD-1:PD-L1/PD-L2 axis were analyzed in healthy donors and chronically infected patients in different clinical phases of disease. A functional assay was performed to quantify baseline HBV-specific T cell responses in chronically infected patients. Baseline responses were then compared to those attained in the presence of an anti-PD-L1 monoclonal antibody (MEDI2790). Results: Chronically infected patients were characterized by the upregulation of PD-1 within the T cell compartment and a concomitant upregulation of PD-L1 on myeloid dendritic cells. The upregulation was maximal in HBV e antigen (HBeAg)-positive patients but persisted after HBeAg negativization and was not restored by long-term treatment. HBV reactivity, measured as frequency of HBV-specific T cells, was significantly higher in HBeAg-negative patients with lower HBV DNA levels, independently of HBV surface antigen or alanine aminotransferase levels. Anti-PD-L1 blockade with MEDI2790 increased both the number of IFN-γ-producing T cells and the amount of IFN-γ produced per cell in 97% of patients with detectable HBV reactivity, independently of patients' clinical or treatment status. Conclusion: Patients with lower levels of HBV DNA and the absence of HBeAg have more intact HBV-specific T cell immunity and may benefit the most from PD-L1 blockade as a monotherapy.

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A Rare Case of Pembrolizumab-Induced Reactivation of Hepatitis B

Cited by 41 publications

References 17 publications

Reactivation of hepatitis B virus infection in patients with hematologic disorders

Reactivation of hepatitis B virus infection in patients with hematologic disorders

Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition

HBeAg seroconversion is associated with a more effective PD-L1 blockade during chronic hepatitis B infection

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