Acute Liver Failure following a Single Dose of Atezolizumab, as Assessed for Causality Using the Updated RUCAM

Tzadok, Roie; Levy, Sharon; Aouizerate, Jessie; Shibolet, Oren

doi:10.1155/2022/5090200

Cited by 9 publications

(20 citation statements)

References 20 publications

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“…For monotherapy, atezolizumab might show the strongest risk signal of hepatic failure. There has been one case of acute hepatic failure reported with atezolizumab 5 ; however, it has been reported that ipilimumab, pembrolizumab, and nivolumab were more associated with liver damage. 17 , 18 Considering that atezolizumab was approved later and its adverse effects have only been identified in recent years, our findings may not be enough to conclude that atezolizumab has the highest risk of hepatic failure among all ICIs.…”

Section: Discussionmentioning

confidence: 99%

“… 3 , 4 Recently, some case reports have raised awareness of hepatic failure induced by ICIs. 5 , 6 , 7 A systematic review concluded that the incidence of grade 3 and 4 liver damage induced by ICIs was 0.6%–11% and the incidence of hepatic failure was 0.1%–0.2%. 3 A pharmacovigilance study based on the WHO VigiBase database reported 613 ICI‐associated fatal adverse events from 2009 to January 2018, of which 124 (20.2%) cases were associated with liver damage.…”

Section: Introductionmentioning

confidence: 99%

“…Although most ICI‐associated liver damage usually presents as mild elevations of liver enzymes, hepatic failure induced by ICIs is rare but potentially life‐threatening 3,4 . Recently, some case reports have raised awareness of hepatic failure induced by ICIs 5–7 . A systematic review concluded that the incidence of grade 3 and 4 liver damage induced by ICIs was 0.6%–11% and the incidence of hepatic failure was 0.1%–0.2% 3 .…”

Section: Introductionmentioning

confidence: 99%

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Hepatic failure associated with immune checkpoint inhibitors: An analysis of the Food and Drug Administration Adverse Event Reporting System database

Yan

Zhao

et al. 2023

Cancer Medicine

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Background Hepatic failure induced by immune checkpoint inhibitors (ICIs) has been reported in only a few case series and case reports. Objective We aimed to explore the association between ICIs and hepatic failure and characterize the clinical features of ICI‐associated hepatic failure in the pharmacovigilance database. Methods Data from the first quarter (Q1) of 2015 to the fourth quarter (Q4) of 2021 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved for disproportionality and Bayesian analysis. Reporting odds ratios (ROR) and information component (IC) were used to evaluate correlations between ICIs and hepatic failure. Results Hepatic failure occurred in 0.19% (18,454/9,647,655) of all cases in the FAERS database, of which 654 cases were associated with ICIs. The overall median time from ICIs initiation to hepatic failure onset was 38 days, 72.3% of the adverse events occurred within the first 3 months, and 68.65% of the cases died after developing hepatic failure. In general, a strong signal was shown between ICIs and hepatic failure (ROR 025 = 2.70, IC 025 = 1.39). For the three categories of ICIs, programmed cell death 1 ligand 1 inhibitors (ROR 025 = 3.09, IC 025 = 1.57) had a higher risk signal than programmed cell death protein 1 inhibitors and cytotoxic T lymphocyte‐associated protein 4 inhibitors. For monotherapy, atezolizumab showed the strongest risk signal (ROR 025 = 4.07, IC 025 = 1.90). The combination of nivolumab and ipilimumab showed stronger signals of hepatic failure compared with nivolumab or ipilimumab alone (nivolumab + ipilimumab vs. ipilimumab: ROR 025 = 1.40, IC 025 = 0.16; nivolumab + ipilimumab vs. nivolumab: ROR 025 = 1.24, IC 025 = 0.34). Considering the concomitant agents used with ICIs, the majority of these regimens showed stronger signals than ICI monotherapy, such as acetaminophen (ICIs + acetaminophen vs. ICIs: ROR 025 = 1.06, IC 025 = 0.32). Conclusions ICIs had possible strong signals associated with hepatic failure, and most cases of hepatic failure occurred within the first 3 months and had poor outcomes, which should attract clinical attention.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatic failure associated with immune checkpoint inhibitors: An analysis of the Food and Drug Administration Adverse Event Reporting System database

