Hepatitis B virus reactivation in patients undergoing immune checkpoint inhibition: systematic review with meta-analysis

Ding, Zi-Niu; Meng, Guang-Xiao; Xue, Jun-Shuai; Yan, Lun-Jie; Liu, Hui; Yan, Yu-Chuan; Chen, Zhiqiang; Hong, Jian‐Guo; Wang, Dongxu; Dong, Zhao‐Ru; Li, Tao

doi:10.1007/s00432-022-04133-8

Cited by 12 publications

(10 citation statements)

References 65 publications

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“…HBV reactivation was only found in two patients, both of whom were in the HBsAg (+) group. This result is consistent with previous reports 21–28 . The two patients who developed HBV reactivation did not receive antiviral prophylaxis.…”

Section: Discussionsupporting

confidence: 93%

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Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune‐related hepatitis in non–small cell lung cancer patients with chronic hepatitis B

Hong,

Lee,

Park

et al. 2024

Cancer

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BackgroundThe safety of immune‐checkpoint inhibitors (ICIs) has not been thoroughly investigated in non–small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). The authors analyzed the incidence of hepatitis B virus (HBV) reactivation, immune‐related hepatitis and jaundice in NSCLC patients in a real‐world setting.MethodsA total of 1277 NSCLC patients treated with ICIs were analyzed. Among them, 52 patients were hepatitis B surface antigen (HBsAg) (+) (group A, CHB), 759 patients were HBsAg (–)/hepatitis B core antibody immunoglobulin G (anti‐HBc IgG) (+) (group B, OBI), and 466 patients were HBsAg (–)/anti‐HBc IgG (–) (group C). Among the 52 patients with CHB, 38 (73.1%) were receiving antiviral therapy. The primary end point was HBV reactivation, immune‐related hepatitis, and jaundice. The secondary end points included other immune‐related adverse events and efficacy.ResultsHBV reactivation was observed in two patients (0.2%) who were both in group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed in 14.3% (2 of 14 patients). The incidences of immune‐related hepatitis and jaundice were comparable among the three groups. The incidence of ≥grade 3 other immune‐related adverse events and efficacy were all comparable among the three groups (p > .05 for all comparisons).ConclusionsIn this large, real‐world cohort study, the safety and efficacy of ICIs were comparable in patients with CHB and OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with OBI, the risk of HBV reactivation was minimal.

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Section: Discussionsupporting

confidence: 93%

“…This result is consistent with previous reports. [21][22][23][24][25][26][27][28] The two patients who developed HBV reactivation did not receive antiviral prophylaxis. Fortunately, both patients responded well to treatment with an additional antiviral agent for treatment of HBV reactivation.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune‐related hepatitis in non–small cell lung cancer patients with chronic hepatitis B

Hong,

Lee,

Park

et al. 2024

Cancer

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“…A recent review of 13 ICIs-related studies with 2561 patients showed that chronic hepatitis B (CHB) patients were at higher risk of HBV reactivation than those with past infection (1.0% vs 0%) ( Ding et al., 2022 ). However, we found that 2 patients with past HBV infection developed HBV reactivation.…”

Section: Discussionmentioning

confidence: 99%

“…HBV reactivation was also observed to occur in patients treated with TKIs in combination with ICIs, and combination therapy was an independent risk factor for viral reactivation ( Lei et al., 2023 ; Pan et al., 2022 ). To our best knowledge, previous clinical trials limited to patients with monotherapy and baseline undetectable HBV DNA or less than 100 IU/mL ( Cheng et al., 2020 ; Ding et al., 2022 ). In real world, TACE combined with TKIs plus ICIs are usually used in unresectable advanced stage of HCC patients.…”

Section: Introductionmentioning

confidence: 99%

HBV reactivation and its effect on survival in HBV-related hepatocarcinoma patients undergoing transarterial chemoembolization combined with tyrosine kinase inhibitors plus immune checkpoint inhibitors

Shen

Wang

et al. 2023

Front. Cell. Infect. Microbiol.

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ObjectiveThis study aimed to access hepatitis B virus (HBV) reactivation and its effect on survival in HBV-related hepatocarcinoma (HCC) patients who underwent transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs).MethodsIn this single-center retrospective study, we enrolled 119 HBV-related unresectable advanced HCC patients receiving TACE combined with TKIs plus ICIs. Risk factors for HBV reactivation were analyzed by logistic regression. Kaplan-Meier method was applied to draw the survival curve, and log-rank test was used to compare survival between patients with and without HBV reactivation.ResultsA total of 12 patients (10.1%) encountered HBV reactivation in our study, of which only 4 patients received antiviral prophylaxis. The incidence of HBV reactivation was 1.8% (1/57) in patients with detectable baseline HBV DNA and 4.2% (4/95) in patients with antiviral prophylaxis respectively. Lack of prophylactic antiviral treatment (OR=0.047, 95%CI 0.008-0.273, P=0.001) and undetectable HBV DNA (OR=0.073, 95%CI 0.007-0.727, P=0.026) were independent risk factors for HBV reactivation. The median survival time (MST) for all patients was 22.4 months. No survival difference was observed in patients with or without HBV reactivation. (MST: undefined vs 22.4 months, log-rank test: P=0.614).ConclusionHBV reactivation could occur in HBV-related HCC patients who treated with TACE in combination with TKIs plus ICIs. Before and during the combination treatment, it is necessary to routinely monitor HBV DNA and to take effective prophylactic antiviral therapy.

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“…A total of 13 studies, including 2,561 patients, were included in the meta-analysis. This study reported a pooled incidence rate of HBV reactivation of 10.0% (95% CI, 4–18%), 1.0% (95% CI, 0–2%), and 0.0% (95% CI, 0–0%) in patients with chronic HBV infection without antiviral prophylaxis, chronic HBV infection with antiviral prophylaxis, and past HBV infection, respectively [65]. This was unexpected, and the mechanism of HBV reactivation induced by anti-PD-1/PD-L1 therapy is unclear.…”

Section: Hbv Reactivation Induced By Pd-1/pd-l1 Inhibitorsmentioning

confidence: 99%

Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection

Su,

Ye,

et al. 2023

Dig Dis

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Chronic hepatitis B (CHB) infection is still a major global public health problem, with nearly two billion patients. Although antiviral drugs can inhibit viral replication and reduce hepatitis B virus (HBV) related complications, it is difficult to achieve clinical endpoints due to drug resistance. Immune checkpoint inhibitors (ICIs) are an important strategy to reverse T-cell exhaustion, and rebuilding an effective functional T-cell response is a promising immunomodulatory approach for CHB patients. However, there are still many controversies in the application of ICIs in treating patients with CHB. This article reviews the research progress of ICIs in CHB infection and related issues.

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Hepatitis B virus reactivation in patients undergoing immune checkpoint inhibition: systematic review with meta-analysis

Cited by 12 publications

References 65 publications

Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune‐related hepatitis in non–small cell lung cancer patients with chronic hepatitis B

Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune‐related hepatitis in non–small cell lung cancer patients with chronic hepatitis B

HBV reactivation and its effect on survival in HBV-related hepatocarcinoma patients undergoing transarterial chemoembolization combined with tyrosine kinase inhibitors plus immune checkpoint inhibitors

Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection

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