Incidence of grade 3-4 liver injury under immune checkpoints inhibitors: A retrospective study

Parlati, Lucia; Vallet-Pichard, Anaı̈s; Batista, Rui; Hernvann, Alain; Sogni, Philippe; Pol, Stanislas; Mallet, Vincent

doi:10.1016/j.jhep.2018.08.014

Cited by 44 publications

(33 citation statements)

References 7 publications

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“…Reportedly, extrahepatic bile duct could also be involved, which represented dilatation of extrahepatic biliary [32]. Elevation of alkaline phosphatase, γ-glutamyl transpeptidase and bilirubin are predominant laboratory findings in the cases with cholangiopathy [43].…”

Section: Difference Of Clinical and Pathological Feature Between Automentioning

confidence: 99%

Liver damage related to immune checkpoint inhibitors

Nishida

Kudo

2019

Hepatol Int

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Recently, immune checkpoint inhibitors are becoming one of the key agents of systemic treatment of cancer. The anti-cancer mechanism of this type of agent is totally different from that of conventional therapies; blockade of regulatory receptors and ligand of immune checkpoint molecules arose anti-tumor immunity with durable response. However, owing to its unique action to host immune system, immune checkpoint inhibitors sometimes induce immune-related adverse events (irAEs) which has not been observed for conventional chemotherapies. It has been reported that irAEs are manageable by discontinuation of immune checkpoint inhibitors and corticosteroid. However, severe irAEs might lead to the unsuccessful management of cancer treatment. It is conceivable that irAEs during the treatment of immune checkpoint blockade might mimic the autoimmune disease of the specific organ, such as autoimmune hepatitis (AIH). However, detail of the pathogenesis of irAEs has not been well estimated. In this review, we specially focused on this important issue and discussed the liver toxicity of this type of agent in the context of comparison of clinical and pathological findings of liver damage related to irAEs and AIH.

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Section: Difference Of Clinical and Pathological Feature Between Automentioning

confidence: 99%

Liver damage related to immune checkpoint inhibitors

Nishida

Kudo

2019

Hepatol Int

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“…Considering the paucity of symptoms related to liver damage, the American Society of Clinical Oncology (ASCO) recommends monitoring AST, ALT and bilirubin prior to each infusion and/or weekly if a grade 1 liver function test elevations is detected . In a single‐centre retrospective analysis, 23.1% of patients who received immune checkpoint inhibitors developed a more than grade 3 liver function test abnormality with cholestatic liver injury, hepatocellular liver injury and mixed hepatocellular/cholestatic liver injury occurring in 41 (60.3%), 20 (29.4%) and 7 (10.3%) patients, respectively . The degree of irAEs should be classified according to the Common Terminology Criteria for Adverse Events (CTCAE), taking in account that in patients with advanced liver disease those systems can underestimate the damage.…”

Section: Liver Side Effects During Therapy With Checkpoint Inhibitorsmentioning

confidence: 99%

“…Liver biopsy is the gold standard to confirm the diagnosis of liver‐involving irAEs and to assess the degree of liver damage but it is optional in patients with a CTCAE grade 2 hepatitis and is recommended only in patients with CTCAE grade 3‐4 hepatitis . Toxicity related to anti‐CTLA‐4 mAb is associated with the presence of granulomatous hepatitis including fibrin ring granulomas and central vein endotheliitis whereas anti‐PD‐1/PD‐L1 toxicity is characterised by lobular hepatitis without granuloma …”

Section: Liver Side Effects During Therapy With Checkpoint Inhibitorsmentioning

confidence: 99%

“…67 Toxicity related to anti-CTLA-4 mAb is associated with the presence of granulomatous hepatitis including fibrin ring granulomas and central vein endotheliitis whereas anti-PD-1/PD-L1 toxicity is characterised by lobular hepatitis without granuloma. 65 The key elements for the management of irAEs during check- Moreover, for steroid and mycophenolate-refractory cases, there is anecdotal evidence that tacrolimus or antithymocyte globulin may be employed as third line of treatment. 71,72 Of note, despite being commonly used as an alternative to steroids in the management of irAEs, infliximab should not be used in this setting due to its wellestablished role as cause of liver injury.…”