Yan

Zhao

et al. 2023

Cancer Medicine

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show abstract

“…For monotherapy, atezolizumab showed the strongest risk signal of hepatic failure. There has been one case of acute hepatic failure reported with atezolizumab [5] , however, it has been reported that ipilimumab, pembrolizumab, and nivolumab were more associated with liver damage [15,16] . Considering that atezolizumab was approved later and its adverse effects have only been identi ed in recent years, our ndings may not be enough to conclude that atezolizumab has the highest risk of hepatic failure among all ICIs.…”

Section: Discussionmentioning

confidence: 99%

“…Although most ICI-associated liver damage usually presented as mild elevations of liver enzymes, hepatic failure induced by ICIs was rare but potentially life-threatening [3,4] . Recently, some case reports have raised awareness of hepatic failure induced by ICIs [5,6,7] . A systematic review concluded that the incidence of grade 3 and 4 liver damage induced by ICIs was 0.6-11% and the incidence of hepatic failure was 0.1-0.2% [3] .…”

Section: Introductionmentioning

confidence: 99%

Hepatic Failure Associated with Immune Checkpoint Inhibitors: A Real-world Study from the Food and Drug Administration Adverse Event Reporting System (FAERS) Database

Yan

Zhao

et al. 2022

Preprint

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Background Although Immune checkpoint inhibitors (ICIs) associated liver damage usually presented as mild elevations of liver enzymes, hepatic failure induced by ICIs have been reported in only a few case series and case reports. Objective We aimed to explore the association between ICIs and hepatic failure, and characterize the clinical features of ICI-associated hepatic failure in the real-world database. Methods Data from the first quarter (Q1) of 2015 to the fourth quarter (Q4) of 2021 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved for disproportionality and bayesian analysis. Reporting odds ratios (ROR) and information component (IC) were used to evaluate correlations between ICIs and hepatic failure. Results A total of 654 reports of ICI-associated hepatic failure were identified. The overall median time from ICIs initiation to hepatic failure onset was 38 days, and 72.3% of the adverse events occurred within the first 3 months. Death cases accounted for 68.65%. Generally, a strong signal was shown between ICIs and hepatic failure (ROR025 = 2.70, IC025 = 1.39). For three categories of ICIs, anti-PD-1s (ROR025 = 2.54, IC025 = 1.32) had a higher risk signal than anti-PD-L1s and anti-CTLA-4s. For monotherapy, atezolizumab showed the strongest risk signal (ROR025 = 4.07, IC025 = 1.90). The combination of nivolumab and ipilimumab showed stronger signals of hepatic failure compared with nivolumab or ipilimumab alone(nivolumab + ipilimumab vs. ipilimumab: ROR025 = 1.40, IC025 = 0.16; nivolumab + ipilimumab vs. nivolumab: ROR025 = 1.24, IC025 = 0.34). Considering the concomitant used agents with ICIs, the majority of these regimens showed stronger signals than ICI monotherapy, such as acetaminophen (ICIs + acetaminophen vs. ICIs: ROR025 = 1.06, IC025 = 0.32). Conclusion ICIs had possible strong signals associated with hepatic failure, and most cases of hepatic failure occurred within the first three months and had poor outcomes, which should attract clinical attention.

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Checkpoint Inhibitor Induced Acute Liver Failure

Ezeani,

Ugochukwu,

Johnson

et al. 2024

Journal of Investigative Medicine High Impact Case Reports

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Immune checkpoint inhibitors have become essential antineoplastic agents in medical oncology over the past decade. However, they are associated with potentially fatal multisystem abnormalities, with increasing concern in gastrointestinal tract and its associated organs. We present a patient with advanced renal cell carcinoma, who presented with acute liver failure after the first dose of combined immunotherapy with nivolumab and ipilimumab. A thorough evaluation for viral, metabolic, and autoimmune causes was unremarkable. He was managed with steroids and made significant improvement. To our knowledge, this is the first documented case of acute liver failure following ipilimumab and nivolumab.

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Acute Liver Failure following a Single Dose of Atezolizumab, as Assessed for Causality Using the Updated RUCAM

Cited by 9 publications

References 20 publications

Hepatic failure associated with immune checkpoint inhibitors: An analysis of the Food and Drug Administration Adverse Event Reporting System database

Hepatic failure associated with immune checkpoint inhibitors: An analysis of the Food and Drug Administration Adverse Event Reporting System database

Hepatic Failure Associated with Immune Checkpoint Inhibitors: A Real-world Study from the Food and Drug Administration Adverse Event Reporting System (FAERS) Database

Checkpoint Inhibitor Induced Acute Liver Failure

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