Section: Liver S Ide Effec Ts During Ther Apy With Check P Oint Inhmentioning

confidence: 99%

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Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects

Lombardi

Mondelli

2019

Aliment Pharmacol Ther

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Summary Background Immune checkpoint inhibitors have revolutionised the oncological landscape in the last few years. Possible applications include the treatment of hepatocellular carcinoma and cholangiocarcinoma. Unfortunately, new immune‐related adverse effects have been associated with the use of these agents and the liver is one of the organs most frequently involved. Aims To provide a general overview of the potential impact of immune checkpoint inhibitors on the liver Methods We reviewed the literature and abstracts/presentations on immune checkpoint inhibitors at most relevant hepatology meetings over the last 5 years. Results The role of immune checkpoint inhibitors has been investigated both for the treatment of viral hepatitis and primary liver cancer. Hepatocellular carcinoma and chronic hepatitis B show the greatest potential for treatment with these drugs in the near future. However, immune‐related adverse events involving the liver are a growing concern related to their widespread use. Conclusions Immune checkpoint inhibitors represent an exciting new class of drugs with currently limited application in malignant and non‐malignant liver disease. Caution must be exercised on the emergence of potentially severe immune adverse reactions.

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“…7 Recently, percentages as high as 23% of grade 3 liver function test abnormality in clinical practice has been reported for combined CPI. 8 In addition, in some cases of irH, histological findings of autoimmune hepatitis have been reported, 9 and corticosteroids have been proposed as the treatment of choice in line with the treatment of autoimmune hepatitis (AIH). 4 However, to date, similarities and differences between irH and autoimmune hepatitis have been scarcely reported.…”

Section: Introductionmentioning

confidence: 99%

Immune‐related hepatitis related to checkpoint inhibitors: Clinical and prognostic factors

Riveiro‐Barciela

Barreira‐Díaz

Vidal‐González

et al. 2020

Liver International

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Background & Aims: Check point inhibitors (CPI) have improved survival of oncology patients but adverse effects that mimic autoimmune disorders have been reported. Our aim was describe the characteristics of immune-related hepatitis (irH) and prognosis, and compared them to those of patients with autoimmune hepatitis (AIH). Methods: This is a retrospective study including all grade ≥ 3 (severe) irH diagnosed among 414 patients treated with CPI from 2016 to 2018. Results: Twenty-eight cases of severe irH were recorded: 10 on anti-CTLA-4 ± anti-PD1/PD-L1 and 18 on anti-PD1/PD-L1. Half were female, age 63 years, median time on CPI three cycles. Four (14.3%) presented acute liver injury or failure and one (3.6%) died as consequence. 94% presented normal immunoglobulin G (IgG). Six (21.4%) patients were retreated with CPI and none presented relapse or new immune-related adverse events after a median cycles of 11 (range 6-36). Subjects with irH were older and had lower IgG values than a cohort of AIH (N = 38). Presentation tended to be more severe in AIH. Twenty-five percent of irH and 84% AIH presented ANAs ≥ 1:80 (P = .001). In irH Initial dose of corticosteroids was higher (60 vs 30 mg, P < .001) but duration shorter (2.3 vs 7 months, P < .001) and frequently in monotherapy (41.7% vs 91.3%, P < .001). Conclusions: Immune-related hepatitis can lead to acute liver failure, with absence of increased values of IgG and ANAs. In contrast to autoimmune hepatitis, initial corticosteroids dose were higher, duration shorter with few requiring additional immunosuppression. Retreatment with CPI was not associated with recurrence.

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Incidence of grade 3-4 liver injury under immune checkpoints inhibitors: A retrospective study

Cited by 44 publications

References 7 publications

Liver damage related to immune checkpoint inhibitors

Liver damage related to immune checkpoint inhibitors

Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects

Immune‐related hepatitis related to checkpoint inhibitors: Clinical and prognostic factors

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